Melatonin for sedative withdrawal in older patients with primary insomnia: a randomized double-blind placebo-controlled trial

作者：Lahteenmaki Ritva; Puustinen Juha^*; Vahlberg Tero; Lyles Alan; Neuvonen Pertti J; Partinen Markku; Raiha Ismo; Kivela Sirkka Liisa

来源：British Journal of Clinical Pharmacology, 2014, 77(6): 975-985.

DOI：10.1111/bcp.12294

• controlled trial
• melatonin
• temazepam
• withdrawal
• zolpidem
• zopiclone

Aim We compared the efficacy of melatonin and placebo as adjuvants in the withdrawal of patients from long term temazepam, zopiclone or zolpidem (here BZD%26apos;) use. Methods A double-blind, placebo-controlled, randomized trial was conducted in a primary health care outpatient clinic. Ninety-two men or women (55years) with primary insomnia and chronic BZD use received controlled release melatonin 2mg (CRM) (n=46) or placebo (n=46) during the 1month withdrawal from BZDs. Psychosocial support was provided. Follow-up continued for up to 6months. Successful BZD withdrawal by the end of 1month was confirmed by BZD plasma determinations, while reduction in BZD use and abstinence continuing for 6months were noted. Results There were two drop-outs on CRM and one on placebo. After a 1month withdrawal, 31 participants (67%; 95% CI 54, 81) on CRM and 39 (85%; 74, 95) on placebo had withdrawn completely (intention-to-treat analysis between groups, P=0.051; per protocol P=0.043). Reduction in BZD use was similar or even more rare in the CRM than in the placebo group (P = 0.052 per protocol). After 6months, 14 participants in the CRM group and 20 in the placebo group remained non-users of BZD (NS between groups). BZD doses were higher in the CRM than in the placebo group at the end of the 6month follow-up (P=0.025). Withdrawal symptoms did not differ between the groups. Conclusions Gradual dose reduction of BZDs combined with CRM or placebo, and psychosocial support produced high short term and moderate long term BZD abstinence. CRM showed no withdrawal benefit compared with placebo.

• 出版日期2014-6