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Calculated Shard: 66 (from laksa165)

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curl -X POST \
  'http://laksa066.int.ahrefs:8124/' \
  -H 'Content-Type: text/plain' \
  -H 'X-ClickHouse-Database: crawler3' \
  -H 'Authorization: Basic YXBpOg==' \
  -d 'SELECT getAhrefsURLFromUnparsed(src_unparsed) AS found_url, ifNull(toUnixTimestamp(download_stamp), 0) AS crawl_time, ifNull(toUnixTimestamp(props_url_first_seen), 0) AS first_indexed_time, download_http_code AS http_code, src_unparsed AS src_unparsed, src_root_hash AS src_root_hash, history_drop_reason AS history_drop_reason, meta_title AS meta_title, meta_descriptions AS meta_descriptions, attrs_boilerpipe_text AS attrs_boilerpipe_text, attrs_markdown AS attrs_markdown, attrs_readable_markdown AS attrs_readable_markdown, meta_canonical AS meta_canonical FROM crawler3.page_info_local FINAL PREWHERE (src_root_hash, src_unparsed) IN ((getAhrefsRootHashFromUnparsed(getAhrefsUnparsedNoserviceFromURL(\'https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html\')), getAhrefsUnparsedNoserviceFromURL(\'https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html\'))) FORMAT JSONEachRow'

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{"found_url":"https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html","crawl_time":1775656504,"first_indexed_time":1697401458,"http_code":200,"src_unparsed":"au,org,tg!australianprescriber,\/articles\/choosing-an-antidepressant.html s443","src_root_hash":"17146461990236247466","history_drop_reason":null,"meta_title":"Choosing an antidepressant","meta_descriptions":["In addition to efficacy and safety, the choice of antidepressant can be guided by the clinical presentation and the patient’s preferences."],"attrs_boilerpipe_text":"SUMMARY\nA biopsychosocial and lifestyle approach should be used when managing depression. Many patients seen in primary care do not require drug therapy.\nEvidence-based treatments such as psychological therapies and antidepressant drugs are effective for depression. All patients should receive education about depression.\nShared decision making with the patient is critical if an antidepressant is prescribed. The choice of antidepressant depends on its efficacy and tolerability, the depressive presentation, patient preference and drug interactions.\nIntroduction\nMajor depression is best conceptualised using a biopsychosocial and lifestyle model.\n1\nAll those factors need to be considered when formulating a management plan. Lifestyle factors (such as alcohol or substance misuse, lack of exercise or poor sleep habits) that may be contributing to the onset and maintenance of the depressive episode need to be dealt with concurrently (see\nTable 1\n). There is a need to be mindful of any psychosocial factors, such as unemployment or interpersonal stress, that maintain the depression.\nAll patients should receive psychoeducation with a discussion about the symptoms of depression, contributing factors and management options. When appropriate this education can involve other people close to the patient.\nTable 1 - Lifestyle factors and interventions for depression\nPotential lifestyle risk factors\nInterventions\nPoor sleep pattern\nEncourage good sleep hygiene – regular   bedtime and wake up time, bed is   for sleep and   not for other   activities (TV, social   media). There are useful apps that provide basic psychoeducation and   a sleep diary.\nAlcohol misuse\nEncourage   safe drinking. If there is heavy use and the patient is seeking   treatment,   refer to an   addiction medicine service. If they are   not seeking treatment, do a brief   intervention.\nSubstance misuse\nProvide psychoeducation about the harmful   effects of substances, advise abstinence,   formal counselling or refer to addiction medicine services.\nSmoking\nEncourage smoking cessation,   and consider motivational interviewing and   nicotine replacement therapy.\nUnhealthy diet\nPsychoeducation about healthy diet and the   harms associated with processed   food. Encourage Mediterranean diet and increased intake of fruit and vegetables.\nLack of exercise\nEncourage   regular exercise (e.g. daily   walks), emphasising a graded approach to exercise.\nSpecific treatments\nWhile attending to lifestyle factors and providing psychoeducation may be helpful for some patients, others need more specific treatments. These are formulation-based psychological treatment and antidepressant drugs. The efficacy of psychological treatment, such as cognitive behavioural therapy, is equivalent to drug therapy in mild–moderate disease. Ideally, psychological treatment should be offered first, unless the patient refuses or is unable to access or afford psychological treatment, or expresses a strong preference for drug treatment. Sometimes there is a clear indication for prescribing an antidepressant drug.\nIndications for drug therapy\nAntidepressant drugs are indicated for patients with:\nmajor depression (characterised by marked symptoms and functional impairment)\nmelancholia (characterised by significant psychomotor symptoms – agitation or retardation)\npsychotic depression (depression with delusions or hallucinations).\nAntidepressants are also indicated for patients who have had a previous good response to them and for when psychological therapies are not accessible or have been ineffective. Even if a drug is indicated, psychoeducation along with basic counselling is still required.\nDrug selection\nThe choice of antidepressant for a particular patient should be based on four major considerations:\nfinding the right balance between efficacy and tolerability\nmatching the antidepressant to the type of depression and its presenting features\nsafety – risk of overdose, interactions with other drugs or medical disorders (some groups need special consideration, such as older patients and women during pregnancy and lactation, as the baby will be exposed to the antidepressant)\n2\npatient preference.\nThere is not yet sufficient evidence confirming that the choice of antidepressant should routinely be made using pharmacogenetic data. Patients, particularly those vulnerable to marketing messages, can be advised that, except in some very special cases, genetic testing is not essential. They can save money by not paying for genetic tests.\nBalancing efficacy with tolerability\nThe efficacy of antidepressant drugs has been confirmed in a network meta-analysis.\n3\nEach antidepressant was compared with other antidepressants using data from randomised placebo-controlled trials. ‘Dual-acting’ antidepressants that target more than one neurotransmitter system, such as the serotonin noradrenaline reuptake inhibitors (SNRIs) and tricyclics, are more efficacious than ‘single-action’ drugs, such as the selective serotonin reuptake inhibitors (SSRIs) like sertraline and escitalopram, based on the odds ratio of achieving a 50% response (see\nTable 2\n).\n3\nThis meta-analysis also examined the acceptability of the various antidepressants by comparing the drop-out rates in clinical trials. While this is a useful metric of acceptability, the rates of adverse effects for each antidepressant are more useful in clinical practice.\nTable 2 - Efficacy of antidepressants compared to placebo\nAntidepressant\nOdds   ratio\n95% confidence interval\nAmitriptyline\n2.13\n1.89–2.41\nMirtazapine\n1.89\n1.64–2.20\nDuloxetine\n1.85\n1.66–2.07\nVenlafaxine\n1.78\n1.61–1.96\nParoxetine\n1.75\n1.61–1.90\nFluvoxamine\n1.69\n1.41–2.02\nEscitalopram\n1.68\n1.50–1.87\nSertraline\n1.67\n1.49–1.87\nVortioxetine\n1.66\n1.45–1.92\nAgomelatine\n1.65\n1.44–1.88\nFluoxetine\n1.52\n1.40–1.66\nCitalopram\n1.52\n1.33–1.74\nClomipramine\n1.49\n1.21–1.85\nDesvenlafaxine\n1.49\n1.24–1.79\nReboxetine\n1.37\n1.16–1.63\nEfficacy is given as the odds ratio of achieving a response (>50% reduction in severity). These studies generally used the typical dose to treat depression (although some of the studies were ‘dose finding’ studies in which lower doses were used).\nSource: adapted from reference 3\nTable 3\nsummarises the common adverse effects ranked according to a ‘limitation’ score for each of the antidepressant classes. The frequency of adverse effects can vary greatly between antidepressant classes, due to having different mechanisms of action. There are fewer differences between drugs in the same antidepressant class, although there are some exceptions.\nTable 3 - Antidepressant adverse effects and their limitations on use\nClass\nMajor adverse effects\nEase of switching   (half-life)\nWeight gain\nCNS effects – sedation\/agitation\nSexual\nWithdrawal syndrome\nSelective serotonin   reuptake inhibitors (SSRIs)\n•\n••\n•••\n••\n†\n••\nSerotonin   noradrenaline reuptake inhibitors (SNRIs)\n•\n••\n•••\n•••\n••\nSerotonin modulator   (vortioxetine)\n•\n•\n••\n••\n•••\nNoradrenaline   reuptake inhibitor (reboxetine)\n•\n•\n••\n•\n••\nTricyclic   antidepressants (TCAs)\n•••\n•••\n•••\n•••\n•••\nReversible   inhibitor of monoamine oxidase A (moclobemide)\n•\n••\n•\n•\n•••\nTetracyclic   (mianserin)\n••\n••\n•\n••\n•\nNoradrenergic   and specific serotonergic (mirtazapine)\n•••\n•••\n••\n••\n•\nMonoamine oxidase   inhibitors (MAOIs)\n••\n•••\n••\n••\n•••\nMelatonergic   (agomelatine)\n•\n•\n•\n•\n•\n• Minimal limitation\n•• Some limitation\n••• Marked limitation\n† There is little variation in the severity of adverse effects within classes of antidepressants (but patients may differ in the adverse effects they experience). One exception is the withdrawal symptoms following discontinuation of SSRIs. There is an absence of withdrawal symptoms for fluoxetine but very severe withdrawal symptoms for paroxetine.\nIn general, for an uncomplicated mild–moderate depression, the first choice of antidepressant should be a drug that will be well tolerated and has good efficacy. The ease of switching treatment\n4\nshould be considered because the first antidepressant may not lead to full remission, requiring the patient to change to a different antidepressant.\n5\nFor patients with a severe depression or melancholia (characterised by significant psychomotor change), the prime consideration is efficacy rather than tolerability. The first choice will then be one of the more potent antidepressants, generally a dual mode-of-action drug, such as an SNRI or a tricyclic antidepressant.\nMatching the antidepressant to the clinical presentation\nAntidepressants differ in the specific symptoms that they target, so it is possible to choose an antidepressant according to the patient’s clinical presentation. It is also possible to use the adverse effects to target specific symptoms. For example, mirtazapine is sedating, so it is an option for patients with significant insomnia. Mirtazapine is also associated with weight gain so it may be useful for major depression accompanied by significant weight loss.\n6\nIn short-term trials, the serotonin modulator vortioxetine benefited patients who had major depression with marked cognitive deficits.\n7\nThe choice of an antidepressant also depends, to some degree, on the symptom profile of the patient or a specific subtype of depression.\n8\nTable 4\nlists the antidepressants that are preferred for different depressive symptom profiles. Many patients with major depression in primary care also have significant symptoms of anxiety or have a comorbid anxiety disorder. The antidepressant of choice here is an SSRI.\n9\nFor patients with a melancholic depression, which has a clear biological underpinning characterised by vegetative symptoms and psychomotor change such as agitation or retardation, a dual-action antidepressant should be the first option. The tricyclic antidepressants or duloxetine may be used in certain neuropathic pain conditions. While they can be prescribed for patients with pain and associated depression, the doses of a tricyclic used to treat major depression need to be higher than those used for adjunctive therapy in pain management.\nTable 4 - Symptoms and initial antidepressant choice\nSymptoms\nPreferred   antidepressant\nAnxiety\nSelective serotonin reuptake inhibitors\nMoclobemide\nWeight loss, reduced appetite\nMirtazapine\nMianserin\nSleep disturbance, insomnia\nAgomelatine\nMirtazapine\nMianserin\nTricyclic antidepressants\nSexual dysfunction\nAgomelatine\nBlunting, anhedonia, demotivation\nSelective serotonin reuptake inhibitors\nSerotonin noradrenaline reuptake inhibitors\nAgomelatine\nMonoamine oxidase inhibitors\nReboxetine\nMelancholia, severe depression\nSerotonin noradrenaline reuptake inhibitors\nTricyclic antidepressants\nVortioxetine\nMonoamine oxidase inhibitors\nPain\nDuloxetine\nTricyclic antidepressants\nCognitive difficulties\nVortioxetine\nSafety considerations\nPatients with depression can often have suicidal thoughts and may try to commit suicide. This needs to be considered when prescribing an antidepressant. A suicidal patient should not be given quantities of a drug that could be fatal in an overdose. The SSRIs have a much lower potential lethality than the tricyclic antidepressants.\nAsk about any other drugs the patient may be taking to avoid potential interactions. For example, there is an increased risk of serotonin toxicity when taking SSRIs in combination with tramadol, St John’s wort or monoamine oxidase inhibitors (MAOIs). SSRIs are also associated with increased bleeding due to changes in platelet function. Caution is therefore needed if they are taken with anticoagulants or non- steroidal anti-inflammatory drugs (NSAIDs). With the increased risk of bleeding, there is a need to consider any comorbid conditions that may add to this risk. In order to limit potential drug and disease interactions, it is recommended that prescribers only use a few antidepressants that they know and understand well.\n10\nPatient preference\nA key consideration is patient preference. Adherence to antidepressants is essential to ensure remission of the depression. A significant proportion of patients will stop their antidepressant.\n11\nAdherence is improved if the patient is involved in the decision about which treatment to take. This involves a discussion about the expected benefits of the antidepressant and its potential adverse effects. Some adverse effects, such as sedation, may be more acceptable to patients, but others such as weight gain may be less acceptable. Be aware that patients might have misinformation from the internet or through word of mouth that the adverse effects of an antidepressant are ‘dreadful and nobody should ever take it’. In such situations, it is essential to listen to the patient’s concerns and present them with clear and accurate information about the drug, including providing them with consumer fact sheets. This approach will improve adherence.\nConclusion\nAfter deciding that a patient needs to take an antidepressant, the choice of drug depends on the severity and symptom pattern of the depressive episode. There has to be a balance between efficacy and tolerability, which also considers patient safety and preference.\nConflicts of interest: Philip\nBoyce\nhas\nreceived\nconsultancy\nand speaker fees, and educational support from Servier. He is on an advisory board and has received educational support\nfrom\nLundbeck.\nAustralian Prescriber welcomes\nFeedback\n.\nReferences\nMalhi GS, Bassett D, Boyce P, Bryant R, Fitzgerald PB, Fritz K, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust N Z J Psychiatry 2015;49:1087-206.\nCentre of Perinatal Excellence. National perinatal mental health guideline. 2017 Oct 27. [cited 2021 Jan 4]\nCipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet 2018;391:1357-66.\nKeks N, Hope J, Keogh S. Switching and stopping antidepressants. Aust Prescr 2016;39:76-83.\nBoyce P, Hopwood M, Morris G, Hamilton A, Bassett D, Baune BT, et al. Switching antidepressants in the treatment of major depression: When, how and what to switch to? J Affect Disord 2020;261:160-3.\nNutt DJ. Tolerability and safety aspects of mirtazapine. Hum Psychopharmacol 2002;17 Suppl 1:S37-41.\nMcIntyre RS, Harrison J, Loft H, Jacobson W, Olsen CK. The effects of vortioxetine on cognitive function in patients with major depressive disorder: a meta-analysis of three randomized controlled trials. Int J Neuropsychopharmacol 2016;19:pyw055.\nBaune BT, Boyce P, Morris G, Hamilton A, Bassett D, Hopwood M, et al. Organising the front line: Is there a rationale for the first-line pharmacotherapy of major depressive disorder? Aust N Z J Psychiatry 2019;53:279-81.\nCoplan JD, Aaronson CJ, Panthangi V, Kim Y. Treating comorbid anxiety and depression: Psychosocial and pharmacological approaches. World J Psychiatry 2015;5:366-78.\nSnyder BD, Polasek TM, Doogue MP. Drug interactions: principles and practice. Aust Prescr 2012;35:85-8.\nKeyloun KR, Hansen RN, Hepp Z, Gillard P, Thase ME, Devine EB. Adherence and persistence across antidepressant therapeutic classes: a retrospective claims analysis among insured US patients with major depressive disorder (MDD). CNS Drugs 2017;31:421-32.","attrs_markdown":"[Skip to main content](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#main)\n\n- [The organisation](\"The organisation\")\n  - [The organisation](https:\/\/www.tg.org.au\/the-organisation\/ \"The organisation\")\n  - [Governance](https:\/\/www.tg.org.au\/the-organisation\/governance\/ \"Governance\")\n  - [Board of directors](https:\/\/www.tg.org.au\/the-organisation\/board-of-directors\/ \"Board of directors\")\n  - [Expert groups](https:\/\/www.tg.org.au\/the-organisation\/expert-groups-2\/ \"Expert groups\")\n  - [Members of Company](https:\/\/www.tg.org.au\/the-organisation\/members-of-company\/ \"Members of Company\")\n  - [History](https:\/\/www.tg.org.au\/the-organisation\/history-of-therapeutic-guidelines\/ \"History\")\n  - [History Timeline](https:\/\/www.tg.org.au\/historytimeline\/ \"History Timeline\")\n  - [Careers](https:\/\/www.tg.org.au\/the-organisation\/careers\/ \"Careers\")\n  - [Guideline development](https:\/\/www.tg.org.au\/the-organisation\/guideline-development\/ \"Guideline development\")\n  - [Partnership program](https:\/\/www.tg.org.au\/the-organisation\/partnership-program\/ \"Partnership program\")\n  - [Research funding](https:\/\/www.tg.org.au\/the-organisation\/research-funding\/ \"Research funding\")\n- [News](https:\/\/www.tg.org.au\/news\/ \"News\")\n- [Products](\"Products\")\n  - [Therapeutic Guidelines](https:\/\/tgldcdp.tg.org.au\/etgcomplete \"Therapeutic Guidelines\")\n  - [Australian Prescriber](https:\/\/australianprescriber.tg.org.au\/ \"Australian Prescriber\")\n  - [Books](https:\/\/www.tg.org.au\/books \"Books\")\n  - [Antibiotic prescribing in primary care: summary table](https:\/\/ccmsfiles.tg.org.au\/s3\/PDFs\/GPSummary_v15.pdf \"Antibiotic prescribing in primary care: summary table\")\n- [Updates](https:\/\/www.tg.org.au\/content-updates\/ \"Updates\")\n- [Contact us](https:\/\/www.tg.org.au\/contact-us\/ \"Contact us\")\n\n- Menu\n\n- [Home](https:\/\/www.tg.org.au\/ \"Home\")\n- [The organisation](https:\/\/www.tg.org.au\/the-organisation\/ \"The organisation\")\n- [News](https:\/\/www.tg.org.au\/news\/ \"News\")\n- [Products](https:\/\/www.tg.org.au\/products\/ \"Products\")\n- [Updates](https:\/\/www.tg.org.au\/content-updates\/ \"Updates\")\n- [Contact us](https:\/\/www.tg.org.au\/contact-us\/ \"Contact us\")\n\n- [Home](https:\/\/australianprescriber.tg.org.au\/)\n- [Choosing an antidepressant](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html)\n\n- [A](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html)\n- [A](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html)\n\n[![Australian Prescriber An independent Review Logo](data:image\/gif;base64,R0lGODlhAQABAIAAAP\/\/\/wAAACH5BAEAAAAALAAAAAABAAEAAAICRAEAOw==)](https:\/\/australianprescriber.tg.org.au\/)\n\n- [All Issues](https:\/\/australianprescriber.tg.org.au\/volumes\/49\/issues\/2.html)\n- [Podcasts](https:\/\/australianprescriber.tg.org.au\/podcast.html)\n- [CPD for GPs](https:\/\/australianprescriber.tg.org.au\/CPD-GP.html)\n- [CPD for Pharmacists](https:\/\/australianprescriber.tg.org.au\/CPD-Pharmacists.html)\n\n[ISSUE 1 FEBRUARY](https:\/\/australianprescriber.tg.org.au\/volumes\/44\/issues\/1.html)\n\n##### Article\n# Choosing an antidepressant\n- Philip Boyce, Cassandra Ma\n\n- Aust Prescr 2021;44:12-15\n- 1 February 2021\n- DOI: [10\\.18773\/austprescr.2020.064](https:\/\/doi.org\/10.18773\/austprescr.2020.064)\n\n- [depression](https:\/\/australianprescriber.tg.org.au\/search?scope=ap&q=depression)\n- [selective serotonin reuptake inhibitors](https:\/\/australianprescriber.tg.org.au\/search?scope=ap&q=selective%20serotonin%20reuptake%20inhibitors)\n- [tricyclic antidepressants](https:\/\/australianprescriber.tg.org.au\/search?scope=ap&q=tricyclic%20antidepressants)\n\n- [Share](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html)\n  \n  - [email](<mailto:?subject=Australian Prescriber - &body=Check out this site for Australian Prescriber, the independent, peer-reviewed journal providing critical commentary on drugs and therapeutics for health professionals: https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html>)\n  - [Facebook]()\n  - [twitter]()\n  - [linkedin]()\n- [Download PDF](https:\/\/australianprescriber.tg.org.au\/assets\/p12-Boyce-Ma_v2.pdf)\n- [Citation](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html)\n  \n  Boyce P, Ma C. Choosing an antidepressant. Aust Prescr 2021;44:12-15. <https:\/\/doi.org\/10.18773\/austprescr.2020.064>\n  \n  [Download .RIS file](https:\/\/australianprescriber.tg.org.au\/download-ris-file\/500441\/austprescr-2020-064.ris)\n\n- [![Podcast](https:\/\/australianprescriber.tg.org.au\/assets\/ecfe6245e791691a-15a4b10e8b90-podcast-new.png)](https:\/\/australianprescriber.tg.org.au\/podcast\/episode-99-how-to-choose-an-antidepressant.html)\n\n[**Subscribe to** **Australian Prescriber**](https:\/\/australianprescriber.tg.org.au\/subscribe)\n\n## SUMMARY\nA biopsychosocial and lifestyle approach should be used when managing depression. Many patients seen in primary care do not require drug therapy.\n\nEvidence-based treatments such as psychological therapies and antidepressant drugs are effective for depression. All patients should receive education about depression.\n\nShared decision making with the patient is critical if an antidepressant is prescribed. The choice of antidepressant depends on its efficacy and tolerability, the depressive presentation, patient preference and drug interactions.\n\n## Introduction\nMajor depression is best conceptualised using a biopsychosocial and lifestyle model.[1](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r1) All those factors need to be considered when formulating a management plan. Lifestyle factors (such as alcohol or substance misuse, lack of exercise or poor sleep habits) that may be contributing to the onset and maintenance of the depressive episode need to be dealt with concurrently (see [Table 1](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#t1)). There is a need to be mindful of any psychosocial factors, such as unemployment or interpersonal stress, that maintain the depression.\n\nAll patients should receive psychoeducation with a discussion about the symptoms of depression, contributing factors and management options. When appropriate this education can involve other people close to the patient.\n\n## Table 1 - Lifestyle factors and interventions for depression\n|   |   |\n|---|---|\n| **Potential lifestyle risk factors** | **Interventions** |\n| Poor sleep pattern | Encourage good sleep hygiene – regular bedtime and wake up time, bed is for sleep and not for other activities (TV, social media). There are useful apps that provide basic psychoeducation and a sleep diary. |\n| Alcohol misuse | Encourage safe drinking. If there is heavy use and the patient is seeking treatment, refer to an addiction medicine service. If they are not seeking treatment, do a brief intervention. |\n| Substance misuse | Provide psychoeducation about the harmful effects of substances, advise abstinence, formal counselling or refer to addiction medicine services. |\n| Smoking | Encourage smoking cessation, and consider motivational interviewing and nicotine replacement therapy. |\n| Unhealthy diet | Psychoeducation about healthy diet and the harms associated with processed food. Encourage Mediterranean diet and increased intake of fruit and vegetables. |\n| Lack of exercise | Encourage regular exercise (e.g. daily walks), emphasising a graded approach to exercise. |\n\n## Specific treatments\nWhile attending to lifestyle factors and providing psychoeducation may be helpful for some patients, others need more specific treatments. These are formulation-based psychological treatment and antidepressant drugs. The efficacy of psychological treatment, such as cognitive behavioural therapy, is equivalent to drug therapy in mild–moderate disease. Ideally, psychological treatment should be offered first, unless the patient refuses or is unable to access or afford psychological treatment, or expresses a strong preference for drug treatment. Sometimes there is a clear indication for prescribing an antidepressant drug.\n\n## Indications for drug therapy\nAntidepressant drugs are indicated for patients with:\n\n- major depression (characterised by marked symptoms and functional impairment)\n- melancholia (characterised by significant psychomotor symptoms – agitation or retardation)\n- psychotic depression (depression with delusions or hallucinations).\n\nAntidepressants are also indicated for patients who have had a previous good response to them and for when psychological therapies are not accessible or have been ineffective. Even if a drug is indicated, psychoeducation along with basic counselling is still required.\n\n## Drug selection\nThe choice of antidepressant for a particular patient should be based on four major considerations:\n\n- finding the right balance between efficacy and tolerability\n- matching the antidepressant to the type of depression and its presenting features\n- safety – risk of overdose, interactions with other drugs or medical disorders (some groups need special consideration, such as older patients and women during pregnancy and lactation, as the baby will be exposed to the antidepressant)[2](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r2)\n- patient preference.\n\nThere is not yet sufficient evidence confirming that the choice of antidepressant should routinely be made using pharmacogenetic data. Patients, particularly those vulnerable to marketing messages, can be advised that, except in some very special cases, genetic testing is not essential. They can save money by not paying for genetic tests.\n\n## Balancing efficacy with tolerability\nThe efficacy of antidepressant drugs has been confirmed in a network meta-analysis.[3](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r3) Each antidepressant was compared with other antidepressants using data from randomised placebo-controlled trials. ‘Dual-acting’ antidepressants that target more than one neurotransmitter system, such as the serotonin noradrenaline reuptake inhibitors (SNRIs) and tricyclics, are more efficacious than ‘single-action’ drugs, such as the selective serotonin reuptake inhibitors (SSRIs) like sertraline and escitalopram, based on the odds ratio of achieving a 50% response (see [Table 2](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#t2)).[3](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r3) This meta-analysis also examined the acceptability of the various antidepressants by comparing the drop-out rates in clinical trials. While this is a useful metric of acceptability, the rates of adverse effects for each antidepressant are more useful in clinical practice.\n\n## Table 2 - Efficacy of antidepressants compared to placebo\n|   |   |   |\n|---|---|---|\n| **Antidepressant** | **Odds ratio** | **95% confidence interval** |\n| Amitriptyline | 2\\.13 | 1\\.89–2.41 |\n| Mirtazapine | 1\\.89 | 1\\.64–2.20 |\n| Duloxetine | 1\\.85 | 1\\.66–2.07 |\n| Venlafaxine | 1\\.78 | 1\\.61–1.96 |\n| Paroxetine | 1\\.75 | 1\\.61–1.90 |\n| Fluvoxamine | 1\\.69 | 1\\.41–2.02 |\n| Escitalopram | 1\\.68 | 1\\.50–1.87 |\n| Sertraline | 1\\.67 | 1\\.49–1.87 |\n| Vortioxetine | 1\\.66 | 1\\.45–1.92 |\n| Agomelatine | 1\\.65 | 1\\.44–1.88 |\n| Fluoxetine | 1\\.52 | 1\\.40–1.66 |\n| Citalopram | 1\\.52 | 1\\.33–1.74 |\n| Clomipramine | 1\\.49 | 1\\.21–1.85 |\n| Desvenlafaxine | 1\\.49 | 1\\.24–1.79 |\n| Reboxetine | 1\\.37 | 1\\.16–1.63 |\n\nEfficacy is given as the odds ratio of achieving a response (\\>50% reduction in severity). These studies generally used the typical dose to treat depression (although some of the studies were ‘dose finding’ studies in which lower doses were used).\n\nSource: adapted from reference 3\n\n[Table 3](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#t3) summarises the common adverse effects ranked according to a ‘limitation’ score for each of the antidepressant classes. The frequency of adverse effects can vary greatly between antidepressant classes, due to having different mechanisms of action. There are fewer differences between drugs in the same antidepressant class, although there are some exceptions.\n\n## Table 3 - Antidepressant adverse effects and their limitations on use\n|   |   |   |   |   |   |\n|---|---|---|---|---|---|\n| **Class** | **Major adverse effects** | **Ease of switching (half-life)** |   |   |   |\n| **Weight gain** | **CNS effects – sedation\/agitation** | **Sexual** | **Withdrawal syndrome** |   |   |\n| Selective serotonin reuptake inhibitors (SSRIs) | **•** | **••** | **•••** | **••**† | **••** |\n| Serotonin noradrenaline reuptake inhibitors (SNRIs) | **•** | **••** | **•••** | **•••** | **••** |\n| Serotonin modulator (vortioxetine) | **•** | **•** | **••** | **••** | **•••** |\n| Noradrenaline reuptake inhibitor (reboxetine) | **•** | **•** | **••** | **•** | **••** |\n| Tricyclic antidepressants (TCAs) | **•••** | **•••** | **•••** | **•••** | **•••** |\n| Reversible inhibitor of monoamine oxidase A (moclobemide) | **•** | **••** | **•** | **•** | ••• |\n| Tetracyclic (mianserin) | **••** | **••** | **•** | **••** | **•** |\n| Noradrenergic and specific serotonergic (mirtazapine) | **•••** | **•••** | **••** | **••** | **•** |\n| Monoamine oxidase inhibitors (MAOIs) | **••** | **•••** | **••** | **••** | **•••** |\n| Melatonergic (agomelatine) | **•** | **•** | **•** | **•** | **•** |\n\n• Minimal limitation\n\n•• Some limitation\n\n••• Marked limitation\n\n† There is little variation in the severity of adverse effects within classes of antidepressants (but patients may differ in the adverse effects they experience). One exception is the withdrawal symptoms following discontinuation of SSRIs. There is an absence of withdrawal symptoms for fluoxetine but very severe withdrawal symptoms for paroxetine.\n\nIn general, for an uncomplicated mild–moderate depression, the first choice of antidepressant should be a drug that will be well tolerated and has good efficacy. The ease of switching treatment[4](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r4) should be considered because the first antidepressant may not lead to full remission, requiring the patient to change to a different antidepressant.[5](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r5)\n\nFor patients with a severe depression or melancholia (characterised by significant psychomotor change), the prime consideration is efficacy rather than tolerability. The first choice will then be one of the more potent antidepressants, generally a dual mode-of-action drug, such as an SNRI or a tricyclic antidepressant.\n\n## Matching the antidepressant to the clinical presentation\nAntidepressants differ in the specific symptoms that they target, so it is possible to choose an antidepressant according to the patient’s clinical presentation. It is also possible to use the adverse effects to target specific symptoms. For example, mirtazapine is sedating, so it is an option for patients with significant insomnia. Mirtazapine is also associated with weight gain so it may be useful for major depression accompanied by significant weight loss.[6](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r6) In short-term trials, the serotonin modulator vortioxetine benefited patients who had major depression with marked cognitive deficits.[7](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r7)\n\nThe choice of an antidepressant also depends, to some degree, on the symptom profile of the patient or a specific subtype of depression.[8](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r8) [Table 4](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#t4) lists the antidepressants that are preferred for different depressive symptom profiles. Many patients with major depression in primary care also have significant symptoms of anxiety or have a comorbid anxiety disorder. The antidepressant of choice here is an SSRI.[9](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r9) For patients with a melancholic depression, which has a clear biological underpinning characterised by vegetative symptoms and psychomotor change such as agitation or retardation, a dual-action antidepressant should be the first option. The tricyclic antidepressants or duloxetine may be used in certain neuropathic pain conditions. While they can be prescribed for patients with pain and associated depression, the doses of a tricyclic used to treat major depression need to be higher than those used for adjunctive therapy in pain management.\n\n## Table 4 - Symptoms and initial antidepressant choice\n|   |   |\n|---|---|\n| **Symptoms** | **Preferred antidepressant** |\n| Anxiety | Selective serotonin reuptake inhibitors Moclobemide |\n| Weight loss, reduced appetite | Mirtazapine Mianserin |\n| Sleep disturbance, insomnia | Agomelatine Mirtazapine Mianserin Tricyclic antidepressants |\n| Sexual dysfunction | Agomelatine |\n| Blunting, anhedonia, demotivation | Selective serotonin reuptake inhibitors Serotonin noradrenaline reuptake inhibitors Agomelatine Monoamine oxidase inhibitors Reboxetine |\n| Melancholia, severe depression | Serotonin noradrenaline reuptake inhibitors Tricyclic antidepressants Vortioxetine Monoamine oxidase inhibitors |\n| Pain | Duloxetine Tricyclic antidepressants |\n| Cognitive difficulties | Vortioxetine |\n\n## Safety considerations\nPatients with depression can often have suicidal thoughts and may try to commit suicide. This needs to be considered when prescribing an antidepressant. A suicidal patient should not be given quantities of a drug that could be fatal in an overdose. The SSRIs have a much lower potential lethality than the tricyclic antidepressants.\n\nAsk about any other drugs the patient may be taking to avoid potential interactions. For example, there is an increased risk of serotonin toxicity when taking SSRIs in combination with tramadol, St John’s wort or monoamine oxidase inhibitors (MAOIs). SSRIs are also associated with increased bleeding due to changes in platelet function. Caution is therefore needed if they are taken with anticoagulants or non- steroidal anti-inflammatory drugs (NSAIDs). With the increased risk of bleeding, there is a need to consider any comorbid conditions that may add to this risk. In order to limit potential drug and disease interactions, it is recommended that prescribers only use a few antidepressants that they know and understand well.[10](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r10)\n\n## Patient preference\nA key consideration is patient preference. Adherence to antidepressants is essential to ensure remission of the depression. A significant proportion of patients will stop their antidepressant.[11](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r11) Adherence is improved if the patient is involved in the decision about which treatment to take. This involves a discussion about the expected benefits of the antidepressant and its potential adverse effects. Some adverse effects, such as sedation, may be more acceptable to patients, but others such as weight gain may be less acceptable. Be aware that patients might have misinformation from the internet or through word of mouth that the adverse effects of an antidepressant are ‘dreadful and nobody should ever take it’. In such situations, it is essential to listen to the patient’s concerns and present them with clear and accurate information about the drug, including providing them with consumer fact sheets. This approach will improve adherence.\n\n## Conclusion\nAfter deciding that a patient needs to take an antidepressant, the choice of drug depends on the severity and symptom pattern of the depressive episode. There has to be a balance between efficacy and tolerability, which also considers patient safety and preference.\n\n*Conflicts of interest: Philip* *Boyce* *has* *received* *consultancy* *and speaker fees, and educational support from Servier. He is on an advisory board and has received educational support* *from* *Lundbeck.*\n\nAustralian Prescriber welcomes [Feedback](https:\/\/australianprescriber.tg.org.au\/contact-us.html).\n\n## References\n1. [Malhi GS, Bassett D, Boyce P, Bryant R, Fitzgerald PB, Fritz K, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust N Z J Psychiatry 2015;49:1087-206.](https:\/\/doi.org\/10.1177\/0004867415617657)\n2. [Centre of Perinatal Excellence. National perinatal mental health guideline. 2017 Oct 27. \\[cited 2021 Jan 4\\]](http:\/\/www.cope.org.au\/health-professionals\/health-professionals-3\/review-of-new-perinatal-mental-health-guidelines)\n3. [Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet 2018;391:1357-66.](https:\/\/doi.org\/10.1016\/S0140-6736\\(17\\)32802-7)\n4. Keks N, Hope J, Keogh S. Switching and stopping antidepressants. Aust Prescr 2016;39:76-83.\n5. [Boyce P, Hopwood M, Morris G, Hamilton A, Bassett D, Baune BT, et al. Switching antidepressants in the treatment of major depression: When, how and what to switch to? J Affect Disord 2020;261:160-3.](https:\/\/doi.org\/10.1016\/j.jad.2019.09.082)\n6. [Nutt DJ. Tolerability and safety aspects of mirtazapine. Hum Psychopharmacol 2002;17 Suppl 1:S37-41.](https:\/\/doi.org\/10.1002\/hup.388)\n7. [McIntyre RS, Harrison J, Loft H, Jacobson W, Olsen CK. The effects of vortioxetine on cognitive function in patients with major depressive disorder: a meta-analysis of three randomized controlled trials. Int J Neuropsychopharmacol 2016;19:pyw055.](https:\/\/doi.org\/10.1093\/ijnp\/pyw055)\n8. [Baune BT, Boyce P, Morris G, Hamilton A, Bassett D, Hopwood M, et al. Organising the front line: Is there a rationale for the first-line pharmacotherapy of major depressive disorder? Aust N Z J Psychiatry 2019;53:279-81.](https:\/\/doi.org\/10.1177\/0004867418824026)\n9. [Coplan JD, Aaronson CJ, Panthangi V, Kim Y. Treating comorbid anxiety and depression: Psychosocial and pharmacological approaches. World J Psychiatry 2015;5:366-78.](https:\/\/doi.org\/10.5498\/wjp.v5.i4.366)\n10. [Snyder BD, Polasek TM, Doogue MP. Drug interactions: principles and practice. Aust Prescr 2012;35:85-8.](https:\/\/doi.org\/10.18773\/austprescr.2012.037)\n11. [Keyloun KR, Hansen RN, Hepp Z, Gillard P, Thase ME, Devine EB. Adherence and persistence across antidepressant therapeutic classes: a retrospective claims analysis among insured US patients with major depressive disorder (MDD). CNS Drugs 2017;31:421-32.](https:\/\/doi.org\/10.1007\/s40263-017-0417-0)\n\n![](https:\/\/i.creativecommons.org\/l\/by-nc-nd\/4.0\/88x31.png)\n\nRELATED ARTICLES\n\nLetters to the Editor\n\n[Antidepressants and sexual adverse effects](https:\/\/australianprescriber.tg.org.au\/articles\/antidepressants-and-sexual-adverse-effects.html) Aust Prescr 2021;44:77\n\n[![Article has an altmetric score of 32](https:\/\/badges.altmetric.com\/?size=240&score=32&types=rtttttto)](https:\/\/www.altmetric.com\/details.php?domain=australianprescriber.tg.org.au&citation_id=99172897)\n\n#### Philip Boyce\nProfessor of Psychiatry, Specialty of Psychiatry, Westmead Clinical School, Sydney Medical School, Faculty of Medicine and Health, University of Sydney\n\n![](https:\/\/australianprescriber.tg.org.au\/assets\/ORCIDiD_icon.svg) <https:\/\/orcid.org\/0000-0002-9816-7356>\n\n#### Cassandra Ma\nResearch assistant, Specialty of Psychiatry, Westmead Clinical School, Sydney Medical School, Faculty of Medicine and Health, University of Sydney\n\n![](https:\/\/australianprescriber.tg.org.au\/assets\/ORCIDiD_icon.svg) <https:\/\/orcid.org\/0000-0001-9950-0950>\n\nPage Sections\n\n- [SUMMARY](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#summary)\n- [Introduction](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#introduction)\n- [Specific treatments](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#specific-treatments)\n- [Indications for drug therapy](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#indications-for-drug-therapy)\n- [Drug selection](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#drug-selection)\n- [Conclusion](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#conclusion)\n- [References](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#references)\n\nRELATED ARTICLES\n\nLetters to the Editor\n\n[Antidepressants and sexual adverse effects](https:\/\/australianprescriber.tg.org.au\/articles\/antidepressants-and-sexual-adverse-effects.html) Aust Prescr 2021;44:77\n\n[**Subscribe to** **Australian Prescriber**](https:\/\/australianprescriber.tg.org.au\/subscribe)\n\n[![Article has an altmetric score of 32](https:\/\/badges.altmetric.com\/?size=240&score=32&types=rtttttto)](https:\/\/www.altmetric.com\/details.php?domain=australianprescriber.tg.org.au&citation_id=99172897)\n\n- [![HONConduct664672\\_hr\\_AP\\_2](data:image\/gif;base64,R0lGODlhAQABAIAAAP\/\/\/wAAACH5BAEAAAAALAAAAAABAAEAAAICRAEAOw==)](https:\/\/www.hon.ch\/HONcode\/Conduct.html?HONConduct664672)\n- [![International Society of Drug Bulletins](data:image\/gif;base64,R0lGODlhAQABAIAAAP\/\/\/wAAACH5BAEAAAAALAAAAAABAAEAAAICRAEAOw==)](http:\/\/www.isdbweb.org\/)\n- [![Crossref](data:image\/gif;base64,R0lGODlhAQABAIAAAP\/\/\/wAAACH5BAEAAAAALAAAAAABAAEAAAICRAEAOw==)](http:\/\/www.crossref.org\/)\n\n- [About Australian Prescriber](https:\/\/australianprescriber.tg.org.au\/about-us.html)\n- [Contact us](https:\/\/australianprescriber.tg.org.au\/contact-us.html)\n## Date published: 01 February 2021\n\n## Footer\n- [Conditions of use and disclaimer](https:\/\/www.tg.org.au\/conditions-of-use-and-disclaimer\/)\n- [Privacy policy](https:\/\/www.tg.org.au\/privacy-policy\/)\n- [Licence agreement](https:\/\/www.tg.org.au\/license-agreement\/)\n- [Copyright permission](https:\/\/www.tg.org.au\/copyright-permission\/)\n- [Support and FAQ](https:\/\/www.tg.org.au\/faq\/)\n\n© 2026 Therapeutic Guidelines Limited. All rights reserved.   \nABN 45 074 766 224\n\n[Posted by **39** X users](https:\/\/www.altmetric.com\/details.php?domain=australianprescriber.tg.org.au&citation_id=99172897&tab=twitter)\n\n[Reddited by **1**](https:\/\/www.altmetric.com\/details.php?domain=australianprescriber.tg.org.au&citation_id=99172897&tab=reddit)\n\n[Picked up by **1** podcasts](https:\/\/www.altmetric.com\/details.php?domain=australianprescriber.tg.org.au&citation_id=99172897&tab=podcasts)\n\n**80** readers on Mendeley\n\n[See more details](https:\/\/www.altmetric.com\/details.php?domain=australianprescriber.tg.org.au&citation_id=99172897)\n\n[Posted by **39** X users](https:\/\/www.altmetric.com\/details.php?domain=australianprescriber.tg.org.au&citation_id=99172897&tab=twitter)\n\n[Reddited by **1**](https:\/\/www.altmetric.com\/details.php?domain=australianprescriber.tg.org.au&citation_id=99172897&tab=reddit)\n\n[Picked up by **1** podcasts](https:\/\/www.altmetric.com\/details.php?domain=australianprescriber.tg.org.au&citation_id=99172897&tab=podcasts)\n\n**80** readers on Mendeley\n\n[See more details](https:\/\/www.altmetric.com\/details.php?domain=australianprescriber.tg.org.au&citation_id=99172897)","attrs_readable_markdown":"## SUMMARY\nA biopsychosocial and lifestyle approach should be used when managing depression. Many patients seen in primary care do not require drug therapy.\n\nEvidence-based treatments such as psychological therapies and antidepressant drugs are effective for depression. All patients should receive education about depression.\n\nShared decision making with the patient is critical if an antidepressant is prescribed. The choice of antidepressant depends on its efficacy and tolerability, the depressive presentation, patient preference and drug interactions.\n\n## Introduction\nMajor depression is best conceptualised using a biopsychosocial and lifestyle model.[1](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r1) All those factors need to be considered when formulating a management plan. Lifestyle factors (such as alcohol or substance misuse, lack of exercise or poor sleep habits) that may be contributing to the onset and maintenance of the depressive episode need to be dealt with concurrently (see [Table 1](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#t1)). There is a need to be mindful of any psychosocial factors, such as unemployment or interpersonal stress, that maintain the depression.\n\nAll patients should receive psychoeducation with a discussion about the symptoms of depression, contributing factors and management options. When appropriate this education can involve other people close to the patient.\n\n## Table 1 - Lifestyle factors and interventions for depression\n|   |   |\n|---|---|\n| **Potential lifestyle risk factors** | **Interventions** |\n| Poor sleep pattern | Encourage good sleep hygiene – regular bedtime and wake up time, bed is for sleep and not for other activities (TV, social media). There are useful apps that provide basic psychoeducation and a sleep diary. |\n| Alcohol misuse | Encourage safe drinking. If there is heavy use and the patient is seeking treatment, refer to an addiction medicine service. If they are not seeking treatment, do a brief intervention. |\n| Substance misuse | Provide psychoeducation about the harmful effects of substances, advise abstinence, formal counselling or refer to addiction medicine services. |\n| Smoking | Encourage smoking cessation, and consider motivational interviewing and nicotine replacement therapy. |\n| Unhealthy diet | Psychoeducation about healthy diet and the harms associated with processed food. Encourage Mediterranean diet and increased intake of fruit and vegetables. |\n| Lack of exercise | Encourage regular exercise (e.g. daily walks), emphasising a graded approach to exercise. |\n\n## Specific treatments\nWhile attending to lifestyle factors and providing psychoeducation may be helpful for some patients, others need more specific treatments. These are formulation-based psychological treatment and antidepressant drugs. The efficacy of psychological treatment, such as cognitive behavioural therapy, is equivalent to drug therapy in mild–moderate disease. Ideally, psychological treatment should be offered first, unless the patient refuses or is unable to access or afford psychological treatment, or expresses a strong preference for drug treatment. Sometimes there is a clear indication for prescribing an antidepressant drug.\n\n## Indications for drug therapy\nAntidepressant drugs are indicated for patients with:\n\n- major depression (characterised by marked symptoms and functional impairment)\n- melancholia (characterised by significant psychomotor symptoms – agitation or retardation)\n- psychotic depression (depression with delusions or hallucinations).\n\nAntidepressants are also indicated for patients who have had a previous good response to them and for when psychological therapies are not accessible or have been ineffective. Even if a drug is indicated, psychoeducation along with basic counselling is still required.\n\n## Drug selection\nThe choice of antidepressant for a particular patient should be based on four major considerations:\n\n- finding the right balance between efficacy and tolerability\n- matching the antidepressant to the type of depression and its presenting features\n- safety – risk of overdose, interactions with other drugs or medical disorders (some groups need special consideration, such as older patients and women during pregnancy and lactation, as the baby will be exposed to the antidepressant)[2](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r2)\n- patient preference.\n\nThere is not yet sufficient evidence confirming that the choice of antidepressant should routinely be made using pharmacogenetic data. Patients, particularly those vulnerable to marketing messages, can be advised that, except in some very special cases, genetic testing is not essential. They can save money by not paying for genetic tests.\n\n## Balancing efficacy with tolerability\nThe efficacy of antidepressant drugs has been confirmed in a network meta-analysis.[3](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r3) Each antidepressant was compared with other antidepressants using data from randomised placebo-controlled trials. ‘Dual-acting’ antidepressants that target more than one neurotransmitter system, such as the serotonin noradrenaline reuptake inhibitors (SNRIs) and tricyclics, are more efficacious than ‘single-action’ drugs, such as the selective serotonin reuptake inhibitors (SSRIs) like sertraline and escitalopram, based on the odds ratio of achieving a 50% response (see [Table 2](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#t2)).[3](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r3) This meta-analysis also examined the acceptability of the various antidepressants by comparing the drop-out rates in clinical trials. While this is a useful metric of acceptability, the rates of adverse effects for each antidepressant are more useful in clinical practice.\n\n## Table 2 - Efficacy of antidepressants compared to placebo\n|   |   |   |\n|---|---|---|\n| **Antidepressant** | **Odds ratio** | **95% confidence interval** |\n| Amitriptyline | 2\\.13 | 1\\.89–2.41 |\n| Mirtazapine | 1\\.89 | 1\\.64–2.20 |\n| Duloxetine | 1\\.85 | 1\\.66–2.07 |\n| Venlafaxine | 1\\.78 | 1\\.61–1.96 |\n| Paroxetine | 1\\.75 | 1\\.61–1.90 |\n| Fluvoxamine | 1\\.69 | 1\\.41–2.02 |\n| Escitalopram | 1\\.68 | 1\\.50–1.87 |\n| Sertraline | 1\\.67 | 1\\.49–1.87 |\n| Vortioxetine | 1\\.66 | 1\\.45–1.92 |\n| Agomelatine | 1\\.65 | 1\\.44–1.88 |\n| Fluoxetine | 1\\.52 | 1\\.40–1.66 |\n| Citalopram | 1\\.52 | 1\\.33–1.74 |\n| Clomipramine | 1\\.49 | 1\\.21–1.85 |\n| Desvenlafaxine | 1\\.49 | 1\\.24–1.79 |\n| Reboxetine | 1\\.37 | 1\\.16–1.63 |\n\nEfficacy is given as the odds ratio of achieving a response (\\>50% reduction in severity). These studies generally used the typical dose to treat depression (although some of the studies were ‘dose finding’ studies in which lower doses were used). Source: adapted from reference 3\n\n[Table 3](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#t3) summarises the common adverse effects ranked according to a ‘limitation’ score for each of the antidepressant classes. The frequency of adverse effects can vary greatly between antidepressant classes, due to having different mechanisms of action. There are fewer differences between drugs in the same antidepressant class, although there are some exceptions.\n\n## Table 3 - Antidepressant adverse effects and their limitations on use\n|   |   |   |   |   |   |\n|---|---|---|---|---|---|\n| **Class** | **Major adverse effects** | **Ease of switching (half-life)** |   |   |   |\n| **Weight gain** | **CNS effects – sedation\/agitation** | **Sexual** | **Withdrawal syndrome** |   |   |\n| Selective serotonin reuptake inhibitors (SSRIs) | **•** | **••** | **•••** | **••**† | **••** |\n| Serotonin noradrenaline reuptake inhibitors (SNRIs) | **•** | **••** | **•••** | **•••** | **••** |\n| Serotonin modulator (vortioxetine) | **•** | **•** | **••** | **••** | **•••** |\n| Noradrenaline reuptake inhibitor (reboxetine) | **•** | **•** | **••** | **•** | **••** |\n| Tricyclic antidepressants (TCAs) | **•••** | **•••** | **•••** | **•••** | **•••** |\n| Reversible inhibitor of monoamine oxidase A (moclobemide) | **•** | **••** | **•** | **•** | ••• |\n| Tetracyclic (mianserin) | **••** | **••** | **•** | **••** | **•** |\n| Noradrenergic and specific serotonergic (mirtazapine) | **•••** | **•••** | **••** | **••** | **•** |\n| Monoamine oxidase inhibitors (MAOIs) | **••** | **•••** | **••** | **••** | **•••** |\n| Melatonergic (agomelatine) | **•** | **•** | **•** | **•** | **•** |\n\n• Minimal limitation •• Some limitation ••• Marked limitation † There is little variation in the severity of adverse effects within classes of antidepressants (but patients may differ in the adverse effects they experience). One exception is the withdrawal symptoms following discontinuation of SSRIs. There is an absence of withdrawal symptoms for fluoxetine but very severe withdrawal symptoms for paroxetine.\n\nIn general, for an uncomplicated mild–moderate depression, the first choice of antidepressant should be a drug that will be well tolerated and has good efficacy. The ease of switching treatment[4](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r4) should be considered because the first antidepressant may not lead to full remission, requiring the patient to change to a different antidepressant.[5](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r5)\n\nFor patients with a severe depression or melancholia (characterised by significant psychomotor change), the prime consideration is efficacy rather than tolerability. The first choice will then be one of the more potent antidepressants, generally a dual mode-of-action drug, such as an SNRI or a tricyclic antidepressant.\n\n## Matching the antidepressant to the clinical presentation\nAntidepressants differ in the specific symptoms that they target, so it is possible to choose an antidepressant according to the patient’s clinical presentation. It is also possible to use the adverse effects to target specific symptoms. For example, mirtazapine is sedating, so it is an option for patients with significant insomnia. Mirtazapine is also associated with weight gain so it may be useful for major depression accompanied by significant weight loss.[6](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r6) In short-term trials, the serotonin modulator vortioxetine benefited patients who had major depression with marked cognitive deficits.[7](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r7)\n\nThe choice of an antidepressant also depends, to some degree, on the symptom profile of the patient or a specific subtype of depression.[8](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r8) [Table 4](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#t4) lists the antidepressants that are preferred for different depressive symptom profiles. Many patients with major depression in primary care also have significant symptoms of anxiety or have a comorbid anxiety disorder. The antidepressant of choice here is an SSRI.[9](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r9) For patients with a melancholic depression, which has a clear biological underpinning characterised by vegetative symptoms and psychomotor change such as agitation or retardation, a dual-action antidepressant should be the first option. The tricyclic antidepressants or duloxetine may be used in certain neuropathic pain conditions. While they can be prescribed for patients with pain and associated depression, the doses of a tricyclic used to treat major depression need to be higher than those used for adjunctive therapy in pain management.\n\n## Table 4 - Symptoms and initial antidepressant choice\n|   |   |\n|---|---|\n| **Symptoms** | **Preferred antidepressant** |\n| Anxiety | Selective serotonin reuptake inhibitors Moclobemide |\n| Weight loss, reduced appetite | Mirtazapine Mianserin |\n| Sleep disturbance, insomnia | Agomelatine Mirtazapine Mianserin Tricyclic antidepressants |\n| Sexual dysfunction | Agomelatine |\n| Blunting, anhedonia, demotivation | Selective serotonin reuptake inhibitors Serotonin noradrenaline reuptake inhibitors Agomelatine Monoamine oxidase inhibitors Reboxetine |\n| Melancholia, severe depression | Serotonin noradrenaline reuptake inhibitors Tricyclic antidepressants Vortioxetine Monoamine oxidase inhibitors |\n| Pain | Duloxetine Tricyclic antidepressants |\n| Cognitive difficulties | Vortioxetine |\n\n## Safety considerations\nPatients with depression can often have suicidal thoughts and may try to commit suicide. This needs to be considered when prescribing an antidepressant. A suicidal patient should not be given quantities of a drug that could be fatal in an overdose. The SSRIs have a much lower potential lethality than the tricyclic antidepressants.\n\nAsk about any other drugs the patient may be taking to avoid potential interactions. For example, there is an increased risk of serotonin toxicity when taking SSRIs in combination with tramadol, St John’s wort or monoamine oxidase inhibitors (MAOIs). SSRIs are also associated with increased bleeding due to changes in platelet function. Caution is therefore needed if they are taken with anticoagulants or non- steroidal anti-inflammatory drugs (NSAIDs). With the increased risk of bleeding, there is a need to consider any comorbid conditions that may add to this risk. In order to limit potential drug and disease interactions, it is recommended that prescribers only use a few antidepressants that they know and understand well.[10](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r10)\n\n## Patient preference\nA key consideration is patient preference. Adherence to antidepressants is essential to ensure remission of the depression. A significant proportion of patients will stop their antidepressant.[11](https:\/\/australianprescriber.tg.org.au\/articles\/choosing-an-antidepressant.html#r11) Adherence is improved if the patient is involved in the decision about which treatment to take. This involves a discussion about the expected benefits of the antidepressant and its potential adverse effects. Some adverse effects, such as sedation, may be more acceptable to patients, but others such as weight gain may be less acceptable. Be aware that patients might have misinformation from the internet or through word of mouth that the adverse effects of an antidepressant are ‘dreadful and nobody should ever take it’. In such situations, it is essential to listen to the patient’s concerns and present them with clear and accurate information about the drug, including providing them with consumer fact sheets. This approach will improve adherence.\n\n## Conclusion\nAfter deciding that a patient needs to take an antidepressant, the choice of drug depends on the severity and symptom pattern of the depressive episode. There has to be a balance between efficacy and tolerability, which also considers patient safety and preference.\n\n*Conflicts of interest: Philip* *Boyce* *has* *received* *consultancy* *and speaker fees, and educational support from Servier. He is on an advisory board and has received educational support* *from* *Lundbeck.*\n\nAustralian Prescriber welcomes [Feedback](https:\/\/australianprescriber.tg.org.au\/contact-us.html).\n\n## References\n1. [Malhi GS, Bassett D, Boyce P, Bryant R, Fitzgerald PB, Fritz K, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust N Z J Psychiatry 2015;49:1087-206.](https:\/\/doi.org\/10.1177\/0004867415617657)\n2. [Centre of Perinatal Excellence. National perinatal mental health guideline. 2017 Oct 27. \\[cited 2021 Jan 4\\]](http:\/\/www.cope.org.au\/health-professionals\/health-professionals-3\/review-of-new-perinatal-mental-health-guidelines)\n3. [Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet 2018;391:1357-66.](https:\/\/doi.org\/10.1016\/S0140-6736\\(17\\)32802-7)\n4. Keks N, Hope J, Keogh S. Switching and stopping antidepressants. Aust Prescr 2016;39:76-83.\n5. [Boyce P, Hopwood M, Morris G, Hamilton A, Bassett D, Baune BT, et al. Switching antidepressants in the treatment of major depression: When, how and what to switch to? J Affect Disord 2020;261:160-3.](https:\/\/doi.org\/10.1016\/j.jad.2019.09.082)\n6. [Nutt DJ. Tolerability and safety aspects of mirtazapine. Hum Psychopharmacol 2002;17 Suppl 1:S37-41.](https:\/\/doi.org\/10.1002\/hup.388)\n7. [McIntyre RS, Harrison J, Loft H, Jacobson W, Olsen CK. The effects of vortioxetine on cognitive function in patients with major depressive disorder: a meta-analysis of three randomized controlled trials. Int J Neuropsychopharmacol 2016;19:pyw055.](https:\/\/doi.org\/10.1093\/ijnp\/pyw055)\n8. [Baune BT, Boyce P, Morris G, Hamilton A, Bassett D, Hopwood M, et al. Organising the front line: Is there a rationale for the first-line pharmacotherapy of major depressive disorder? Aust N Z J Psychiatry 2019;53:279-81.](https:\/\/doi.org\/10.1177\/0004867418824026)\n9. [Coplan JD, Aaronson CJ, Panthangi V, Kim Y. Treating comorbid anxiety and depression: Psychosocial and pharmacological approaches. World J Psychiatry 2015;5:366-78.](https:\/\/doi.org\/10.5498\/wjp.v5.i4.366)\n10. [Snyder BD, Polasek TM, Doogue MP. Drug interactions: principles and practice. Aust Prescr 2012;35:85-8.](https:\/\/doi.org\/10.18773\/austprescr.2012.037)\n11. [Keyloun KR, Hansen RN, Hepp Z, Gillard P, Thase ME, Devine EB. Adherence and persistence across antidepressant therapeutic classes: a retrospective claims analysis among insured US patients with major depressive disorder (MDD). CNS Drugs 2017;31:421-32.](https:\/\/doi.org\/10.1007\/s40263-017-0417-0)","meta_canonical":null}

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Boilerpipe Text	SUMMARY A biopsychosocial and lifestyle approach should be used when managing depression. Many patients seen in primary care do not require drug therapy. Evidence-based treatments such as psychological therapies and antidepressant drugs are effective for depression. All patients should receive education about depression. Shared decision making with the patient is critical if an antidepressant is prescribed. The choice of antidepressant depends on its efficacy and tolerability, the depressive presentation, patient preference and drug interactions. Introduction Major depression is best conceptualised using a biopsychosocial and lifestyle model. 1 All those factors need to be considered when formulating a management plan. Lifestyle factors (such as alcohol or substance misuse, lack of exercise or poor sleep habits) that may be contributing to the onset and maintenance of the depressive episode need to be dealt with concurrently (see Table 1 ). There is a need to be mindful of any psychosocial factors, such as unemployment or interpersonal stress, that maintain the depression. All patients should receive psychoeducation with a discussion about the symptoms of depression, contributing factors and management options. When appropriate this education can involve other people close to the patient. Table 1 - Lifestyle factors and interventions for depression Potential lifestyle risk factors Interventions Poor sleep pattern Encourage good sleep hygiene – regular bedtime and wake up time, bed is for sleep and not for other activities (TV, social media). There are useful apps that provide basic psychoeducation and a sleep diary. Alcohol misuse Encourage safe drinking. If there is heavy use and the patient is seeking treatment, refer to an addiction medicine service. If they are not seeking treatment, do a brief intervention. Substance misuse Provide psychoeducation about the harmful effects of substances, advise abstinence, formal counselling or refer to addiction medicine services. Smoking Encourage smoking cessation, and consider motivational interviewing and nicotine replacement therapy. Unhealthy diet Psychoeducation about healthy diet and the harms associated with processed food. Encourage Mediterranean diet and increased intake of fruit and vegetables. Lack of exercise Encourage regular exercise (e.g. daily walks), emphasising a graded approach to exercise. Specific treatments While attending to lifestyle factors and providing psychoeducation may be helpful for some patients, others need more specific treatments. These are formulation-based psychological treatment and antidepressant drugs. The efficacy of psychological treatment, such as cognitive behavioural therapy, is equivalent to drug therapy in mild–moderate disease. Ideally, psychological treatment should be offered first, unless the patient refuses or is unable to access or afford psychological treatment, or expresses a strong preference for drug treatment. Sometimes there is a clear indication for prescribing an antidepressant drug. Indications for drug therapy Antidepressant drugs are indicated for patients with: major depression (characterised by marked symptoms and functional impairment) melancholia (characterised by significant psychomotor symptoms – agitation or retardation) psychotic depression (depression with delusions or hallucinations). Antidepressants are also indicated for patients who have had a previous good response to them and for when psychological therapies are not accessible or have been ineffective. Even if a drug is indicated, psychoeducation along with basic counselling is still required. Drug selection The choice of antidepressant for a particular patient should be based on four major considerations: finding the right balance between efficacy and tolerability matching the antidepressant to the type of depression and its presenting features safety – risk of overdose, interactions with other drugs or medical disorders (some groups need special consideration, such as older patients and women during pregnancy and lactation, as the baby will be exposed to the antidepressant) 2 patient preference. There is not yet sufficient evidence confirming that the choice of antidepressant should routinely be made using pharmacogenetic data. Patients, particularly those vulnerable to marketing messages, can be advised that, except in some very special cases, genetic testing is not essential. They can save money by not paying for genetic tests. Balancing efficacy with tolerability The efficacy of antidepressant drugs has been confirmed in a network meta-analysis. 3 Each antidepressant was compared with other antidepressants using data from randomised placebo-controlled trials. ‘Dual-acting’ antidepressants that target more than one neurotransmitter system, such as the serotonin noradrenaline reuptake inhibitors (SNRIs) and tricyclics, are more efficacious than ‘single-action’ drugs, such as the selective serotonin reuptake inhibitors (SSRIs) like sertraline and escitalopram, based on the odds ratio of achieving a 50% response (see Table 2 ). 3 This meta-analysis also examined the acceptability of the various antidepressants by comparing the drop-out rates in clinical trials. While this is a useful metric of acceptability, the rates of adverse effects for each antidepressant are more useful in clinical practice. Table 2 - Efficacy of antidepressants compared to placebo Antidepressant Odds ratio 95% confidence interval Amitriptyline 2.13 1.89–2.41 Mirtazapine 1.89 1.64–2.20 Duloxetine 1.85 1.66–2.07 Venlafaxine 1.78 1.61–1.96 Paroxetine 1.75 1.61–1.90 Fluvoxamine 1.69 1.41–2.02 Escitalopram 1.68 1.50–1.87 Sertraline 1.67 1.49–1.87 Vortioxetine 1.66 1.45–1.92 Agomelatine 1.65 1.44–1.88 Fluoxetine 1.52 1.40–1.66 Citalopram 1.52 1.33–1.74 Clomipramine 1.49 1.21–1.85 Desvenlafaxine 1.49 1.24–1.79 Reboxetine 1.37 1.16–1.63 Efficacy is given as the odds ratio of achieving a response (>50% reduction in severity). These studies generally used the typical dose to treat depression (although some of the studies were ‘dose finding’ studies in which lower doses were used). Source: adapted from reference 3 Table 3 summarises the common adverse effects ranked according to a ‘limitation’ score for each of the antidepressant classes. The frequency of adverse effects can vary greatly between antidepressant classes, due to having different mechanisms of action. There are fewer differences between drugs in the same antidepressant class, although there are some exceptions. Table 3 - Antidepressant adverse effects and their limitations on use Class Major adverse effects Ease of switching (half-life) Weight gain CNS effects – sedation/agitation Sexual Withdrawal syndrome Selective serotonin reuptake inhibitors (SSRIs) • •• ••• •• † •• Serotonin noradrenaline reuptake inhibitors (SNRIs) • •• ••• ••• •• Serotonin modulator (vortioxetine) • • •• •• ••• Noradrenaline reuptake inhibitor (reboxetine) • • •• • •• Tricyclic antidepressants (TCAs) ••• ••• ••• ••• ••• Reversible inhibitor of monoamine oxidase A (moclobemide) • •• • • ••• Tetracyclic (mianserin) •• •• • •• • Noradrenergic and specific serotonergic (mirtazapine) ••• ••• •• •• • Monoamine oxidase inhibitors (MAOIs) •• ••• •• •• ••• Melatonergic (agomelatine) • • • • • • Minimal limitation •• Some limitation ••• Marked limitation † There is little variation in the severity of adverse effects within classes of antidepressants (but patients may differ in the adverse effects they experience). One exception is the withdrawal symptoms following discontinuation of SSRIs. There is an absence of withdrawal symptoms for fluoxetine but very severe withdrawal symptoms for paroxetine. In general, for an uncomplicated mild–moderate depression, the first choice of antidepressant should be a drug that will be well tolerated and has good efficacy. The ease of switching treatment 4 should be considered because the first antidepressant may not lead to full remission, requiring the patient to change to a different antidepressant. 5 For patients with a severe depression or melancholia (characterised by significant psychomotor change), the prime consideration is efficacy rather than tolerability. The first choice will then be one of the more potent antidepressants, generally a dual mode-of-action drug, such as an SNRI or a tricyclic antidepressant. Matching the antidepressant to the clinical presentation Antidepressants differ in the specific symptoms that they target, so it is possible to choose an antidepressant according to the patient’s clinical presentation. It is also possible to use the adverse effects to target specific symptoms. For example, mirtazapine is sedating, so it is an option for patients with significant insomnia. Mirtazapine is also associated with weight gain so it may be useful for major depression accompanied by significant weight loss. 6 In short-term trials, the serotonin modulator vortioxetine benefited patients who had major depression with marked cognitive deficits. 7 The choice of an antidepressant also depends, to some degree, on the symptom profile of the patient or a specific subtype of depression. 8 Table 4 lists the antidepressants that are preferred for different depressive symptom profiles. Many patients with major depression in primary care also have significant symptoms of anxiety or have a comorbid anxiety disorder. The antidepressant of choice here is an SSRI. 9 For patients with a melancholic depression, which has a clear biological underpinning characterised by vegetative symptoms and psychomotor change such as agitation or retardation, a dual-action antidepressant should be the first option. The tricyclic antidepressants or duloxetine may be used in certain neuropathic pain conditions. While they can be prescribed for patients with pain and associated depression, the doses of a tricyclic used to treat major depression need to be higher than those used for adjunctive therapy in pain management. Table 4 - Symptoms and initial antidepressant choice Symptoms Preferred antidepressant Anxiety Selective serotonin reuptake inhibitors Moclobemide Weight loss, reduced appetite Mirtazapine Mianserin Sleep disturbance, insomnia Agomelatine Mirtazapine Mianserin Tricyclic antidepressants Sexual dysfunction Agomelatine Blunting, anhedonia, demotivation Selective serotonin reuptake inhibitors Serotonin noradrenaline reuptake inhibitors Agomelatine Monoamine oxidase inhibitors Reboxetine Melancholia, severe depression Serotonin noradrenaline reuptake inhibitors Tricyclic antidepressants Vortioxetine Monoamine oxidase inhibitors Pain Duloxetine Tricyclic antidepressants Cognitive difficulties Vortioxetine Safety considerations Patients with depression can often have suicidal thoughts and may try to commit suicide. This needs to be considered when prescribing an antidepressant. A suicidal patient should not be given quantities of a drug that could be fatal in an overdose. The SSRIs have a much lower potential lethality than the tricyclic antidepressants. Ask about any other drugs the patient may be taking to avoid potential interactions. For example, there is an increased risk of serotonin toxicity when taking SSRIs in combination with tramadol, St John’s wort or monoamine oxidase inhibitors (MAOIs). SSRIs are also associated with increased bleeding due to changes in platelet function. Caution is therefore needed if they are taken with anticoagulants or non- steroidal anti-inflammatory drugs (NSAIDs). With the increased risk of bleeding, there is a need to consider any comorbid conditions that may add to this risk. In order to limit potential drug and disease interactions, it is recommended that prescribers only use a few antidepressants that they know and understand well. 10 Patient preference A key consideration is patient preference. Adherence to antidepressants is essential to ensure remission of the depression. A significant proportion of patients will stop their antidepressant. 11 Adherence is improved if the patient is involved in the decision about which treatment to take. This involves a discussion about the expected benefits of the antidepressant and its potential adverse effects. Some adverse effects, such as sedation, may be more acceptable to patients, but others such as weight gain may be less acceptable. Be aware that patients might have misinformation from the internet or through word of mouth that the adverse effects of an antidepressant are ‘dreadful and nobody should ever take it’. In such situations, it is essential to listen to the patient’s concerns and present them with clear and accurate information about the drug, including providing them with consumer fact sheets. This approach will improve adherence. Conclusion After deciding that a patient needs to take an antidepressant, the choice of drug depends on the severity and symptom pattern of the depressive episode. There has to be a balance between efficacy and tolerability, which also considers patient safety and preference. Conflicts of interest: Philip Boyce has received consultancy and speaker fees, and educational support from Servier. He is on an advisory board and has received educational support from Lundbeck. Australian Prescriber welcomes Feedback . References Malhi GS, Bassett D, Boyce P, Bryant R, Fitzgerald PB, Fritz K, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust N Z J Psychiatry 2015;49:1087-206. Centre of Perinatal Excellence. National perinatal mental health guideline. 2017 Oct 27. [cited 2021 Jan 4] Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet 2018;391:1357-66. Keks N, Hope J, Keogh S. Switching and stopping antidepressants. Aust Prescr 2016;39:76-83. Boyce P, Hopwood M, Morris G, Hamilton A, Bassett D, Baune BT, et al. Switching antidepressants in the treatment of major depression: When, how and what to switch to? J Affect Disord 2020;261:160-3. Nutt DJ. Tolerability and safety aspects of mirtazapine. Hum Psychopharmacol 2002;17 Suppl 1:S37-41. McIntyre RS, Harrison J, Loft H, Jacobson W, Olsen CK. The effects of vortioxetine on cognitive function in patients with major depressive disorder: a meta-analysis of three randomized controlled trials. Int J Neuropsychopharmacol 2016;19:pyw055. Baune BT, Boyce P, Morris G, Hamilton A, Bassett D, Hopwood M, et al. Organising the front line: Is there a rationale for the first-line pharmacotherapy of major depressive disorder? Aust N Z J Psychiatry 2019;53:279-81. Coplan JD, Aaronson CJ, Panthangi V, Kim Y. Treating comorbid anxiety and depression: Psychosocial and pharmacological approaches. World J Psychiatry 2015;5:366-78. Snyder BD, Polasek TM, Doogue MP. Drug interactions: principles and practice. Aust Prescr 2012;35:85-8. Keyloun KR, Hansen RN, Hepp Z, Gillard P, Thase ME, Devine EB. Adherence and persistence across antidepressant therapeutic classes: a retrospective claims analysis among insured US patients with major depressive disorder (MDD). CNS Drugs 2017;31:421-32.
Markdown	[Skip to main content](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#main) - [The organisation]("The organisation") - [The organisation](https://www.tg.org.au/the-organisation/ "The organisation") - [Governance](https://www.tg.org.au/the-organisation/governance/ "Governance") - [Board of directors](https://www.tg.org.au/the-organisation/board-of-directors/ "Board of directors") - [Expert groups](https://www.tg.org.au/the-organisation/expert-groups-2/ "Expert groups") - [Members of Company](https://www.tg.org.au/the-organisation/members-of-company/ "Members of Company") - [History](https://www.tg.org.au/the-organisation/history-of-therapeutic-guidelines/ "History") - [History Timeline](https://www.tg.org.au/historytimeline/ "History Timeline") - [Careers](https://www.tg.org.au/the-organisation/careers/ "Careers") - [Guideline development](https://www.tg.org.au/the-organisation/guideline-development/ "Guideline development") - [Partnership program](https://www.tg.org.au/the-organisation/partnership-program/ "Partnership program") - [Research funding](https://www.tg.org.au/the-organisation/research-funding/ "Research funding") - [News](https://www.tg.org.au/news/ "News") - [Products]("Products") - [Therapeutic Guidelines](https://tgldcdp.tg.org.au/etgcomplete "Therapeutic Guidelines") - [Australian Prescriber](https://australianprescriber.tg.org.au/ "Australian Prescriber") - [Books](https://www.tg.org.au/books "Books") - [Antibiotic prescribing in primary care: summary table](https://ccmsfiles.tg.org.au/s3/PDFs/GPSummary_v15.pdf "Antibiotic prescribing in primary care: summary table") - [Updates](https://www.tg.org.au/content-updates/ "Updates") - [Contact us](https://www.tg.org.au/contact-us/ "Contact us") - Menu - [Home](https://www.tg.org.au/ "Home") - [The organisation](https://www.tg.org.au/the-organisation/ "The organisation") - [News](https://www.tg.org.au/news/ "News") - [Products](https://www.tg.org.au/products/ "Products") - [Updates](https://www.tg.org.au/content-updates/ "Updates") - [Contact us](https://www.tg.org.au/contact-us/ "Contact us") - [Home](https://australianprescriber.tg.org.au/) - [Choosing an antidepressant](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html) - [A](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html) - [A](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html) [![Australian Prescriber An independent Review Logo](data:image/gif;base64,R0lGODlhAQABAIAAAP///wAAACH5BAEAAAAALAAAAAABAAEAAAICRAEAOw==)](https://australianprescriber.tg.org.au/) - [All Issues](https://australianprescriber.tg.org.au/volumes/49/issues/2.html) - [Podcasts](https://australianprescriber.tg.org.au/podcast.html) - [CPD for GPs](https://australianprescriber.tg.org.au/CPD-GP.html) - [CPD for Pharmacists](https://australianprescriber.tg.org.au/CPD-Pharmacists.html) [ISSUE 1 FEBRUARY](https://australianprescriber.tg.org.au/volumes/44/issues/1.html) ##### Article # Choosing an antidepressant - Philip Boyce, Cassandra Ma - Aust Prescr 2021;44:12-15 - 1 February 2021 - DOI: [10\.18773/austprescr.2020.064](https://doi.org/10.18773/austprescr.2020.064) - [depression](https://australianprescriber.tg.org.au/search?scope=ap&q=depression) - [selective serotonin reuptake inhibitors](https://australianprescriber.tg.org.au/search?scope=ap&q=selective%20serotonin%20reuptake%20inhibitors) - [tricyclic antidepressants](https://australianprescriber.tg.org.au/search?scope=ap&q=tricyclic%20antidepressants) - [Share](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html) - [email](<mailto:?subject=Australian Prescriber - &body=Check out this site for Australian Prescriber, the independent, peer-reviewed journal providing critical commentary on drugs and therapeutics for health professionals: https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html>) - [Facebook]() - [twitter]() - [linkedin]() - [Download PDF](https://australianprescriber.tg.org.au/assets/p12-Boyce-Ma_v2.pdf) - [Citation](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html) Boyce P, Ma C. Choosing an antidepressant. Aust Prescr 2021;44:12-15. <https://doi.org/10.18773/austprescr.2020.064> [Download .RIS file](https://australianprescriber.tg.org.au/download-ris-file/500441/austprescr-2020-064.ris) - [![Podcast](https://australianprescriber.tg.org.au/assets/ecfe6245e791691a-15a4b10e8b90-podcast-new.png)](https://australianprescriber.tg.org.au/podcast/episode-99-how-to-choose-an-antidepressant.html) [Subscribe to Australian Prescriber](https://australianprescriber.tg.org.au/subscribe) ## SUMMARY A biopsychosocial and lifestyle approach should be used when managing depression. Many patients seen in primary care do not require drug therapy. Evidence-based treatments such as psychological therapies and antidepressant drugs are effective for depression. All patients should receive education about depression. Shared decision making with the patient is critical if an antidepressant is prescribed. The choice of antidepressant depends on its efficacy and tolerability, the depressive presentation, patient preference and drug interactions. ## Introduction Major depression is best conceptualised using a biopsychosocial and lifestyle model.[1](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r1) All those factors need to be considered when formulating a management plan. Lifestyle factors (such as alcohol or substance misuse, lack of exercise or poor sleep habits) that may be contributing to the onset and maintenance of the depressive episode need to be dealt with concurrently (see [Table 1](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#t1)). There is a need to be mindful of any psychosocial factors, such as unemployment or interpersonal stress, that maintain the depression. All patients should receive psychoeducation with a discussion about the symptoms of depression, contributing factors and management options. When appropriate this education can involve other people close to the patient. ## Table 1 - Lifestyle factors and interventions for depression \| \| \| \|---\|---\| \| Potential lifestyle risk factors \| Interventions \| \| Poor sleep pattern \| Encourage good sleep hygiene – regular bedtime and wake up time, bed is for sleep and not for other activities (TV, social media). There are useful apps that provide basic psychoeducation and a sleep diary. \| \| Alcohol misuse \| Encourage safe drinking. If there is heavy use and the patient is seeking treatment, refer to an addiction medicine service. If they are not seeking treatment, do a brief intervention. \| \| Substance misuse \| Provide psychoeducation about the harmful effects of substances, advise abstinence, formal counselling or refer to addiction medicine services. \| \| Smoking \| Encourage smoking cessation, and consider motivational interviewing and nicotine replacement therapy. \| \| Unhealthy diet \| Psychoeducation about healthy diet and the harms associated with processed food. Encourage Mediterranean diet and increased intake of fruit and vegetables. \| \| Lack of exercise \| Encourage regular exercise (e.g. daily walks), emphasising a graded approach to exercise. \| ## Specific treatments While attending to lifestyle factors and providing psychoeducation may be helpful for some patients, others need more specific treatments. These are formulation-based psychological treatment and antidepressant drugs. The efficacy of psychological treatment, such as cognitive behavioural therapy, is equivalent to drug therapy in mild–moderate disease. Ideally, psychological treatment should be offered first, unless the patient refuses or is unable to access or afford psychological treatment, or expresses a strong preference for drug treatment. Sometimes there is a clear indication for prescribing an antidepressant drug. ## Indications for drug therapy Antidepressant drugs are indicated for patients with: - major depression (characterised by marked symptoms and functional impairment) - melancholia (characterised by significant psychomotor symptoms – agitation or retardation) - psychotic depression (depression with delusions or hallucinations). Antidepressants are also indicated for patients who have had a previous good response to them and for when psychological therapies are not accessible or have been ineffective. Even if a drug is indicated, psychoeducation along with basic counselling is still required. ## Drug selection The choice of antidepressant for a particular patient should be based on four major considerations: - finding the right balance between efficacy and tolerability - matching the antidepressant to the type of depression and its presenting features - safety – risk of overdose, interactions with other drugs or medical disorders (some groups need special consideration, such as older patients and women during pregnancy and lactation, as the baby will be exposed to the antidepressant)[2](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r2) - patient preference. There is not yet sufficient evidence confirming that the choice of antidepressant should routinely be made using pharmacogenetic data. Patients, particularly those vulnerable to marketing messages, can be advised that, except in some very special cases, genetic testing is not essential. They can save money by not paying for genetic tests. ## Balancing efficacy with tolerability The efficacy of antidepressant drugs has been confirmed in a network meta-analysis.[3](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r3) Each antidepressant was compared with other antidepressants using data from randomised placebo-controlled trials. ‘Dual-acting’ antidepressants that target more than one neurotransmitter system, such as the serotonin noradrenaline reuptake inhibitors (SNRIs) and tricyclics, are more efficacious than ‘single-action’ drugs, such as the selective serotonin reuptake inhibitors (SSRIs) like sertraline and escitalopram, based on the odds ratio of achieving a 50% response (see [Table 2](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#t2)).[3](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r3) This meta-analysis also examined the acceptability of the various antidepressants by comparing the drop-out rates in clinical trials. While this is a useful metric of acceptability, the rates of adverse effects for each antidepressant are more useful in clinical practice. ## Table 2 - Efficacy of antidepressants compared to placebo \| \| \| \| \|---\|---\|---\| \| Antidepressant \| Odds ratio \| 95% confidence interval \| \| Amitriptyline \| 2\.13 \| 1\.89–2.41 \| \| Mirtazapine \| 1\.89 \| 1\.64–2.20 \| \| Duloxetine \| 1\.85 \| 1\.66–2.07 \| \| Venlafaxine \| 1\.78 \| 1\.61–1.96 \| \| Paroxetine \| 1\.75 \| 1\.61–1.90 \| \| Fluvoxamine \| 1\.69 \| 1\.41–2.02 \| \| Escitalopram \| 1\.68 \| 1\.50–1.87 \| \| Sertraline \| 1\.67 \| 1\.49–1.87 \| \| Vortioxetine \| 1\.66 \| 1\.45–1.92 \| \| Agomelatine \| 1\.65 \| 1\.44–1.88 \| \| Fluoxetine \| 1\.52 \| 1\.40–1.66 \| \| Citalopram \| 1\.52 \| 1\.33–1.74 \| \| Clomipramine \| 1\.49 \| 1\.21–1.85 \| \| Desvenlafaxine \| 1\.49 \| 1\.24–1.79 \| \| Reboxetine \| 1\.37 \| 1\.16–1.63 \| Efficacy is given as the odds ratio of achieving a response (\>50% reduction in severity). These studies generally used the typical dose to treat depression (although some of the studies were ‘dose finding’ studies in which lower doses were used). Source: adapted from reference 3 [Table 3](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#t3) summarises the common adverse effects ranked according to a ‘limitation’ score for each of the antidepressant classes. The frequency of adverse effects can vary greatly between antidepressant classes, due to having different mechanisms of action. There are fewer differences between drugs in the same antidepressant class, although there are some exceptions. ## Table 3 - Antidepressant adverse effects and their limitations on use \| \| \| \| \| \| \| \|---\|---\|---\|---\|---\|---\| \| Class \| Major adverse effects \| Ease of switching (half-life) \| \| \| \| \| Weight gain \| CNS effects – sedation/agitation \| Sexual \| Withdrawal syndrome \| \| \| \| Selective serotonin reuptake inhibitors (SSRIs) \| • \| •• \| ••• \| ••† \| •• \| \| Serotonin noradrenaline reuptake inhibitors (SNRIs) \| • \| •• \| ••• \| ••• \| •• \| \| Serotonin modulator (vortioxetine) \| • \| • \| •• \| •• \| ••• \| \| Noradrenaline reuptake inhibitor (reboxetine) \| • \| • \| •• \| • \| •• \| \| Tricyclic antidepressants (TCAs) \| ••• \| ••• \| ••• \| ••• \| ••• \| \| Reversible inhibitor of monoamine oxidase A (moclobemide) \| • \| •• \| • \| • \| ••• \| \| Tetracyclic (mianserin) \| •• \| •• \| • \| •• \| • \| \| Noradrenergic and specific serotonergic (mirtazapine) \| ••• \| ••• \| •• \| •• \| • \| \| Monoamine oxidase inhibitors (MAOIs) \| •• \| ••• \| •• \| •• \| ••• \| \| Melatonergic (agomelatine) \| • \| • \| • \| • \| • \| • Minimal limitation •• Some limitation ••• Marked limitation † There is little variation in the severity of adverse effects within classes of antidepressants (but patients may differ in the adverse effects they experience). One exception is the withdrawal symptoms following discontinuation of SSRIs. There is an absence of withdrawal symptoms for fluoxetine but very severe withdrawal symptoms for paroxetine. In general, for an uncomplicated mild–moderate depression, the first choice of antidepressant should be a drug that will be well tolerated and has good efficacy. The ease of switching treatment[4](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r4) should be considered because the first antidepressant may not lead to full remission, requiring the patient to change to a different antidepressant.[5](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r5) For patients with a severe depression or melancholia (characterised by significant psychomotor change), the prime consideration is efficacy rather than tolerability. The first choice will then be one of the more potent antidepressants, generally a dual mode-of-action drug, such as an SNRI or a tricyclic antidepressant. ## Matching the antidepressant to the clinical presentation Antidepressants differ in the specific symptoms that they target, so it is possible to choose an antidepressant according to the patient’s clinical presentation. It is also possible to use the adverse effects to target specific symptoms. For example, mirtazapine is sedating, so it is an option for patients with significant insomnia. Mirtazapine is also associated with weight gain so it may be useful for major depression accompanied by significant weight loss.[6](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r6) In short-term trials, the serotonin modulator vortioxetine benefited patients who had major depression with marked cognitive deficits.[7](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r7) The choice of an antidepressant also depends, to some degree, on the symptom profile of the patient or a specific subtype of depression.[8](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r8) [Table 4](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#t4) lists the antidepressants that are preferred for different depressive symptom profiles. Many patients with major depression in primary care also have significant symptoms of anxiety or have a comorbid anxiety disorder. The antidepressant of choice here is an SSRI.[9](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r9) For patients with a melancholic depression, which has a clear biological underpinning characterised by vegetative symptoms and psychomotor change such as agitation or retardation, a dual-action antidepressant should be the first option. The tricyclic antidepressants or duloxetine may be used in certain neuropathic pain conditions. While they can be prescribed for patients with pain and associated depression, the doses of a tricyclic used to treat major depression need to be higher than those used for adjunctive therapy in pain management. ## Table 4 - Symptoms and initial antidepressant choice \| \| \| \|---\|---\| \| Symptoms \| Preferred antidepressant \| \| Anxiety \| Selective serotonin reuptake inhibitors Moclobemide \| \| Weight loss, reduced appetite \| Mirtazapine Mianserin \| \| Sleep disturbance, insomnia \| Agomelatine Mirtazapine Mianserin Tricyclic antidepressants \| \| Sexual dysfunction \| Agomelatine \| \| Blunting, anhedonia, demotivation \| Selective serotonin reuptake inhibitors Serotonin noradrenaline reuptake inhibitors Agomelatine Monoamine oxidase inhibitors Reboxetine \| \| Melancholia, severe depression \| Serotonin noradrenaline reuptake inhibitors Tricyclic antidepressants Vortioxetine Monoamine oxidase inhibitors \| \| Pain \| Duloxetine Tricyclic antidepressants \| \| Cognitive difficulties \| Vortioxetine \| ## Safety considerations Patients with depression can often have suicidal thoughts and may try to commit suicide. This needs to be considered when prescribing an antidepressant. A suicidal patient should not be given quantities of a drug that could be fatal in an overdose. The SSRIs have a much lower potential lethality than the tricyclic antidepressants. Ask about any other drugs the patient may be taking to avoid potential interactions. For example, there is an increased risk of serotonin toxicity when taking SSRIs in combination with tramadol, St John’s wort or monoamine oxidase inhibitors (MAOIs). SSRIs are also associated with increased bleeding due to changes in platelet function. Caution is therefore needed if they are taken with anticoagulants or non- steroidal anti-inflammatory drugs (NSAIDs). With the increased risk of bleeding, there is a need to consider any comorbid conditions that may add to this risk. In order to limit potential drug and disease interactions, it is recommended that prescribers only use a few antidepressants that they know and understand well.[10](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r10) ## Patient preference A key consideration is patient preference. Adherence to antidepressants is essential to ensure remission of the depression. A significant proportion of patients will stop their antidepressant.[11](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r11) Adherence is improved if the patient is involved in the decision about which treatment to take. This involves a discussion about the expected benefits of the antidepressant and its potential adverse effects. Some adverse effects, such as sedation, may be more acceptable to patients, but others such as weight gain may be less acceptable. Be aware that patients might have misinformation from the internet or through word of mouth that the adverse effects of an antidepressant are ‘dreadful and nobody should ever take it’. In such situations, it is essential to listen to the patient’s concerns and present them with clear and accurate information about the drug, including providing them with consumer fact sheets. This approach will improve adherence. ## Conclusion After deciding that a patient needs to take an antidepressant, the choice of drug depends on the severity and symptom pattern of the depressive episode. There has to be a balance between efficacy and tolerability, which also considers patient safety and preference. Conflicts of interest: Philip Boyce has received consultancy and speaker fees, and educational support from Servier. He is on an advisory board and has received educational support from Lundbeck. Australian Prescriber welcomes [Feedback](https://australianprescriber.tg.org.au/contact-us.html). ## References 1. [Malhi GS, Bassett D, Boyce P, Bryant R, Fitzgerald PB, Fritz K, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust N Z J Psychiatry 2015;49:1087-206.](https://doi.org/10.1177/0004867415617657) 2. [Centre of Perinatal Excellence. National perinatal mental health guideline. 2017 Oct 27. \[cited 2021 Jan 4\]](http://www.cope.org.au/health-professionals/health-professionals-3/review-of-new-perinatal-mental-health-guidelines) 3. [Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet 2018;391:1357-66.](https://doi.org/10.1016/S0140-6736\(17\)32802-7) 4. Keks N, Hope J, Keogh S. Switching and stopping antidepressants. Aust Prescr 2016;39:76-83. 5. [Boyce P, Hopwood M, Morris G, Hamilton A, Bassett D, Baune BT, et al. Switching antidepressants in the treatment of major depression: When, how and what to switch to? J Affect Disord 2020;261:160-3.](https://doi.org/10.1016/j.jad.2019.09.082) 6. [Nutt DJ. Tolerability and safety aspects of mirtazapine. Hum Psychopharmacol 2002;17 Suppl 1:S37-41.](https://doi.org/10.1002/hup.388) 7. [McIntyre RS, Harrison J, Loft H, Jacobson W, Olsen CK. The effects of vortioxetine on cognitive function in patients with major depressive disorder: a meta-analysis of three randomized controlled trials. Int J Neuropsychopharmacol 2016;19:pyw055.](https://doi.org/10.1093/ijnp/pyw055) 8. [Baune BT, Boyce P, Morris G, Hamilton A, Bassett D, Hopwood M, et al. Organising the front line: Is there a rationale for the first-line pharmacotherapy of major depressive disorder? Aust N Z J Psychiatry 2019;53:279-81.](https://doi.org/10.1177/0004867418824026) 9. [Coplan JD, Aaronson CJ, Panthangi V, Kim Y. Treating comorbid anxiety and depression: Psychosocial and pharmacological approaches. World J Psychiatry 2015;5:366-78.](https://doi.org/10.5498/wjp.v5.i4.366) 10. [Snyder BD, Polasek TM, Doogue MP. Drug interactions: principles and practice. Aust Prescr 2012;35:85-8.](https://doi.org/10.18773/austprescr.2012.037) 11. [Keyloun KR, Hansen RN, Hepp Z, Gillard P, Thase ME, Devine EB. Adherence and persistence across antidepressant therapeutic classes: a retrospective claims analysis among insured US patients with major depressive disorder (MDD). CNS Drugs 2017;31:421-32.](https://doi.org/10.1007/s40263-017-0417-0) ![](https://i.creativecommons.org/l/by-nc-nd/4.0/88x31.png) RELATED ARTICLES Letters to the Editor [Antidepressants and sexual adverse effects](https://australianprescriber.tg.org.au/articles/antidepressants-and-sexual-adverse-effects.html) Aust Prescr 2021;44:77 [![Article has an altmetric score of 32](https://badges.altmetric.com/?size=240&score=32&types=rtttttto)](https://www.altmetric.com/details.php?domain=australianprescriber.tg.org.au&citation_id=99172897) #### Philip Boyce Professor of Psychiatry, Specialty of Psychiatry, Westmead Clinical School, Sydney Medical School, Faculty of Medicine and Health, University of Sydney ![](https://australianprescriber.tg.org.au/assets/ORCIDiD_icon.svg) <https://orcid.org/0000-0002-9816-7356> #### Cassandra Ma Research assistant, Specialty of Psychiatry, Westmead Clinical School, Sydney Medical School, Faculty of Medicine and Health, University of Sydney ![](https://australianprescriber.tg.org.au/assets/ORCIDiD_icon.svg) <https://orcid.org/0000-0001-9950-0950> Page Sections - [SUMMARY](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#summary) - [Introduction](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#introduction) - [Specific treatments](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#specific-treatments) - [Indications for drug therapy](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#indications-for-drug-therapy) - [Drug selection](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#drug-selection) - [Conclusion](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#conclusion) - [References](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#references) RELATED ARTICLES Letters to the Editor [Antidepressants and sexual adverse effects](https://australianprescriber.tg.org.au/articles/antidepressants-and-sexual-adverse-effects.html) Aust Prescr 2021;44:77 [Subscribe to Australian Prescriber](https://australianprescriber.tg.org.au/subscribe) [![Article has an altmetric score of 32](https://badges.altmetric.com/?size=240&score=32&types=rtttttto)](https://www.altmetric.com/details.php?domain=australianprescriber.tg.org.au&citation_id=99172897) - [![HONConduct664672\_hr\_AP\_2](data:image/gif;base64,R0lGODlhAQABAIAAAP///wAAACH5BAEAAAAALAAAAAABAAEAAAICRAEAOw==)](https://www.hon.ch/HONcode/Conduct.html?HONConduct664672) - [![International Society of Drug Bulletins](data:image/gif;base64,R0lGODlhAQABAIAAAP///wAAACH5BAEAAAAALAAAAAABAAEAAAICRAEAOw==)](http://www.isdbweb.org/) - [![Crossref](data:image/gif;base64,R0lGODlhAQABAIAAAP///wAAACH5BAEAAAAALAAAAAABAAEAAAICRAEAOw==)](http://www.crossref.org/) - [About Australian Prescriber](https://australianprescriber.tg.org.au/about-us.html) - [Contact us](https://australianprescriber.tg.org.au/contact-us.html) ## Date published: 01 February 2021 ## Footer - [Conditions of use and disclaimer](https://www.tg.org.au/conditions-of-use-and-disclaimer/) - [Privacy policy](https://www.tg.org.au/privacy-policy/) - [Licence agreement](https://www.tg.org.au/license-agreement/) - [Copyright permission](https://www.tg.org.au/copyright-permission/) - [Support and FAQ](https://www.tg.org.au/faq/) © 2026 Therapeutic Guidelines Limited. 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Readable Markdown	## SUMMARY A biopsychosocial and lifestyle approach should be used when managing depression. Many patients seen in primary care do not require drug therapy. Evidence-based treatments such as psychological therapies and antidepressant drugs are effective for depression. All patients should receive education about depression. Shared decision making with the patient is critical if an antidepressant is prescribed. The choice of antidepressant depends on its efficacy and tolerability, the depressive presentation, patient preference and drug interactions. ## Introduction Major depression is best conceptualised using a biopsychosocial and lifestyle model.[1](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r1) All those factors need to be considered when formulating a management plan. Lifestyle factors (such as alcohol or substance misuse, lack of exercise or poor sleep habits) that may be contributing to the onset and maintenance of the depressive episode need to be dealt with concurrently (see [Table 1](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#t1)). There is a need to be mindful of any psychosocial factors, such as unemployment or interpersonal stress, that maintain the depression. All patients should receive psychoeducation with a discussion about the symptoms of depression, contributing factors and management options. When appropriate this education can involve other people close to the patient. ## Table 1 - Lifestyle factors and interventions for depression \| \| \| \|---\|---\| \| Potential lifestyle risk factors \| Interventions \| \| Poor sleep pattern \| Encourage good sleep hygiene – regular bedtime and wake up time, bed is for sleep and not for other activities (TV, social media). There are useful apps that provide basic psychoeducation and a sleep diary. \| \| Alcohol misuse \| Encourage safe drinking. If there is heavy use and the patient is seeking treatment, refer to an addiction medicine service. If they are not seeking treatment, do a brief intervention. \| \| Substance misuse \| Provide psychoeducation about the harmful effects of substances, advise abstinence, formal counselling or refer to addiction medicine services. \| \| Smoking \| Encourage smoking cessation, and consider motivational interviewing and nicotine replacement therapy. \| \| Unhealthy diet \| Psychoeducation about healthy diet and the harms associated with processed food. Encourage Mediterranean diet and increased intake of fruit and vegetables. \| \| Lack of exercise \| Encourage regular exercise (e.g. daily walks), emphasising a graded approach to exercise. \| ## Specific treatments While attending to lifestyle factors and providing psychoeducation may be helpful for some patients, others need more specific treatments. These are formulation-based psychological treatment and antidepressant drugs. The efficacy of psychological treatment, such as cognitive behavioural therapy, is equivalent to drug therapy in mild–moderate disease. Ideally, psychological treatment should be offered first, unless the patient refuses or is unable to access or afford psychological treatment, or expresses a strong preference for drug treatment. Sometimes there is a clear indication for prescribing an antidepressant drug. ## Indications for drug therapy Antidepressant drugs are indicated for patients with: - major depression (characterised by marked symptoms and functional impairment) - melancholia (characterised by significant psychomotor symptoms – agitation or retardation) - psychotic depression (depression with delusions or hallucinations). Antidepressants are also indicated for patients who have had a previous good response to them and for when psychological therapies are not accessible or have been ineffective. Even if a drug is indicated, psychoeducation along with basic counselling is still required. ## Drug selection The choice of antidepressant for a particular patient should be based on four major considerations: - finding the right balance between efficacy and tolerability - matching the antidepressant to the type of depression and its presenting features - safety – risk of overdose, interactions with other drugs or medical disorders (some groups need special consideration, such as older patients and women during pregnancy and lactation, as the baby will be exposed to the antidepressant)[2](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r2) - patient preference. There is not yet sufficient evidence confirming that the choice of antidepressant should routinely be made using pharmacogenetic data. Patients, particularly those vulnerable to marketing messages, can be advised that, except in some very special cases, genetic testing is not essential. They can save money by not paying for genetic tests. ## Balancing efficacy with tolerability The efficacy of antidepressant drugs has been confirmed in a network meta-analysis.[3](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r3) Each antidepressant was compared with other antidepressants using data from randomised placebo-controlled trials. ‘Dual-acting’ antidepressants that target more than one neurotransmitter system, such as the serotonin noradrenaline reuptake inhibitors (SNRIs) and tricyclics, are more efficacious than ‘single-action’ drugs, such as the selective serotonin reuptake inhibitors (SSRIs) like sertraline and escitalopram, based on the odds ratio of achieving a 50% response (see [Table 2](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#t2)).[3](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r3) This meta-analysis also examined the acceptability of the various antidepressants by comparing the drop-out rates in clinical trials. While this is a useful metric of acceptability, the rates of adverse effects for each antidepressant are more useful in clinical practice. ## Table 2 - Efficacy of antidepressants compared to placebo \| \| \| \| \|---\|---\|---\| \| Antidepressant \| Odds ratio \| 95% confidence interval \| \| Amitriptyline \| 2\.13 \| 1\.89–2.41 \| \| Mirtazapine \| 1\.89 \| 1\.64–2.20 \| \| Duloxetine \| 1\.85 \| 1\.66–2.07 \| \| Venlafaxine \| 1\.78 \| 1\.61–1.96 \| \| Paroxetine \| 1\.75 \| 1\.61–1.90 \| \| Fluvoxamine \| 1\.69 \| 1\.41–2.02 \| \| Escitalopram \| 1\.68 \| 1\.50–1.87 \| \| Sertraline \| 1\.67 \| 1\.49–1.87 \| \| Vortioxetine \| 1\.66 \| 1\.45–1.92 \| \| Agomelatine \| 1\.65 \| 1\.44–1.88 \| \| Fluoxetine \| 1\.52 \| 1\.40–1.66 \| \| Citalopram \| 1\.52 \| 1\.33–1.74 \| \| Clomipramine \| 1\.49 \| 1\.21–1.85 \| \| Desvenlafaxine \| 1\.49 \| 1\.24–1.79 \| \| Reboxetine \| 1\.37 \| 1\.16–1.63 \| Efficacy is given as the odds ratio of achieving a response (\>50% reduction in severity). These studies generally used the typical dose to treat depression (although some of the studies were ‘dose finding’ studies in which lower doses were used). Source: adapted from reference 3 [Table 3](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#t3) summarises the common adverse effects ranked according to a ‘limitation’ score for each of the antidepressant classes. The frequency of adverse effects can vary greatly between antidepressant classes, due to having different mechanisms of action. There are fewer differences between drugs in the same antidepressant class, although there are some exceptions. ## Table 3 - Antidepressant adverse effects and their limitations on use \| \| \| \| \| \| \| \|---\|---\|---\|---\|---\|---\| \| Class \| Major adverse effects \| Ease of switching (half-life) \| \| \| \| \| Weight gain \| CNS effects – sedation/agitation \| Sexual \| Withdrawal syndrome \| \| \| \| Selective serotonin reuptake inhibitors (SSRIs) \| • \| •• \| ••• \| ••† \| •• \| \| Serotonin noradrenaline reuptake inhibitors (SNRIs) \| • \| •• \| ••• \| ••• \| •• \| \| Serotonin modulator (vortioxetine) \| • \| • \| •• \| •• \| ••• \| \| Noradrenaline reuptake inhibitor (reboxetine) \| • \| • \| •• \| • \| •• \| \| Tricyclic antidepressants (TCAs) \| ••• \| ••• \| ••• \| ••• \| ••• \| \| Reversible inhibitor of monoamine oxidase A (moclobemide) \| • \| •• \| • \| • \| ••• \| \| Tetracyclic (mianserin) \| •• \| •• \| • \| •• \| • \| \| Noradrenergic and specific serotonergic (mirtazapine) \| ••• \| ••• \| •• \| •• \| • \| \| Monoamine oxidase inhibitors (MAOIs) \| •• \| ••• \| •• \| •• \| ••• \| \| Melatonergic (agomelatine) \| • \| • \| • \| • \| • \| • Minimal limitation •• Some limitation ••• Marked limitation † There is little variation in the severity of adverse effects within classes of antidepressants (but patients may differ in the adverse effects they experience). One exception is the withdrawal symptoms following discontinuation of SSRIs. There is an absence of withdrawal symptoms for fluoxetine but very severe withdrawal symptoms for paroxetine. In general, for an uncomplicated mild–moderate depression, the first choice of antidepressant should be a drug that will be well tolerated and has good efficacy. The ease of switching treatment[4](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r4) should be considered because the first antidepressant may not lead to full remission, requiring the patient to change to a different antidepressant.[5](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r5) For patients with a severe depression or melancholia (characterised by significant psychomotor change), the prime consideration is efficacy rather than tolerability. The first choice will then be one of the more potent antidepressants, generally a dual mode-of-action drug, such as an SNRI or a tricyclic antidepressant. ## Matching the antidepressant to the clinical presentation Antidepressants differ in the specific symptoms that they target, so it is possible to choose an antidepressant according to the patient’s clinical presentation. It is also possible to use the adverse effects to target specific symptoms. For example, mirtazapine is sedating, so it is an option for patients with significant insomnia. Mirtazapine is also associated with weight gain so it may be useful for major depression accompanied by significant weight loss.[6](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r6) In short-term trials, the serotonin modulator vortioxetine benefited patients who had major depression with marked cognitive deficits.[7](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r7) The choice of an antidepressant also depends, to some degree, on the symptom profile of the patient or a specific subtype of depression.[8](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r8) [Table 4](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#t4) lists the antidepressants that are preferred for different depressive symptom profiles. Many patients with major depression in primary care also have significant symptoms of anxiety or have a comorbid anxiety disorder. The antidepressant of choice here is an SSRI.[9](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r9) For patients with a melancholic depression, which has a clear biological underpinning characterised by vegetative symptoms and psychomotor change such as agitation or retardation, a dual-action antidepressant should be the first option. The tricyclic antidepressants or duloxetine may be used in certain neuropathic pain conditions. While they can be prescribed for patients with pain and associated depression, the doses of a tricyclic used to treat major depression need to be higher than those used for adjunctive therapy in pain management. ## Table 4 - Symptoms and initial antidepressant choice \| \| \| \|---\|---\| \| Symptoms \| Preferred antidepressant \| \| Anxiety \| Selective serotonin reuptake inhibitors Moclobemide \| \| Weight loss, reduced appetite \| Mirtazapine Mianserin \| \| Sleep disturbance, insomnia \| Agomelatine Mirtazapine Mianserin Tricyclic antidepressants \| \| Sexual dysfunction \| Agomelatine \| \| Blunting, anhedonia, demotivation \| Selective serotonin reuptake inhibitors Serotonin noradrenaline reuptake inhibitors Agomelatine Monoamine oxidase inhibitors Reboxetine \| \| Melancholia, severe depression \| Serotonin noradrenaline reuptake inhibitors Tricyclic antidepressants Vortioxetine Monoamine oxidase inhibitors \| \| Pain \| Duloxetine Tricyclic antidepressants \| \| Cognitive difficulties \| Vortioxetine \| ## Safety considerations Patients with depression can often have suicidal thoughts and may try to commit suicide. This needs to be considered when prescribing an antidepressant. A suicidal patient should not be given quantities of a drug that could be fatal in an overdose. The SSRIs have a much lower potential lethality than the tricyclic antidepressants. Ask about any other drugs the patient may be taking to avoid potential interactions. For example, there is an increased risk of serotonin toxicity when taking SSRIs in combination with tramadol, St John’s wort or monoamine oxidase inhibitors (MAOIs). SSRIs are also associated with increased bleeding due to changes in platelet function. Caution is therefore needed if they are taken with anticoagulants or non- steroidal anti-inflammatory drugs (NSAIDs). With the increased risk of bleeding, there is a need to consider any comorbid conditions that may add to this risk. In order to limit potential drug and disease interactions, it is recommended that prescribers only use a few antidepressants that they know and understand well.[10](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r10) ## Patient preference A key consideration is patient preference. Adherence to antidepressants is essential to ensure remission of the depression. A significant proportion of patients will stop their antidepressant.[11](https://australianprescriber.tg.org.au/articles/choosing-an-antidepressant.html#r11) Adherence is improved if the patient is involved in the decision about which treatment to take. This involves a discussion about the expected benefits of the antidepressant and its potential adverse effects. Some adverse effects, such as sedation, may be more acceptable to patients, but others such as weight gain may be less acceptable. Be aware that patients might have misinformation from the internet or through word of mouth that the adverse effects of an antidepressant are ‘dreadful and nobody should ever take it’. In such situations, it is essential to listen to the patient’s concerns and present them with clear and accurate information about the drug, including providing them with consumer fact sheets. This approach will improve adherence. ## Conclusion After deciding that a patient needs to take an antidepressant, the choice of drug depends on the severity and symptom pattern of the depressive episode. There has to be a balance between efficacy and tolerability, which also considers patient safety and preference. Conflicts of interest: Philip Boyce has received consultancy and speaker fees, and educational support from Servier. He is on an advisory board and has received educational support from Lundbeck. Australian Prescriber welcomes [Feedback](https://australianprescriber.tg.org.au/contact-us.html). ## References 1. [Malhi GS, Bassett D, Boyce P, Bryant R, Fitzgerald PB, Fritz K, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust N Z J Psychiatry 2015;49:1087-206.](https://doi.org/10.1177/0004867415617657) 2. [Centre of Perinatal Excellence. National perinatal mental health guideline. 2017 Oct 27. \[cited 2021 Jan 4\]](http://www.cope.org.au/health-professionals/health-professionals-3/review-of-new-perinatal-mental-health-guidelines) 3. [Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet 2018;391:1357-66.](https://doi.org/10.1016/S0140-6736\(17\)32802-7) 4. Keks N, Hope J, Keogh S. Switching and stopping antidepressants. Aust Prescr 2016;39:76-83. 5. [Boyce P, Hopwood M, Morris G, Hamilton A, Bassett D, Baune BT, et al. Switching antidepressants in the treatment of major depression: When, how and what to switch to? J Affect Disord 2020;261:160-3.](https://doi.org/10.1016/j.jad.2019.09.082) 6. [Nutt DJ. Tolerability and safety aspects of mirtazapine. Hum Psychopharmacol 2002;17 Suppl 1:S37-41.](https://doi.org/10.1002/hup.388) 7. [McIntyre RS, Harrison J, Loft H, Jacobson W, Olsen CK. The effects of vortioxetine on cognitive function in patients with major depressive disorder: a meta-analysis of three randomized controlled trials. Int J Neuropsychopharmacol 2016;19:pyw055.](https://doi.org/10.1093/ijnp/pyw055) 8. [Baune BT, Boyce P, Morris G, Hamilton A, Bassett D, Hopwood M, et al. Organising the front line: Is there a rationale for the first-line pharmacotherapy of major depressive disorder? Aust N Z J Psychiatry 2019;53:279-81.](https://doi.org/10.1177/0004867418824026) 9. [Coplan JD, Aaronson CJ, Panthangi V, Kim Y. Treating comorbid anxiety and depression: Psychosocial and pharmacological approaches. World J Psychiatry 2015;5:366-78.](https://doi.org/10.5498/wjp.v5.i4.366) 10. [Snyder BD, Polasek TM, Doogue MP. Drug interactions: principles and practice. Aust Prescr 2012;35:85-8.](https://doi.org/10.18773/austprescr.2012.037) 11. [Keyloun KR, Hansen RN, Hepp Z, Gillard P, Thase ME, Devine EB. Adherence and persistence across antidepressant therapeutic classes: a retrospective claims analysis among insured US patients with major depressive disorder (MDD). CNS Drugs 2017;31:421-32.](https://doi.org/10.1007/s40263-017-0417-0)
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