LAUSR

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. 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). 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. 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. NIDA, grant#: R01DA038177 awarded to Dr. Roehrs.