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0345 BZRA Hypnotic Receptor Specificity and Ability to Discontinue Chronic Hypnotic Use
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0345 BZRA Hypnotic Receptor Specificity and Ability to Discontinue Chronic Hypnotic Use
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Journal Article
0345 BZRA Hypnotic Receptor Specificity and Ability to Discontinue Chronic Hypnotic Use
2023
Overview
Introduction Clinicians prescribing hypnotics remain concerned regarding the inability to discontinue hypnotics after chronic use. In a controlled prospective study using self-administration choice procedures we tested whether BZRA hypnotic receptor specificity is predictive of discontinuation difficulty in a clinical trial in which insomnia subjects are instructed to stop taking their study medication after 6 months of nightly use. Methods DSM-V diagnosed insomnia subjects, aged 23-61 yrs, (n=41, 36 females), with no other sleep disorders, unstable medical or psychiatric diseases or drug dependency completed the trial. Following a screening polysomnogram and MSLT, participants were randomized to zolpidem XR 12.5 mg (n=16), eszopiclone 3 mg (n=11), or placebo (n=14) nightly for 6 months. After 6 months, nightly use, over a 2-week choice period, they were instructed to discontinue hypnotic use, but if necessary, to self-administer either 1, 2, or 3 capsules of their assigned “blinded” medication (zolpidem XR 6.25 mg, 6.25 mg, placebo; eszopiclone 2 mg, 1 mg, placebo as capsules 1, 2 and 3 respectively; or 3 placebos). Results Over the 14 nights 21 subjects took zero (51%) capsules; among the 20 taking capsules the median total number chosen over the two weeks was 3. Most took one capsule per night; 6 took > 1 capsule on a given night. Overall, the number of capsules taken declined from week 1 to 2 (p< .001). The eszopiclone group took a greater number of capsules than the placebo group (p<.005), with the zolpidem group between. The eszopiclone group also showed a trend (p<.07) to fail to reduce use from week 1 to 2. Conclusion The majority (51%) of the participants discontinued 6-month nightly hypnotic use and among those taking capsules the rate declined from week 1 to 2. The non-hypnotic receptor specific eszopiclone group took a greater number of capsules than the placebo group. This is the first demonstration of differential abuse liability among BzRA hypnotics. Support (if any) NIDA, grant#: R01DA038177 awarded to Dr. Roehrs.
Publisher
Oxford University Press
Subject
