Last reviewed 07/2022

The main indications for selective serotonin reuptake inhibitors include:

  • depression
  • anxiety
  • obsessive compulsive disorders

Advantages over tricyclics include:

  • less sedative
  • cause fewer anticholinergic effects
  • have fewer cardiovascular effects and thus are safer in overdose than tricyclics
  • have a lesser effect on psychomotor performance

Choice of SSRI in depression:

  • clinically important differences exist between commonly prescribed antidepressants for both efficacy and acceptability in favour of escitalopram and sertraline. Sertraline might be the best choice when starting treatment for moderate to severe major depression in adults because it has the most favourable balance between benefits, acceptability, and acquisition cost (1)
  • sertraline, one of the first SSRIs introduced in the market, is a potent and specific inhibitor of serotonin uptake into the presynaptic terminal, with a modest activity as inhibitor of dopamine uptake
    • in a systematic review there was evidence of differences in efficacy, acceptability and tolerability between sertraline and other antidepressants, with meta-analyses highlighting a trend in favour of sertraline over other antidepressants, both in terms of efficacy and acceptability (1)
      • based on currently available evidence, results from this review suggest that sertraline might be a strong candidate as the initial choice of antidepressant in people with acute major depression.
  • NICE have suggested that
    • for people who also have a chronic physical health problem, consider using citalopram or sertraline as these have a lower propensity for interactions (2)


  • in a meta-analysis comparing 12 new generation antidepressants
    • mirtazapine, escitalopram, venlafaxine, and sertraline were significantly more efficacious than duloxetine (odds ratios [OR] 1.39, 1.33, 1.30 and 1.27, respectively), fluoxetine (1.37, 1.32, 1.28, and 1.25, respectively), fluvoxamine (1.41, 1.35, 1.30, and 1.27, respectively), paroxetine (1.35, 1.30, 1.27, and 1.22, respectively), and reboxetine (2.03, 1.95, 1.89, and 1.85, respectively)
    • reboxetine was significantly less efficacious than all the other antidepressants tested
    • escitalopram and sertraline showed the best profile of acceptability, leading to significantly fewer discontinuations than did duloxetine, fluvoxamine, paroxetine, reboxetine, and venlafaxine