Greater incidence of depression with hypnotic use than with placebo.

Publisher: BioMed Central Country of Publication: England NLM ID: 100968559 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-244X (Electronic) Linking ISSN: 1471244X NLM ISO Abbreviation: BMC Psychiatry Subsets: MEDLINE

Original Publication: London : BioMed Central, [2001-

Depressive Disorder, Major/*chemically induced ; Hypnotics and Sedatives/*adverse effects ; Sleep Initiation and Maintenance Disorders/*drug therapy; Acetamides/adverse effects ; Acetamides/therapeutic use ; Azabicyclo Compounds/adverse effects ; Azabicyclo Compounds/therapeutic use ; Cross-Sectional Studies ; Depressive Disorder, Major/diagnosis ; Depressive Disorder, Major/epidemiology ; Drug Prescriptions ; Eszopiclone ; Follow-Up Studies ; Humans ; Hypnotics and Sedatives/therapeutic use ; Incidence ; Indenes/adverse effects ; Indenes/therapeutic use ; Long-Term Care ; Odds Ratio ; Piperazines/adverse effects ; Piperazines/therapeutic use ; Pyridines/adverse effects ; Pyridines/therapeutic use ; Pyrimidines/adverse effects ; Pyrimidines/therapeutic use ; Randomized Controlled Trials as Topic ; Sleep Initiation and Maintenance Disorders/epidemiology ; United States ; United States Food and Drug Administration ; Zolpidem

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).
Conclusion: 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.

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R01 MH068545 United States MH NIMH NIH HHS; MH68545 United States MH NIMH NIH HHS; R56 HL071123 United States HL NHLBI NIH HHS; HL071123 United States HL NHLBI NIH HHS; R01 HL071123 United States HL NHLBI NIH HHS

0 (Acetamides)
0 (Azabicyclo Compounds)
0 (Hypnotics and Sedatives)
0 (Indenes)
0 (Piperazines)
0 (Pyridines)
0 (Pyrimidines)
7K383OQI23 (Zolpidem)
901AS54I69 (ramelteon)
S62U433RMH (zaleplon)
UZX80K71OE (Eszopiclone)

Date Created: 20070823 Date Completed: 20071210 Latest Revision: 20181201

20231215

PMC1994947

10.1186/1471-244X-7-42

17711589