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4.3 Antidepressant drugs

General Information

The recommended first line choice is an SSRI prescribed generically. SSRIs are equally effective as other antidepressants but have a more favourable side-effect profile. The choice of which drug to use must take into consideration licensed indication, any concurrent disease states or other medication, patient preference and outcomes of any antidepressants previously prescribed. See BNF.

Once a response is obtained the dose should be maintained for 6 to 12 months after disappearance of symptoms. In recurrent depression, and for the elderly, therapy may need to be continued for several years.

Withdrawal reactions may occur if any antidepressant is suddenly stopped after regular administration for 8 weeks or more. SSRIs, in particular Paroxetine and also Venlafaxine, have been associated with a specific withdrawal syndrome.

Gastrointestinal symptoms of nausea, vomiting and anorexia, accompanied by headache, giddiness, 'chills' and insomnia may occur. Extrapyramidal reactions (including orofacial dystonias) have also been reported following abrupt Paroxetine withdrawal.

All antidepressants should be tapered gradually over a period of at least 4 weeks before stopping. Patients should be informed about the possibility of withdrawal effects occurring on stopping, missing doses or, occasionally, on reducing doses.

Please see - 'Guidelines for Choosing an Antidepressant for Adults' - Derbyshire Healthcare NHS Foundation Trust


4.3.1 Tricyclic and related antidepressant drugs

*Amitriptyline tablets, oral solution
*Imipramine tablets, syrup
*Clomipramine capsules
*Dosulepin (Dothiepin) capsules, tablets - see note
Lofepramine tablets, oral suspension (2nd Line)
Trazodone capsules, tablets (2nd Line)
Doxepin (specialist dermatology use for severe pruritus after trial of conventional antihistamines) (BROWN drug)
Nortriptyline (specialist use for facial pain - see note) tablets (BROWN drug)

*Indicates older tricyclics which are cardiotoxic and have higher risk in overdose.


  1. MHRA Drug Safety Update December 2007
    Dosulepin has a small margin of safety between the (maximum) therapeutic dose and potentially fatal doses. Use in new patients should be avoided; where necessary, only specialist-care prescribers should start treatment for patients who have not previously received dosulepin, and prescribers should limit the amount issued per prescription. To reduce the risk of fatal overdose, dosulepin has been available only in child-resistant blister packs since November 2007.

  2. Nortriptyline is very expensive, and other tricyclics (e.g. amitriptyline, imipramine) should be considered first for neuropathic pain.



4.3.2 Monoamine-oxidase inhibitors - Specialist use only

Phenelzine tablets (MAO1)
Moclobemide (Reversible inhibitor of MAO type A)
For dietary restrictions and interactions refer to BNF.


4.3.3 SSRIs

Fluoxetine capsules, dispersible tablet, liquid - 1st line choice
Citalopram tablets - 2nd line choice (see note below regarding maximum dose and risk of prolonged QT interval)
Sertraline tablets
Paroxetine tablets, liquid


4.3.4 Other antidepressants

Venlafaxine  (Consultant Psychiatrist only) tablets, MR capsules - see notes
Mirtazapine (2nd line) - see notes
Duloxetine (Consultant Psychiatrist only - 3rd line)


1. SSRIs are usually recommended as first line agents of the SSRIs, Fluoxetine is the cheapest SSRI and causes fewer withdrawal effects than other SSRIs. WIth all SSRIs, caution is advised in these patients as there is a high risk of GI bleed. Sertraline is first-choice SSRI in patients with cardiovascular disease. Citalopram is associated with dose-dependent QT interval prolongation. The maximum dose is now 40mg daily (20mg if >65 years or in patients with reduced hepatic function). It is contraindicated in patients with known QT-interval prolongation or with other drugs known to prolong the QT interval. See Drug Safety Update Dec 2011.

2. SSRIs, Mirtazapine, Lofepramine or Trazodone are options for second-line treatment.

3. MHRA guidance is available on SSRIs and SNRIs, their use, side-effects, and safety in pregnancy, and the risk of suicidal behaviour.

4. CSM advice - Hyponatraemia (especially in the elderly) has been associated with all types of antidepressants and should be considered in all patients who develop drowsiness, confusion or convulsions while taking an antidepressant. This effect may be partially dose-dependent. 

5. CSM advice - SSRIs are known to increase the risks of gastrointestinal bleeding especially in the elderly or where drugs that increase the risk of bleeding are used concurrently 

Also, following a coroner’s case of death due to a subarachnoid haemorrhage in a patient who took citalopram whilst misusing cocaine, the MHRA have issued a reminder that the SSRIs can increase bleeding risk, and advise that prescribers should enquire about illicit drug use when SSRIs are prescribed (see DSU July 2016).

6. Lofepramine is less sedating, less anticholinergic and is safer in overdose and cardiovascular disease than other tricyclic antidepressants.

7. Tricyclic and related antidepressants are contra-indicated in recent myocardial infarction. In general, however SSRIs are less likely to cause cardiac problems than the older tricyclic agents. Limited evidence suggests Sertraline may provide an acceptable risk level where cardiac problems co-exist.
8. Mirtazapine or Trazodone may be useful in patients experiencing sexual dysfunction with other antidepressants. 
9. Reversible white blood cell disorders including agranulocytosis, leucopenia and granulocytopenia have been reported as a rare occurence with Mirtazapine. This mostly appears after 4-6 weeks treatment and is, in general, reversible after termination of treatment. With repect to agranulocytosis the physician should be alert to symptoms such as fever, sore throat, stomatitis or other signs of infection; when such symptoms occur, treatment should be stopped and blood counts taken. Patients should also be advised of the importance of these symptoms. 
10. Venlafaxine is included as a third-line option for specialist initiation only. It requires baseline ECG and blood pressure checks, then BP monitoring during treatment.  Of the newer antidepressants, SSRIs and Mirtazapine are probably safer in overdose than venlafaxine.

11.CSM advice - SSRIs (other than Fluoxetine) and Venlafaxine should not be used in children and adolescents under the age of 18yrs for depression. Trials suggest an increase in harmful outcomes.

12. MAOI - for dietary restrictions and interactions refer to the BNF.

13. RIMA (moclobemide) poses little dietary restrictions and few interactions.

14. Hyponatraemia (usually in the elderly) has been associated with all types of antidepressants and should be considered in all patients who develop drowsiness, confusion or convulsions while taking an antidepressant.


For link to BNF section: 4.3 Antidepressant drugs