Twelve months of nightly zolpidem does not lead to dose escalation: a prospective placebo-controlled study

Abstract

Study objectives: To assess hypnotic self-administration and likelihood of dose escalation over 12 months of nightly use of zolpidem versus placebo in primary insomniacs.

Design: Randomized, double-blind, placebo-controlled, clinical trial.

Setting: Outpatient with tri-monthly one-week, sleep laboratory assessments.

Participants: Thirty-three primary insomniacs, without psychiatric disorders or drug and alcohol abuse, 32-64 yrs old, 14 men and 19 women.

Interventions: Participants were randomized to take zolpidem 10 mg (n = 17) or placebo (n = 16) nightly for 12 months. In probes during month 1, 4, and 12, after sampling color-coded placebo or zolpidem capsules on 2 nights, color-coded zolpidem or placebo was chosen on 5 consecutive nights and 1, 2, or 3 of the chosen capsules (5 mg each) could be self-administered on a given choice night.

Results: Zolpidem was chosen more nights than placebo (80% of nights) and number of nights zolpidem was chosen did not differ over the 12 months. More zolpidem than placebo capsules were self-administered, and the total number of placebo or zolpidem capsules self-administered did not differ as a function of duration of use. In contrast, the total number of placebo capsules self-administered by the placebo group increased across time. The nightly capsule self-administration on zolpidem nights did not differ from that on placebo nights and neither nightly self-administration rates increased over the 12 months. An average 9.3 mg nightly dose was self-administered.

Conclusions: Zolpidem was preferred to placebo, but its self-administration did not increase with 12 months of use. Chronic hypnotic use by primary insomniacs does not lead to dose escalation.

Trial registration: ClinicalTrials.gov NCT01006525.

Keywords: Primary insomnia; chronic nightly use; self-administration; zolpidem.

Figures

Figure 1

Total number of placebo and zolpidem (5 mg) capsules chosen by the Zolpidem group and the total number of placebo capsules chosen by the Placebo group during the 5 choice nights of each month. A total of 15 capsules, 3 per night, was available at each month's assessment. Number of zolpidem capsules chosen by the zolpidem group differed from the number of placebo capsules (F = 46.56, P

Figure 2

The percent of participants in the placebo and zolpidem groups that increased (Panel A) or decreased (Panel B) relative to month 1 the number of capsules (i.e., dose) that they self-administered in month 4 and 12. Percents increasing and decreasing within a group do add to 100% as a percent within each group did not change. A greater percentage of zolpidem versus placebo participants decreased dose in month 4 and 12 (χ2 = 11.22, P < 0.001).