Clinical Presentations and Treatment of Phenibut Toxicity and Withdrawal: A Systematic Literature Review

Abstract

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.

Phenibut: Review and Pharmacologic Approaches to Treating Withdrawal

“…2 This is problematic because nearly all publications involving phenibut cite this article. 4,5,14 As a result, information that cannot be validated continues to be perpetuated over time. Throughout this review, we will clarify when information being discussed was not retrieved from a primary source.…”

“…30 Other adverse reactions associated with phenibut intoxication include a reduced level of consciousness, decreased respiratory rate, decreased muscle tone, stupor, and hypothermia. 5 In a recent investigation of online reports, phenibut users noted a wide range of effects, including euphoria, difficulty speaking, headache, difficulty concentrating, vision impairment, nausea, vomiting, and diarrhea. 6 Psychotic symptoms, including auditory or visual hallucinations, and paranoia may also be present (Table 1).…”

“…It is used to treat a variety of central nervous system disorders, including generalized and social anxiety, post-traumatic stress disorder (PTSD), depression, insomnia, vestibular disorders, alcohol withdrawal, stuttering, attention deficit hyperactivity disorder, motor tics, and restless leg syndrome. 1,4,5 Phenibut is also marketed as a "synthetic amino acid derivative" and nootropic (ie, "smart drug"), used to improve cognitive performance, as a mood enhancer, as an aid to boost sexual performance, and as an exercise recovery aid for body builders. 3,6 Over the last decade, phenibut has gained popularity in the USA, where it is used to reduce social anxiety, enhance empathy, produce sexual arousal, reduce alcohol and/or benzodiazepine cravings, increase physical and mental stimulation (at low doses), and produce euphoria, when recommended doses are exceeded.…”

“…2,9 Increased public awareness of phenibut and the ease with which it can be purchased from online vendors has led to increased reports of its abuse in the USA. 5,10,11 There have been over 60 case reports of acute phenibut intoxication or withdrawal, and accounts from poison control centers show an increase in calls pertaining to phenibut since 2018. 5 A Minnesota Poison Control System reported 56 calls pertaining to phenibut exposure over the last 19 years, with 48 of these calls (85.7%) occurring within 5 years of publication.…”

“…5,10,11 There have been over 60 case reports of acute phenibut intoxication or withdrawal, and accounts from poison control centers show an increase in calls pertaining to phenibut since 2018. 5 A Minnesota Poison Control System reported 56 calls pertaining to phenibut exposure over the last 19 years, with 48 of these calls (85.7%) occurring within 5 years of publication. 11 Between 2009 and 2019, US poison control centers received 1320 calls reporting phenibut exposures from all 50 states and Washington, DC.…”