Selective serotonin re- uptake inhibitors

4.3.3 Selective serotonin re- uptake inhibitors

Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline selectively inhibit the re- uptake of serotonin (5-hydroxytryptamine, 5-HT); they are termed selective serotonin re-uptake inhibitors (SSRIs). For a general comment on the management of depression and on the comparison between tricyclic and related antidepressants and the SSRIs and related antidepressants , see section 4.3.

CSM advice (depressive illness in children and adolescents) The CSM has advised that the balance of risks and benefits for the treatment of depressive illness in individuals under 18 years is considered unfavour- able for the SSRIs citalopram, escitalopram, par- oxetine, and sertraline, and for mirtazapine and venlafaxine. Clinical trials have failed to show effi- cacy and have shown an increase in harmful out- comes. However, it is recognised that specialists may sometimes decide to use these drugs in response to individual clinical need; children and adolescents should be monitored carefully for suici- dal behaviour, self-harm or hostility, particularly at the beginning of treatment. Only fluoxetine has been shown in clinical trials to

be effective for treating depressive illness in children and adolescents. However, it is possible that, in common with the other SSRIs, it is associated with

a small risk of self-harm and suicidal thoughts. Over- all, the balance of risks and benefits for fluoxetine in the treatment of depressive illness in individuals under 18 years is considered favourable, but children and adolescents must be carefully monitored as above.

212

4.3.3 Selective serotonin re-uptake inhibitors BNF 57

C entra

l nervous

sys

tem

BNF 57

4.3.3 Selective serotonin re-uptake inhibitors 213

Cautions SSRIs should be used with caution in patients turbance, increased salivation, rhinitis, tinnitus, poly- with epilepsy (avoid if poorly controlled, discontinue if

uria, micturition disorders, euphoria; paradoxical convulsions develop), cardiac disease, diabetes mellitus,

increased anxiety during initial treatment of panic susceptibility to angle-closure glaucoma, a history of

disorder (reduce dose) mania or bleeding disorders (especially gastro-intestinal

Dose

bleeding), and if used with other drugs that increase the risk of bleeding, hepatic impairment (Appendix 2), renal

. Depressive illness, 20 mg once daily increased if necessary in steps of 20 mg daily at intervals of 3–4 impairment (Appendix 3), pregnancy (Appendix 4), and

weeks; max. 60 mg daily ( breast-feeding (Appendix 5). They should also be used

ELDERLY over 65 years, max.

under 18 years, see BNF for with caution in those receiving concurrent electro-

40 mg daily);

CHILD

Children and CSM advice, p. 212 convulsive therapy (prolonged seizures reported with

fluoxetine). SSRIs may also impair performance of . Panic disorder, ADULT over 18 years, initially 10 mg skilled tasks (e.g. driving). Interactions: see below and

daily increased gradually if necessary in steps of Appendix 1 (antidepressants, SSRI).

10 mg daily, usual dose 20–30 mg daily; max. 60 mg daily ( ELDERLY over 65 years, max. 40 mg daily) Note

Withdrawal oral drops is equivalent in

8 mg (4 drops) Cipramil

Gastro-intestinal disturbances, headache, therapeutic effect to 10-mg citalopram tablet anxiety, dizziness, paraesthesia, sleep disturbances, fati- gue, influenza-like symptoms, and sweating are the

Citalopram (Non-proprietary) A most common features of abrupt withdrawal of an

Tablets , citalopram (as hydrobromide) 10 mg, net SSRI or marked reduction of the dose; the dose should

price 28-tab pack = £1.08; 20 mg, 28-tab pack = £1.25;

be tapered over a few weeks to avoid these effects.

40 mg, 28-tab pack = £1.46. Counselling, driving Cipramil c (Lundbeck)

Interactions An SSRI or related antidepressant should

A Tablets , f/c, citalopram (as hydrobromide) 10 mg, net not be started until 2 weeks after stopping an MAOI.

price 28-tab pack = £8.97; 20 mg (scored), 28-tab pack Conversely, an MAOI should not be started until at least

= £14.91; 40 mg, 28-tab pack = £25.20. Counselling,

a week after an SSRI or related antidepressant has been

driving

stopped (2 weeks in the case of sertraline, at least 5 weeks in the case of fluoxetine). For guidance relating to

Oral drops , sugar-free, citalopram (as hydrochloride) the reversible monoamine oxidase inhibitor, moclobe-

40 mg/mL, net price 15 mL = £20.16. Counselling, mide, see above. For other SSRI antidepressant interac-

driving, administration tions, see Appendix 1 (antidepressants, SSRI). Dose depressive illness, 16 mg daily as a single dose increased if necessary in steps of 16 mg daily at intervals of 3–4 weeks; max.

48 mg daily ( ELDERLY over 65 years, max. 32 mg daily); CHILD

Contra-indications SSRIs should not be used if the

under 18 years, see BNF for Children and CSM advice, p. 212

entral

patient enters a manic phase. Panic disorder, initially 8 mg daily as a single dose increased gradually if necessary in steps of 8 mg, usual dose 16–24 mg daily; max. 48 mg daily; ( ELDERLY over 65 years, max. 32 mg daily);

nervous Side-effects

SSRIs are less sedating and have fewer CHILD under 18 years not recommended

antimuscarinic and cardiotoxic effects than tricyclic

Excipients include alcohol

antidepressants (section 4.3). Side-effects of the SSRIs

8 mg (4 drops) Cipramil oral drops can be considered include gastro-intestinal effects (dose-related and fairly

Note

equivalent in therapeutic effect to 10-mg citalopram tablet Mix with water, orange juice, or apple juice before taking

syst

common—include nausea, vomiting, dyspepsia, abdo- minal pain, diarrhoea, constipation), anorexia with

em

weight loss (increased appetite and weight gain also reported) and hypersensitivity reactions including rash

ESCITALOPRAM

(consider discontinuation—may be sign of impending Note Escitalopram is the active enantiomer of citalopram serious systemic reaction, possibly associated with vas-

Indications see under Dose culitis), urticaria, angioedema, anaphylaxis, arthralgia,

Cautions see notes above myalgia and photosensitivity; other side-effects include

Contra-indications see notes above dry mouth, nervousness, anxiety, headache, insomnia,

Side-effects see notes above; also sinusitis, yawning; tremor, dizziness, asthenia, hallucinations, drowsiness,

fatigue, restlessness, abnormal dreams, paraesthesia; convulsions (see Cautions above), galactorrhoea, sexual

pyrexia; less commonly taste disturbance, bruxism, dysfunction, urinary retention, sweating, hypomania or

syncope, tachycardia, oedema, confusion, menstrual mania (see Cautions above), movement disorders and

disturbances, epistaxis, mydriasis, tinnitus, pruritus, dyskinesias, visual disturbances, hyponatraemia (see

and alopecia; rarely bradycardia, aggression, and Hyponatraemia and Antidepressant Therapy, p. 206),

depersonalisation; hepatitis, postural hypotension, QT and bleeding disorders including ecchymoses and

interval prolongation, and thrombocytopenia also purpura. Suicidal behaviour has been linked with anti-

reported; paradoxical increased anxiety during initial depressants (see p. 206). Angle-closure glaucoma may

treatment of panic disorder (reduce dose) very rarely be precipitated by treatment with SSRIs.

Dose . ADULT over 18 years, depressive illness, generalised

anxiety disorder, and obsessive-compulsive disorder, Indications

CITALOPRAM

10 mg once daily increased if necessary to max. 20 mg depressive illness, panic disorder

daily; ELDERLY initially half adult dose, lower mainte- Cautions see notes above

nance dose may be sufficient; CHILD not recom- Contra-indications see notes above

mended (see CSM advice, p. 212) Side-effects see notes above; also palpitation, tachy-

. ADULT over 18 years, panic disorder, initially 5 mg once cardia, postural hypotension, coughing, yawning,

daily increased to 10 mg daily after 7 days; max. confusion, impaired concentration, malaise, amnesia,

20 mg daily; ELDERLY initially half adult dose, lower migraine, paraesthesia, abnormal dreams, taste dis-

maintenance dose may be sufficient

4.3.3 Selective serotonin re-uptake inhibitors BNF 57 . ADULT over 18 years, social anxiety disorder, initially

Cautions see notes above

10 mg once daily adjusted after 2–4 weeks; usual dose CSM advice The CSM has advised that concomitant use of 5–20 mg daily

fluvoxamine and theophylline or aminophylline should usually be avoided; see also interactions: Appendix 1 Cipralex c (Lundbeck) A (antidepressants, SSRIs)

Tablets , f/c, escitalopram (as oxalate) 5 mg, net price Contra-indications see notes above 28-tab pack = £8.97; 10 mg (scored), 28-tab pack =

Side-effects see notes above; palpitation, tachycardia £14.91; 20 mg (scored), 28-tab pack = £25.20. Coun-

(may also cause bradycardia); rarely postural hypo- selling, driving

tension, confusion, ataxia, paraesthesia, malaise, taste Oral drops , sugar-free, escitalopram (as oxalate)

disturbance, neuroleptic malignant syndrome-like

10 mg/mL, net price 28 mL = £18.82. Counselling, event, abnormal liver function tests, usually sympto- driving, administration

matic (discontinue treatment) Note Can be mixed with water, orange juice, or apple juice

Dose

before taking . Depression, ADULT over 18 years, initially 50–100 mg The Scottish Medicines Consortium (p. 3) has advised that esci- talopram (Cipralex ) is not recommended within NHS Scotland

daily in the evening, increased gradually if necessary for the treatment of social anxiety disorder (April 2008)

to max. 300 mg daily (over 150 mg in divided doses); usual maintenance dose 100 mg daily

. Obsessive-compulsive disorder, initially 50 mg in the

FLUOXETINE evening increased gradually if necessary after some tem

weeks to max. 300 mg daily (over 150 mg in divided Indications see under Dose

doses); usual maintenance dose 100–300 mg daily; sys Cautions see notes above

CHILD over 8 years initially 25 mg daily increased if Contra-indications see notes above

necessary in steps of 25 mg every 4–7 days to max. Side-effects see notes above; also vasodilatation,

200 mg daily (over 50 mg in 2 divided doses) Note If no improvement in obsessive-compulsive disorder

nervous

l within 10 weeks, treatment should be reconsidered

postural hypotension, pharyngitis, dyspnoea, chills,

taste disturbances, sleep disturbances, euphoria, confusion, yawning, impaired concentration, changes

Fluvoxamine (Non-proprietary) A

entra

in blood sugar, alopecia, urinary frequency; rarely Tablets , fluvoxamine maleate 50 mg, net price 60-tab

C pulmonary inflammation and fibrosis; very rarely pack = £6.80; 100 mg, 30-tab pack = £8.34. Counsel-

4 hepatitis, toxic epidermal necrolysis, and neuroleptic

ling, driving

Dose A

malignant syndrome-like event

Faverin c (Solvay)

Tablets , f/c, scored, fluvoxamine maleate 50 mg, net . Major depression, 20 mg once daily increased after 3–

price 60-tab pack = £17.10; 100 mg, 30-tab pack =

4 weeks if necessary, and at appropriate intervals £17.10. Counselling, driving thereafter; max. 60 mg once daily ( ELDERLY usual max.

40 mg once daily but 60 mg can be used); CHILD 8–18 years, 10 mg once daily increased after 1–2 weeks if

PAROXETINE

necessary, max. 20 mg once daily (but see also CSM Indications major depression, obsessive-compulsive advice, p. 212)

disorder, panic disorder; social anxiety disorder; post- . Bulimia nervosa, ADULT over 18 years, 60 mg once

traumatic stress disorder; generalised anxiety disorder daily

Cautions see notes above; also achlorhydria or high . Obsessive-compulsive disorder, ADULT over 18 years,

gastric pH (reduced absorption of oral suspension)

20 mg once daily; if inadequate response after 2 weeks CSM advice Extrapyramidal reactions (including orofacial increase gradually to max. 60 mg once daily ( ELDERLY

dystonias) and withdrawal syndrome are reported to the usual max. 40 mg once daily but 60 mg can be used)

CSM more commonly with paroxetine than with other SSRIs Long duration of action Consider the long half-life of fluox-

Contra-indications see notes above etine when adjusting dosage (or in overdosage)

Side-effects see notes above; also yawning; raised Fluoxetine (Non-proprietary)

A cholesterol; less commonly arrhythmias, transient Capsules , fluoxetine (as hydrochloride) 20 mg, net

changes in blood pressure, confusion, urinary price 30-cap pack = £1.02; 60 mg, 30-cap pack =

incontinence; rarely panic attacks and paradoxical £55.76. Counselling, driving

increased anxiety during initial treatment of panic Brands include Oxactin

disorder (reduce dose), depersonalisation, and Liquid neuroleptic malignant syndrome-like event; very rarely , fluoxetine (as hydrochloride) 20 mg/5 mL, net peripheral oedema, acute glaucoma, hepatic disorders

price 70 mL = £7.41. Counselling, driving Brands include Prozep

(e.g. hepatitis), and priapism Dose Prozac c (Lilly) A . Major depression, social anxiety disorder, post-trau-

Capsules , fluoxetine (as hydrochloride) 20 mg matic stress disorder, generalised anxiety disorder, (green/yellow), net price 30-cap pack = £14.21.

ADULT over 18 years, usually 20 mg each morning, Counselling, driving

higher doses on specialist advice only (see also CSM Liquid , fluoxetine (as hydrochloride) 20 mg/5 mL, net

40 mg price 70 mL = £13.26. Counselling, driving

advice, below); max. 50 mg daily ( ELDERLY

daily); CHILD not recommended (see CSM advice, p. 212)

. Obsessive-compulsive disorder, ADULT over 18 years,

FLUVOXAMINE MALEATE

initially 20 mg each morning, increased gradually in steps of 10 mg to usual dose of 40 mg daily, higher

Indications depressive illness, obsessive-compulsive doses on specialist advice only (see also CSM advice, disorder

below); max. 60 mg daily ( ELDERLY

40 mg daily)

BNF 57

4.3.4 Other antidepressant drugs 215

. Panic disorder, ADULT over 18 years, initially 10 mg each morning, increased gradually in steps of 10 mg

4.3.4 Other antidepressant

to usual dose of 40 mg daily, higher doses on specialist advice only (see also CSM advice, below); max. 60 mg

drugs

daily ( ELDERLY

40 mg daily) CSM advice The recommended dose for the treatment of

Duloxetine inhibits the re-uptake of both serotonin and depression, social anxiety disorder, generalised anxiety dis-

noradrenaline and is licensed to treat major depressive order, and post-traumatic stress disorder is 20 mg daily and

disorder.

for obsessive-compulsive disorder and panic disorder it is 40 mg daily. There is no evidence that higher doses are more

The thioxanthene flupentixol (Fluanxol c ) has anti- effective

depressant properties, and low doses (1 to 3 mg daily) are given by mouth for this purpose. Flupentixol is also Paroxetine (Non-proprietary) A used for the treatment of psychoses (section 4.2.1 and

Tablets , paroxetine (as hydrochloride) 20 mg, net

section 4.2.2)

price 30-tab pack = £2.92; 30 mg, 30-tab pack = £6.46. Label: 21, counselling, driving

Mirtazapine, a presynaptic alpha -adrenoreceptor antagonist, increases central noradrenergic and seroto-

A nergic neurotransmission. It has few antimuscarinic , f/c, scored, paroxetine (as hydrochloride)

Tablets effects, but causes sedation during initial treatment.

Seroxat c (GSK)

10 mg, net price 28-tab pack = £12.32; 20 mg, 30-tab Reboxetine, a selective inhibitor of noradrenaline re- pack = £13.21; 30 mg (blue), 30-tab pack = £23.18.

uptake, has been introduced for the treatment of depres- Label: 21, counselling, driving

sive illness.

Oral suspension , orange, sugar-free, paroxetine (as Tryptophan is licensed as adjunctive therapy for hydrochloride) 10 mg/5 mL. Net price 150-mL pack =

depression resistant to standard antidepressants; it has £9.49. Label: 5, 21, counselling, driving

been associated with eosinophilia-myalgia syndrome. Tryptophan should be initiated under specialist super- vision.

Venlafaxine is a serotonin and noradrenaline re-uptake