Toxidrome of an Easily Obtainable Nootropic: A Case Report of Phenibut Intoxication and Withdrawal Delirium.

PURPOSE/BACKGROUND: Phenibut (4-amino-3-phenyl-butyric acid) is a structural analog of GABA with central nervous system depressant and anxiolytic properties, developed in the former Soviet Union for anxiety, insomnia, and alcohol withdrawal. Its primary mechanism of action is believed to be a GABA-B receptor agonist-with high affinity at the α 2 δ subunit-containing voltage-dependent calcium channels and therefore gabapentinoid activity-as well as, to a lesser extent, GABA-A agonist activity. While not approved or regulated by the FDA, phenibut is easily obtainable online, where it is marketed as a nootropic, or cognitive enhancer. However, phenibut can lead to problems related to intoxication, dependency, and withdrawal, similar to other sedatives. METHODS/PROCEDURES: We present a case of phenibut intoxication and withdrawal delirium that provided diagnostic and management challenges because of a patient that was initially not forthcoming about his phenibut use which resulted in five presentations to the hospital including two admissions. FINDINGS/RESULTS: Initial differential including adrenergic, serotonergic or anticholinergic toxidrome based on clinical picture and history reported at that time, however phenibut use of 50 g daily was eventually revealed, an amount exceeding the highest reported cases in our review of the English literature. IMPLICATIONS/CONCLUSIONS: High-dose phenibut intoxication and withdrawal can appear as dramatic and dangerous as high-dose sedative withdrawal, however given its specified receptor affinity and binding profile we found that a pharmacotherapeutic approach targeting GABA-B, GABA-A, and gabapentenoid receptors were effective in stabilizing this patient, eventually leading to the patient's full and sustained recovery.

Demographic recruitment bias of adults in United States randomized clinical trials by disease categories between 2008 to 2019: a systematic review and meta-analysis.

To promote health equity within the United States (US), randomized clinical trials should strive for unbiased representation. Thus, there is impetus to identify demographic disparities overall and by disease category in US clinical trial recruitment, by trial phase, level of masking, and multi-center status, relative to national demographics. A systematic review and meta-analysis were conducted using MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov, between 01/01/2008 to 12/30/2019. Clinical trials (N = 5,388) were identified based on the following inclusion criteria: study type, location, phase, and participant age. Each clinical trial was independently screened by two researchers. Data was pooled using a random-effects model. Median proportions for gender, race, and ethnicity of each trial were compared to the 2010 US Census proportions, matched by age. A second analysis was performed comparing gender, race, and ethnicity proportions by trial phase, multi-institutional status, quality, masking, and study start year. 2977 trials met inclusion criteria (participants, n = 607,181) for data extraction. 36% of trials reported ethnicity and 53% reported race. Three trials (0.10%) included transgender participants (n = 5). Compared with 2010 US Census data, females (48.3%, 95% CI 47.2-49.3, p < 0.0001), Hispanics (11.6%, 95% CI 10.8-12.4, p < 0.0001), American Indians and Alaskan Natives (AIAN, 0.19%, 95% CI 0.15-0.23, p < 0.0001), Asians (1.27%, 95% CI 1.13-1.42, p < 0.0001), Whites (77.6%, 95% CI 76.4-78.8, p < 0.0001), and multiracial participants (0.25%, 95% CI 0.21-0.31, p < 0.0001) were under-represented, while Native Hawaiians and Pacific Islanders (0.76%, 95% CI 0.71-0.82, p < 0.0001) and Blacks (17.0%, 95% CI 15.9-18.1, p < 0.0001) were over-represented. Inequitable representation was mirrored in analysis by phase, institutional status, quality assessment, and level of masking. Between 2008 to 2019 representation improved for only females and Hispanics. Analysis stratified by 44 disease categories (i.e., psychiatric, obstetric, neurological, etc.) exhibited significant yet varied disparities, with Asians, AIAN, and multiracial individuals the most under-represented. These results demonstrate disparities in US randomized clinical trial recruitment between 2008 to 2019, with the reporting of demographic data and representation of most minorities not having improved over time.