Greater incidence of depression with hypnotic use than with placebo.
BACKGROUND
Although it has been claimed that insomnia causes an increased risk for depression, adequate controlled trials testing this hypothesis have not been available. This study contrasted the incidence of depression among subjects receiving hypnotics in randomized controlled trials versus those receiving placebo.


METHODS
The incidence of depression among patients randomized to hypnotic drugs or placebo was compiled from prescribing information approved by the United States Food and Drug Administration (FDA) and from FDA New Drug Application documents. Available data for zolpidem, zaleplon, eszopiclone, and ramelteon were accessed.


RESULTS
Data for 5535 patients randomized to a hypnotic and for 2318 randomized to placebo were compiled. The incidence of depression was 2.0% among participants randomized to hypnotics as compared to 0.9% among those randomized in parallel to placebo (p < 0.002).


CONCLUSIONS
Modern hypnotics were associated with an increased incidence of depression in data released by the FDA. This suggests that when there is a risk of depression, hypnotics may be contra-indicated. Preventive treatments such as antidepressant drugs, cognitive-behavioral therapy, or bright light might be preferred. Limitations in the FDA data prevented a formal meta-analysis, and there was a lack of information about drop-out rates and definitions of depression. Trials specifically designed to detect incident depression when treating insomnia with hypnotic drugs and better summarization of adverse events in trials submitted to the FDA are both necessary.
Kripke
Daniel F
DF
The Scripps Clinic Sleep Center, 10666 North Torrey Pines Road, La Jolla, California 92037, USA. Kripke.Daniel@ScrippsHealth.org
D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use; D053961:Azabicyclo Compounds / Q000009:adverse effects / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D011307:Drug Prescriptions; D000069582:Eszopiclone; D005500:Follow-Up Studies; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D007192:Indenes / Q000009:adverse effects / Q000627:therapeutic use; D008134:Long-Term Care; D016017:Odds Ratio; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000453:epidemiology; D014481:United States; D014486:United States Food and Drug Administration; D000077334:Zolpidem
D000081:Acetamides; D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D007192:Indenes; D010879:Piperazines; D011725:Pyridines; D011743:Pyrimidines; D000077334:Zolpidem; C495910:ramelteon; C085665:zaleplon; D000069582:Eszopiclone
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