l TREATMENT CESSATION 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 treatment).

l DIRECTIONS FOR ADMINISTRATION Cipramil ® oral drops

should be mixed with water, orange juice, or apple juice

before taking.

l PATIENT AND CARER ADVICE Counselling on

administration of oral drops is advised.

Driving and skilled tasks Patients should be advised of the

effects of citalopram on driving and skilled tasks.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Oral drops

EXCIPIENTS: May contain Alcohol

▶ Citalopram (Non-proprietary)

Citalopram (as Citalopram hydrochloride) 40 mg per

1 ml Citalopram 40mg/ml oral drops sugar free sugar-free | 15 ml P £14.09 DT = £5.21

▶ Cipramil (Lundbeck Ltd)

Citalopram (as Citalopram hydrochloride) 40 mg per

1 ml Cipramil 40mg/ml drops sugar-free | 15 ml P £10.08 DT =

£5.21

Tablet

▶ Citalopram (Non-proprietary)

Citalopram (as Citalopram hydrobromide) 10 mg Citalopram

10mg tablets | 28 tablet P £6.00 DT = £0.89

Citalopram (as Citalopram hydrobromide) 20 mg Citalopram

20mg tablets | 28 tablet P £9.00 DT = £0.88

Citalopram (as Citalopram hydrobromide) 40 mg Citalopram

40mg tablets | 28 tablet P £15.12 DT = £0.96

▶ Cipramil (Lundbeck Ltd)

Citalopram (as Citalopram hydrobromide) 20 mg Cipramil 20mg

tablets | 28 tablet P £8.95 DT = £0.88

364 Mental health disorders BNF 78

Nervous system

4

eiiiF 363i

Escitalopram 13-Jul-2018

l DRUG ACTION Escitalopram is the active enantiomer of

citalopram.

l INDICATIONS AND DOSE

Depressive illness | Generalised anxiety disorder |

Obsessive-compulsive disorder

▶ BY MOUTH

▶ Adult: 10 mg once daily; increased if necessary up to

20 mg daily

▶ Elderly: Initially 5 mg once daily; maximum 10 mg per

day

Panic disorder

▶ BY MOUTH

▶ Adult: Initially 5 mg once daily for 7 days, then

increased to 10 mg daily; maximum 20 mg per day

▶ Elderly: Initially 2.5 mg once daily; maximum 10 mg

per day

Social anxiety disorder

▶ BY MOUTH

▶ Adult: Initially 10 mg once daily for 2–4 weeks, dose to

be adjusted after 2-4 weeks of treatment; usual dose

5–20 mg daily

l CONTRA-INDICATIONS QT-interval prolongation

l CAUTIONS Susceptibility to QT-interval prolongation

l INTERACTIONS → Appendix 1: SSRIs

l SIDE-EFFECTS

▶ Common or very common Sinusitis

▶ Uncommon Oedema

l BREAST FEEDING Present in breast milk; avoid.

l HEPATIC IMPAIRMENT

Dose adjustments Manufacturer advises initially 5 mg once

daily for 2 weeks in mild to moderate impairment,

thereafter increased to 10 mg once daily according to

response; titrate dose with extra caution in severe

impairment.

l RENAL IMPAIRMENT Caution if eGFR less than

30 mL/minute/1.73m2

.

l TREATMENT CESSATION 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 treatment).

l DIRECTIONS FOR ADMINISTRATION Oral drops can be

mixed with water, orange juice, or apple juice before

taking.

l PATIENT AND CARER ADVICE Counselling on

administration of oral drops advised.

Driving and skilled tasks Patients should be counselled

about the effects on driving.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Oral drops

▶ Cipralex (Lundbeck Ltd)

Escitalopram (as Escitalopram oxalate) 20 mg per 1 ml Cipralex

20mg/ml oral drops sugar-free | 15 ml P £20.16 DT = £20.16

Tablet

▶ Escitalopram (Non-proprietary)

Escitalopram (as Escitalopram oxalate) 5 mg Escitalopram 5mg

tablets | 28 tablet P £8.97 DT = £0.91

Escitalopram (as Escitalopram oxalate) 10 mg Escitalopram 10mg

tablets | 28 tablet P £14.91 DT = £1.13

Escitalopram (as Escitalopram oxalate) 20 mg Escitalopram 20mg

tablets | 28 tablet P £25.20 DT = £1.47

▶ Cipralex (Lundbeck Ltd)

Escitalopram (as Escitalopram oxalate) 5 mg Cipralex 5mg tablets

| 28 tablet P £8.97 DT = £0.91

Escitalopram (as Escitalopram oxalate) 10 mg Cipralex 10mg

tablets | 28 tablet P £14.91 DT = £1.13

Escitalopram (as Escitalopram oxalate) 20 mg Cipralex 20mg

tablets | 28 tablet P £25.20 DT = £1.47

eiiiF 363i

Fluoxetine 23-Jul-2018

l INDICATIONS AND DOSE

Major depression

▶ BY MOUTH

▶ Adult: Initially 20 mg daily, dose is increased after

3–4 weeks if necessary, and at appropriate intervals

thereafter, daily dose may be administered as a single

or divided dose; maximum 60 mg per day

▶ Elderly: Initially 20 mg daily, dose is increased after

3–4 weeks if necessary, and at appropriate intervals

thereafter, daily dose may be administered as a single

or divided dose, usual maximum dose is 40 mg daily but

doses up to 60 mg daily can be used

Bulimia nervosa

▶ BY MOUTH

▶ Adult: 60 mg daily, daily dose may be administered as a

single or divided dose

▶ Elderly: Up to 40 mg daily, daily dose may be

administered as a single or divided dose, usual

maximum dose is 40 mg daily but doses up to 60 mg

daily can be used

Obsessive-compulsive disorder

▶ BY MOUTH

▶ Adult: 20 mg daily, increased if necessary up to 60 mg

daily, daily dose may be administered as a single or

divided dose, dose to be increased gradually, review

treatment if inadequate response after 10 weeks;

maximum 60 mg per day

▶ Elderly: 20 mg daily, increased if necessary up to 40 mg

daily, daily dose may be administered as a single or

divided dose, dose to be increased gradually, review

treatment if inadequate response after 10 weeks, usual

maximum dose is 40 mg daily but doses up to 60 mg

daily can be used

Menopausal symptoms, particularly hot flushes, in women

with breast cancer (except those taking tamoxifen)

▶ BY MOUTH

▶ Adult: 20 mg once daily

PHARMACOKINETICS

▶ Consider the long half-life of fluoxetine when adjusting

dosage (or in overdosage).

l UNLICENSED USE g Fluoxetine is used for menopausal

symptoms, ibut it is not licensed for this indication.

l INTERACTIONS → Appendix 1: SSRIs

l SIDE-EFFECTS

▶ Common or very common Chills . feeling abnormal . postmenopausal haemorrhage . uterine disorder. vasodilation . vision blurred

▶ Uncommon Cold sweat. dysphagia . dyspnoea . hypotension . mood altered . muscle twitching . selfinjurious behaviour.temperature sensation altered . thinking abnormal

▶ Rare or very rare Buccoglossal syndrome . leucopenia . neutropenia . oesophageal pain . pharyngitis .respiratory

disorders . serum sickness . speech disorder. vasculitis

▶ Frequency not known Bone fracture

l BREAST FEEDING Present in milk—avoid.

l HEPATIC IMPAIRMENT

Dose adjustments Manufacturer advises dose reduction or

increasing dose interval.

l DIRECTIONS FOR ADMINISTRATION Dispersible tablets can

be dispersed in water for administration or swallowed

whole with plenty of water.

l PATIENT AND CARER ADVICE Patients and carers should be

counselled on the administration of dispersible tablets.

BNF 78 Depression 365

Nervous system

4

Driving and skilled tasks Patients should be counselled

about the effects on driving and skilled tasks.

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, oral

solution

Tablet

▶ Fluoxetine (Non-proprietary)

Fluoxetine (as Fluoxetine hydrochloride) 10 mg Fluoxetine 10mg

tablets | 30 tablet P £44.00 DT = £44.00

Dispersible tablet

CAUTIONARY AND ADVISORY LABELS 10

▶ Olena (Advanz Pharma)

Fluoxetine (as Fluoxetine hydrochloride) 20 mg Olena 20mg

dispersible tablets sugar-free | 28 tablet P £3.44 DT = £3.44

Oral solution

▶ Fluoxetine (Non-proprietary)

Fluoxetine (as Fluoxetine hydrochloride) 4 mg per 1 ml Fluoxetine

20mg/5ml oral solution | 70 ml P £12.75 DT = £2.93

Fluoxetine 20mg/5ml oral solution sugar free sugar-free | 70 ml P £12.95 DT = £12.95

▶ Prozac (Eli Lilly and Company Ltd)

Fluoxetine (as Fluoxetine hydrochloride) 4 mg per 1 ml Prozac

20mg/5ml liquid | 70 ml P £11.12 DT = £2.93

▶ Prozep (Chemidex Pharma Ltd)

Fluoxetine (as Fluoxetine hydrochloride) 4 mg per 1 ml Prozep

20mg/5ml oral solution sugar-free | 70 ml P £12.95 DT = £12.95

Capsule

▶ Fluoxetine (Non-proprietary)

Fluoxetine (as Fluoxetine hydrochloride) 10 mg Fluoxetine 10mg

capsules | 30 capsule P £57.34 DT = £44.68

Fluoxetine (as Fluoxetine hydrochloride) 20 mg Fluoxetine 20mg

capsules | 30 capsule P £2.51 DT = £0.93

Fluoxetine (as Fluoxetine hydrochloride) 30 mg Fluoxetine 30mg

capsules | 30 capsule P £1.80 DT = £1.80

Fluoxetine (as Fluoxetine hydrochloride) 40 mg Fluoxetine 40mg

capsules | 30 capsule P £1.80 DT = £1.80

Fluoxetine (as Fluoxetine hydrochloride) 60 mg Fluoxetine 60mg

capsules | 30 capsule P £54.36 DT = £6.53

▶ Oxactin (Discovery Pharmaceuticals)

Fluoxetine (as Fluoxetine hydrochloride) 20 mg Oxactin 20mg

capsules | 30 capsule P £0.72 DT = £0.93

▶ Prozac (Eli Lilly and Company Ltd)

Fluoxetine (as Fluoxetine hydrochloride) 20 mg Prozac 20mg

capsules | 30 capsule P £1.50 DT = £0.93

eiiiF 363i

Fluvoxamine maleate 23-Jul-2018

l INDICATIONS AND DOSE

Depressive illness

▶ BY MOUTH

▶ Adult: Initially 50–100 mg daily, dose to be taken in the

evening, dose to be increased gradually, increased if

necessary up to 300 mg daily, doses over 150 mg daily

are given in divided doses; maintenance 100 mg daily

Obsessive-compulsive disorder

▶ BY MOUTH

▶ Adult: Initially 50 mg daily, dose to be taken in the

evening, dose is increased gradually if necessary after

several weeks, increased if necessary up to 300 mg

daily; maintenance 100–300 mg daily, doses over

150 mg daily are given in divided doses, if no

improvement in obsessive-compulsive disorder within

10 weeks, treatment should be reconsidered

l INTERACTIONS → Appendix 1: SSRIs

l SIDE-EFFECTS

▶ Rare or very rare Hepatic function abnormal (discontinue)

▶ Frequency not known Bone fracture . glaucoma . neuroleptic malignant-like syndrome . withdrawal

syndrome neonatal

l BREAST FEEDING Present in milk—avoid.

l HEPATIC IMPAIRMENT

Dose adjustments Manufacturer advises low initial dose.

l RENAL IMPAIRMENT

Dose adjustments Start with low dose.

l TREATMENT CESSATION 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 treatment).

l PATIENT AND CARER ADVICE

Driving and skilled tasks Patients should be counselled

about the effects on driving and skilled tasks.

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

Tablet

▶ Fluvoxamine maleate (Non-proprietary)

Fluvoxamine maleate 50 mg Fluvoxamine 50mg tablets | 60 tablet P £20.98 DT = £17.54

Fluvoxamine maleate 100 mg Fluvoxamine 100mg tablets | 30 tablet P £20.98 DT = £17.69

▶ Faverin (Mylan)

Fluvoxamine maleate 50 mg Faverin 50mg tablets |

60 tablet P £17.10 DT = £17.54

Fluvoxamine maleate 100 mg Faverin 100mg tablets | 30 tablet P £17.10 DT = £17.69

eiiiF 363i

Paroxetine 19-Jul-2017

l INDICATIONS AND DOSE

Major depression | Social anxiety disorder | Post-traumatic

stress disorder | Generalised anxiety disorder

▶ BY MOUTH

▶ Adult: 20 mg daily, dose to be taken in the morning, no

evidence of greater efficacy at higher doses; maximum

50 mg per day

▶ Elderly: 20 mg daily, dose to be taken in the morning,

no evidence of greater efficacy at higher doses;

maximum 40 mg per day

Obsessive-compulsive disorder

▶ BY MOUTH

▶ Adult: Initially 20 mg daily, dose to be taken in the

morning, increased in steps of 10 mg, dose to be

increased gradually, increased to 40 mg daily, no

evidence of greater efficacy at higher doses; maximum

60 mg per day

▶ Elderly: Initially 20 mg daily, dose to be taken in the

morning, increased in steps of 10 mg, dose to be

increased gradually; maximum 40 mg per day

Panic disorder

▶ BY MOUTH

▶ Adult: Initially 10 mg daily, dose to be taken in the

morning, increased in steps of 10 mg, dose to be

increased gradually, increased to 40 mg daily, no

evidence of greater efficacy at higher doses; maximum

60 mg per day

▶ Elderly: Initially 10 mg daily, dose to be taken in the

morning, increased in steps of 10 mg, dose to be

increased gradually; maximum 40 mg per day

Menopausal symptoms, particularly hot flushes, in women

with breast cancer (except those taking tamoxifen).

▶ BY MOUTH

▶ Adult: 10 mg once daily

l UNLICENSED USE g Paroxetine is used for menopausal

symptoms, ibut it is not licensed for this indication.

l CAUTIONS Achlorhydria . high gastric pH

CAUTIONS, FURTHER INFORMATION

▶ Achlorhydria or high gastric pH Causes reduced absorption of

the oral suspension.

l INTERACTIONS → Appendix 1: SSRIs

366 Mental health disorders BNF 78

Nervous system

4

l SIDE-EFFECTS

▶ Common or very common Vision blurred

▶ Uncommon Diabetic control impaired

▶ Rare or very rare Acute glaucoma . hepatic disorders . peripheral oedema

l PREGNANCY Increased risk of congenital malformations,

especially if used in the first trimester.

l BREAST FEEDING Present in milk but amount too small to

be harmful.

l HEPATIC IMPAIRMENT

Dose adjustments Manufacturer advises dose at the lower

end of the range.

l RENAL IMPAIRMENT

Dose adjustments Reduce dose if eGFR less than

30 mL/minute/1.73 m2

.

autonomic dysfunction (tachycardia, blood pressure

changes, hyperthermia, diaphoresis, shivering, diarrhoea),

and altered mental state (agitation, confusion, mania).

BNF 78 Depression 359

Nervous system

4

Treatment consists of withdrawal of the serotonergic

medication and supportive care; specialist advice should be

sought.

Failure to respond

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

considered.

Panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, and phobic states such as social

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

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

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

nortriptyline p. 378.

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 sideeffects than other tricyclic and related antidepressants.

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

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 oncedaily administration, usually at night; the use of modifiedrelease 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.

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 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

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 p. 385 (Fluanxol ®) has

antidepressant properties when given by mouth in low

doses. Flupentixol is also used for the treatment of

psychoses.

Vortioxetine p. 380, an antidepressant thought to directly

modulate serotonergic receptor activity and inhibit the reuptake of serotonin, is recommended in patients whose

condition has responded inadequately to 2 antidepressants

within the current episode.

360 Mental health disorders BNF 78

Nervous system

4

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

specialists.

Other drugs used for Depression Lithium carbonate, p. 357 . Lithium citrate, p. 358

ANTIDEPRESSANTS › MELATONIN RECEPTOR

AGONISTS

Agomelatine 11-Sep-2018

l DRUG ACTION A melatonin receptor agonist and a

selective serotonin-receptor antagonist; it does not affect

the uptake of serotonin, noradrenaline, or dopamine.

l INDICATIONS AND DOSE

Major depression

▶ BY MOUTH

▶ 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

age

l CAUTIONS Alcoholism . bipolar disorder. diabetes . excessive alcohol consumption . hypomania . mania . nonalcoholic fatty liver disease . obesity

l INTERACTIONS → Appendix 1: agomelatine

l SIDE-EFFECTS

▶ Common or very common Abdominal pain . anxiety . back

pain . constipation . diarrhoea . dizziness . drowsiness . fatigue . headaches . nausea . sleep disorders . vomiting . weight changes

▶ Uncommon Aggression . confusion . hyperhidrosis . mood

altered . movement disorders . paraesthesia . skin reactions . suicidal tendencies .tinnitus . vision blurred

▶ 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

normal.

l RENAL IMPAIRMENT Caution in moderate to severe

impairment.

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

disorder.

l PATIENT AND CARER ADVICE

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

pain, or pruritus develop.

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.

Tablet

▶ 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

DT = £30.00

ANTIDEPRESSANTS › MONOAMINE-OXIDASE

INHIBITORS

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

patients . blood disorders . cardiovascular disease . concurrent electroconvulsive therapy . diabetes mellitus . elderly (great caution). epilepsy . severe hypertensive

reactions to certain drugs and foods . surgery

l SIDE-EFFECTS Akathisia . anxiety . appetite increased . arrhythmia . asthenia . behaviour abnormal . blood

disorder. confusion . constipation . dizziness . drowsiness . dry mouth . dysuria . hallucination . headache . hyperhidrosis . insomnia . jaundice . nausea . paraesthesia . peripheral neuritis . postural hypotension (more common

in elderly).reflexes increased . skin reactions . suicidal

tendencies .tremor. vision blurred . vomiting . weight

increased

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

reasons.

l HEPATIC IMPAIRMENT In general, manufacturers advise

avoid.

l MONITORING REQUIREMENTS Monitor blood pressure (risk

of postural hypotension and hypertensive responses).

l TREATMENT CESSATION

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

should be withdrawn slowly.

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

treatment).

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

(low alcohol) drinks.

BNF 78 Depression 361

Nervous system

4

Driving and skilled tasks Drowsiness may affect

performance of skilled tasks (e.g. driving).

ANTIDEPRESSANTS › MONOAMINEOXIDASE A AND B INHIBITORS,

IRREVERSIBLE

eiiiF 361i

Isocarboxazid 30-Mar-2017

l INDICATIONS AND DOSE

Depressive illness

▶ BY MOUTH

▶ 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

40 mg daily may be required

▶ Elderly: 5–10 mg daily

l INTERACTIONS → Appendix 1: monoamine-oxidase A and

B inhibitors, irreversible

l SIDE-EFFECTS Granulocytopenia . peripheral oedema . sexual dysfunction

l BREAST FEEDING Avoid.

l RENAL IMPAIRMENT Use with caution.

l LESS SUITABLE FOR PRESCRIBING Less suitable for

prescribing.

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

Tablet

CAUTIONARY AND ADVISORY LABELS 3, 10

▶ Isocarboxazid (Non-proprietary)

Isocarboxazid 10 mg Isocarboxazid 10mg tablets | 56 tablet P £239.52 DT = £228.64

eiiiF 361i

Phenelzine

l INDICATIONS AND DOSE

Depressive illness

▶ BY MOUTH

▶ 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

B inhibitors, irreversible

l SIDE-EFFECTS Cardiovascular insufficiency . delirium . electrolyte imbalance .fatal progressive hepatocellular

necrosis .feeling jittery . fever. gastrointestinal disorder. glaucoma . hypermetabolism . hypertensive crisis . impaired driving ability . intracranial haemorrhage . lupuslike syndrome . malaise . mood altered . movement

disorders . muscle tone increased . muscle twitching . neuroleptic malignant syndrome . nystagmus . oedema . respiratory disorders . schizophrenia . seizure . sexual

dysfunction . shock-like coma . speech repetitive

l BREAST FEEDING Avoid—no information available.

l LESS SUITABLE FOR PRESCRIBING Less suitable for

prescribing.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Tablet

CAUTIONARY AND ADVISORY LABELS 3, 10

▶ Nardil (Kyowa Kirin Ltd)

Phenelzine (as Phenelzine sulfate) 15 mg Nardil 15mg tablets | 100 tablet P £22.50 DT = £22.50

eiiiF 361i

Tranylcypromine

l INDICATIONS AND DOSE

Depressive illness

▶ BY MOUTH

▶ 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

10 mg daily

l CONTRA-INDICATIONS Congestive heart failure . history of

hepatic disease . hyperthyroidism

l INTERACTIONS → Appendix 1: monoamine-oxidase A and

B inhibitors, irreversible

l SIDE-EFFECTS

▶ Rare or very rare Hepatocellular injury

▶ Frequency not known Chest pain . diarrhoea . drug

dependence . extrasystole . flushing . hypertension . hypomania . mydriasis . pain . pallor. photophobia . sleep

disorder.throbbing headache

l BREAST FEEDING Present in milk in animal studies.

l LESS SUITABLE FOR PRESCRIBING Less suitable for

prescribing.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Tablet

CAUTIONARY AND ADVISORY LABELS 3, 10

▶ Tranylcypromine (Non-proprietary)

Tranylcypromine (as Tranylcypromine sulfate)

10 mg Tranylcypromine 10mg tablets | 28 tablet P £311.18 DT =

£287.07

ANTIDEPRESSANTS › MONOAMINE-OXIDASE A

INHIBITORS, REVERSIBLE

Moclobemide

l DRUG ACTION Moclobemide is reported to act by reversible

inhibition of monoamine oxidase type A (it is therefore

termed a RIMA).

l INDICATIONS AND DOSE

Depressive illness

▶ BY MOUTH

▶ Adult: Initially 300 mg daily in divided doses, adjusted

according to response; usual dose 150–600 mg daily,

dose to be taken after food

Social anxiety disorder

▶ BY MOUTH

▶ Adult: Initially 300 mg daily for 3 days, then increased

to 600 mg daily in 2 divided doses continued for

8–12 weeks to assess efficacy

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

Nervous system

4

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

l SIDE-EFFECTS

▶ Common or very common Anxiety . constipation . diarrhoea . dizziness . dry mouth . headache . hypotension . irritability . nausea . paraesthesia . skin reactions . sleep

disorder. vomiting

▶ Uncommon Asthenia . confusion . flushing . oedema . suicidal tendencies .taste altered . visual impairment

▶ 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

compelling reasons.

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

treatment).

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

soya bean products).

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

Tablet

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

REUPTAKE INHIBITORS

Reboxetine

l DRUG ACTION Reboxetine is a selective inhibitor of

noradrenaline re-uptake.

l INDICATIONS AND DOSE

Major depression

▶ BY MOUTH

▶ Adult: 4 mg twice daily for 3–4 weeks, then increased if

necessary to 10 mg daily in divided doses; maximum

12 mg per day

l CAUTIONS Bipolar disorder. history of cardiovascular

disease . history of epilepsy . prostatic hypertrophy .

susceptibility to angle-closure glaucoma . urinary

retention

l INTERACTIONS → Appendix 1: reboxetine

l SIDE-EFFECTS

▶ Common or very common Accommodation disorder. akathisia . anxiety . appetite decreased . chills . constipation . dizziness . dry mouth . headache . hyperhidrosis . hypertension . hypotension . insomnia . nausea . palpitations . paraesthesia . sexual dysfunction . skin reactions .tachycardia .taste altered . urinary

disorders . urinary tract infection . vasodilation . vomiting

▶ Uncommon Mydriasis . vertigo

▶ Rare or very rare Glaucoma

▶ Frequency not known Aggression . hallucination . hyponatraemia . irritability . peripheral coldness . potassium depletion (long term use). Raynaud’s

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

of increased exposure).

Dose adjustments Manufacturer advises initial dose

reduction to 2 mg twice daily, increased according to

tolerance.

l RENAL IMPAIRMENT

Dose adjustments Initial dose 2 mg twice daily, increased

according to tolerance.

l TREATMENT CESSATION Caution— avoid abrupt

withdrawal.

l PATIENT AND CARER ADVICE

Driving and skilled tasks Counselling advised.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Tablet

▶ Edronax (Pfizer Ltd)

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

inhibitors

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

l SIDE-EFFECTS

▶ Common or very common Anxiety . appetite abnormal . arrhythmias . arthralgia . asthenia . concentration impaired . confusion . constipation . depersonalisation. diarrhoea . dizziness . drowsiness . dry mouth . fever. gastrointestinal

discomfort. haemorrhage . headache . hyperhidrosis . malaise . memory loss . menstrual cycle irregularities . myalgia . mydriasis . nausea (dose-related). palpitations . paraesthesia . QT interval prolongation . sexual

dysfunction . skin reactions . sleep disorders .taste altered .tinnitus .tremor. urinary disorders . visual impairment. vomiting . weight changes . yawning

▶ Uncommon Alopecia . angioedema . behaviour abnormal . hallucination . mania . movement disorders .

BNF 78 Depression 363

Nervous system

4

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

been reported.

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.

l PATIENT AND CARER ADVICE

Driving and skilled tasks May also impair performance of

skilled tasks (e.g. driving, operating machinery).

eiiiF 363i

Citalopram 31-Jul-2018

l INDICATIONS AND DOSE

Depressive illness

▶ BY MOUTH USING TABLETS

▶ 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

▶ BY MOUTH USING ORAL DROPS

▶ 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

Panic disorder

▶ BY MOUTH USING TABLETS

▶ 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;

maximum 20 mg per day

▶ BY MOUTH USING ORAL DROPS

▶ 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;

maximum 16 mg per day

DOSE EQUIVALENCE AND CONVERSION

▶ 4 oral drops (8 mg) is equivalent in therapeutic effect to

10 mg tablet.

l CONTRA-INDICATIONS QT-interval prolongation

l CAUTIONS Susceptibility to QT-interval prolongation

l INTERACTIONS → Appendix 1: SSRIs

l SIDE-EFFECTS

▶ Common or very common Acute angle closure glaucoma . apathy . flatulence . hypersalivation . migraine .rhinitis

▶ Uncommon Oedema

▶ Rare or very rare Cough . generalised tonic-clonic seizure

▶ Frequency not known Hypokalaemia

l BREAST FEEDING Present in milk—use with caution.

l HEPATIC IMPAIRMENT

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

impairment.

l RENAL IMPAIRMENT No information available for eGFR

less than 20 mL/minute/1.73 m2

.