4.3 Antidepressant drugs 

Related Topics :
Treatment of Depression

4.3 Antidepressant drugs
Amitriptyline injection 10mg/10ml	F
Amitriptyline tablets 10mg, 25mg, 50mg	F
Citalopram tablets 10mg, 20mg, 40mg	R	Patients who have not tolerated 1st line agents
Clomipramine capsules 10mg, 25mg, 50mg	F
Clomipramine injection 25mg/2ml	F
Clomipramine mixture 25mg/5ml	F
Dosulepin capsules 25mg	F
Dosulepin tablets 75mg	F
Fluoxetine capsules 20mg	F
Fluoxetine liquid 20mg/5ml	F
Fluvoxamine tablets 50mg	F
Imipramine mixture 25mg/5ml	F
Imipramine tablets 10mg, 25mg	F
Lofepramine tablets 70mg	F
Lofepramine suspension 70mg/5ml	F
Mirtazapine tablets 30mg	R	Patients who have not tolerated 1st line agents
Paroxetine tablets 20mg, 30mg	F
Paroxetine liquid 10mg/5ml	F
Sertraline tablets 50mg	F
Venlafaxine tablets 37.5mg, 50mg, 75mg	R	Patients who have not tolerated 1st line agents
Venlafaxine XL capsules75mg. 150mg	R

* Monoamine oxidase inhibitor precautions apply.

Notes about choice of antidepressant drugs

There is no evidence of a significant difference in efficacy between tricyclics, and any of the newer antidepressants. All antidepressants take at least 2 weeks before being effective and in the elderly it may take up to 6 weeks to see an effect. Dose titration to a therapeutic dose should be undertaken.

• Amitriptyline is more sedating than imipramine.

• Lofepramine has fewer anticholinergic side effects and is less toxic in overdose.

• The SSRIs are significantly more expensive but usually have fewer side effects.

Prescribing of the newer agents, if deemed appropriate, should be guided by the following:

• Fluoxetine and paroxetine have alerting properties; mirtazepine is more sedating.

• Fluoxetine may cause weight loss and should be avoided in malnourished and cachectic.

• Mirtazapine causes weight gain. Paroxetine and citalopram may also result in weight gain.

• Paroxetine should not be prescribed at doses >20mg when treating depression.

• The principal adverse effects of SSRIs are nausea, vomiting and diarrhoea, particularly with fluvoxamine. They do not have significant anticholinergic properties.

• Fluoxetine and paroxetine may be used in the elderly. Caution: fluoxetine may cause agitation.

• Sertraline may be associated with fewer adverse effects in the elderly but is more expensive, particularly if the dose escalates.

• EPS symptoms have been reported to the CSM more commonly with paroxetine than other SSRIs.

• Patients at risk of suicide should be prescribed an SSRI, or lofepramine, since these are safer in overdose than TCAs.

• Citalopram is the most appropriate SSRI to be prescribed for patients receiving warfarin. INR has been raised in a few cases, therefore monitoring is advised.

• Withdrawal reactions have been associated with stopping paroxetine and venlafaxine abruptly. It should be tapered over at least a fortnight before discontinuation.

• In renal impairment, imipramine & paroxetine are appropriate.

• Pregnant patients should be referred to a psychiatrist. Older tricyclics are preferred if treatment is deemed necessary. Avoid 1st trimester wherever possible.

• Mirtazapine is a useful antidepressant if sexual problems result from other agents.

Venlafaxine

Venlafaxine should only be used for patients who have failed to respond to several other agents. Due to concerns regarding the cardiotoxicity and toxicity in overdose associated with venlafaxine, the CSM has advised the following:

• Venlafaxine should only be initiated by specialist mental health medical practitioners, including GPs with a special interest in mental health

Further recommendations from NICE include:

• Venlafaxine should not be prescribed for patients with pre-existing heart disease.

• Patients currently taking venlafaxine should undergo cardiac monitoring, eg ECG, pulse, blood pressure.

• Before prescribing venlafaxine and ECG should be carried out and blood pressure monitored.

NICE guidance on the Management of Depression in Primary and Secondary Care (Dec 2004)

• In mild depression the placebo response is greatest and randomised controlled trial evidence indicates that for many patients there is little clinically important difference between antidepressants and placebo. Therefore, antidepressants are not recommended for the inital treatment of mild depression, because the risk-benefit ratio is poor.

• An SSRI should be prescribed because they are as effective as TCAs and their use is less likely to be discontinued due to side effects.

•  A generic SSRI, eg. fluoxetine or citalopram would be a reasonable choice because they are generally associated with fewer discontinuation/withdrawal symptoms. Note the high propensity of fluoxetine for drug interactions.

• Treatment such as dosulepin, combined antidepressants and lithium augmentation of antidepressants should be routinely initiated only by specialist mental healthcare professionals.

• Reserve venlafaxine for specialists as above.

• In patients with ischaemic heart disease consider sertraline which has the best evidence base.

• Second line drugs include mirtazapine, reboxetine or a TCA, eg lofepramine.

Comparative costs of antidepressants

Agent	Dose	Cost of four weeks supply (basic NHS cost)
Amitriptyline	50 - 150mg OD	£1.36 - £4.08
Imipramine	75 - 200mg OD	£4.98 - £13.28
Dosulepin	75 - 225mg OD	£1.50 - £4.50
Fluoxetine	20 - 40*mg OD	£1.38 - £2.76
Mirtazepine	15 - 45mg	£17.91
Paroxetine	20 - 50mg OD	£6.50 - £32.48
Sertraline	50 - 200mg OD	£16.20 - £53.02
Venlafaxine	75mg - 225mg OD	£23.41 - £62.44

4.3.3 Compound antidepressant preparations
Motival tablets	R	Dr Whorwell