Zolpidem stimulant effect: Induced mania case report and systematic review of cases.

INTRODUCTION: Zolpidem is the most widely prescribed hypnotic agent worldwide. This easy-access drug seems to have a high addictive potential among specific populations and is now listed by the World Health Organization (WHO) as being as dangerous as benzodiazepines for dependence and abuse. Many side effects have been reported, but drug-induced mania is still extremely rare. We conducted a systematic review to study the zolpidem-induced stimulation, euphoric or manic effects. METHODS: MEDLINE, PsycINFO, Science Direct, and Google Scholar were searched for articles in English, French, German, Italian and Spanish published up to the 15th October 2018. RESULTS: Eighteen relevant cases were identified, highlighting the need for more reports; therefore, one case that occurred in our department was included. The mean usual dose was 363.31 mg (± 292.2), the minimum dose was 10 mg, the maximum dose was 2000 mg, and the mean intake duration was 35.20 months (±48.0). We found that 89.4% of cases were euphoric and 15.7% had drug-induced mania with delusions. A total of 15.7% of cases took zolpidem for relaxant and stimulant effects, 47% of cases suffered various depression or anxiety disorders, of which 62.5% used zolpidem to cope with depression or an anxiety disorder. A total of 26.3% of cases had concomitant drug dependence or abuse. Seventy-five percent of cases suffering from depression consumed zolpidem for more than 1 year, with significantly more increased daily doses than in non-depressed cases (p < .5). CONCLUSIONS: The latest FDA recommendations for lowering zolpidem doses should be adopted by all countries. Zolpidem prescriptions should be contraindicated for populations with identified risk factors.

Sensitivity to asbestos is increased in patients with mesothelioma and pathogenic germline variants in BAP1 or other DNA repair genes.

Pathogenic germline variants in the BAP1 tumor suppressor gene can cause a cancer syndrome called BAP1 tumor predisposition syndrome (BAP1-TPDS), which is characterized by predisposition to mesothelioma, melanoma, renal cell carcinoma, basal cell carcinoma, and other tumors. Other genes that may predispose to mesothelioma are CDKN2A and DNA repair genes. Asbestos exposure has often been reported in patients with malignant pleural mesothelioma (MPM) and germline variants in BAP1, but this exposure has never been quantified. We aimed to search for germline variants in BAP1 among 25 new Italian probands with suspected BAP1-TPDS, summarize the prevalence of these variants in 39 Italian patients with familial MPM and other tumors recruited over a 5-year period, and compare cumulative asbestos exposure in 14 patients with MPM and pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes with that of 67 patients without germline variants in 94 cancer-predisposing genes. We report here a new pathogenic germline variant in BAP1: c.783 + 2 T > C. The prevalence of pathogenic germline variants in BAP1 was 7.7% among patients with familial MPM (3/39). Patients with pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes showed lower cumulative asbestos exposure than patients without germline variants in 94 cancer-predisposing genes (P = .00002). This suggests an interaction between genetic risk factors and asbestos in the development of mesothelioma.