4.3 Antidepressant drugs

DEPRESSION

Mild depression

Antidepressants are not recommended for the initial treatment of mild depression, because the risk-benefit ratio is poor. However

where mild depression persists after other interventions, or is associated with psychosocial and medical problems, consider the

use of an antidepressant.

Moderate depression

Offer antidepressant medication to all patients routinely, before psychological interventions.

Choice of drug

Discuss the choice of an antidepressant with the patient including side effect profile, discontinuation symptoms, any potential

interactions with other medication including herbal medicines and the individual perception of previous treatment and its effect.

When an antidepressant is to be prescribed in routine care it should be a generic SSRI because they are as effective as tricyclic

antidepressants and their use is less likely to be discontinued due to side effects. Fluoxetine or citalopram should be used first line

because they are generally associated with fewer discontinuation/withdrawal symptoms.

Changing therapy

Treatment should be continued for a minimum of 4 weeks (6 weeks in the elderly) before considering that it is ineffective. If a

partial response has occurred reassess response after a further six weeks. If there is no response check compliance and consider

changing drug.

Duration of therapy

Continue antidepressant therapy for at least 6 months after remission. For patients who have had two or more depressive

episodes in the recent past, and who have experienced significant functional impairment during the episodes, continue therapy

for two years.

Prescribing in older adults

When prescribing in older adults the dose prescribed should be age appropriate taking into account the physical health and

concomitant medication. Side effects should be monitored closely when prescribing in older adults.

Augmentation of an Antidepressant Regime

The following recommendations are made for augmentation of an antidepressant regime under a specialist mental health team:

¤ The drugs that can be used to augment an antidepressant are lithium, an anti-psychotic such as aripiprazole,
olanzapine, quetiapine or risperidone, or another antidepressant such as mianserin or mirtazapine.

¤ Consideration must be given to the potential increase in side effects.

¤ When prescribing lithium the monitoring of lithium should be undertaken as per the Trust guidelines

¤ Patients prescribed anti-psychotics must be monitored for weight, lipids, glucose level and relevant side effects.

¤ The following drugs should not be used to augment and antidepressant regime: - buspirone, carbamazepine, lamotrigine,

valproate pindolol and thyroid hormones.

¤ Benzodiazepines should only be used concurrently with an antidepressant for a maximum of 2 weeks.

GENERALISED ANXIETY DISORDER

Consider offering:

¤ Support and information

¤ Problem solving

¤ Benzodiazepines for 2-4 weeks maximum

¤ Sedative antihistamines e.g. hydroxyzine

Pharmacological Treatment

¤ Before prescribing consider age, previous response to treatment, risk of deliberate self-Harm or accidental overdose,

patient preference and cost effectiveness.

¤ Offer an SSRI unless otherwise indicated (Paroxetine and escitalopram have a license for GAD)

¤ If one SSRI is not suitable or there is no improvement after 12 weeks then offer another SSRI.

¤ Minimise side effects by starting low and titrating slowly

¤ Long term treatment and doses at the upper end of the dose range may be required

¤ Review efficacy and side effects after 2 weeks then at 4,6 and 12 weeks.

¤ If treatment is long term then review at 8-12 week intervals.

¤ Follow SPCs for specific monitoring

¤ If improvement after 12 weeks then continue treatment for 6 months then slowly taper off over an extended period.

¤ If no improvement after 12 weeks then consider a different intervention OR venlafaxine up to a maximum of 75mg.

NB venlafaxine is contra- indicated in patients with an identified very high risk of serious cardiac ventricular arrhythmia ,

cardiac ventricular arrhythmia , Venlafaxine should be used with caution in patients with established cardiac disease

that may increase the risk of ventricular arrhythmias (e.g. recent myocardial infarction). Regular measurement of

blood pressure is recommended for patients receiving venlafaxine.

¤ If no improvement after two interventions review and if appropriate offer referral to specialist mental health service.

Pregabalin - AMBER - initiation by LSCFT specialist clinician [Position Statement]

Prescribing of Pregabalin in primary care for the treatment of Generalised Anxiety Disorder can be continued provided that the

treatment is initiated by a specialist and that certain prior criteria have been met. See Position Statement

Click here for The Joint Formulary for psychotropic Medication (LCFT)

PANIC DISORDER

¤ Offer an SSRI licensed for panic disorder, unless otherwise indicated (citalopram, paroxetine and escitalopram)

¤ If SSRI not suitable or no response after 12 weeks consider clomipramine or imipramine

¤ Benzodiazepines, sedating antihistamines and antipsychotics should NOT be prescribed for panic disorder

¤ Review efficacy and side effects after 2 weeks then at 4, 6 and 12 weeks.

¤ Long term treatment and doses at the upper end of the dose range may be required.

¤ If treatment is long term then review at 8-12 week intervals.

¤ Follow SPCs for specific monitoring

¤ If no improvement after two interventions review and if appropriate offer referral to specialist mental health services.

BUSPIRONE

¤ The evidence for buspirone is equivocal and its use is NOT recommended by NICE.

¤ Buspirone should not be used in patients with epilepsy, severe renal impairment (defined as creatinine clearance of 20

ml/minute or below, or a plasma creatinine above 200 micromoles/litre) or in patients with severe hepatic disease.

¤ Buspirone is licensed for short term use. Any patients initiated on buspirone by specialist mental health services and

discharged to primary care should have buspirone stopped after two months of treatment, unless otherwise specified.

Information from the manufacturer of buspirone indicates patients aren’t likely to suffer from withdrawal after stopping

buspirone.

Stopping or reducing antidepressants

All patients prescribed antidepressants should be informed that, although the drugs are not associated with tolerance or craving,

discontinuation symptoms may occur on stopping, missing doses or, occasionally, on reducing the dose of the drug. These

symptoms are usually mild and self-limiting (in which case monitor and reassure) but occasionally can be severe. Cessation of

therapy should be managed over a minimum of 4 weeks.

4.3.1 Tricyclic and related antidepressant drugs

Tricyclics should be used only where SSRIs have proved ineffective. Care should be taken with their use because of potential

cardiotoxicity and also toxicity in overdose. Lofepramine is an appropriate first choice. In the elderly, start with low dose and

increase cautiously.

Sedative

GREEN Amitriptyline

tablets 10mg, 25mg, 50mg

liquid 25mg/5mL

GREEN Clomipramine capsules 10mg, 25mg, 50mg

AMBER Doxepin capsules 25mg, 50mg

(LCFT)

Less sedative

GREEN Imipramine - (nocturnal enuresis ONLY)

tablets 10mg, 25mg

syrup 25mg/5mL

AMBER Imipramine - for use by LSCFT in exceptional circumstances only

BLACK Imipramine is not recommended for use in depression or neuropathic pain in primary care

GREEN Lofepramine

tablets 70mg suspension 70mg/5mL

Dosulepin (dothiepin) is not recommended by NICE due to its association with ischaemic heart disease, cardiac arrhythmias

and fatalities following overdose

Trazodone

Trazodone is licensed for use in depressive illness, particularly where sedation is required. It is related to the tricyclic anti-

depressants.

GREEN Trazodone

capsules 50mg, 100mg

tablets 150mg

GREEN Trazodone oral solution SF 50mg/5mL [For titration/dose reduction and patients with swallowing difficulties]

restricted use

4.3.3 Selective serotonin re-uptake inhibitors (SSRI)

SSRIs selectively inhibit reuptake of serotonin. NICE recommend that the initial choice of antidepressant should be an SSRI that is

available as a generic drug (currently citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline). Locally fluoxetine, citalopram

and sertraline are primarily recommended as first and second line choices.

Fluoxetine has a higher propensity for drug interactions although it is less likely to cause a withdrawal reaction. Fluoxetine has

shown to have a favourable balance of risks and benefits for the treatment of depressive illness in under 18's. Citalopram is an

alternative first line SSRI which may be better tolerated and has fewer drug interactions than most other SSRIs. Sertraline is the

SSRI of choice in ischaemic heart disease.

Consider that fluoxetine, fluvoxamine and paroxetine have a higher propensity for drug interactions. Paroxetine is associated with

a higher risk of discontinuation symptoms. However, all SSRIs can precipitate such withdrawal symptoms - consult the BNF for

tailoring of dose recommendations, do not stop treatment abruptly.

First & Second Line

GREEN Fluoxetine

capsules 20mg

dispersible tablets 20mg (for patients unable to swallow standard capsules)

liquid 20mg/5mL

GREEN Citalopram tablets 10mg, 20mg

GREEN Sertraline tablets 50mg, 100mg

Escitalopram: Major Depressive Illness

Escitalopram should be reserved for patients with major depressive illness only [As per product license]

GREEN Escitalopram tablets 5mg, 10mg, 20mg
restricted use
MHRA Drug Safety Update - Citalopram and escitalopram: QT interval prolongation

Alternatives - see notes above

GREEN Paroxetine tablets 20mg, 30mg

Escitalopram in generalised anxiety disorder

See notes on generalised anxiety disorder above.

GREEN Escitalopram tablets 5mg, 10mg, 20mg

Daily selective serotonin re-uptake inhibitors (SSRIs) in the treatment of premature ejaculation (PE)

Daily SSRI's may be used as an option to treat acquired PE but only after psychotherapy and management of the causative

problem have failed to resolve the issue.

Patients should be referred to the psycho-sexual service in order to determine if a daily SSRI would be an appropriate treatment

option.

AMBER Daily SSRIs for the treatment of PE

4.3.4 Other antidepressant drugs

Third line only

Mirtazapine

Mirtazapine can very rarley cause blood disorders - Patients should be advised to report any fever, sore throat, stomatitis or other

signs of infection during treatment. Blood count should be performed and the drug stopped immediatley if blood dyscrasia

suspected. Can also increase appetite and weight gain, and cause anti-cholinergic side effects such as dry mouth and postural

hypotension. Nausea, vomiting, dizziness, agitation, anxiety, and headache are most common features of withdrawal if treatment

stopped abruptly or if dose reduced markedly; dose should be reduced over several weeks.

GREEN Mirtazapine

tablets 15mg, 30mg, 45mg

orodispersable tablets 15mg, 30mg, 45mg (only for those with swallowing difficulties)

Venlafaxine

Take into account the toxicity in overdose for people at serious risk of suicide and be aware that venlafaxine is associated with a

greater risk of death in overdose.

When prescribing antidepressants other than an SSRI take into account the increased likelihood of the patient stopping treatment

because of side effects and the need to increase the dose gradually with venlafaxine, duloxetine and tricyclic antidepressants.

Treatment with venlafaxine should be initiated under specialist supervision/recommendation when used at 300mg/day or above. It

is contra-indicated in patients with an identified very high risk of serious cardiac ventricular arrythmia (e.g. those with a significant

left ventricular dysfunction, NYHA Class III/IV), or those with uncontrolled hypertension. Venlafaxine should be used with caution in

patients with established cardiac disease that may increase the risk of ventricular arrhythmias (e.g. recent myocardial infarction).

Regular measurement of blood pressure is recommeded for patients receiving venlafaxine.

GREEN Venlafaxine

tablets/capsules m/r 75mg, 150mg, 225mg, 300mg, 375mg

tablets 37.5mg, 75mg

Vortioxetine

Vortioxetine is recommended as an option for the treatment of major depression episodes in adults by NICE TA367

Where the condition has responded inadequately to 2 antidepressants within the current episode.

GREEN Vortioxetine (Brintellix®)

tablets 5mg, 10mg, 20mg

Duloxetine for depression - prescribe by brand name only

When prescribing antidepressants other than an SSRI take into account the increased likelihood of the patient stopping treatment

because of side effects and the need to increase the dose gradually venlafaxine, duloxetine and tricyclic antidepressants. Consider

the specific cautions, contra-indications and monitoring requirements for duloxetine. Regular measurement of blood pressure is

recommended for patients receiving duloxetine.

AMBER Duloxetine (Cymbalta®) capsules 30mg, 60mg

L-Tryptophan

For initiation by a consultant psychiatrist only, in treatment resistant depression. Please see shared care guideline here

SHARED CARE L-Tryptophan tablets 500mg

Other specialists interventions initiated by specialist mental health teams only:

MAOIs phenelzine - AMBER with ongoing specialist review

Antidepressants with lithium augmentation - AMBER with ongoing specialist review

Other antidepressants which may be initiated by LCFT are as follows:

AMBER Mianserin

(LCFT) tablets 10mg, 30mg

AMBER Moclobemide

(LCFT) tablets 150mg, 300mg

AMBER Reboxetine

(LCFT) tablets 4mg

Treatment of diabetic neuropathic pain with duloxetine - prescribe by brand name only.

Duloxetine is to be prescribed for diabetic neuropathic pain when the use of tricyclic antidepressants are inappropriate, not

tolerated or ineffective. Withdraw other antidepressants before initiating duloxetine. Prescribe by brand name only. Treatment

should be reviewed after two weeks to assess tolerability, and then after two months to assess response – additional response

after this time is unlikely.

GREEN Duloxetine (Cymbalta®) capsules 30mg, 60mg

Agomelatine (BLACK traffic Light)

Agomelatine should only be initiated and prescribing continued by a consultant psychiatrist from Lancashire Care Trust, for those

patients who had tried other antidepressant treatments, including where possible the NICE recommended options for the

management of treatment refractory depression. GPs should not be asked to pick up prescribing of agomelatine. All requests

should be directed through the Pharmacy Dept of Lancashire Care Foundation Trust initially for authorisation. Patients must be

monitored for symptoms suggesting hepatic dysfunction. Liver function tests must be performed in all patients: at initiation of

treatment, and then after six weeks, twelve weeks and twenty four weeks. Thereafter liver function tests should be checked

when clinically indicated.

Click here for the Joint Formulary for Psychotropic Medication LCFT.

All material in this section is aimed at health care professionals, but is information currently held in the public domain, members of the

public seeking advice on medicine-related matters are advised to speak with their GP, pharmacist, nurse or contact NHS111 Service

Email: info.elmmb@nhs.net