Selective serotonin reuptake inhibitors

The main indications for selective serotonin reuptake inhibitors include: (1)

• the treatment of moderate and severe depression, either alone, in combination with psychological therapy, or as a second-line option if initial psychological therapy has been ineffective, depending on the person's preferences.
• the treatment of subthreshold and mild depression, although not as a first-line option, unless it is the person's preference.
• treatment of generalised anxiety disorder where there is marked functional impairment, or where low-intensity psychological interventions have been ineffective.
• treatment of moderate to severe panic disorder, if the disorder is long-standing, or if the person has declined or not benefited from psychological treatment.

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 (2)
• 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 (2)
    • 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 (1)

Notes:

• 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 (3)

The Royal College Of Psychiatrists 2019 position statement on antidepressants and depression advises that; (4)

• in moderate-severe depression, evidence-based psychological treatments should be used first-line, and antidepressants considered if:
  • The patient does not engage with treatment.
  • The patient does not respond to treatment.
  • The patient has more severe symptoms.

Reference:

1. NICE. Depression in adults: treatment and management. NICE guideline NG222. Published June 2022
2. Cipriani A et al.Sertraline versus other antidepressive agents for depression. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD006117.
3. Cipriani A et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis.Lancet. 2009 Feb 28;373(9665):746-58.
4. Royal College of Psychiatrists. Position statement on antidepressants and depression. May 2019