BACKGROUND AND PURPOSE:

• Some studies have found an association between levonorgestrel (LNG) IUDs and depression, and antidepressant and anxiolytic use
• Previous studies focused on IUDs containing 52 mg of LNG
• Roland et al. (JAMA, 2022) assessed whether LNG dose was related to use of psychotropic medications

METHODS:

• Matched-cohort study
• Population
  • 13 to 40 years
  • No psychotropic drugs in the previous year
  • No LNG IUD use in the 6 years prior to 2019
• Exposures
  • 52-mg LNG IUD
  • 19.5-mg LNG IUD
• Study design
  • Individuals in the study were matched 1:1 for
    • Age (±3 years)
    • Gravidity in the 10 years prior to the study
    • Month of device dispensation (±3 months)
    • Physician specialty
  • Logistic regression was used to calculate the odds ratio (OR)
  • Adjustments: Sociodemographic characteristics | Childbirth history | Medical history | Matching variables
• Primary outcome
  • 2 or more prescriptions for anxiolytics, hypnotics, and/or antidepressants within 2 years after device insertion

RESULTS:

• 52-mg LNG IUD: 45,736 individuals | 19.5-mg LNG IUD: 45,736 individuals
• Dispensation of a 52-mg LNG IUD, compared to a 19.5-mg LNG IUD, was associated with a significantly increased use of an antidepressant within 2 years
  • 52-mg: 4.0%
  • 19.5-mg: 3.6%
  • aOR 1.13 (95% CI, 1.05 to 1.21)
• The association with antidepressant use persisted in females without a medical history
  • 52-mg: 3.8%
  • 19.5-mg: 3.3%
  • aOR 1.19 (95% CI, 1.09 to 1.31)
• There was no significant difference between the groups in the use of other psychotropic drugs
  • Anxiolytics
    • 52-mg: 5.2%
    • 19.5-mg: 4.9%
    • aOR 1.05 (95% CI 0.99 to 1.12)
  • Hypnotics
    • 52-mg: 2.9%
    • 19.5-mg: 2.6%
    • aOR 1.09 (95% CI, 0.99 to 1.19)
• Individuals <25 years who were using a 52-mg LNG IUD were at higher risk of using hypnotics
  • 52-mg: 3.2%
  • 19.5-mg: 2.2%
  • aOR 1.61 (95% CI, 1.04 to 2.48)
• There were no other significant associations between LNG IUD dose and psychotropic drug use for other age categories

CONCLUSION:

• Compared to the 19.5-mg LNG IUD, the 52-mg IUD was associated with a small but significant increase in the risk of new antidepressant use
• These differences in antidepressant use by IUD dose are unlikely to be clinically significant on an individual level
• The authors state

The lack of a strong dose-response relationship may suggest that levonorgestrel, and thereby serum progestin, does not markedly cause mood disturbances in females using a levonorgestrel intrauterine system 

Learn More – Primary Sources:

Association Between Doses of Levonorgestrel Intrauterine Systems and Subsequent Use of Psychotropic Drugs in France

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