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
Failure to respond to initial treatment with an SSRI may
require an increase in the dose, or switching to a different
SSRI or mirtazapine p. 372. Other second-line choices
include lofepramine p. 377, moclobemide p. 362, and
reboxetine p. 363. Other tricyclic antidepressants and
venlafaxine p. 368 should be considered for more severe
forms of depression; irreversible MAOIs should only be
prescribed by specialists. Failure to respond to a second
antidepressant may require the addition of another
antidepressant of a different class, or use of an augmenting
agent (such as lithium, aripiprazole p. 395 [unlicensed],
olanzapine p. 398 [unlicensed], quetiapine p. 401, or
risperidone p. 402 [unlicensed]), but such adjunctive
treatment should be initiated only by doctors with special
experience of these combinations. Electroconvulsive therapy
may be initiated in severe refractory depression.
Anxiety disorders and obsessive-compulsive disorder
Management of acute anxiety generally involves the use of a
benzodiazepine or buspirone hydrochloride p. 342. 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
p. 365, paroxetine p. 366, or sertraline p. 367 [unlicensed],
can be used. Duloxetine p. 367 and venlafaxine p. 368
(serotonin and noradrenaline reuptake inhibitors) are also
recommended for the treatment of generalised anxiety
disorder; if the patient cannot tolerate SSRIs or serotonin
and noradrenaline reuptake inhibitors (or if treatment has
failed to control symptoms), pregabalin p. 324 can be
anxiety disorder are treated with SSRIs. Clomipramine
hydrochloride p. 373 or imipramine hydrochloride p. 376 can
be used second-line in panic disorder [unlicensed];
clomipramine hydrochloride can also be used second-line for
obsessive-compulsive disorder. Moclobemide p. 362 is
licensed for the treatment of social anxiety disorder.
Tricyclic and related antidepressant drugs
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
p. 372, clomipramine hydrochloride, dosulepin
hydrochloride p. 374, doxepin p. 375, mianserin
hydrochloride p. 371, trazodone hydrochloride p. 370, and
trimipramine p. 378. Those with less sedative properties
include imipramine hydrochloride, lofepramine p. 377, and
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
Amitriptyline hydrochloride and dosulepin hydrochloride
are effective but they are particularly dangerous in
overdosage and are not recommended for the treatment of
depression; dosulepin hydrochloride should be initiated by a
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
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.
Studies have shown that tricyclic antidepressants are not
effective for treating depression in children.
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
Tranylcypromine p. 362 has a greater stimulant action
than phenelzine p. 362 or isocarboxazid p. 362 and is more
likely to cause a hypertensive crisis. Isocarboxazid and
phenelzine are more likely to cause hepatotoxicity than
Moclobemide should be reserved as a second line
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.
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
. 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
. at least a week after an SSRI or related antidepressant (at
least 5 weeks in the case of fluoxetine) has been stopped
The thioxanthene flupentixol p. 385 (Fluanxol ®) has
antidepressant properties when given by mouth in low
doses. Flupentixol is also used for the treatment of
Vortioxetine p. 380, an antidepressant thought to directly
condition has responded inadequately to 2 antidepressants
360 Mental health disorders BNF 78
Tryptophan is licensed for use in treatment-resistant
depression, used as monotherapy and as an adjunct to other
antidepressant drugs; it should be initiated by hospital
Other drugs used for Depression Lithium carbonate, p. 357 . Lithium citrate, p. 358
ANTIDEPRESSANTS › MELATONIN RECEPTOR
l DRUG ACTION A melatonin receptor agonist and a
selective serotonin-receptor antagonist; it does not affect
the uptake of serotonin, noradrenaline, or dopamine.
▶ Adult: 25 mg daily, dose to be taken at bedtime, dose to
be increased if necessary after 2 weeks, increased if
necessary to 50 mg daily, dose to be taken at bedtime
l CONTRA-INDICATIONS Dementia . patients over 75 years of
l INTERACTIONS → Appendix 1: agomelatine
▶ Common or very common Abdominal pain . anxiety . back
▶ Uncommon Aggression . confusion . hyperhidrosis . mood
▶ Rare or very rare Angioedema . face oedema . hallucination . hepatic disorders . urinary retention
SIDE-EFFECTS, FURTHER INFORMATION 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.
l PREGNANCY Manufacturer advises avoid.
l BREAST FEEDING Avoid—present in milk in animal studies.
l HEPATIC IMPAIRMENT Manufacturer advises caution if
transaminases are elevated; avoid in hepatic impairment
or if transaminases exceed 3 times the upper limit of
l RENAL IMPAIRMENT Caution in moderate to severe
l MONITORING REQUIREMENTS Test liver function before
treatment and after 3, 6, 12 and 24 weeks of treatment,
and then regularly thereafter when clinically indicated
(restart monitoring schedule if dose increased);
discontinue if serum transaminases exceed 3 times the
upper limit of reference range or symptoms of liver
Hepatotoxicity Patients should be told how to recognise
signs of liver disorder, and advised to seek immediate
medical attention if symptoms such as dark urine, light
coloured stools, jaundice, bruising, fatigue, abdominal
Patients should be given a booklet with more
information on the risk of hepatic side-effects.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Agomelatine (Non-proprietary)
Agomelatine 25 mg Agomelatine 25mg tablets | 28 tablet P £27.00–£30.00 DT = £30.00
▶ Valdoxan (Servier Laboratories Ltd)
Agomelatine 25 mg Valdoxan 25mg tablets | 28 tablet P £30.00
ANTIDEPRESSANTS › MONOAMINE-OXIDASE
Monoamine-oxidase inhibitors f
l DRUG ACTION MAOIs inhibit monoamine oxidase, thereby
causing an accumulation of amine neurotransmitters.
l CONTRA-INDICATIONS Cerebrovascular disease . not
indicated in manic phase . phaeochromocytoma
l CAUTIONS Acute porphyrias p. 1058 . avoid in agitated
reactions to certain drugs and foods . surgery
in elderly).reflexes increased . skin reactions . suicidal
tendencies .tremor. vision blurred . vomiting . weight
SIDE-EFFECTS, FURTHER INFORMATION Risk of postural
hypotension and hypertensive responses. Discontinue if
palpitations or frequent headaches occur.
l PREGNANCY Increased risk of neonatal malformations—
manufacturer advises avoid unless there are compelling
l HEPATIC IMPAIRMENT In general, manufacturers advise
l MONITORING REQUIREMENTS Monitor blood pressure (risk
of postural hypotension and hypertensive responses).
Withdrawal If possible avoid abrupt withdrawal.
MAOIs are associated with withdrawal symptoms on
cessation of therapy. Symptoms include agitation,
irritability, ataxia, movement disorders, insomnia,
drowsiness, vivid dreams, cognitive impairment, and
slowed speech. Withdrawal symptoms occasionally
experienced when discontinuing MAOIs include
hallucinations and paranoid delusions. If possible MAOIs
Withdrawal effects may occur within 5 days of stopping
treatment with antidepressant drugs; they are usually mild
and self-limiting, but in some cases may be severe. The
risk of withdrawal symptoms is increased if the
antidepressant is stopped suddenly after regular
administration for 8 weeks or more. The dose should
preferably be reduced gradually over about 4 weeks, or
longer if withdrawal symptoms emerge (6 months in
patients who have been on long-term maintenance
l PATIENT AND CARER ADVICE Patients should be advised to
eat only fresh foods and avoid food that is suspected of
being stale or ‘going off’. This is especially important with
meat, fish, poultry or offal; game should be avoided. The
danger of interaction persists for up to 2 weeks after
treatment with MAOIs is discontinued. Patients should
also be advised to avoid alcoholic drinks or de-alcoholised
Driving and skilled tasks Drowsiness may affect
performance of skilled tasks (e.g. driving).
ANTIDEPRESSANTS › MONOAMINEOXIDASE A AND B INHIBITORS,
▶ Adult: Initially 30 mg daily until improvement occurs,
initial dose may be given in single or divided doses,
dose may be increased if necessary after 4 weeks,
increased to 60 mg daily for 4–6 weeks, dose to be
increased under close supervision only, then reduced
to 10–20 mg daily, usual maintenance dose, but up to
l INTERACTIONS → Appendix 1: monoamine-oxidase A and
l SIDE-EFFECTS Granulocytopenia . peripheral oedema . sexual dysfunction
l RENAL IMPAIRMENT Use with caution.
l LESS SUITABLE FOR PRESCRIBING Less suitable for
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension
CAUTIONARY AND ADVISORY LABELS 3, 10
▶ Isocarboxazid (Non-proprietary)
Isocarboxazid 10 mg Isocarboxazid 10mg tablets | 56 tablet P £239.52 DT = £228.64
▶ Adult: Initially 15 mg 3 times a day, response is usually
seen within first week; dose may be increased if
necessary after 2 weeks if response is not evident,
increased if necessary to 15 mg 4 times a day, doses up
to 30 mg three times a day may be used in hospital
patients; response may not become apparent for up to
4 weeks; once satisfactory response has been achieved,
reduce dose gradually to lowest suitable maintenance
dose (15 mg on alternate days may be adequate)
l INTERACTIONS → Appendix 1: monoamine-oxidase A and
dysfunction . shock-like coma . speech repetitive
l BREAST FEEDING Avoid—no information available.
l LESS SUITABLE FOR PRESCRIBING Less suitable for
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 3, 10
Phenelzine (as Phenelzine sulfate) 15 mg Nardil 15mg tablets | 100 tablet P £22.50 DT = £22.50
▶ Adult: Initially 10 mg twice daily, dose to be taken at a
time no later than 3 p.m, dose may be increased if
necessary after 1 week, increased if necessary to 10 mg
daily, dose to be taken in the morning and 20 mg daily,
dose to be taken in the afternoon, doses above 30 mg
daily, under close supervision only; maintenance
l CONTRA-INDICATIONS Congestive heart failure . history of
hepatic disease . hyperthyroidism
l INTERACTIONS → Appendix 1: monoamine-oxidase A and
▶ Rare or very rare Hepatocellular injury
▶ Frequency not known Chest pain . diarrhoea . drug
l BREAST FEEDING Present in milk in animal studies.
l LESS SUITABLE FOR PRESCRIBING Less suitable for
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 3, 10
▶ Tranylcypromine (Non-proprietary)
Tranylcypromine (as Tranylcypromine sulfate)
10 mg Tranylcypromine 10mg tablets | 28 tablet P £311.18 DT =
ANTIDEPRESSANTS › MONOAMINE-OXIDASE A
l DRUG ACTION Moclobemide is reported to act by reversible
inhibition of monoamine oxidase type A (it is therefore
▶ Adult: Initially 300 mg daily in divided doses, adjusted
according to response; usual dose 150–600 mg daily,
▶ Adult: Initially 300 mg daily for 3 days, then increased
to 600 mg daily in 2 divided doses continued for
DOSE ADJUSTMENTS DUE TO INTERACTIONS
▶ Manufacturer advises reduce dose to half or one-third
of the usual dose with concurrent use of cimetidine.
l CONTRA-INDICATIONS Acute confusional states . phaeochromocytoma
362 Mental health disorders BNF 78
l CAUTIONS Avoid in agitated or excited patients (or give
with sedative for up to 2–3 weeks). may provoke manic
episodes in bipolar disorders .thyrotoxicosis
l INTERACTIONS → Appendix 1: moclobemide
▶ Rare or very rare Appetite decreased . delusions . hyponatraemia . serotonin syndrome
l PREGNANCY Safety in pregnancy has not been
established—manufacturer advises avoid unless there are
l BREAST FEEDING Amount too small to be harmful, but
patient information leaflet advises avoid.
l HEPATIC IMPAIRMENT Manufacturer advises caution in
severe impairment (risk of decreased metabolism).
Dose adjustments Manufacturer advises dose reduction to
half or one-third of the daily dose in severe impairment,
l TREATMENT CESSATION Withdrawal effects may occur
within 5 days of stopping treatment with antidepressant
drugs; they are usually mild and self-limiting, but in some
cases may be severe. The risk of withdrawal symptoms is
increased if the antidepressant is stopped suddenly after
regular administration for 8 weeks or more. The dose
should preferably be reduced gradually over about 4 weeks,
or longer if withdrawal symptoms emerge (6 months in
patients who have been on long-term maintenance
l PATIENT AND CARER ADVICE Moclobemide is claimed to
cause less potentiation of the pressor effect of tyramine
than the traditional (irreversible) MAOIs, but patients
should avoid consuming large amounts of tyramine-rich
food (such as mature cheese, yeast extracts and fermented
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension
CAUTIONARY AND ADVISORY LABELS 10, 21
▶ Moclobemide (Non-proprietary)
Moclobemide 150 mg Moclobemide 150mg tablets | 30 tablet P £22.12 DT = £22.10
Moclobemide 300 mg Moclobemide 300mg tablets | 30 tablet P £15.00 DT = £13.99
▶ Manerix (Meda Pharmaceuticals Ltd)
Moclobemide 150 mg Manerix 150mg tablets | 30 tablet P £9.33 DT = £22.10
Moclobemide 300 mg Manerix 300mg tablets | 30 tablet P £13.99 DT = £13.99
ANTIDEPRESSANTS › NORADRENALINE
l DRUG ACTION Reboxetine is a selective inhibitor of
▶ Adult: 4 mg twice daily for 3–4 weeks, then increased if
necessary to 10 mg daily in divided doses; maximum
l CAUTIONS Bipolar disorder. history of cardiovascular
disease . history of epilepsy . prostatic hypertrophy .
susceptibility to angle-closure glaucoma . urinary
l INTERACTIONS → Appendix 1: reboxetine
disorders . urinary tract infection . vasodilation . vomiting
▶ Uncommon Mydriasis . vertigo
phenomenon . suicidal tendencies .testicular pain
l PREGNANCY Use only if potential benefit outweighs risk—
limited information available.
l BREAST FEEDING Small amount present in milk—use only
if potential benefit outweighs risk.
l HEPATIC IMPAIRMENT Manufacturer advises caution (risk
Dose adjustments Manufacturer advises initial dose
reduction to 2 mg twice daily, increased according to
Dose adjustments Initial dose 2 mg twice daily, increased
l TREATMENT CESSATION Caution— avoid abrupt
Driving and skilled tasks Counselling advised.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Reboxetine (as Reboxetine mesilate) 4 mg Edronax 4mg tablets | 60 tablet P £18.91 DT = £18.91
ANTIDEPRESSANTS › SELECTIVE SEROTONIN REUPTAKE INHIBITORS
Selective serotonin re-uptake f
l DRUG ACTION Selectively inhibit the re-uptake of
serotonin (5-hydroxytryptamine, 5-HT).
l CONTRA-INDICATIONS Poorly controlled epilepsy . SSRIs
should not be used if the patient enters a manic phase.
l CAUTIONS Cardiac disease . concurrent electroconvulsive
therapy . diabetes mellitus . epilepsy (discontinue if
convulsions develop). history of bleeding disorders
(especially gastro-intestinal bleeding). history of mania . susceptibility to angle-closure glaucoma
▶ Uncommon Alopecia . angioedema . behaviour abnormal . hallucination . mania . movement disorders .
photosensitivity reaction . postural hypotension . seizure . suicidal tendencies . syncope
▶ Rare or very rare Galactorrhoea . hepatitis . hyperprolactinaemia . hyponatraemia . serotonin
syndrome . severe cutaneous adverse reactions (SCARs). SIADH .thrombocytopenia
▶ Frequency not known Withdrawal syndrome
SIDE-EFFECTS, FURTHER INFORMATION Overdose
Symptoms of poisoning by selective serotonin re-uptake
inhibitors include nausea, vomiting, agitation, tremor,
nystagmus, drowsiness, and sinus tachycardia;
convulsions may occur. Rarely, severe poisoning results in
the serotonin syndrome, with marked neuropsychiatric
effects, neuromuscular hyperactivity, and autonomic
instability; hyperthermia, rhabdomyolysis, renal failure,
and coagulopathies may develop.
For details on the management of poisoning, see
Selective serotonin re-uptake inhibitors, under Emergency
treatment of poisoning p. 1359.
l PREGNANCY Manufacturers advise avoid during pregnancy
unless the potential benefit outweighs the risk. There is a
small increased risk of congenital heart defects when taken
during early pregnancy. If used during the third trimester
there is a risk of neonatal withdrawal symptoms, and
persistent pulmonary hypertension in the newborn has
l HEPATIC IMPAIRMENT In general, manufacturers advise
caution (prolonged half-life).
l TREATMENT CESSATION Gastro-intestinal disturbances,
headache, anxiety, dizziness, paraesthesia, electric shock
sensation in the head, neck, and spine, tinnitus, sleep
disturbances, fatigue, influenza-like symptoms, and
sweating are the most common features of abrupt
withdrawal of an SSRI or marked reduction of the dose;
palpitation and visual disturbances can occur less
commonly. The dose should be tapered over at least a few
weeks to avoid these effects. For some patients, it may be
necessary to withdraw treatment over a longer period;
consider obtaining specialist advice if symptoms persist.
Withdrawal effects may occur within 5 days of stopping
treatment with antidepressant drugs; they are usually mild
and self-limiting, but in some cases may be severe. The
risk of withdrawal symptoms is increased if the
antidepressant is stopped suddenly after regular
administration for 8 weeks or more.
Driving and skilled tasks May also impair performance of
skilled tasks (e.g. driving, operating machinery).
▶ Adult: 20 mg once daily, increased in steps of 20 mg
daily if required, dose to be increased at intervals of
3–4 weeks; maximum 40 mg per day
▶ Elderly: 10–20 mg once daily; maximum 20 mg per day
▶ Adult: 16 mg once daily, increased in steps of 16 mg
daily if required, dose to be increased at intervals of
3–4 weeks; maximum 32 mg per day
▶ Elderly: 8–16 mg daily; maximum 16 mg per day
▶ Adult: Initially 10 mg daily, increased in steps of 10 mg
daily if required, dose to be increased gradually; usual
dose 20–30 mg daily; maximum 40 mg per day
▶ Elderly: Initially 10 mg daily, increased in steps of
10 mg daily if required, dose to be increased gradually;
▶ Adult: Initially 8 mg once daily, increased in steps of
8 mg if required, dose to be increased gradually; usual
dose 16–24 mg daily; maximum 32 mg per day
▶ Elderly: Initially 8 mg once daily, increased in steps of
8 mg if required, dose to be increased gradually;
DOSE EQUIVALENCE AND CONVERSION
▶ 4 oral drops (8 mg) is equivalent in therapeutic effect to
l CONTRA-INDICATIONS QT-interval prolongation
l CAUTIONS Susceptibility to QT-interval prolongation
l INTERACTIONS → Appendix 1: SSRIs
▶ Rare or very rare Cough . generalised tonic-clonic seizure
▶ Frequency not known Hypokalaemia
l BREAST FEEDING Present in milk—use with caution.
Dose adjustments For tablets manufacturer advises initial
dose of 10 mg daily for the first two weeks in mild to
moderate impairment—dose may be increased to max.
20 mg daily; use with extra caution and careful dose
titration in severe impairment.
For oral drops manufacturer advises initial dose of 8 mg
daily for the first two weeks in mild to moderate
impairment—dose may be increased to max. 16 mg daily;
use with extra caution and careful dose titration in severe
l RENAL IMPAIRMENT No information available for eGFR
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