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4.3.1 Mild, moderate and severe depression

Please note antidepressants are not routinely recommended for the initial treatment of MILD depression because the risk-benefit ratio is poor

Non pharmacological treatment is a preferable 1st line option for most people


1st choicesCitalopram tablets 10mg, 20mg, 40mg

Dose: Citalopram tablets: depressive illness, 20mg once daily, increased if necessary in steps of 20mg daily at intervals of 3-4 weeks; max 40mg daily (Elderly over 65 years, 10–20mg once daily, max 20mg daily)

Fluoxetine capsules 20mgDose:
Major depression, 20mg once daily increased after 3-4 weeks if necessary, and at appropriate intervals thereafter; max 60mg once daily

(Elderly usual max 40mg once daily but 60mg can be used)
Sertraline tablets 50mg, 100mgDose:
Depressive illness, initially 50mg daily, increased if necessary by increments of 50mg at intervals of at least 1 week to max 200mg; usual maintenance dose 50mg daily

Prescribing Notes

  • Refer to NICE CG90 Depression in adults
  • Antidepressants are not routinely recommended for the initial treatment of mild depression because the risk-benefit ratio is poor. Antidepressants can be considered for people with
    • a history of moderate to severe depression
    • people with subthreshold depressive symptoms that have persisted for a long period (typically at least 2 years)
    • mild depression that is complicating the care of a chronic physical health problem
  • Before starting antidepressants refer to NICE NG215 for information that should be considered and discussed with the patient, including steps to reduce the risk of dependence or withdrawal symptoms
  • If previous treatment with any antidepressant has been successful it should be considered again for treatment of recurrence
  • SSRIs are better tolerated than tricyclic antidepressants (TCAs). They are first choice because of reduced toxicity in overdose and, for most patients, a better adverse effect profile
  • If a TCA is required:
    • Trimipramine should not be routinely prescribed due to availability of more cost-effective TCAs (trimipramine 25mg TDS costs over £600, DT Nov 19)
    • Dosulepin is not recommended because it has a high chance of causing heart problems, is toxic in overdose and there are other anti-depressants available which are safer to use. Dosulepin should not be initiated in primary care for any indication and existing patients should be reviewed for suitability for switching to a safer agent. This may require consultation with a specialist. Dosulepin should not be stopped abruptly unless serious side effects have occurred. Refer to Medicines Management March 2018 newsletter for further information
  • Antidepressants all have a delayed onset of action and substantial effects may not be achieved for at least 2-4 weeks
  • Advise people to be vigilant for worsening depressive symptoms and suicidal ideas, particularly when starting and changing medications
  • Treatment for a first depressive episode should normally be continued, at the dose that brought about remission, for at least 6 months after response (and often up to one year)
  • After recurrent or resistant depressive episodes, consider continuing treatment for up to 2 years. Some patients may require life-long treatment at therapeutic doses
  • For doses of fluoxetine 60mg it is more cost-effective to prescribe this dose as 3 x 20mg capsules
  • Sertraline is the SSRI of choice in Coronary Heart Disease (CHD); more data exists for sertraline in a population with pre-existing heart disease than the other SSRIs. It has a lower propensity for interactions
  • Liquid formulations should be reserved for patients who are unable to swallow tablets. ‘Specials’ should be avoided and licensed medicines used where possible, e.g. it may be appropriate to switch to a different medicine (fluoxetine liquid may be a suitable alternative to sertraline tablets). Refer to resources on Specials
  • Although there is evidence that St John’s Wort may be of benefit in mild or moderate depression, practitioners should not prescribe or advise its use by people with depression because of uncertainty about appropriate doses, persistence of effect, variation in the nature of preparations and potential serious interactions with other drugs (including oral contraceptives, anticoagulants and anticonvulsants)


  • The elderly are generally more sensitive to all side-effects of antidepressants
  • All antidepressants may be associated with a discontinuation syndrome and, if taken continuously for 6 weeks or longer, should be withdrawn gradually unless a serious adverse effect has occurred. See NICE NG215 for further information on withdrawing
  • Due to the risk of gastrointestinal bleeding, SSRIs should be avoided if possible, or used with caution, in patients aged over 80 years, those with prior upper gastrointestinal bleeding, or in those also taking aspirin or another NSAID
  • SSRIs can cause sleeplessness and GI/anorexic problems in older patients. Mirtazapine has often a better profile due to sleep effects and increased appetite. This can avoid the need for night sedation
  • Hyponatraemia (usually in the elderly) has been associated with all types of antidepressants; however it has been reported more frequently with SSRIs. Hyponatraemia should be considered in all patients who develop drowsiness, confusion, or convulsions while taking an antidepressant
  • TCAs are cardiotoxic in older people and are contraindicated in patients with dementia
  • Caution on concurrent use of amitriptyline (e.g. for neuropathic pain) with other antidepressants. When amitriptyline is co-prescribed with another antidepressant the maximum daily dose of amitriptyline is 25mg
  • Dosulepin (dothiepin) and doxepin are not recommended due to their association with ischaemic heart disease, cardiac arrhythmias and fatalities following overdose
  • Citalopram and escitalopram are associated with dose-dependent QT interval prolongation and should not be used in those with: congenital long QT syndrome; known pre-existing QT interval prolongation; or in combination with other medicines that prolong the QT interval. See MHRA Drug Safety Update
  • Agomelatine (Valdoxan®) is associated with a dose related risk of hepatotoxicity and liver failure. MHRA Drug Safety Update November 2014 has full details of the advice for healthcare professionals