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2288 pages added, reviewed or updated during the last month (last updated: 19/4/2021)

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choosing an antidepressant

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Choice of antidepressant treatment

  • normally choice is an SSRI in generic form. Clinicians should also consider::
    • SSRIs are associated with an increased risk of bleeding
        • SSRIs are associated with an increased risk of bleeding, especially in older people or in people taking other drugs that have the potential to damage the gastrointestinal mucosa or interfere with clotting
      • consider prescribing a gastroprotective drug in older people who are taking non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin
    • fluoxetine, fluvoxamine and paroxetine have a higher propensity for drug interactions
    • for people who also have a chronic physical health problem, consider using citalopram or sertraline as these have a lower propensity for interactions (1)
    • paroxetine is associated with a higher incidence of discontinuation symptoms

  • consider toxicity in overdose for people at significant risk of suicide:
    • compared with other equally effective antidepressants recommended in primary care, venlafaxine is associated with a greater risk of death from overdose
    • greatest risk in overdose is with tricyclic antidepressants (TCAs), except for lofepramine

  • when prescribing drugs other than SSRIs, take into account (1,2):
    • increased likelihood of the person stopping treatment because of side effects, and the consequent need to increase the dose gradually, with venlafaxine, duloxetine and TCAs

    • dosulepin, phenelzine, combined antidepressants, and lithium augmentation of antidepressants should only be routinely initiated by specialist mental health professionals,
      • monoamine oxidase inhibitors (MAOIs) may be less effective than tricyclic antidepressants (TCAs) in hospitalised patients; however conversely MAOIs were more effective in the treatment of patients with 'atypical depression' (4)
      • the evidence for better tolerability and relative safety is strongest for SSRIs, mirtazapine, lofepramine, reboxetine and venlafaxine (4)

    • if considering use of venlafaxine then detailed advice is contained within the 2007 NICE guidance but not the updated guidline (3):
      • practitioners should take into account the increased likelihood of patients stopping treatment because of side effects, and its higher cost, compared with equally effective SSRIs
      • practitioners should ensure pre-existing hypertension is controlled in line with the current NICE guideline on hypertension. Venlafaxine should not be prescribed for patients with uncontrolled hypertension
      • for patients prescribed venlafaxine, blood pressure should be checked on initiation and regularly during treatment, particularly during dosage titration. For patients who experience a sustained increase in blood pressure, the dose should be reduced or discontinuation considered
      • practitioners should monitor patients prescribed venlafaxine for the signs and symptoms of cardiac dysfunction, particularly in those with known cardiovascular disease, and take appropriate action as necessary
      • venlafaxine should only be prescribed at high dose (300 mg/day or more) under the supervision or advice of a specialist mental health medical practitioner (1)

    • venlafaxine and tricyclic antidepressants (with the exception of lofepramine) should not be prescribed for patients with a (1):
      • high risk of serious cardiac arrhythmias
      • recent myocardial infarction

    • if a depressed patient being treated with an SSRI develops increased agitation early in treatment, the prescriber should provide appropriate information, and if the patient prefers the drug should be changed to a different antidepressant. Alternatively, a brief period of concomitant treatment with a benzodiazepine should be considered, followed by a clinical review within 2 weeks

    • St John's wort may be of benefit in mild or moderate depression - however healthcare professionals should not prescribe or advise its use by patients because of uncertainty about appropriate doses, variation in the nature of preparations and potential serious interactions with other drugs (including oral contraceptives, anticoagulants and anticonvulsants


    • dosulepin should not be prescribed

    • when prescribing antidepressants for older adults:
      • prescribe at an age-appropriate dose taking into account physical health and concomitant medication
      • monitor carefully for side effects

    • additional considerations for people with a chronic physical health problem
      • clinicians should be aware of potential drug interactions associated with prescribing antidepressants and seek specialist advice if uncertain. If needed, refer the person to specialist mental health services for continued prescribing
      • do not prescribe subtherapeutic doses of antidepressants

    • patients with cardiovascular disease
      • when initiating treatment in a patient with a recent myocardial infarction or unstable angina, sertraline is the treatment of choice as it has the most evidence for safe use in this situation (1)

    • if a person with depression develops side effects early in antidepressant treatment, provide appropriate information and consider one of the following strategies:
        • monitor symptoms closely where side effects are mild and acceptable to the person or
        • stop the antidepressant or change to a different antidepressant if the person prefers or
        • in discussion with the person, consider short-term concomitant treatment with a benzodiazepine if anxiety, agitation and/or insomnia are problematic (except in people with chronic symptoms of anxiety); this should usually be for no longer than 2 weeks in order to prevent the development of dependence
      • if the person's depression shows no improvement after 2 to 4 weeks with the first antidepressant, check that the drug has been taken regularly and in the prescribed dose
      • if response is absent or minimal after 3 to 4 weeks of treatment with a therapeutic dose of an antidepressant, increase the level of support (for example, by weekly face-to-face or telephone contact) and consider:
        • increasing the dose in line with the SPC if there are no significant side effects or
        • switching to another antidepressant if there are side effects or if the person prefers
        • when switching from one antidepressant to another, prescribers should be aware of the need for gradual and modest incremental increases of dose, of interactions between antidepressants and the risk of serotonin syndrome when combinations of serotonergic antidepressants are prescribed. Features include confusion, delirium, shivering, sweating, changes in blood pressure and myoclonus
      • if the person's depression shows some improvement by 4 weeks, continue treatment for another 2 to 4 weeks. Consider switching to another antidepressant if
        • response is still not adequate or
        • there are side effects or
        • the person prefers to change treatment

For more detailed guidance then consult full guideline (3)


  1. NICE (April 2007). Management of depression in primary and secondary care.
  2. NICE (October 2009) Depression - updated guideline.
  3. NICE (April 2018). Depression.
  4. Anderson IM et al (2000). Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 1993 British Association for Psychopharmacology guidelines. J Psychopharmacol, 14, 3-20.

Last edited 08/2018