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2/26/23

 


. referral to a psychiatrist experienced in working with

patients who have learning disabilities and mental health

problems;

. annual documentation of the reasons for continuing a

prescription if the antipsychotic is not reduced in dose or

discontinued h.

Side effects of antipsychotic drugs

Side-effects caused by antipsychotic drugs are common and

contribute significantly to non-adherence to therapy.

Extrapyramidal symptoms

Extrapyramidal symptoms occur most frequently with the

piperazine phenothiazines (fluphenazine, perphenazine,

prochlorperazine, and trifluoperazine), the butyrophenones

(benperidol and haloperidol), and the first-generation depot

preparations. They are easy to recognise but cannot be

predicted accurately because they depend on the dose, the

type of drug, and on individual susceptibility.

Extrapyramidal symptoms consist of:

. parkinsonian symptoms (including tremor), which may

occur more commonly in adults or the elderly and may

appear gradually;

. dystonia (abnormal face and body movements) and

dyskinesia, which occur more commonly in children or

young adults and appear after only a few doses;

. akathisia (restlessness), which characteristically occurs

after large initial doses and may resemble an exacerbation

of the condition being treated;

. tardive dyskinesia (rhythmic, involuntary movements of

tongue, face, and jaw), which usually develops on longterm therapy or with high dosage, but it may develop on

short-term treatment with low doses—short-lived tardive

dyskinesia may occur after withdrawal of the drug.

Parkinsonian symptoms remit if the drug is withdrawn and

may be suppressed by the administration of antimuscarinic

drugs. However, routine administration of such drugs is not

justified because not all patients are affected and they may

unmask or worsen tardive dyskinesia.

Tardive dyskinesia is the most serious manifestation of

extrapyramidal symptoms; it is of particular concern because

it may be irreversible on withdrawing therapy and treatment

is usually ineffective. In children, tardive dyskinesia is more

likely to occur when the antipsychotic drug is withdrawn.

However, some manufacturers suggest that drug withdrawal

at the earliest signs of tardive dyskinesia (fine vermicular

movements of the tongue) may halt its full development.

Tardive dyskinesia occurs fairly frequently, especially in the

elderly, and treatment must be carefully and regularly

reviewed.

Hyperprolactinaemia

Most antipsychotic drugs, both first- and second-generation,

increase prolactin concentration to some extent because

dopamine inhibits prolactin release. Aripiprazole reduces

prolactin because it is a dopamine-receptor partial agonist.

Risperidone, amisulpride, and first-generation antipsychotic

drugs are most likely to cause symptomatic

hyperprolactinaemia. The clinical symptoms of

hyperprolactinaemia include sexual dysfunction, reduced

bone mineral density, menstrual disturbances, breast

enlargement, and galactorrhoea.

Sexual dysfunction

Sexual dysfunction is one of the main causes of nonadherence to antipsychotic medication; physical illness,

psychiatric illness, and substance misuse are contributing

factors. Antipsychotic-induced sexual dysfunction is caused

by more than one mechanism. Reduced dopamine

transmission and hyperprolactinaemia decrease libido;

antimuscarinic effects can cause disorders of arousal; and

alpha1-adrenoceptor antagonists are associated with

erection and ejaculation problems in men. Risperidone and

haloperidol commonly cause sexual dysfunction. If sexual

dysfunction is thought to be antipsychotic-induced, dose

reduction or switching medication should be considered.

Cardiovascular side-effects

Antipsychotic drugs have been associated with

cardiovascular side-effects such as tachycardia, arrhythmias,

and hypotension. QT-interval prolongation is a particular

concern with pimozide and haloperidol. There is also a

higher probability of QT-interval prolongation in patients

using any intravenous antipsychotic drug, or any

antipsychotic drug or combination of antipsychotic drugs

with doses exceeding the recommended maximum. Cases of

sudden death have occurred.

Hyperglycaemia and weight gain

Hyperglycaemia, and sometimes diabetes, can occur with

antipsychotic drugs, particularly clozapine, olanzapine,

quetiapine, and risperidone. All antipsychotic drugs may

cause weight gain, but the risk and extent varies. Clozapine

and olanzapine commonly cause weight gain.

Hypotension and interference with temperature regulation

Hypotension and interference with temperature regulation

are dose-related side-effects that are liable to cause

dangerous falls and hypothermia or hyperthermia in the

elderly. Clozapine, chlorpromazine, lurasidone, and

quetiapine can cause postural hypotension (especially

during initial dose titration) which may be associated with

syncope or reflex tachycardia in some patients.

Neuroleptic malignant syndrome

Neuroleptic malignant syndrome (hyperthermia, fluctuating

level of consciousness, muscle rigidity, and autonomic

dysfunction with pallor, tachycardia, labile blood pressure,

sweating, and urinary incontinence) is a rare but potentially

fatal side-effect of all antipsychotic drugs. Discontinuation

of the antipsychotic drug is essential because there is no

proven effective treatment, but bromocriptine and

dantrolene have been used. The syndrome, which usually

lasts for 5–7 days after drug discontinuation, may be unduly

prolonged if depot preparations have been used.

Blood dyscrasias

Perform blood counts if unexplained infection or fever

develops.

Choice

There is little meaningful difference in efficacy between each

of the antipsychotic drugs (other than clozapine p. 396), and

response and tolerability to each antipsychotic drug varies.

There is no first-line antipsychotic drug which is suitable for

all patients. Choice of antipsychotic medication is influenced

by the patient’s medication history, the degree of sedation

required (although tolerance to this usually develops), and

consideration of individual patient factors such as risk of

extrapyramidal side-effects, weight gain, impaired glucose

tolerance, QT-interval prolongation, or the presence of

negative symptoms.

Negative symptoms

Second generation antipsychotic drugs may be better at

treating the negative symptoms of schizophrenia.

Extrapyramidal side-effects

Second-generation antipsychotic drugs should be prescribed

if extrapyramidal side-effects are a particular concern. Of

these, aripiprazole p. 395, clozapine, olanzapine p. 398, and

quetiapine p. 401 are least likely to cause extrapyramidal

side-effects. Although amisulpride p. 394 is a dopaminereceptor antagonist, extrapyramidal side-effects are less

common than with the first-generation antipsychotic drugs

because amisulpride selectively blocks mesolimbic dopamine

receptors, and extrapyramidal symptoms are caused by

blockade of the striatal dopamine pathway.

QT interval

Aripiprazole has negligible effect on the QT interval. Other

antipsychotic drugs with a reduced tendency to prolong QT

interval include amisulpride, clozapine, flupentixol p. 385,

382 Mental health disorders BNF 78

Nervous system

4

fluphenazine decanoate p. 392, olanzapine, perphenazine,

prochlorperazine p. 389, risperidone p. 402, and sulpiride

p. 390.

Diabetes

Schizophrenia is associated with insulin resistance and

diabetes; the risk of diabetes is increased in patients with

schizophrenia who take antipsychotic drugs. Firstgeneration antipsychotic drugs are less likely to cause

diabetes than second-generation antipsychotic drugs, and of

the first-generation antipsychotic drugs, fluphenazine

decanoate and haloperidol p. 386 are lowest risk.

Amisulpride and aripiprazole have the lowest risk of diabetes

of the second-generation antipsychotic drugs. Amisulpride,

aripiprazole, haloperidol, sulpiride, and trifluoperazine

p. 390 are least likely to cause weight gain.

Sexual dysfunction and prolactin

The antipsychotic drugs with the lowest risk of sexual

dysfunction are aripiprazole and quetiapine. Olanzapine

may be considered if sexual dysfunction is judged to be

secondary to hyperprolactinaemia. Hyperprolactinaemia is

usually not clinically significant with aripiprazole, clozapine,

olanzapine, and quetiapine treatment. When changing from

other antipsychotic drugs, a reduction in prolactin

concentration may increase fertility.

Patients should receive an antipsychotic drug for

4–6 weeks before it is deemed ineffective. Prescribing more

than one antipsychotic drug at a time should be avoided

except in exceptional circumstances (e.g. clozapine

augmentation or when changing medication during

titration) because of the increased risk of adverse effects

such as extrapyramidal symptoms, QT-interval

prolongation, and sudden cardiac death.

Clozapine is licensed for the treatment of schizophrenia in

patients unresponsive to, or intolerant of, other

antipsychotic drugs. Clozapine should be introduced if

schizophrenia is not controlled despite the sequential use of

two or more antipsychotic drugs (one of which should be a

second-generation antipsychotic drug), each for at least

6–8 weeks. If symptoms do not respond adequately to an

optimised dose of clozapine, plasma-clozapine

concentration should be checked before adding a second

antipsychotic drug to augment clozapine; allow 8–10 weeks’

treatment to assess response. Patients must be registered

with a clozapine patient monitoring service.

Monitoring

Full blood count, urea and electrolytes, and liver function

test monitoring is required at the start of therapy with

antipsychotic drugs, and then annually thereafter.

Blood lipids and weight should be measured at baseline, at

3 months (weight should be measured at frequent intervals

during the first 3 months), and then yearly.

Fasting blood glucose should be measured at baseline, at

4–6 months, and then yearly.

Before initiating antipsychotic drugs, an ECG may be

required, particularly if physical examination identifies

cardiovascular risk factors, if there is a personal history of

cardiovascular disease, or if the patient is being admitted as

an inpatient.

Blood pressure monitoring is advised before starting

therapy and frequently during dose titration of antipsychotic

drugs.

Other uses

Some antipsychotic drugs can be used for the treatment of

nausea and vomiting, choreas, and motor tics.

Chlorpromazine hydrochloride p. 384 and haloperidol p. 386

can be used for intractable hiccup. Benperidol p. 380 is used

in deviant antisocial sexual behaviour but its value is not

established.

Psychomotor agitation should be investigated for an

underlying cause; it can be managed with low doses of

chlorpromazine hydrochloride or haloperidol used for short

periods. Antipsychotic drugs can be used with caution for the

short-term treatment of severe agitation and restlessness in

the elderly.

Equivalent doses of oral antipsychotics

These equivalences are intended only as an approximate

guide; individual dosage instructions should also be

checked; patients should be carefully monitored after any

change in medication. Equivalent daily dose of antipsychotic

drug:

. Chlorpromazine 100 mg

. Clozapine 50 mg

. Haloperidol 2–3 mg

. Pimozide 2 mg

. Risperidone 0.5–1 mg

. Sulpiride 200 mg

. Trifluoperazine 5 mg

Important: These equivalences must not be extrapolated

beyond the maximum dose for the drug. Higher doses require

careful titration in specialist units and the equivalences

shown here may not be appropriate.

Dosage

After an initial period of stabilisation, in most patients, the

total daily oral dose can be given as a single dose. The Royal

College of Psychiatrists has published advice on doses of

antipsychotic drugs above BNF upper limit.

Antipsychotic depot injections

Long-acting depot injections are used for maintenance

therapy especially when compliance with oral treatment is

unreliable. However, depot injections of conventional

antipsychotics may give rise to a higher incidence of

extrapyramidal reactions than oral preparations;

extrapyramidal reactions occur less frequently with secondgeneration antipsychotic depot preparations, such as

risperidone p. 402 and olanzapine embonate p. 404.

Choice

There is no clear-cut division in the use of the conventional

antipsychotics, but zuclopenthixol p. 391 may be suitable for

the treatment of agitated or aggressive patients whereas

flupentixol decanoate p. 392 can cause over-excitement in

such patients. Zuclopenthixol decanoate p. 394 may be more

effective in preventing relapses than other conventional

antipsychotic depot preparations. The incidence of

extrapyramidal reactions is similar for the conventional

antipsychotics.

Dosage

Individual responses to neuroleptic drugs are variable and to

achieve optimum effect, dosage and dosage interval must be

titrated according to the patient’s response.

Equivalent doses of depot antipsychotics

Antipsychotic drug/interval Dosage (mg)

Flupentixol decanoate / 2 weeks 40

Fluphenazine decanoate / 2 weeks 25

Haloperidol (as decanoate) / 4 weeks 100

Zuclopenthixol decanoate / 2 weeks 200

Important: These equivalences must not be extrapolated beyond

the maximum dose for the drug

These equivalences are intended only as an approximate

guide; individual dosage instructions should also be

checked; patients should be carefully monitored after any

change in medication.

BNF 78 Psychoses and schizophrenia 383

Nervous system

4

ANTIPSYCHOTICS

Antipsychotic drugs f

l CAUTIONS Blood dyscrasias . cardiovascular disease . conditions predisposing to seizures . depression . diabetes

(may raise blood glucose). epilepsy . history of jaundice . myasthenia gravis . Parkinson’s disease (may be

exacerbated)(in adults). photosensitisation (may occur

with higher dosages). prostatic hypertrophy (in adults). severe respiratory disease . susceptibility to angle-closure

glaucoma

CAUTIONS, FURTHER INFORMATION

▶ Cardiovascular disease An ECG may be required, particularly

if physical examination identifies cardiovascular risk

factors, personal history of cardiovascular disease, or if the

patient is being admitted as an inpatient.

l SIDE-EFFECTS

▶ Common or very common Agitation . amenorrhoea . arrhythmias . constipation . dizziness . drowsiness . dry

mouth . erectile dysfunction . galactorrhoea . gynaecomastia . hyperprolactinaemia . hypotension (doserelated). insomnia . leucopenia . movement disorders . neutropenia . parkinsonism . QT interval prolongation . rash . seizure .tremor. urinary retention . vomiting . weight increased

▶ Uncommon Agranulocytosis . embolism and thrombosis . neuroleptic malignant syndrome (discontinue—potentially

fatal)

▶ Rare or very rare Sudden death . withdrawal syndrome

neonatal

SIDE-EFFECTS, FURTHER INFORMATION For depot

antipsychotics—side-effects may persist until the drug has

been cleared from its depot site.

Overdose Phenothiazines cause less depression of

consciousness and respiration than other sedatives.

Hypotension, hypothermia, sinus tachycardia, and

arrhythmias may complicate poisoning. For details on the

management of poisoning see Antipsychotics under

Emergency treatment of poisoning p. 1359.

l PREGNANCY Extrapyramidal effects and withdrawal

syndrome have been reported occasionally in the neonate

when antipsychotic drugs are taken during the third

trimester of pregnancy. Following maternal use of

antipsychotic drugs in the third trimester, neonates should

be monitored for symptoms including agitation,

hypertonia, hypotonia, tremor, drowsiness, feeding

problems, and respiratory distress.

l BREAST FEEDING There is limited information available on

the short- and long-term effects of antipsychotic drugs on

the breast-fed infant. Animal studies indicate possible

adverse effects of antipsychotic medicines on the

developing nervous system. Chronic treatment with

antipsychotic drugs whilst breast-feeding should be

avoided unless absolutely necessary. Phenothiazine

derivatives are sometimes used in breast-feeding women

for short-term treatment of nausea and vomiting.

l MONITORING REQUIREMENTS

▶ It is advisable to monitor prolactin concentration at the

start of therapy, at 6 months, and then yearly. Patients

taking antipsychotic drugs not normally associated with

symptomatic hyperprolactinaemia should be considered

for prolactin monitoring if they show symptoms of

hyperprolactinaemia (such as breast enlargement and

galactorrhoea).

▶ Patients with schizophrenia should have physical health

monitoring (including cardiovascular disease risk

assessment) at least once per year.

▶ In children Regular clinical monitoring of endocrine

function should be considered when children are taking an

antipsychotic drug known to increase prolactin levels; this

includes measuring weight and height, assessing sexual

maturation, and monitoring menstrual function.

l TREATMENT CESSATION There is a high risk of relapse if

medication is stopped after 1–2 years. Withdrawal of

antipsychotic drugs after long-term therapy should always

be gradual and closely monitored to avoid the risk of acute

withdrawal syndromes or rapid relapse. Patients should be

monitored for 2 years after withdrawal of antipsychotic

medication for signs and symptoms of relapse.

l PATIENT AND CARER ADVICE As photosensitisation may

occur with higher dosages, patients should avoid direct

sunlight.

Driving and skilled tasks Drowsiness may affect

performance of skilled tasks (e.g. driving or operating

machinery), especially at start of treatment; effects of

alcohol are enhanced.

ANTIPSYCHOTICS › FIRST-GENERATION

eiii F abovei

Chlorpromazine hydrochloride 09-Jul-2018

l INDICATIONS AND DOSE

Schizophrenia and other psychoses | Mania | Short-term

adjunctive management of severe anxiety | Psychomotor

agitation, excitement, and violent or dangerously

impulsive behaviour

▶ BY MOUTH

▶ Adult: Initially 25 mg 3 times a day, adjusted according

to response, alternatively initially 75 mg once daily,

adjusted according to response, dose to be taken at

night; maintenance 75–300 mg daily, increased if

necessary up to 1 g daily, this dose may be required in

psychoses; use a third to half adult dose in the elderly

or debilitated patients

▶ BY RECTUM

▶ Adult: 100 mg every 6–8 hours, dose expressed as

chlorpromazine base

Intractable hiccup

▶ BY MOUTH

▶ Adult: 25–50 mg 3–4 times a day

Relief of acute symptoms of psychoses (under expert

supervision)

▶ BY DEEP INTRAMUSCULAR INJECTION

▶ Adult: 25–50 mg every 6–8 hours

Nausea and vomiting in palliative care (where other drugs

have failed or are not available)

▶ BY MOUTH

▶ Child 1–5 years: 500 micrograms/kg every 4–6 hours;

maximum 40 mg per day

▶ Child 6–11 years: 500 micrograms/kg every 4–6 hours;

maximum 75 mg per day

▶ Child 12–17 years: 10–25 mg every 4–6 hours

▶ Adult: 10–25 mg every 4–6 hours

▶ BY DEEP INTRAMUSCULAR INJECTION

▶ Child 1–5 years: 500 micrograms/kg every 6–8 hours;

maximum 40 mg per day

▶ Child 6–11 years: 500 micrograms/kg every 6–8 hours;

maximum 75 mg per day

▶ Child 12–17 years: Initially 25 mg, then 25–50 mg every

3–4 hours until vomiting stops

▶ Adult: Initially 25 mg, then 25–50 mg every 3–4 hours

until vomiting stops

▶ BY RECTUM

▶ Adult: 100 mg every 6–8 hours

DOSE EQUIVALENCE AND CONVERSION

▶ For equivalent therapeutic effect 100 mg

chlorpromazine base given rectally as a suppository :

20–25 mg chlorpromazine hydrochloride by

intramuscular injection: 40–50 mg of chlorpromazine

base or hydrochloride given by mouth.

384 Mental health disorders BNF 78

Nervous system

4

l UNLICENSED USE Rectal route is not licensed.

l CONTRA-INDICATIONS CNS depression . comatose states . hypothyroidism . phaeochromocytoma

l INTERACTIONS → Appendix 1: phenothiazines

l SIDE-EFFECTS

GENERAL SIDE-EFFECTS

▶ Common or very common Anxiety . glucose tolerance

impaired . mood altered . muscle tone increased

▶ Frequency not known Accommodation disorder. angioedema . atrioventricular block . cardiac arrest. eye

deposit. eye disorders . gastrointestinal disorders . hepatic

disorders . hyperglycaemia . hypertriglyceridaemia . hyponatraemia . photosensitivity reaction .respiratory

disorders . sexual dysfunction . SIADH . skin reactions . systemic lupus erythematosus (SLE).temperature

regulation disorder.trismus

SPECIFIC SIDE-EFFECTS

▶ With intramuscular use Muscle rigidity . nasal congestion

SIDE-EFFECTS, FURTHER INFORMATION Acute dystonic

reactions may occur; children are particularly susceptible.

l HEPATIC IMPAIRMENT Manufacturer advises caution in

severe hepatic failure (increased risk of accumulation).

l RENAL IMPAIRMENT

Dose adjustments Start with small doses in severe renal

impairment because of increased cerebral sensitivity.

l MONITORING REQUIREMENTS

▶ With intramuscular use Patients should remain supine, with

blood pressure monitoring for 30 minutes after

intramuscular injection.

l PRESCRIBING AND DISPENSING INFORMATION

Palliative care For further information on the use of

chlorpromazine hydrochloride in palliative care, see

www.medicinescomplete.com/#/content/palliative/

antipsychotics.

l HANDLING AND STORAGE Owing to the risk of contact

sensitisation, pharmacists, nurses, and other health

workers should avoid direct contact with chlorpromazine;

tablets should not be crushed and solutions should be

handled with care.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug. Forms available

from special-order manufacturers include: tablet, capsule, oral

suspension, oral solution, suppository

Tablet

CAUTIONARY AND ADVISORY LABELS 2, 11

▶ Chlorpromazine hydrochloride (Non-proprietary)

Chlorpromazine hydrochloride 25 mg Chlorpromazine 25mg

tablets | 28 tablet P £44.78 DT = £41.72

Chlorpromazine hydrochloride 50 mg Chlorpromazine 50mg

tablets | 28 tablet P £48.00 DT = £41.81

Chlorpromazine hydrochloride 100 mg Chlorpromazine 100mg

tablets | 28 tablet P £46.25 DT = £41.56

Solution for injection

▶ Largactil (Sanofi)

Chlorpromazine hydrochloride 25 mg per 1 ml Largactil 50mg/2ml

solution for injection ampoules | 10 ampoule P £7.51

Oral solution

CAUTIONARY AND ADVISORY LABELS 2, 11

▶ Chlorpromazine hydrochloride (Non-proprietary)

Chlorpromazine hydrochloride 5 mg per 1 ml Chlorpromazine

25mg/5ml syrup | 150 ml P £2.35 DT = £2.35

Chlorpromazine 25mg/5ml oral solution sugar free sugar-free |

150 ml P £2.35 DT = £2.35

Chlorpromazine 25mg/5ml oral solution | 150 ml P £2.35 DT =

£2.35

Chlorpromazine hydrochloride 20 mg per 1 ml Chlorpromazine

100mg/5ml oral solution | 150 ml P £5.50 DT = £5.50

eiiiF 384i

Flupentixol 23-Jul-2018

(Flupenthixol)

l INDICATIONS AND DOSE

Schizophrenia and other psychoses, particularly with

apathy and withdrawal but not mania or psychomotor

hyperactivity

▶ BY MOUTH

▶ Adult: Initially 3–9 mg twice daily, adjusted according

to response, for debilitated patients, use elderly dose;

maximum 18 mg per day

▶ Elderly: Initially 0.75–4.5 mg twice daily, adjusted

according to response

Depressive illness

▶ BY MOUTH

▶ Adult: Initially 1 mg once daily, dose to be taken in the

morning, increased if necessary to 2 mg after 1 week,

doses above 2 mg to be given in divided doses, last dose

to be taken before 4 pm; discontinue if no response

after 1 week at maximum dosage; maximum 3 mg per

day

▶ Elderly: Initially 500 micrograms daily, dose to be taken

in the morning, then increased if necessary to 1 mg

after 1 week, doses above 1 mg to be given in divided

doses, last dose to be taken before 4 pm; discontinue if

no response after 1 week at maximum dosage;

maximum 1.5 mg per day

l CONTRA-INDICATIONS Circulatory collapse . CNS

depression . comatose states . excitable patients . impaired

consciousness . overactive patients . phaeochromocytoma

l CAUTIONS Cardiac disorders . cardiovascular disease . cerebral arteriosclerosis . elderly . hyperthyroidism . hypothyroidism . parkinsonism . QT-interval prolongation . senile confusional states

l INTERACTIONS → Appendix 1: flupentixol

l SIDE-EFFECTS

▶ Common or very common Appetite abnormal . asthenia . concentration impaired . depression . diarrhoea . dyspnoea . gastrointestinal discomfort. headache . hyperhidrosis . hypersalivation . muscle complaints . nervousness . palpitations . sexual dysfunction . skin reactions . urinary

disorder. vision disorders

▶ Uncommon Confusion . flatulence . hot flush . nausea . oculogyration . photosensitivity reaction . speech disorder

▶ Rare or very rare Glucose tolerance impaired . hyperglycaemia . jaundice .thrombocytopenia

▶ Frequency not known Suicidal tendencies

l PREGNANCY Avoid unless potential benefit outweighs risk.

l BREAST FEEDING Present in breast milk—avoid.

l HEPATIC IMPAIRMENT Manufacturer advises caution—

monitor serum drug concentration.

l RENAL IMPAIRMENT Manufacturer advises caution in renal

failure.

Dose adjustments Start with small doses of antipsychotic

drugs in severe renal impairment because of increased

cerebral sensitivity.

l PATIENT AND CARER ADVICE Although drowsiness may

occur, can also have an alerting effect so should not be

taken in the evening.

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

CAUTIONARY AND ADVISORY LABELS 2

▶ Depixol (Lundbeck Ltd)

Flupentixol (as Flupentixol dihydrochloride) 3 mg Depixol 3mg

tablets | 100 tablet P £13.92 DT = £13.92

BNF 78 Psychoses and schizophrenia 385

Nervous system

4

▶ Fluanxol (Lundbeck Ltd)

Flupentixol (as Flupentixol dihydrochloride)

500 microgram Fluanxol 500microgram tablets | 60 tablet P £2.88 DT = £2.88

Flupentixol (as Flupentixol dihydrochloride) 1 mg Fluanxol 1mg

tablets | 60 tablet P £4.86 DT = £4.86

eiiiF 384i

Haloperidol 20-Jul-2018

l INDICATIONS AND DOSE

Prophylaxis of postoperative nausea and vomiting [in

patients at moderate to high risk and when alternatives

ineffective or not tolerated]

▶ BY INTRAMUSCULAR INJECTION

▶ Adult: 1–2 mg, to be given at induction or 30 minutes

before the end of anaesthesia

▶ Elderly: 500 micrograms, to be given at induction or

30 minutes before the end of anaesthesia

Combination treatment of postoperative nausea and

vomiting [when alternatives ineffective or not tolerated]

▶ BY INTRAMUSCULAR INJECTION

▶ Adult: 1–2 mg

▶ Elderly: 500 micrograms

Nausea and vomiting in palliative care

▶ BY MOUTH

▶ Adult: Initially 1.5 mg 1–2 times a day, increased if

necessary to 5–10 mg daily in divided doses

▶ BY SUBCUTANEOUS INFUSION

▶ Adult: 2.5–10 mg/24 hours

Schizophrenia and schizoaffective disorder

▶ BY MOUTH

▶ Adult: 2–10 mg daily in 1–2 divided doses; usual dose

2–4 mg daily, in first-episode schizophrenia, up to

10 mg daily, in multiple-episode schizophrenia, dose

adjusted according to response at intervals of 1–7 days.

Individual benefit-risk should be assessed when

considering doses above 10 mg daily; maximum 20 mg

per day

▶ Elderly: Initially, use half the lowest adult dose, then

adjust gradually according to response up to maximum

5 mg daily, doses above 5 mg daily should only be

considered in patients who have tolerated higher doses

and after reassessment of the individual benefit-risk

Acute delirium [when non-pharmacological treatments

ineffective]

▶ BY MOUTH

▶ Adult: 1–10 mg daily in 1–3 divided doses, treatment

should be started at the lowest possible dose and

adjusted in increments at 2–4 hourly intervals if

required; maximum 10 mg per day

▶ Elderly: Initially, use half the lowest adult dose, then

adjust gradually according to response up to maximum

5 mg daily, doses above 5 mg daily should only be

considered in patients who have tolerated higher doses

and after reassessment of the individual benefit-risk

▶ BY INTRAMUSCULAR INJECTION

▶ Adult: 1–10 mg, treatment should be started at the

lowest possible dose and adjusted in increments at

2–4 hourly intervals if required; maximum 10 mg per

day

▶ Elderly: Initially 500 micrograms, dose adjusted

gradually according to response up to maximum 5 mg

daily, doses above 5 mg daily should only be considered

in patients who have tolerated higher doses and after

reassessment of the individual benefit-risk

Moderate to severe manic episodes associated with

bipolar I disorder

▶ BY MOUTH

▶ Adult: 2–10 mg daily in 1–2 divided doses, dose

adjusted according to response at intervals of 1–3 days.

Individual benefit-risk should be assessed when

considering doses above 10 mg daily; continued use

should be evaluated early in treatment; maximum

15 mg per day

▶ Elderly: Initially, use half the lowest adult dose, then

adjust gradually according to response up to maximum

5 mg daily, doses above 5 mg daily should only be

considered in patients who have tolerated higher doses

and after reassessment of the individual benefit-risk;

continued use should be evaluated early in treatment

Acute psychomotor agitation associated with psychotic

disorder or manic episodes of bipolar I disorder

▶ BY MOUTH

▶ Adult: 5–10 mg, dose may be repeated after 12 hours if

necessary; continued use should be evaluated early in

treatment; maximum 20 mg per day

▶ Elderly: Initially 2.5 mg, dose may be repeated after

12 hours if necessary up to maximum 5 mg daily, doses

above 5 mg daily should only be considered in patients

who have tolerated higher doses and after

reassessment of the individual benefit-risk; continued

use should be evaluated early in treatment

Rapid control of severe acute psychomotor agitation

associated with psychotic disorder or manic episodes of

bipolar I disorder [when oral therapy is not appropriate]

▶ BY INTRAMUSCULAR INJECTION

▶ Adult: 5 mg, dose may be repeated hourly if required—

up to 15 mg daily is usually sufficient; continued use

should be evaluated early in treatment; maximum

20 mg per day

▶ Elderly: 2.5 mg, dose may be repeated hourly if

required up to maximum 5 mg daily, doses above 5 mg

daily should only be considered in patients who have

tolerated higher doses and after reassessment of the

individual benefit-risk; continued use should be

evaluated early in treatment

Persistent aggression and psychotic symptoms in

moderate to severe Alzheimer’s dementia and vascular

dementia [when non-pharmacological treatments

ineffective and there is a risk of harm to self or others]

▶ BY MOUTH

▶ Adult: 0.5–5 mg daily in 1–2 divided doses, dose

adjusted according to response at intervals of 1–3 days.

Reassess treatment after no more than 6 weeks

▶ Elderly: 500 micrograms daily, reassess treatment after

no more than 6 weeks

Severe tic disorders, including Tourette’s syndrome [when

educational, psychological and other pharmacological

treatments ineffective]

▶ BY MOUTH

▶ Adult: 0.5–5 mg daily in 1–2 divided doses, dose

adjusted according to response at intervals of 1–7 days.

Reassess treatment every 6–12 months

▶ Elderly: Initially, use half the lowest adult dose, then

adjust gradually according to response up to maximum

5 mg daily. Reassess treatment every 6–12 months

Mild to moderate chorea in Huntington’s disease [when

alternatives ineffective or not tolerated]

▶ BY MOUTH

▶ Adult: 2–10 mg daily in 1–2 divided doses, dose

adjusted according to response at intervals of 1–3 days

▶ Elderly: Initially, use half the lowest adult dose, then

adjust gradually according to response up to maximum

5 mg daily, doses above 5 mg daily should only be

considered in patients who have tolerated higher doses

and after reassessment of the individual benefit-risk

386 Mental health disorders BNF 78

Nervous system

4

Mild to moderate chorea in Huntington’s disease [when

alternatives ineffective or not tolerated and oral therapy

inappropriate]

▶ BY INTRAMUSCULAR INJECTION

▶ Adult: 2–5 mg, dose may be repeated hourly if

required; maximum 10 mg per day

▶ Elderly: Initially 1 mg, dose may be repeated hourly if

required up to maximum 5 mg daily, doses above 5 mg

daily should only be considered in patients who have

tolerated higher doses and after reassessment of the

individual benefit-risk

Restlessness and confusion in palliative care

▶ BY MOUTH

▶ Adult: 2 mg, then 2 mg every 2 hours if required

▶ BY SUBCUTANEOUS INJECTION

▶ Adult: 2.5 mg, then 2.5 mg every 2 hours if required

▶ BY SUBCUTANEOUS INFUSION

▶ Adult: 5–15 mg/24 hours

l UNLICENSED USE Not licensed for use in palliative care.

IMPORTANT SAFETY INFORMATION

When prescribing, dispensing or administering, check

that this injection is the correct preparation—this

preparation is usually used in hospital for the rapid

control of an acute episode and should not be confused

with depot preparations which are usually used in the

community or clinics for maintenance treatment.

l CONTRA-INDICATIONS CNS depression . comatose states . congenital long QT syndrome . dementia with Lewy bodies . history of torsade de pointes . history of ventricular

arrhythmia . Parkinson’s disease . progressive supranuclear

palsy . QTc-interval prolongation .recent acute myocardial

infarction . uncompensated heart failure . uncorrected

hypokalaemia

l CAUTIONS Bradycardia . electrolyte disturbances (correct

before treatment initiation). family history of QTcinterval prolongation . history of heavy alcohol exposure . hyperthyroidism . hypotension (including orthostatic

hypotension). prolactin-dependent tumours . prolactinaemia .risk factors for stroke

l INTERACTIONS → Appendix 1: haloperidol

l SIDE-EFFECTS

GENERAL SIDE-EFFECTS

▶ Common or very common Depression . eye disorders . headache . hypersalivation . nausea . neuromuscular

dysfunction . psychotic disorder. vision disorders . weight

decreased

▶ Uncommon Breast abnormalities . confusion . dyspnoea . gait abnormal . hepatic disorders . hyperhidrosis . menstrual cycle irregularities . muscle complaints . musculoskeletal stiffness . oedema . photosensitivity

reaction .restlessness . sexual dysfunction . skin reactions . temperature regulation disorders

▶ Rare or very rare Hypoglycaemia .respiratory disorders . SIADH .trismus

▶ Frequency not known Hypersensitivity vasculitis . pancytopenia .rhabdomyolysis .thrombocytopenia

SPECIFIC SIDE-EFFECTS

▶ With oral use Angioedema

▶ With parenteral use Hypertension . severe cutaneous

adverse reactions (SCARs)

SIDE-EFFECTS, FURTHER INFORMATION Haloperiol is a less

sedating antipsychotic.

l PREGNANCY Manufacturer advises it is preferable to

avoid—moderate amount of data indicate no malformative

or fetal/neonatal toxicity, however there are isolated case

reports of birth defects following fetal exposure, mostly in

combination with other drugs; reproductive toxicity

shown in animal studies.

l HEPATIC IMPAIRMENT Manufacturer advises caution.

Dose adjustments Manufacturer advises halve initial dose

and then adjust if necessary with smaller increments and

at longer intervals.

l RENAL IMPAIRMENT Manufacturer advises use with

caution.

Dose adjustments Manufacturer advises consider lower

initial dose in severe impairment and then adjust if

necessary with smaller increments and at longer intervals.

l MONITORING REQUIREMENTS

▶ Manufacturer advises monitor electrolytes before

treatment initiation and periodically during treatment.

▶ Manufacturer advises perform ECG before treatment

initiation and assess need for further ECGs during

treatment on an individual basis; continuous ECG

monitoring is recommended for repeated intramuscular

doses, and for up to 6 hours after administration of

intramuscular doses for prophylaxis or treatment of

postoperative nausea and vomiting.

l PRESCRIBING AND DISPENSING INFORMATION

Palliative care For further information on the use of

haloperidol in palliative care, see www.medicinescomplete.

com/#/content/palliative/haloperidol.

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

CAUTIONARY AND ADVISORY LABELS 2

▶ Haloperidol (Non-proprietary)

Haloperidol 500 microgram Haloperidol 500microgram tablets | 28 tablet P £22.05–£30.00 DT = £29.59

Haloperidol 1.5 mg Haloperidol 1.5mg tablets | 28 tablet P £15.10 DT = £15.10

Haloperidol 5 mg Haloperidol 5mg tablets | 28 tablet P £16.58

DT = £16.50

Haloperidol 10 mg Haloperidol 10mg tablets | 28 tablet P £19.85 DT = £19.36

Solution for injection

▶ Haloperidol (Non-proprietary)

Haloperidol 5 mg per 1 ml Haloperidol 5mg/1ml solution for

injection ampoules | 10 ampoule P £35.00 DT = £35.00

Oral solution

CAUTIONARY AND ADVISORY LABELS 2

▶ Haloperidol (Non-proprietary)

Haloperidol 1 mg per 1 ml Haloperidol 5mg/5ml oral solution sugar

free sugar-free | 100 ml P £35.99 DT = £6.47 sugar-free | 500 ml P £32.35

Haloperidol 2 mg per 1 ml Haloperidol 10mg/5ml oral solution

sugar free sugar-free | 100 ml P £46.75 DT = £7.10 sugar-free | 500 ml P £35.50

▶ Haldol (Janssen-Cilag Ltd)

Haloperidol 2 mg per 1 ml Haldol 2mg/ml oral solution sugar-free |

100 ml P £4.45 DT = £7.10

▶ Halkid (Thame Laboratories Ltd)

Haloperidol 200 microgram per 1 ml Halkid 200micrograms/ml

oral solution sugar-free | 100 ml P £89.90

Capsule

CAUTIONARY AND ADVISORY LABELS 2

▶ Serenace (Teva UK Ltd)

Haloperidol 500 microgram Serenace 500microgram capsules |

30 capsule P £1.18 DT = £1.18

BNF 78 Psychoses and schizophrenia 387

Nervous system

4

 



l PRESCRIBING AND DISPENSING INFORMATION Limited

quantities of tricyclic antidepressants should be prescribed

at any one time because their cardiovascular and

epileptogenic effects are dangerous in overdosage.

l PATIENT AND CARER ADVICE

Medicines for Children leaflet: Imipramine for various conditions

www.medicinesforchildren.org.uk/imipramine-variousconditions

Driving and skilled tasks Drowsiness may affect the

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

Effects of alcohol enhanced.

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

Oral solution

CAUTIONARY AND ADVISORY LABELS 2

▶ Imipramine hydrochloride (Non-proprietary)

Imipramine hydrochloride 5 mg per 1 ml Imipramine 25mg/5ml

oral solution sugar free sugar-free | 150 ml P £45.00 DT = £45.00

Tablet

CAUTIONARY AND ADVISORY LABELS 2

▶ Imipramine hydrochloride (Non-proprietary)

Imipramine hydrochloride 10 mg Imipramine 10mg tablets | 28 tablet P £0.81 DT = £0.80

Imipramine hydrochloride 25 mg Imipramine 25mg tablets |

28 tablet P £0.83 DT = £0.83

Lofepramine

l INDICATIONS AND DOSE

Depressive illness

▶ BY MOUTH

▶ Adult: 140–210 mg daily in divided doses

▶ Elderly: May respond to lower doses

l CONTRA-INDICATIONS Acute porphyrias p. 1058 . arrhythmias . during the manic phase of bipolar disorder. heart block . immediate recovery period after myocardial

infarction

l CAUTIONS Cardiovascular disease . chronic constipation . diabetes . epilepsy . history of bipolar disorder. history of

psychosis . hyperthyroidism (risk of arrhythmias). increased intra-ocular pressure . patients with a significant

risk of suicide . phaeochromocytoma (risk of arrhythmias). prostatic hypertrophy . susceptibility to angle-closure

glaucoma . urinary retention

CAUTIONS, FURTHER INFORMATION Treatment should be

stopped if the patient enters a manic phase.

Elderly patients are particularly susceptible to many of

the side-effects of tricyclic antidepressants; low initial

doses should be used, with close monitoring, particularly

for psychiatric and cardiac side-effects.

l INTERACTIONS → Appendix 1: tricyclic antidepressants

l SIDE-EFFECTS Accommodation disorder. agitation . agranulocytosis . arrhythmias . bone marrow disorders . cardiac conduction disorder. confusion . constipation . coordination abnormal . dizziness . drowsiness . dry mouth . eosinophilia .face oedema . galactorrhoea . glaucoma . granulocytopenia . gynaecomastia . hallucination . headache . heart failure aggravated . hepatic disorders . hyperhidrosis (on discontinuation). hyponatraemia . hypotension . increased risk of fracture . leucopenia . malaise . mood altered . mucositis . nausea . paraesthesia . paranoid delusions . photosensitivity reaction . psychosis . respiratory depression . seizure . sexual dysfunction . SIADH . skin haemorrhage . skin reactions . sleep disorder. suicidal tendencies .taste altered .testicular disorders . thrombocytopenia .tinnitus .tremor. urinary disorders . vomiting . withdrawal syndrome

SIDE-EFFECTS, FURTHER INFORMATION The risk of sideeffects is reduced by titrating slowly to the minimum

effective dose (every 2–3 days). Consider using a lower

starting dose in elderly patients.

Overdose Tricyclic and related antidepressants cause dry

mouth, coma of varying degree, hypotension,

hypothermia, hyperreflexia, extensor plantar responses,

convulsions, respiratory failure, cardiac conduction

defects, and arrhythmias. Dilated pupils and urinary

retention also occur. Lofepramine is associated with the

lowest risk of fatality in overdosage, in comparison with

other tricyclic antidepressant drugs. For details on the

management of poisoning see Tricyclic and related

antidepressants under Emergency treatment of poisoning

p. 1359.

l PREGNANCY Neonatal withdrawal symptoms and

respiratory depression reported if used during third

trimester.

l BREAST FEEDING The amount secreted into breast milk is

too small to be harmful.

l HEPATIC IMPAIRMENT Manufacturer advises caution in

mild to moderate impairment; avoid in severe impairment.

l RENAL IMPAIRMENT Avoid 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). If possible tricyclic and related antidepressants

should be withdrawn slowly.

l PRESCRIBING AND DISPENSING INFORMATION Limited

quantities of tricyclic antidepressants should be prescribed

at any one time because their cardiovascular and

epileptogenic effects are dangerous in overdosage.

l PATIENT AND CARER ADVICE

Driving and skilled tasks Drowsiness may affect the

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

alcohol enhanced.

BNF 78 Depression 377

Nervous system

4

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

Oral suspension

CAUTIONARY AND ADVISORY LABELS 2

▶ Lofepramine (Non-proprietary)

Lofepramine (as Lofepramine hydrochloride) 14 mg per

1 ml Lofepramine 70mg/5ml oral suspension sugar free sugar-free | 150 ml P £30.00 DT = £30.00

Tablet

CAUTIONARY AND ADVISORY LABELS 2

▶ Lofepramine (Non-proprietary)

Lofepramine (as Lofepramine hydrochloride) 70 mg Lofepramine

70mg tablets | 56 tablet P £59.97 DT = £17.21

Nortriptyline

l INDICATIONS AND DOSE

Depressive illness

▶ BY MOUTH

▶ Adult: To be initiated at a low dose, then increased if

necessary to 75–100 mg daily in divided doses,

alternatively increased if necessary to 75–100 mg once

daily; maximum 150 mg per day

▶ Elderly: To be initiated at a low dose, then increased if

necessary to 30–50 mg daily in divided doses

Neuropathic pain

▶ BY MOUTH

▶ Adult: Initially 10 mg once daily, to be taken at night,

increased if necessary to 75 mg daily, dose to be

increased gradually; higher doses to be given under

specialist supervision

l UNLICENSED USE Not licensed for use in neuropathic pain.

l CONTRA-INDICATIONS Arrhythmias . during the manic

phase of bipolar disorder. heart block . immediate recovery

period after myocardial infarction

l CAUTIONS Cardiovascular disease . chronic constipation . diabetes . epilepsy . history of bipolar disorder. history of

psychosis . hyperthyroidism (risk of arrhythmias). increased intra-ocular pressure . patients with a significant

risk of suicide . phaeochromocytoma (risk of arrhythmias). prostatic hypertrophy . susceptibility to angle-closure

glaucoma . urinary retention

CAUTIONS, FURTHER INFORMATION Treatment should be

stopped if the patient enters a manic phase.

Elderly patients are particularly susceptible to many of

the side-effects of tricyclic antidepressants; low initial

doses should be used, with close monitoring, particularly

for psychiatric and cardiac side-effects.

l INTERACTIONS → Appendix 1: tricyclic antidepressants

l SIDE-EFFECTS Agranulocytosis . alopecia . anxiety . appetite decreased . arrhythmias . asthenia . atrioventricular block . bone marrow disorders . breast

enlargement. confusion . constipation . delusions . diarrhoea . dizziness . drowsiness . drug cross-reactivity . drug fever. dry mouth . eosinophilia . fever. flushing . galactorrhoea . gastrointestinal discomfort. gynaecomastia . hallucination . headache . hepatic

disorders . hyperhidrosis . hypertension . hypomania . hypotension . increased risk of fracture . increased risk of

infection . malaise . movement disorders . mydriasis . myocardial infarction . nausea . oedema . oral disorders . palpitations . paralytic ileus . peripheral neuropathy . photosensitivity reaction . psychosis exacerbated . seizure . sensation abnormal . sexual dysfunction . SIADH . skin

reactions . sleep disorders . stroke . suicidal tendencies . taste altered .testicular swelling .thrombocytopenia . tinnitus .tremor. urinary disorders . urinary tract dilation . vision disorders . vomiting . weight changes

SIDE-EFFECTS, FURTHER INFORMATION The risk of sideeffects is reduced by titrating slowly to the minimum

effective dose (every 2–3 days). Consider using a lower

starting dose in elderly patients.

Overdose Tricyclic and related antidepressants cause dry

mouth, coma of varying degree, hypotension,

hypothermia, hyperreflexia, extensor plantar responses,

convulsions, respiratory failure, cardiac conduction

defects, and arrhythmias. Dilated pupils and urinary

retention also occur. For details on the management of

poisoning see Tricyclic and related antidepressants under

Emergency treatment of poisoning p. 1359.

l PREGNANCY Use only if potential benefit outweighs risk.

l BREAST FEEDING The amount secreted into breast milk is

too small to be harmful.

l HEPATIC IMPAIRMENT Manufacture advises avoid in severe

impairment.

l MONITORING REQUIREMENTS

▶ Manufacturer advises plasma-nortriptyline concentration

monitoring if dose above 100 mg daily, but evidence of

practical value uncertain.

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). If possible tricyclic and related antidepressants

should be withdrawn slowly.

l PRESCRIBING AND DISPENSING INFORMATION Limited

quantities of tricyclic antidepressants should be prescribed

at any one time because their cardiovascular and

epileptogenic effects are dangerous in overdosage.

l PATIENT AND CARER ADVICE Drowsiness may affect the

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

alcohol enhanced.

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

CAUTIONARY AND ADVISORY LABELS 2

▶ Nortriptyline (Non-proprietary)

Nortriptyline (as Nortriptyline hydrochloride) 10 mg Nortriptyline

10mg tablets | 30 tablet P £6.87–£11.79 | 100 tablet P £68.41 DT = £4.29

Nortriptyline (as Nortriptyline hydrochloride) 25 mg Nortriptyline

25mg tablets | 30 tablet P £6.81–£12.43 | 100 tablet P £41.44 DT = £8.77

Nortriptyline (as Nortriptyline hydrochloride) 50 mg Nortriptyline

50mg tablets | 30 tablet P £24.86 DT = £24.86

Trimipramine

l INDICATIONS AND DOSE

Depressive illness (particularly where sedation required)

▶ BY MOUTH

▶ Adult: Initially 50–75 mg daily in divided doses,

alternatively initially 50–75 mg once daily, dose to be

taken at bedtime, increased if necessary to 150–300 mg

daily

▶ Elderly: Initially 10–25 mg 3 times a day, maintenance

75–150 mg daily

l CONTRA-INDICATIONS Acute porphyrias p. 1058 . arrhythmias . during the manic phase of bipolar disorder.

378 Mental health disorders BNF 78

Nervous system

4

heart block . immediate recovery period after myocardial

infarction

l CAUTIONS Cardiovascular disease . chronic constipation . diabetes . epilepsy . history of bipolar disorder. history of

psychosis . hyperthyroidism (risk of arrhythmias). increased intra-ocular pressure . patients with a significant

risk of suicide . phaeochromocytoma (risk of arrhythmias). prostatic hypertrophy . susceptibility to angle-closure

glaucoma . urinary retention

CAUTIONS, FURTHER INFORMATION Treatment should be

stopped if the patient enters a manic phase.

Elderly patients are particularly susceptible to many of

the side-effects of tricyclic antidepressants; low initial

doses should be used, with close monitoring, particularly

for psychiatric and cardiac side-effects.

l INTERACTIONS → Appendix 1: tricyclic antidepressants

l SIDE-EFFECTS Accommodation disorder. agitation . agranulocytosis . anticholinergic syndrome . arrhythmias . bone fracture . bone marrow depression . constipation . drowsiness . dry mouth . hyperglycaemia . hyperhidrosis . hypotension . jaundice cholestatic . mood altered . paranoid delusions . peripheral neuropathy .rash . respiratory depression . seizure . sexual dysfunction . suicidal tendencies .tremor. urinary hesitation . withdrawal syndrome

SIDE-EFFECTS, FURTHER INFORMATION The risk of sideeffects is reduced by titrating slowly to the minimum

effective dose (every 2–3 days). Consider using a lower

starting dose in elderly patients.

Overdose Tricyclic and related antidepressants cause dry

mouth, coma of varying degree, hypotension,

hypothermia, hyperreflexia, extensor plantar responses,

convulsions, respiratory failure, cardiac conduction

defects, and arrhythmias. Dilated pupils and urinary

retention also occur. For details on the management of

poisoning see Tricyclic and related antidepressants under

Emergency treatment of poisoning p. 1359.

l PREGNANCY Use only if potential benefit outweighs risk.

l BREAST FEEDING The amount secreted into breast milk is

too small to be harmful.

l HEPATIC IMPAIRMENT Manufacturer advises avoid 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). If possible tricyclic and related antidepressants

should be withdrawn slowly.

l PRESCRIBING AND DISPENSING INFORMATION Limited

quantities of tricyclic antidepressants should be prescribed

at any one time because their cardiovascular and

epileptogenic effects are dangerous in overdosage.

l PATIENT AND CARER ADVICE

Driving and skilled tasks Drowsiness may affect the

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

alcohol enhanced.

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

CAUTIONARY AND ADVISORY LABELS 2

▶ Trimipramine (Non-proprietary)

Trimipramine (as Trimipramine maleate) 10 mg Trimipramine

10mg tablets | 28 tablet P £197.18 DT = £179.15

Trimipramine (as Trimipramine maleate) 25 mg Trimipramine

25mg tablets | 28 tablet P £205.44 DT = £200.50

Capsule

CAUTIONARY AND ADVISORY LABELS 2

▶ Trimipramine (Non-proprietary)

Trimipramine (as Trimipramine maleate) 50 mg Trimipramine

50mg capsules | 28 capsule P £217.50 DT = £217.08

OTHER ANTIDEPRESSANTS

Tryptophan 04-Oct-2017

(L-Tryptophan)

l DRUG ACTION Tryptophan is an essential dietary amino

acid, and is a precursor of serotonin; it re-establishes the

inhibitory action of serotonin on the amygdaloid nuclei,

thereby reducing feelings of anxiety and depression.

l INDICATIONS AND DOSE

Treatment-resistant depression (used alone or as adjunct

to other antidepressant drugs) (initiated under direction

of hospital consultant)

▶ BY MOUTH

▶ Adult: 1 g 3 times a day; maximum 6 g per day

l CONTRA-INDICATIONS History of eosinophilia myalgia

syndrome following use of tryptophan

l INTERACTIONS → Appendix 1: tryptophan

l SIDE-EFFECTS Asthenia . dizziness . drowsiness . eosinophilia myalgia syndrome . headache . myalgia . myopathy . nausea . oedema . suicidal tendencies

SIDE-EFFECTS, FURTHER INFORMATION If patients

experience any symptoms of eosinophilia myalgia

syndrome (EMS), manufacturer advises to withhold

treatment until possibility of EMS is excluded.

l PREGNANCY Manufacturer advises caution—no

information available.

l BREAST FEEDING Manufacturer advises avoid—no

information available.

l MONITORING REQUIREMENTS Manufacturer advises close

monitoring for signs of suicidal thoughts, particularly in

patients at high risk and during early treatment and dose

changes.

l PATIENT AND CARER ADVICE Manufacturer advises

patients and carers should be advised to seek medical

advice immediately if any clinical worsening, suicidal

thoughts, or unusual behaviour develops.

Driving and skilled tasks Manufacturer advises patients

should be counselled on the effects on driving and

performance of skilled tasks—increased risk of drowsiness.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug. Forms available

from special-order manufacturers include: capsule

Capsule

▶ Optimax (Intrapharm Laboratories Ltd)

Tryptophan 500 mg Optimax 500mg capsules | 84 capsule P £42.00

BNF 78 Depression 379

Nervous system

4

Vortioxetine 02-Feb-2019

l DRUG ACTION Vortioxetine inhibits the re-uptake of

serotonin (5-HT) and is an antagonist at 5-HT3 and an

agonist at 5-HT1A receptors. This multimodal activity

appears to be associated with antidepressant and

anxiolytic-like effects.

l INDICATIONS AND DOSE

Major depression

▶ BY MOUTH

▶ Adult: Initially 10 mg once daily; adjusted according to

response to 5–20 mg once daily

▶ Elderly: Initially 5 mg once daily; increased if necessary

up to 20 mg once daily

l CAUTIONS Bleeding disorders . cirrhosis of the liver (risk of

hyponatraemia). elderly (risk of hyponatraemia) . history

of mania (discontinue if patient entering manic phase). history of seizures . unstable epilepsy

CAUTIONS, FURTHER INFORMATION

▶ Seizures Discontinue treatment in patients who develop

seizures or if there is an increase in seizure frequency.

▶ Elderly Manufacturer advises caution when treating elderly

patients with doses over 10 mg daily—limited information.

l INTERACTIONS → Appendix 1: vortioxetine

l SIDE-EFFECTS

▶ Common or very common Abnormal dreams . constipation . diarrhoea . dizziness . nausea . pruritus . vomiting

▶ Uncommon Flushing . night sweats

▶ Frequency not known Hyponatraemia . neuroleptic

malignant syndrome (discontinue—potentially fatal). serotonin syndrome

l PREGNANCY Manufacturer advises avoid unless potential

benefit outweighs risk—toxicity in animal studies. If used

during the later stages of pregnancy, there is a risk of

neonatal withdrawal symptoms and persistent pulmonary

hypertension in the newborn.

l BREAST FEEDING Manufacturer advises avoid—present in

milk in animal studies.

l HEPATIC IMPAIRMENT Manufacturer advises caution in

severe impairment (no information available).

l RENAL IMPAIRMENT Manufacturer advises caution in

severe impairment—limited information available.

l TREATMENT CESSATION Manufacturer advises treatment

can be stopped abruptly, without need for gradual dose

reduction.

l PATIENT AND CARER ADVICE

Driving and skilled tasks Manufacturer advises patients and

carers should be counselled on the effects on driving and

performance of skilled tasks, especially when starting

treatment or changing the dose.

l NATIONAL FUNDING/ACCESS DECISIONS

NICE decisions

▶ Vortioxetine for treating major depressive episodes

(November 2015) NICE TA367

Vortioxetine (Brintellix ®) is recommended as an option for

treating major depressive episodes in adults whose

condition has responded inadequately to 2

antidepressants within the current episode.

Patients currently receiving vortioxetine whose disease

does not meet the above criteria should be able to

continue treatment until they and their NHS clinician

consider it appropriate to stop.

www.nice.org.uk/guidance/ta367

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Tablet

▶ Brintellix (Lundbeck Ltd)

Vortioxetine (as Vortioxetine hydrobromide) 5 mg Brintellix 5mg

tablets | 28 tablet P £27.72 DT = £27.72

Vortioxetine (as Vortioxetine hydrobromide) 10 mg Brintellix

10mg tablets | 28 tablet P £27.72 DT = £27.72

Vortioxetine (as Vortioxetine hydrobromide) 20 mg Brintellix

20mg tablets | 28 tablet P £27.72 DT = £27.72

3.5 Inappropriate sexual

behaviour

ANTIPSYCHOTICS › FIRST-GENERATION

eiiiF 384i

Benperidol 07-Jun-2018

l INDICATIONS AND DOSE

Control of deviant antisocial sexual behaviour

▶ BY MOUTH

▶ Adult: 0.25–1.5 mg daily in divided doses, adjusted

according to response, for debilitated patients, use

elderly dose

▶ Elderly: Initially 0.125–0.75 mg daily in divided doses,

adjusted according to response

l CONTRA-INDICATIONS CNS depression . comatose states . phaeochromocytoma

l CAUTIONS Risk factors for stroke

l INTERACTIONS → Appendix 1: benperidol

l SIDE-EFFECTS Appetite decreased . blood disorder. cardiac

arrest. confusion . depression . dyspepsia . headache . hepatic disorders . hyperhidrosis . hypersalivation . hypertension . muscle rigidity . nausea . oculogyric crisis . oedema . oligomenorrhoea . paradoxical drug reaction . pruritus . psychiatric disorder.temperature regulation

disorders . weight change

l PREGNANCY Extrapyramidal effects and withdrawal

syndrome have been reported occasionally in the neonate

when antipsychotic drugs are taken during the third

trimester of pregnancy. Following maternal use of

antipsychotic drugs in the third trimester, neonates should

be monitored for symptoms including agitation,

hypertonia, hypotonia, tremor, drowsiness, feeding

problems, and respiratory distress.

l BREAST FEEDING There is limited information available on

the short- and long-term effects of antipsychotic drugs on

the breast-fed infant. Animal studies indicate possible

adverse effects of antipsychotic medicines on the

developing nervous system. Chronic treatment with

antipsychotic drugs whilst breast-feeding should be

avoided unless absolutely necessary.

l HEPATIC IMPAIRMENT Manufacturer advises caution.

l RENAL IMPAIRMENT

Dose adjustments Start with small doses in severe renal

impairment because of increased cerebral sensitivity.

l MONITORING REQUIREMENTS Manufacturer advises

regular blood counts and liver function tests during longterm treatment.

l PRESCRIBING AND DISPENSING INFORMATION The

proprietary name Benquil ® has been used for benperidol

tablets.

380 Mental health disorders BNF 78

Nervous system

4

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 2

▶ Anquil (Kyowa Kirin Ltd)

Benperidol 250 microgram Anquil 250microgram tablets |

112 tablet P £117.31 DT = £117.31

3.6 Psychoses and schizophrenia

Psychoses and related disorders

06-Mar-2017

Advice of Royal College of Psychiatrists on doses of

antipsychotic drugs above BNF upper limit

Unless otherwise stated, doses in the BNF are licensed

doses—any higher dose is therefore unlicensed

. Consider alternative approaches including adjuvant

therapy and newer or second-generation antipsychotic

drugs such as clozapine.

. Bear in mind risk factors, including obesity; particular

caution is indicated in older patients, especially those over

70.

. Consider potential for drug interactions—see interactions:

Appendix 1 (antipsychotics).

. Carry out ECG to exclude untoward abnormalities such as

prolonged QT interval; repeat ECG periodically and reduce

dose if prolonged QT interval or other adverse cardiac

abnormality develops.

. Increase dose slowly and not more often than once weekly.

. Carry out regular pulse, blood pressure, and temperature

checks; ensure that patient maintains adequate fluid

intake.

. Consider high-dose therapy to be for limited period and

review regularly; abandon if no improvement after

3 months (return to standard dosage).

Important: When prescribing an antipsychotic for

administration on an emergency basis, the intramuscular

dose should be lower than the corresponding oral dose

(owing to absence of first-pass effect), particularly if the

patient is very active (increased blood flow to muscle

considerably increases the rate of absorption). The

prescription should specify the dose for each route and

should not imply that the same dose can be given by mouth

or by intramuscular injection. The dose of antipsychotic for

emergency use should be reviewed at least daily.

Antipsychotic drugs

Antipsychotic drugs are also known as ‘neuroleptics’ and

(misleadingly) as ‘major tranquillisers’.

In the short term they are used to calm disturbed patients

whatever the underlying psychopathology, which may be

schizophrenia, brain damage, mania, toxic delirium, or

agitated depression. Antipsychotic drugs are used to

alleviate severe anxiety but this too should be a short-term

measure.

Schizophrenia

The aim of treatment is to alleviate the suffering of the

patient (and carer) and to improve social and cognitive

functioning. Many patients require life-long treatment with

antipsychotic medication. Antipsychotic drugs relieve

positive psychotic symptoms such as thought disorder,

hallucinations, and delusions, and prevent relapse; they are

usually less effective on negative symptoms such as apathy

and social withdrawal. In many patients, negative symptoms

persist between episodes of treated positive symptoms, but

earlier treatment of psychotic illness may protect against the

development of negative symptoms over time. Patients with

acute schizophrenia generally respond better than those

with chronic symptoms.

Long-term treatment of a patient with a definitive

diagnosis of schizophrenia is usually required after the first

episode of illness in order to prevent relapses. Doses that are

effective in acute episodes should generally be continued as

prophylaxis.

First-generation antipsychotic drugs

The first-generation antipsychotic drugs act predominantly

by blocking dopamine D2 receptors in the brain. Firstgeneration antipsychotic drugs are not selective for any of

the four dopamine pathways in the brain and so can cause a

range of side-effects, particularly extrapyramidal symptoms

and elevated prolactin. The phenothiazine derivatives can

be divided into 3 main groups:

. Group 1: chlorpromazine hydrochloride p. 384,

levomepromazine p. 441, and promazine hydrochloride

p. 406, generally characterised by pronounced sedative

effects and moderate antimuscarinic and extrapyramidal

side-effects.

. Group 2: pericyazine p. 388, generally characterised by

moderate sedative effects, but fewer extrapyramidal sideeffects than groups 1 or 3.

. Group 3: fluphenazine decanoate p. 392, perphenazine,

prochlorperazine p. 389, and trifluoperazine p. 390,

generally characterised by fewer sedative and

antimuscarinic effects, but more pronounced

extrapyramidal side-effects than groups 1 and 2.

Butyrophenones (benperidol p. 380 and haloperidol

p. 386) resemble the group 3 phenothiazines in their clinical

properties. Thioxanthenes (flupentixol p. 385 and

zuclopenthixol p. 391) have moderate sedative,

antimuscarinic effects, and extrapyramidal effects.

Diphenylbutylpiperidines (pimozide p. 388) and the

substituted benzamides (sulpiride p. 390) have reduced

sedative, antimuscarinic, and extrapyramidal effects.

Second-generation antipsychotic drugs

The second-generation antipsychotic drugs (sometimes

referred to as atypical antipsychotic drugs) act on a range of

receptors in comparison to first-generation antipsychotic

drugs and have more distinct clinical profiles, particularly

with regard to side-effects.

Prescribing for the elderly

The balance of risks and benefit should be considered before

prescribing antipsychotic drugs for elderly patients. In

elderly patients with dementia, antipsychotic drugs are

associated with a small increased risk of mortality and an

increased risk of stroke or transient ischaemic attack (see

Dementia p. 300). Furthermore, elderly patients are

particularly susceptible to postural hypotension and to

hyper- and hypothermia in hot or cold weather.

It is recommended that:

. Antipsychotic drugs should not be used in elderly patients

to treat mild to moderate psychotic symptoms.

. Initial doses of antipsychotic drugs in elderly patients

should be reduced (to half the adult dose or less), taking

into account factors such as the patient’s weight, comorbidity, and concomitant medication.

. Treatment should be reviewed regularly.

Prescribing of antipsychotic drugs in patients with learning

disabilities

g When prescribing for patients with learning disabilities

who are prescribed antipsychotic drugs and who are not

experiencing psychotic symptoms, the following

considerations should be taken into account:

. a reduction in dose or the discontinuation of long-term

antipsychotic treatment;

. review of the patient’s condition after dose reduction or

discontinuation of an antipsychotic drug;

BNF 78 Psychoses and schizophrenia 381

Nervous system

4

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