Lower dosage is best with second-generation antidepressants

  • Furukawa TA & al.
  • Lancet Psychiatry
  • 6 Jun 2019

  • International Clinical Digest
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Takeaway

  • A meta-analysis of commonly prescribed second-generation antidepressants, including 5 selective serotonin reuptake inhibitors (SSRIs; citalopram [Celexa], escitalopram [Lexapro], fluoxetine [Prozac], paroxetine [Paxil], and sertraline [Zoloft]), venlafaxine (Effexor), and mirtazapine (Remeron), found that the lower range of the licensed dose for each offered the optimum balance between efficacy, tolerability, and acceptability for the acute treatment of major depression in adults.

Why this matters

  • Current guidelines in the U.K. and U.S. offer conflicting recommendations on the optimum target dose of SSRIs.

Study design

  • Meta-analysis of 77 studies involving 19,364 patients with major depressive disorder.
  • Funding: Japan Society for the Promotion of Science.

Key results

  • Dose-response relationship:
    • SSRI: efficacy gradually increased for 20-40 mg dose and then decreased through 41-80 mg dose.
    • Venlafaxine: efficacy increased steeply with 75-150 mg dose and modestly with 151-375 mg doses.
    • Mirtazapine: efficacy increased up to a dose of 30 mg and then declined.
  • Tolerability (dropouts due to adverse effects):
    • SSRIs showed a linear trend with 20-40 mg and exponential through 41-80 mg.
    • Venlafaxine and mirtazapine: steep increase with increasing doses resulting in a dose acceptability curve that was convex at the lower end of licensed dose range.
  • Acceptability:
    • All-cause dropouts increased steeply with increasing dose.

Limitations

  • Fixed-dose regimen may not reflect clinical practice.

Coauthored with Antara Ghosh, PhD