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| URL | https://bnf.nice.org.uk/treatment-summaries/antidepressant-drugs/ | |||||||||
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| Meta Title | Antidepressant drugs | Treatment summaries | BNF | NICE | |||||||||
| Meta Description | This treatment summary topic describes antidepressant drugs | |||||||||
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| Boilerpipe Text | Overview
Choice
The major classes of antidepressant drugs include the tricyclic and related antidepressants, the selective serotonin re-uptake inhibitors (SSRIs), and the monoamine oxidase inhibitors (MAOIs). A number of antidepressant drugs cannot be accommodated easily into this classification.
There is little to choose between the different classes of antidepressant drugs in terms of efficacy, so choice should be based on the individual patient’s requirements, including the presence of concomitant disease, existing therapy, suicide risk, and previous response to antidepressant therapy. During the first few weeks of treatment, there is an increased potential for agitation, anxiety, and suicidal ideation.
SSRIs are better tolerated and are safer in overdose than other classes of antidepressants. In patients with unstable angina or who have had a recent myocardial infarction,
sertraline
has been shown to be safe.
Tricyclic antidepressants have similar efficacy to SSRIs but are more likely to be discontinued because of side-effects; toxicity in overdosage is also a problem. SSRIs are less sedating and have fewer antimuscarinic and cardiotoxic effects than tricyclic antidepressants.
MAOIs have dangerous interactions with some foods and drugs, and should be reserved for use by specialists.
Management
For guidance on the management of depression, see
Depression
.
Patients should be reviewed every 1–2 weeks at the start of antidepressant treatment. Treatment should be continued for at least 4 weeks (6 weeks in the elderly) before considering whether to switch antidepressant due to lack of efficacy. In cases of partial response, continue for a further 2–4 weeks (elderly patients may take longer to respond).
Following remission, antidepressant treatment should be continued at the same dose for at least 6 months (about 12 months in the elderly), or for at least 12 months in patients receiving treatment for generalised anxiety disorder (as the likelihood of relapse is high).
For guidance on the prescribing of antidepressant drugs, and management of withdrawal, see NICE guideline:
Medicines associated with dependence or withdrawal symptoms: safe prescribing and withdrawal management for adults
(available at:
https://www.nice.org.uk/guidance/ng215
).
Hyponatraemia and antidepressant therapy
Hyponatraemia (usually in the elderly and possibly due to inappropriate secretion of antidiuretic hormone) has been associated with all types of antidepressants; however, it has been reported more frequently with SSRIs than with other antidepressants. Hyponatraemia should be considered in all patients who develop drowsiness, confusion, or convulsions while taking an antidepressant.
Suicidal behaviour and antidepressant therapy
The use of antidepressants has been linked with suicidal thoughts and behaviour; children, young adults, and patients with a history of suicidal behaviour are particularly at risk. Where necessary patients should be monitored for suicidal behaviour, self-harm, or hostility, particularly at the beginning of treatment or if the dose is changed.
Serotonin syndrome
Serotonin syndrome or serotonin toxicity is a relatively uncommon adverse drug reaction caused by excessive central and peripheral serotonergic activity. Onset of symptoms, which range from mild to life-threatening, can occur within hours or days following the initiation, dose escalation, or overdose of a serotonergic drug, the addition of a new serotonergic drug, or the replacement of one serotonergic drug by another without allowing a long enough washout period in-between, particularly when the first drug is an irreversible MAOI or a drug with a long half-life. Severe toxicity, which is a medical emergency, usually occurs with a combination of serotonergic drugs, one of which is generally an MAOI.
The characteristic symptoms of serotonin syndrome fall into 3 main areas, although features from each group may not be seen in all patients—neuromuscular hyperactivity (such as tremor, hyperreflexia, clonus, myoclonus, rigidity), autonomic dysfunction (tachycardia, blood pressure changes, hyperthermia, diaphoresis, shivering, diarrhoea), and altered mental state (agitation, confusion, mania).
Treatment consists of withdrawal of the serotonergic medication and supportive care; specialist advice should be sought.
Anxiety disorders and obsessive-compulsive disorder
Management of acute anxiety generally involves the use of a benzodiazepine or
buspirone hydrochloride
. For chronic anxiety (of longer than 4 weeks’ duration) it may be appropriate to use an antidepressant. Combined therapy with a benzodiazepine may be required until the antidepressant takes effect. Patients with
generalised anxiety disorder
, a form of chronic anxiety, should be offered psychological treatment before initiating an antidepressant. If drug treatment is needed, an SSRI such as
escitalopram
,
paroxetine
, or
sertraline
[unlicensed], can be used.
Duloxetine
and
venlafaxine
(serotonin and noradrenaline reuptake inhibitors (SNRIs)) are also recommended for the treatment of generalised anxiety disorder; if the patient cannot tolerate SSRIs or SNRIs (or if treatment has failed to control symptoms),
pregabalin
can be considered.
Panic disorder
is treated with SSRIs; clomipramine hydrochloride [unlicensed] or imipramine hydrochloride [unlicensed] can be used second-line.
Venlafaxine
, an SNRI, is also licensed for panic disorder.
Obsessive-compulsive disorder, post-traumatic stress disorder
, and phobic states such as
social anxiety disorder
are treated with SSRIs.
Clomipramine hydrochloride
can be used second-line for obsessive-compulsive disorder.
Moclobemide
is licensed for the treatment of social anxiety disorder.
Choice
Tricyclic and related antidepressants block the re-uptake of both serotonin and noradrenaline, although to different extents. For example,
clomipramine hydrochloride
is more selective for serotonergic transmission, and
imipramine hydrochloride
is more selective for noradrenergic transmission. Tricyclic and related antidepressant drugs can be roughly divided into those with additional sedative properties and those that are less sedating. Agitated and anxious patients tend to respond best to the sedative compounds, whereas withdrawn and apathetic patients will often obtain most benefit from the less sedating ones. Those with
sedative
properties include
amitriptyline hydrochloride
,
clomipramine hydrochloride
,
dosulepin hydrochloride
,
doxepin
,
mianserin hydrochloride
,
trazodone hydrochloride
, and
trimipramine
. Those with
less sedative
properties include
imipramine hydrochloride
,
lofepramine
, and
nortriptyline
.
Tricyclic and related antidepressants also have varying degrees of antimuscarinic side-effects and cardiotoxicity in overdosage, which may be important in individual patients.
Lofepramine
has a lower incidence of side-effects and is less dangerous in overdosage but is infrequently associated with hepatic toxicity.
Imipramine hydrochloride
is also well established, but has more marked antimuscarinic side-effects than other tricyclic and related antidepressants.
Amitriptyline hydrochloride
and
dosulepin hydrochloride
are effective but they are particularly dangerous in overdosage;
dosulepin hydrochloride
should be initiated by a specialist.
Dosage
About 10 to 20% of patients fail to respond to tricyclic and related antidepressant drugs and inadequate dosage may account for some of these failures. It is important to use doses that are sufficiently high for effective treatment but not so high as to cause toxic effects. Low doses should be used for initial treatment in the
elderly
. In most patients the long half-life of tricyclic antidepressant drugs allows
once-daily
administration, usually at night; the use of modified-release preparations is therefore unnecessary.
Some tricyclic antidepressants are used in the management of
panic
and other
anxiety disorders
. Some tricyclic antidepressants may also have a role in some forms of
neuralgia
and in
nocturnal enuresis
in children.
Children and adolescents
Studies have shown that tricyclic antidepressants are not effective for treating depression in children.
Considerations in the elderly
The use of tricyclic antidepressants in elderly patients is potentially inappropriate (STOPP criteria):
if prescribed in those with dementia, narrow angle glaucoma, cardiac conduction abnormalities, prostatism, or history of urinary retention (risk of worsening these conditions);
if initiated as first-line antidepressant treatment (higher risk of adverse drug reactions than with SSRIs or SNRIs).
For further information, see
STOPP/START criteria
in
Prescribing in the elderly
.
Monoamine-oxidase inhibitors
Monoamine-oxidase inhibitors are used much less frequently than tricyclic and related antidepressants, or SSRIs and related antidepressants because of the dangers of dietary and drug interactions and the fact that it is easier to prescribe MAOIs when tricyclic antidepressants have been unsuccessful than vice versa.
Tranylcypromine
has a greater stimulant action than
phenelzine
or
isocarboxazid
and is more likely to cause a hypertensive crisis.
Isocarboxazid
and
phenelzine
are more likely to cause hepatotoxicity than
tranylcypromine
.
Moclobemide
should be reserved as a second line treatment.
Phobic patients and depressed patients with atypical, hypochondriacal, or hysterical features are said to respond best to MAOIs. However, MAOIs should be tried in any patients who are refractory to treatment with other antidepressants as there is occasionally a dramatic response. Response to treatment may be delayed for 3 weeks or more and may take an additional 1 or 2 weeks to become maximal.
Interactions
Other antidepressants should not be started for 2 weeks after treatment with MAOIs has been stopped (3 weeks if starting clomipramine or imipramine). Conversely, an MAOI should not be started until:
at least 2 weeks after a previous MAOI has been stopped (then started at a reduced dose)
at least 7–14 days after a tricyclic or related antidepressant (3 weeks in the case of clomipramine or imipramine) has been stopped
at least a week after an SSRI or related antidepressant (at least 5 weeks in the case of fluoxetine) has been stopped
Other antidepressant drugs
The thioxanthene
flupentixol
(
Fluanxol
®) has antidepressant properties when given by mouth in low doses.
Flupentixol
is also used for the treatment of psychoses. | |||||||||
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4. Antidepressant drugs
# Antidepressant drugs
## Navigate to section
1. [Overview](https://bnf.nice.org.uk/treatment-summaries/antidepressant-drugs/#overview)
2. [Tricyclic and related antidepressant drugs](https://bnf.nice.org.uk/treatment-summaries/antidepressant-drugs/#tricyclic-and-related-antidepressant-drugs)
3. [Monoamine-oxidase inhibitors](https://bnf.nice.org.uk/treatment-summaries/antidepressant-drugs/#monoamine-oxidase-inhibitors)
4. [Other antidepressant drugs](https://bnf.nice.org.uk/treatment-summaries/antidepressant-drugs/#other-antidepressant-drugs)
5. [Related drugs](https://bnf.nice.org.uk/treatment-summaries/antidepressant-drugs/#related-drugs)
6. [Related treatment summaries](https://bnf.nice.org.uk/treatment-summaries/antidepressant-drugs/#related-treatment-summaries)
## Overview
### Choice
The major classes of antidepressant drugs include the tricyclic and related antidepressants, the selective serotonin re-uptake inhibitors (SSRIs), and the monoamine oxidase inhibitors (MAOIs). A number of antidepressant drugs cannot be accommodated easily into this classification.
There is little to choose between the different classes of antidepressant drugs in terms of efficacy, so choice should be based on the individual patient’s requirements, including the presence of concomitant disease, existing therapy, suicide risk, and previous response to antidepressant therapy. During the first few weeks of treatment, there is an increased potential for agitation, anxiety, and suicidal ideation.
SSRIs are better tolerated and are safer in overdose than other classes of antidepressants. In patients with unstable angina or who have had a recent myocardial infarction, [sertraline](https://bnf.nice.org.uk/drugs/sertraline/ "sertraline") has been shown to be safe.
Tricyclic antidepressants have similar efficacy to SSRIs but are more likely to be discontinued because of side-effects; toxicity in overdosage is also a problem. SSRIs are less sedating and have fewer antimuscarinic and cardiotoxic effects than tricyclic antidepressants.
MAOIs have dangerous interactions with some foods and drugs, and should be reserved for use by specialists.
### Management
For guidance on the management of depression, see [Depression](https://bnf.nice.org.uk/treatment-summaries/depression/ "Depression").
Patients should be reviewed every 1–2 weeks at the start of antidepressant treatment. Treatment should be continued for at least 4 weeks (6 weeks in the elderly) before considering whether to switch antidepressant due to lack of efficacy. In cases of partial response, continue for a further 2–4 weeks (elderly patients may take longer to respond).
Following remission, antidepressant treatment should be continued at the same dose for at least 6 months (about 12 months in the elderly), or for at least 12 months in patients receiving treatment for generalised anxiety disorder (as the likelihood of relapse is high).
For guidance on the prescribing of antidepressant drugs, and management of withdrawal, see NICE guideline: **Medicines associated with dependence or withdrawal symptoms: safe prescribing and withdrawal management for adults** (available at: <https://www.nice.org.uk/guidance/ng215>).
### Hyponatraemia and antidepressant therapy
Hyponatraemia (usually in the elderly and possibly due to inappropriate secretion of antidiuretic hormone) has been associated with all types of antidepressants; however, it has been reported more frequently with SSRIs than with other antidepressants. Hyponatraemia should be considered in all patients who develop drowsiness, confusion, or convulsions while taking an antidepressant.
### Suicidal behaviour and antidepressant therapy
The use of antidepressants has been linked with suicidal thoughts and behaviour; children, young adults, and patients with a history of suicidal behaviour are particularly at risk. Where necessary patients should be monitored for suicidal behaviour, self-harm, or hostility, particularly at the beginning of treatment or if the dose is changed.
### Serotonin syndrome
Serotonin syndrome or serotonin toxicity is a relatively uncommon adverse drug reaction caused by excessive central and peripheral serotonergic activity. Onset of symptoms, which range from mild to life-threatening, can occur within hours or days following the initiation, dose escalation, or overdose of a serotonergic drug, the addition of a new serotonergic drug, or the replacement of one serotonergic drug by another without allowing a long enough washout period in-between, particularly when the first drug is an irreversible MAOI or a drug with a long half-life. Severe toxicity, which is a medical emergency, usually occurs with a combination of serotonergic drugs, one of which is generally an MAOI.
The characteristic symptoms of serotonin syndrome fall into 3 main areas, although features from each group may not be seen in all patients—neuromuscular hyperactivity (such as tremor, hyperreflexia, clonus, myoclonus, rigidity), autonomic dysfunction (tachycardia, blood pressure changes, hyperthermia, diaphoresis, shivering, diarrhoea), and altered mental state (agitation, confusion, mania).
Treatment consists of withdrawal of the serotonergic medication and supportive care; specialist advice should be sought.
### Anxiety disorders and obsessive-compulsive disorder
Management of acute anxiety generally involves the use of a benzodiazepine or [buspirone hydrochloride](https://bnf.nice.org.uk/drugs/buspirone-hydrochloride/ "buspirone hydrochloride"). For chronic anxiety (of longer than 4 weeks’ duration) it may be appropriate to use an antidepressant. Combined therapy with a benzodiazepine may be required until the antidepressant takes effect. Patients with *generalised anxiety disorder*, a form of chronic anxiety, should be offered psychological treatment before initiating an antidepressant. If drug treatment is needed, an SSRI such as [escitalopram](https://bnf.nice.org.uk/drugs/escitalopram/ "escitalopram"), [paroxetine](https://bnf.nice.org.uk/drugs/paroxetine/ "paroxetine"), or [sertraline](https://bnf.nice.org.uk/drugs/sertraline/ "sertraline") \[unlicensed\], can be used. [Duloxetine](https://bnf.nice.org.uk/drugs/duloxetine/ "Duloxetine") and [venlafaxine](https://bnf.nice.org.uk/drugs/venlafaxine/ "venlafaxine") (serotonin and noradrenaline reuptake inhibitors (SNRIs)) are also recommended for the treatment of generalised anxiety disorder; if the patient cannot tolerate SSRIs or SNRIs (or if treatment has failed to control symptoms), [pregabalin](https://bnf.nice.org.uk/drugs/pregabalin/ "pregabalin") can be considered.
*Panic disorder* is treated with SSRIs; clomipramine hydrochloride \[unlicensed\] or imipramine hydrochloride \[unlicensed\] can be used second-line. [Venlafaxine](https://bnf.nice.org.uk/drugs/venlafaxine/ "Venlafaxine"), an SNRI, is also licensed for panic disorder.
*Obsessive-compulsive disorder, post-traumatic stress disorder*, and phobic states such as *social anxiety disorder* are treated with SSRIs. [Clomipramine hydrochloride](https://bnf.nice.org.uk/drugs/clomipramine-hydrochloride/ "Clomipramine hydrochloride") can be used second-line for obsessive-compulsive disorder. [Moclobemide](https://bnf.nice.org.uk/drugs/moclobemide/ "Moclobemide") is licensed for the treatment of social anxiety disorder.
## Tricyclic and related antidepressant drugs
### Choice
Tricyclic and related antidepressants block the re-uptake of both serotonin and noradrenaline, although to different extents. For example, [clomipramine hydrochloride](https://bnf.nice.org.uk/drugs/clomipramine-hydrochloride/ "clomipramine hydrochloride") is more selective for serotonergic transmission, and [imipramine hydrochloride](https://bnf.nice.org.uk/drugs/imipramine-hydrochloride/ "imipramine hydrochloride") is more selective for noradrenergic transmission. Tricyclic and related antidepressant drugs can be roughly divided into those with additional sedative properties and those that are less sedating. Agitated and anxious patients tend to respond best to the sedative compounds, whereas withdrawn and apathetic patients will often obtain most benefit from the less sedating ones. Those with **sedative** properties include [amitriptyline hydrochloride](https://bnf.nice.org.uk/drugs/amitriptyline-hydrochloride/ "amitriptyline hydrochloride"), [clomipramine hydrochloride](https://bnf.nice.org.uk/drugs/clomipramine-hydrochloride/ "clomipramine hydrochloride"), [dosulepin hydrochloride](https://bnf.nice.org.uk/drugs/dosulepin-hydrochloride/ "dosulepin hydrochloride"), [doxepin](https://bnf.nice.org.uk/drugs/doxepin/ "doxepin"), [mianserin hydrochloride](https://bnf.nice.org.uk/drugs/mianserin-hydrochloride/ "mianserin hydrochloride"), [trazodone hydrochloride](https://bnf.nice.org.uk/drugs/trazodone-hydrochloride/ "trazodone hydrochloride"), and [trimipramine](https://bnf.nice.org.uk/drugs/trimipramine/ "trimipramine"). Those with **less sedative** properties include [imipramine hydrochloride](https://bnf.nice.org.uk/drugs/imipramine-hydrochloride/ "imipramine hydrochloride"), [lofepramine](https://bnf.nice.org.uk/drugs/lofepramine/ "lofepramine"), and [nortriptyline](https://bnf.nice.org.uk/drugs/nortriptyline/ "nortriptyline").
Tricyclic and related antidepressants also have varying degrees of antimuscarinic side-effects and cardiotoxicity in overdosage, which may be important in individual patients. [Lofepramine](https://bnf.nice.org.uk/drugs/lofepramine/ "Lofepramine") has a lower incidence of side-effects and is less dangerous in overdosage but is infrequently associated with hepatic toxicity. [Imipramine hydrochloride](https://bnf.nice.org.uk/drugs/imipramine-hydrochloride/ "Imipramine hydrochloride") is also well established, but has more marked antimuscarinic side-effects than other tricyclic and related antidepressants. [Amitriptyline hydrochloride](https://bnf.nice.org.uk/drugs/amitriptyline-hydrochloride/ "Amitriptyline hydrochloride") and [dosulepin hydrochloride](https://bnf.nice.org.uk/drugs/dosulepin-hydrochloride/ "dosulepin hydrochloride") are effective but they are particularly dangerous in overdosage; [dosulepin hydrochloride](https://bnf.nice.org.uk/drugs/dosulepin-hydrochloride/ "dosulepin hydrochloride") should be initiated by a specialist.
### Dosage
About 10 to 20% of patients fail to respond to tricyclic and related antidepressant drugs and inadequate dosage may account for some of these failures. It is important to use doses that are sufficiently high for effective treatment but not so high as to cause toxic effects. Low doses should be used for initial treatment in the **elderly**. In most patients the long half-life of tricyclic antidepressant drugs allows **once-daily** administration, usually at night; the use of modified-release preparations is therefore unnecessary.
Some tricyclic antidepressants are used in the management of *panic* and other *anxiety disorders*. Some tricyclic antidepressants may also have a role in some forms of *neuralgia* and in *nocturnal enuresis* in children.
### Children and adolescents
Studies have shown that tricyclic antidepressants are not effective for treating depression in children.
### Considerations in the elderly
The use of tricyclic antidepressants in elderly patients is potentially inappropriate (STOPP criteria):
- if prescribed in those with dementia, narrow angle glaucoma, cardiac conduction abnormalities, prostatism, or history of urinary retention (risk of worsening these conditions);
- if initiated as first-line antidepressant treatment (higher risk of adverse drug reactions than with SSRIs or SNRIs).
For further information, see *STOPP/START criteria* in [Prescribing in the elderly](https://bnf.nice.org.uk/medicines-guidance/prescribing-in-the-elderly/ "Prescribing in the elderly").
## Monoamine-oxidase inhibitors
Monoamine-oxidase inhibitors are used much less frequently than tricyclic and related antidepressants, or SSRIs and related antidepressants because of the dangers of dietary and drug interactions and the fact that it is easier to prescribe MAOIs when tricyclic antidepressants have been unsuccessful than vice versa.
[Tranylcypromine](https://bnf.nice.org.uk/drugs/tranylcypromine/ "Tranylcypromine") has a greater stimulant action than [phenelzine](https://bnf.nice.org.uk/drugs/phenelzine/ "phenelzine") or [isocarboxazid](https://bnf.nice.org.uk/drugs/isocarboxazid/ "isocarboxazid") and is more likely to cause a hypertensive crisis. [Isocarboxazid](https://bnf.nice.org.uk/drugs/isocarboxazid/ "Isocarboxazid") and [phenelzine](https://bnf.nice.org.uk/drugs/phenelzine/ "phenelzine") are more likely to cause hepatotoxicity than [tranylcypromine](https://bnf.nice.org.uk/drugs/tranylcypromine/ "tranylcypromine").
[Moclobemide](https://bnf.nice.org.uk/drugs/moclobemide/ "Moclobemide") should be reserved as a second line treatment.
Phobic patients and depressed patients with atypical, hypochondriacal, or hysterical features are said to respond best to MAOIs. However, MAOIs should be tried in any patients who are refractory to treatment with other antidepressants as there is occasionally a dramatic response. Response to treatment may be delayed for 3 weeks or more and may take an additional 1 or 2 weeks to become maximal.
### Interactions
Other antidepressants should not be started for 2 weeks after treatment with MAOIs has been stopped (3 weeks if starting clomipramine or imipramine). Conversely, an MAOI should not be started until:
- at least 2 weeks after a previous MAOI has been stopped (then started at a reduced dose)
- at least 7–14 days after a tricyclic or related antidepressant (3 weeks in the case of clomipramine or imipramine) has been stopped
- at least a week after an SSRI or related antidepressant (at least 5 weeks in the case of fluoxetine) has been stopped
## Other antidepressant drugs
The thioxanthene [flupentixol](https://bnf.nice.org.uk/drugs/flupentixol/ "flupentixol") (*Fluanxol*®) has antidepressant properties when given by mouth in low doses. [Flupentixol](https://bnf.nice.org.uk/drugs/flupentixol/ "Flupentixol") is also used for the treatment of psychoses.
## Related drugs
1. [Amitriptyline hydrochloride](https://bnf.nice.org.uk/drugs/amitriptyline-hydrochloride/)
2. [Buspirone hydrochloride](https://bnf.nice.org.uk/drugs/buspirone-hydrochloride/)
3. [Clomipramine hydrochloride](https://bnf.nice.org.uk/drugs/clomipramine-hydrochloride/)
4. [Dosulepin hydrochloride](https://bnf.nice.org.uk/drugs/dosulepin-hydrochloride/)
5. [Doxepin](https://bnf.nice.org.uk/drugs/doxepin/)
6. [Duloxetine](https://bnf.nice.org.uk/drugs/duloxetine/)
7. [Escitalopram](https://bnf.nice.org.uk/drugs/escitalopram/)
8. [Flupentixol](https://bnf.nice.org.uk/drugs/flupentixol/)
9. [Imipramine hydrochloride](https://bnf.nice.org.uk/drugs/imipramine-hydrochloride/)
10. [Isocarboxazid](https://bnf.nice.org.uk/drugs/isocarboxazid/)
11. [Lofepramine](https://bnf.nice.org.uk/drugs/lofepramine/)
12. [Mianserin hydrochloride](https://bnf.nice.org.uk/drugs/mianserin-hydrochloride/)
13. [Moclobemide](https://bnf.nice.org.uk/drugs/moclobemide/)
14. [Nortriptyline](https://bnf.nice.org.uk/drugs/nortriptyline/)
15. [Paroxetine](https://bnf.nice.org.uk/drugs/paroxetine/)
16. [Phenelzine](https://bnf.nice.org.uk/drugs/phenelzine/)
17. [Pregabalin](https://bnf.nice.org.uk/drugs/pregabalin/)
18. [Sertraline](https://bnf.nice.org.uk/drugs/sertraline/)
19. [Tranylcypromine](https://bnf.nice.org.uk/drugs/tranylcypromine/)
20. [Trazodone hydrochloride](https://bnf.nice.org.uk/drugs/trazodone-hydrochloride/)
21. [Trimipramine](https://bnf.nice.org.uk/drugs/trimipramine/)
22. [Venlafaxine](https://bnf.nice.org.uk/drugs/venlafaxine/)
## Related treatment summaries
1. [Cardiovascular disease risk assessment and prevention](https://bnf.nice.org.uk/treatment-summaries/cardiovascular-disease-risk-assessment-and-prevention/)
2. [Depression](https://bnf.nice.org.uk/treatment-summaries/depression/)
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| Readable Markdown | ## Overview
### Choice
The major classes of antidepressant drugs include the tricyclic and related antidepressants, the selective serotonin re-uptake inhibitors (SSRIs), and the monoamine oxidase inhibitors (MAOIs). A number of antidepressant drugs cannot be accommodated easily into this classification.
There is little to choose between the different classes of antidepressant drugs in terms of efficacy, so choice should be based on the individual patient’s requirements, including the presence of concomitant disease, existing therapy, suicide risk, and previous response to antidepressant therapy. During the first few weeks of treatment, there is an increased potential for agitation, anxiety, and suicidal ideation.
SSRIs are better tolerated and are safer in overdose than other classes of antidepressants. In patients with unstable angina or who have had a recent myocardial infarction, [sertraline](https://bnf.nice.org.uk/drugs/sertraline/ "sertraline") has been shown to be safe.
Tricyclic antidepressants have similar efficacy to SSRIs but are more likely to be discontinued because of side-effects; toxicity in overdosage is also a problem. SSRIs are less sedating and have fewer antimuscarinic and cardiotoxic effects than tricyclic antidepressants.
MAOIs have dangerous interactions with some foods and drugs, and should be reserved for use by specialists.
### Management
For guidance on the management of depression, see [Depression](https://bnf.nice.org.uk/treatment-summaries/depression/ "Depression").
Patients should be reviewed every 1–2 weeks at the start of antidepressant treatment. Treatment should be continued for at least 4 weeks (6 weeks in the elderly) before considering whether to switch antidepressant due to lack of efficacy. In cases of partial response, continue for a further 2–4 weeks (elderly patients may take longer to respond).
Following remission, antidepressant treatment should be continued at the same dose for at least 6 months (about 12 months in the elderly), or for at least 12 months in patients receiving treatment for generalised anxiety disorder (as the likelihood of relapse is high).
For guidance on the prescribing of antidepressant drugs, and management of withdrawal, see NICE guideline: **Medicines associated with dependence or withdrawal symptoms: safe prescribing and withdrawal management for adults** (available at: <https://www.nice.org.uk/guidance/ng215>).
### Hyponatraemia and antidepressant therapy
Hyponatraemia (usually in the elderly and possibly due to inappropriate secretion of antidiuretic hormone) has been associated with all types of antidepressants; however, it has been reported more frequently with SSRIs than with other antidepressants. Hyponatraemia should be considered in all patients who develop drowsiness, confusion, or convulsions while taking an antidepressant.
### Suicidal behaviour and antidepressant therapy
The use of antidepressants has been linked with suicidal thoughts and behaviour; children, young adults, and patients with a history of suicidal behaviour are particularly at risk. Where necessary patients should be monitored for suicidal behaviour, self-harm, or hostility, particularly at the beginning of treatment or if the dose is changed.
### Serotonin syndrome
Serotonin syndrome or serotonin toxicity is a relatively uncommon adverse drug reaction caused by excessive central and peripheral serotonergic activity. Onset of symptoms, which range from mild to life-threatening, can occur within hours or days following the initiation, dose escalation, or overdose of a serotonergic drug, the addition of a new serotonergic drug, or the replacement of one serotonergic drug by another without allowing a long enough washout period in-between, particularly when the first drug is an irreversible MAOI or a drug with a long half-life. Severe toxicity, which is a medical emergency, usually occurs with a combination of serotonergic drugs, one of which is generally an MAOI.
The characteristic symptoms of serotonin syndrome fall into 3 main areas, although features from each group may not be seen in all patients—neuromuscular hyperactivity (such as tremor, hyperreflexia, clonus, myoclonus, rigidity), autonomic dysfunction (tachycardia, blood pressure changes, hyperthermia, diaphoresis, shivering, diarrhoea), and altered mental state (agitation, confusion, mania).
Treatment consists of withdrawal of the serotonergic medication and supportive care; specialist advice should be sought.
### Anxiety disorders and obsessive-compulsive disorder
Management of acute anxiety generally involves the use of a benzodiazepine or [buspirone hydrochloride](https://bnf.nice.org.uk/drugs/buspirone-hydrochloride/ "buspirone hydrochloride"). For chronic anxiety (of longer than 4 weeks’ duration) it may be appropriate to use an antidepressant. Combined therapy with a benzodiazepine may be required until the antidepressant takes effect. Patients with *generalised anxiety disorder*, a form of chronic anxiety, should be offered psychological treatment before initiating an antidepressant. If drug treatment is needed, an SSRI such as [escitalopram](https://bnf.nice.org.uk/drugs/escitalopram/ "escitalopram"), [paroxetine](https://bnf.nice.org.uk/drugs/paroxetine/ "paroxetine"), or [sertraline](https://bnf.nice.org.uk/drugs/sertraline/ "sertraline") \[unlicensed\], can be used. [Duloxetine](https://bnf.nice.org.uk/drugs/duloxetine/ "Duloxetine") and [venlafaxine](https://bnf.nice.org.uk/drugs/venlafaxine/ "venlafaxine") (serotonin and noradrenaline reuptake inhibitors (SNRIs)) are also recommended for the treatment of generalised anxiety disorder; if the patient cannot tolerate SSRIs or SNRIs (or if treatment has failed to control symptoms), [pregabalin](https://bnf.nice.org.uk/drugs/pregabalin/ "pregabalin") can be considered.
*Panic disorder* is treated with SSRIs; clomipramine hydrochloride \[unlicensed\] or imipramine hydrochloride \[unlicensed\] can be used second-line. [Venlafaxine](https://bnf.nice.org.uk/drugs/venlafaxine/ "Venlafaxine"), an SNRI, is also licensed for panic disorder.
*Obsessive-compulsive disorder, post-traumatic stress disorder*, and phobic states such as *social anxiety disorder* are treated with SSRIs. [Clomipramine hydrochloride](https://bnf.nice.org.uk/drugs/clomipramine-hydrochloride/ "Clomipramine hydrochloride") can be used second-line for obsessive-compulsive disorder. [Moclobemide](https://bnf.nice.org.uk/drugs/moclobemide/ "Moclobemide") is licensed for the treatment of social anxiety disorder.
### Choice
Tricyclic and related antidepressants block the re-uptake of both serotonin and noradrenaline, although to different extents. For example, [clomipramine hydrochloride](https://bnf.nice.org.uk/drugs/clomipramine-hydrochloride/ "clomipramine hydrochloride") is more selective for serotonergic transmission, and [imipramine hydrochloride](https://bnf.nice.org.uk/drugs/imipramine-hydrochloride/ "imipramine hydrochloride") is more selective for noradrenergic transmission. Tricyclic and related antidepressant drugs can be roughly divided into those with additional sedative properties and those that are less sedating. Agitated and anxious patients tend to respond best to the sedative compounds, whereas withdrawn and apathetic patients will often obtain most benefit from the less sedating ones. Those with **sedative** properties include [amitriptyline hydrochloride](https://bnf.nice.org.uk/drugs/amitriptyline-hydrochloride/ "amitriptyline hydrochloride"), [clomipramine hydrochloride](https://bnf.nice.org.uk/drugs/clomipramine-hydrochloride/ "clomipramine hydrochloride"), [dosulepin hydrochloride](https://bnf.nice.org.uk/drugs/dosulepin-hydrochloride/ "dosulepin hydrochloride"), [doxepin](https://bnf.nice.org.uk/drugs/doxepin/ "doxepin"), [mianserin hydrochloride](https://bnf.nice.org.uk/drugs/mianserin-hydrochloride/ "mianserin hydrochloride"), [trazodone hydrochloride](https://bnf.nice.org.uk/drugs/trazodone-hydrochloride/ "trazodone hydrochloride"), and [trimipramine](https://bnf.nice.org.uk/drugs/trimipramine/ "trimipramine"). Those with **less sedative** properties include [imipramine hydrochloride](https://bnf.nice.org.uk/drugs/imipramine-hydrochloride/ "imipramine hydrochloride"), [lofepramine](https://bnf.nice.org.uk/drugs/lofepramine/ "lofepramine"), and [nortriptyline](https://bnf.nice.org.uk/drugs/nortriptyline/ "nortriptyline").
Tricyclic and related antidepressants also have varying degrees of antimuscarinic side-effects and cardiotoxicity in overdosage, which may be important in individual patients. [Lofepramine](https://bnf.nice.org.uk/drugs/lofepramine/ "Lofepramine") has a lower incidence of side-effects and is less dangerous in overdosage but is infrequently associated with hepatic toxicity. [Imipramine hydrochloride](https://bnf.nice.org.uk/drugs/imipramine-hydrochloride/ "Imipramine hydrochloride") is also well established, but has more marked antimuscarinic side-effects than other tricyclic and related antidepressants. [Amitriptyline hydrochloride](https://bnf.nice.org.uk/drugs/amitriptyline-hydrochloride/ "Amitriptyline hydrochloride") and [dosulepin hydrochloride](https://bnf.nice.org.uk/drugs/dosulepin-hydrochloride/ "dosulepin hydrochloride") are effective but they are particularly dangerous in overdosage; [dosulepin hydrochloride](https://bnf.nice.org.uk/drugs/dosulepin-hydrochloride/ "dosulepin hydrochloride") should be initiated by a specialist.
### Dosage
About 10 to 20% of patients fail to respond to tricyclic and related antidepressant drugs and inadequate dosage may account for some of these failures. It is important to use doses that are sufficiently high for effective treatment but not so high as to cause toxic effects. Low doses should be used for initial treatment in the **elderly**. In most patients the long half-life of tricyclic antidepressant drugs allows **once-daily** administration, usually at night; the use of modified-release preparations is therefore unnecessary.
Some tricyclic antidepressants are used in the management of *panic* and other *anxiety disorders*. Some tricyclic antidepressants may also have a role in some forms of *neuralgia* and in *nocturnal enuresis* in children.
### Children and adolescents
Studies have shown that tricyclic antidepressants are not effective for treating depression in children.
### Considerations in the elderly
The use of tricyclic antidepressants in elderly patients is potentially inappropriate (STOPP criteria):
- if prescribed in those with dementia, narrow angle glaucoma, cardiac conduction abnormalities, prostatism, or history of urinary retention (risk of worsening these conditions);
- if initiated as first-line antidepressant treatment (higher risk of adverse drug reactions than with SSRIs or SNRIs).
For further information, see *STOPP/START criteria* in [Prescribing in the elderly](https://bnf.nice.org.uk/medicines-guidance/prescribing-in-the-elderly/ "Prescribing in the elderly").
## Monoamine-oxidase inhibitors
Monoamine-oxidase inhibitors are used much less frequently than tricyclic and related antidepressants, or SSRIs and related antidepressants because of the dangers of dietary and drug interactions and the fact that it is easier to prescribe MAOIs when tricyclic antidepressants have been unsuccessful than vice versa.
[Tranylcypromine](https://bnf.nice.org.uk/drugs/tranylcypromine/ "Tranylcypromine") has a greater stimulant action than [phenelzine](https://bnf.nice.org.uk/drugs/phenelzine/ "phenelzine") or [isocarboxazid](https://bnf.nice.org.uk/drugs/isocarboxazid/ "isocarboxazid") and is more likely to cause a hypertensive crisis. [Isocarboxazid](https://bnf.nice.org.uk/drugs/isocarboxazid/ "Isocarboxazid") and [phenelzine](https://bnf.nice.org.uk/drugs/phenelzine/ "phenelzine") are more likely to cause hepatotoxicity than [tranylcypromine](https://bnf.nice.org.uk/drugs/tranylcypromine/ "tranylcypromine").
[Moclobemide](https://bnf.nice.org.uk/drugs/moclobemide/ "Moclobemide") should be reserved as a second line treatment.
Phobic patients and depressed patients with atypical, hypochondriacal, or hysterical features are said to respond best to MAOIs. However, MAOIs should be tried in any patients who are refractory to treatment with other antidepressants as there is occasionally a dramatic response. Response to treatment may be delayed for 3 weeks or more and may take an additional 1 or 2 weeks to become maximal.
### Interactions
Other antidepressants should not be started for 2 weeks after treatment with MAOIs has been stopped (3 weeks if starting clomipramine or imipramine). Conversely, an MAOI should not be started until:
- at least 2 weeks after a previous MAOI has been stopped (then started at a reduced dose)
- at least 7–14 days after a tricyclic or related antidepressant (3 weeks in the case of clomipramine or imipramine) has been stopped
- at least a week after an SSRI or related antidepressant (at least 5 weeks in the case of fluoxetine) has been stopped
## Other antidepressant drugs
The thioxanthene [flupentixol](https://bnf.nice.org.uk/drugs/flupentixol/ "flupentixol") (*Fluanxol*®) has antidepressant properties when given by mouth in low doses. [Flupentixol](https://bnf.nice.org.uk/drugs/flupentixol/ "Flupentixol") is also used for the treatment of psychoses. | |||||||||
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