A large real-world analysis names the worst offenders — including some that don’t warn you on the label.
STUDY: Huang X et al, Medicine 2026;105(16):e48160
STUDY TYPE: Pharmacovigilance study (observational)
FUNDING: Independent
Background
Medications cause insomnia more often than we realize, and the evidence is scattered across small studies and case reports. This analysis brings those loose ends together, mining the entire FDA Adverse Event Reporting System (FAERS) database for insomnia signals across drug classes.
The Study
Researchers extracted 179,697 adverse event reports flagging insomnia from the FAERS reporting system (2004–2024), limiting to cases where a drug was the primary suspect. They applied four statistical algorithms, and required all four to flag a drug before calling it a signal. Finally, they ranked the top 30 by signal strength (reporting odds ratio, or ROR).
Results
The strongest signal by far was mefloquine, the antimalarial (ROR 22.22), consistent with its well-known neuropsychiatric toxicity. That was followed by:
- Viloxazine, a non-stimulant for ADHD (ROR 12.29)
- Flibanserin (ROR 12.02)
- Finasteride (ROR 10.93) (and this one lacks a risk of insomnia on the label)
- A hepatitis C antiviral combination (ROR 10.68)
Among psych meds, the ones with the most reports were:
- Varenicline (Chantix) (5,421 reports)
- Duloxetine (3,879)
- Quetiapine (3,383, a paradoxical finding, but it can happen)
- Venlafaxine (2,563)
- Bupropion (2,513)
Stimulants (methylphenidate, amphetamine) showed moderate signals; non-stimulants like viloxazine and atomoxetine showed stronger ones, likely due to their norepinephrine reuptake inhibition (atomoxetine also caused heavy fatigue in another study of this database).
The risk with finasteride here is relatively new. This widely used med for prostate hypertrophy may cause insomnia through long-term impairment of neuroactive steroid synthesis via 5α-reductase inhibition, weakening GABAergic inhibition. Pimavanserin and fexofenadine also generated signals despite no insomnia label warnings.
Limitation: FAERS is a spontaneous reporting system. It can’t establish causality, and underreporting is substantial. Nearly 18% of reports lacked a recorded indication. These signals are hypothesis-generating, not proof.
Practice Implications
- When patients complain of insomnia, ask when it began and whether it was related to these meds.
- TIP: The smoking-cessation med varenicline (Chantix) rose to the top. This one often causes nightmares and vivid dreams, which are treatable with low-dose clonidine (which also has anti-smoking benefits).
— Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
What’s Your Take? Share in Comments
- What meds are you seeing insomnia on?
