Objectives: This systematic review aimed to identify published articles that evaluated all phenibut toxicity and withdrawal cases to understand better their clinical presentations and treatments. Methods: A comprehensive literature search was conducted using Medline (Ovid), Embase (Ovid), and Cochrane Library databases to capture all published cases on the presentations and management of phenibut toxicity or withdrawal. Results: Sixty-two cases from 36 studies on presentation and management of phenibut toxicity or phenibut withdrawal were identified. Of all subjects, 80.7% were male. The average age was 30.9 years (SD, 13.2 years; range, 0-71 years). A total of 86.8% reported obtaining phenibut online, and 63.2% reported concomitant substance use with other addictive agents; benzodiazepines and alcohol were the most combined drugs. The average length of hospital stay was 5.0 days (n = 25; SD, 5.4 days; range, 1-25 days) for phenibut toxicity and 7.7 days (n = 20; SD, 7.8 days; range, 0-30 days) for phenibut withdrawals. The most common symptoms reported during phenibut toxicity were altered mental status, somnolence, psychosis, and movement disorders. Of the phenibut toxicity cases, 48.7% required intubation. Benzodiazepines and antipsychotics were most used to treat phenibut toxicity. For phenibut withdrawal cases, 95.7% reported daily use. The most common symptoms reported during phenibut withdrawals were anxiety, irritability or agitation, insomnia, and psychosis. Sixteen (69.6%) of phenibut withdrawal cases required multiple medications for treatment. Benzodiazepines, baclofen, atypical antipsychotics, gabapentanoids, and barbiturates were commonly used to treat phenibut withdrawals. Conclusions: The seriousness of presentations, combined with the assortments of medications used for both syndromes, reflects the potential dangers of phenibut use and the need for systematized treatment protocols.
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