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Clinical Summary

Safety of Antidepressants in Adults With Obesity and Depression

Takeaway

  • In adults with obesity and depression, antidepressants may be overall and differentially associated with increased risks of some adverse outcomes, including mortality, cardiovascular disease (CVD), diabetes, and falls/fractures.

Why this matters

  • Currently, there is no guidance on the use of antidepressants in overweight/obese people.
  • Physicians should review overweight/obese people at 12 months after the last episode of depression to consider the balance of risks and benefits of continuing their current medication regimen and the risks from depression.

Study design

  • A retrospective study of 32,350 overweight/obese adults with depression from the UK Clinical Practice Research Datalink (CPRD; 2000-2016).
  • Of which, 21,436 (66.3%) were prescribed ≥1 antidepressant.
  • Funding: National Institute for Health Collaboration for Leadership in Applied Research and Health Care East Midlands.

Key results

  • The risk of mortality, CVD, diabetes and fractures/falls by drug class, combinations and by individual drug type were as follows (HR, 99% CI):
    • CVD:
      • selective serotonin reuptake inhibitor (SSRI; 1.32; 1.14-1.53);
      • tricyclic antidepressant (TCA)/other antidepressant (1.26; 1.01-1.58);
      • SSRI plus TCA/other combinations (1.86; 1.23-2.82); and
      • individual antidepressants: citalopram (1.30; 1.07-1.57); sertraline (1.44; 1.06-1.97); and amitriptyline (1.57; 1.15-2.15).
    • diabetes (any type):
      • SSRI (1.28; 1.10-1.49);
      • TCA/other antidepressant (1.52; 1.19-1.94);
      • ≥2 TCAs/other (2.73; 1.25-5.98);
      • SSRI plus TCA/other antidepressants (1.76; 1.12-2.76); and
      • individual antidepressants: citalopram (1.27; 1.04-1.55), fluoxetine (1.35; 1.05-1.75) and mirtazapine (1.70; 1.08-2.69).
    • fractures/falls:
      • TCA/other antidepressants (1.47; 1.15-1.18);
      • ≥2 SSRI (2.57; 1.21-5.45);
      • ≥2 TCAs/other (2.52; 1.01-6.31);
      • SSRI plus TCA/other combinations (2.07; 1.32-3.25); and
      • individual antidepressants: fluoxetine (1.76; 1.35-2.30) and other TCA/other antidepressants (1.55; 1.06-2.25).
    • all-cause mortality:
      • TCA/other antidepressants (1.64; 1.38-1.94);
      • ≥2 SSRI (2.97; 1.71-5.81);
      • ≥2 TCAs/other (2.18; 1.11-4.26);
      • SSRI plus TCA/other combinations (2.98; 2.22-4.01);
      • individual antidepressants: fluoxetine (1.70; 1.39-2.09), sertraline (1.84; 1.44-2.35), amitriptyline (1.76; 1.36-2.27) and other SSRIs (1.67; 1.17-2.40).
  • All commonly prescribed antidepressants except citalopram were associated with an increased risk of mortality.
  • However, the risk of mortality and falls/fractures was increased with ≥1 year prescription of ≥40 mg citalopram, and ≥1 year 100 mg sertraline was associated with an increased risk of falls/fractures.

Limitations

  • Retrospective design.
 

Morriss R, Tyrer F, Zaccardi F, Khunti K. Safety of antidepressants in a primary care cohort of adults with obesity and depression. PLoS One. 2021;16(1):e0245722. doi: 10.1371/journal.pone.0245722. PMID: 33513174View abstract

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.

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