Twelve months of nightly zolpidem does not lead to rebound insomnia or withdrawal symptoms: a prospective placebo-controlled study

Abstract

Rebound insomnia, worsened sleep when discontinuing use of a hypnotic, is reported in some short-term studies. No study has prospectively assessed, using patient reports or nocturnal polysomnography (NPSG), the likelihood of rebound insomnia with chronic hypnotic use. The objectives of this study was to assess in primary insomniacs the likelihood of experiencing rebound insomnia and a withdrawal syndrome on repeated placebo substitutions over 12 months of nightly zolpidem use. A group of 33 primary insomniacs, without psychiatric disorders or drug and alcohol abuse, 32-65 years old, 15 men and 18 women, were randomized to take zolpidem 10 mg (n = 17) or placebo (n = 16) nightly for 12 months. In probes during months 1, 4, and 12, placebo was substituted for 7 consecutive nights in both the zolpidem and placebo groups. NPSGs were collected and Tyrer Bezodiazepine Withdrawal Symptom Questionnaires were completed on the first two discontinuation nights. Rebound insomnia was not observed on the first two and the seventh discontinuation nights and its likelihood did not increase over the 12 months of nightly zolpidem use. Some individuals did show rebound insomnia, approximately 30-40% of participants, but the percentage of 'rebounders' did not differ between the placebo and zolpidem groups and did not increase across 12 months. No clinically significant withdrawal symptoms on the Tyrer were observed on the discontinuation nights over the 12 months of nightly use. Chronic nightly hypnotic use at therapeutic doses by primary insomniacs does not lead to rebound insomnia or withdrawal symptoms.

Conflict of interest statement

Conflict of interest

T Roehrs: consultant – Sanofi, Evotec; grantee – Takeda. S Randall, E Harris, and R Maan: none. T Roth: consultant – Actelion, Addrenex, Cephalon, Eisai, Intec, Merck, Pfizer, Sanofi, Sepracor, Shire, Somaxon, TransOral; speaker – Cephalon, Sanofi; grantee – Merck. This was not an industry supported study.

Figures

Figure 1

Sleep efficiency (total sleep time/time in bed) at baseline and on the first discontinuation night in months 1, 4, and 12 for the placebo and zolpidem groups. Values are the difference scores versus screening (month ′x′ minus screening). A negative score would reflect rebound insomnia.

Figure 2

Percentage of participants whose sleep efficiency (total sleep time/time in bed) was worse than screening on the first discontinuation night of month 1, 4, and 12.