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Although enzyme induction by valproic acid (VPA) has been documented in several case reports, clinical reports of VPA autoinduction are rare. In contrast, other antiepileptic drugs (AED) and/or mood stabilizers, such as carbamazepine and phenytoin, are well-documented to increase other drugs' metabolism as well as their own. This review analyzes data from published case reports of VPA autoinduction to elucidate plausible mechanisms underlying VPA autoinduction to enhance clinicians' awareness of VPA autoinduction and its management. A literature search using the following search terms: (('valproic acid' OR 'valproate' OR 'VPA') AND ('autoinduction' OR 'auto-induction' OR 'induction' OR 'inducibility')) revealed 14 records. However, only three papers described clinical cases of VPA autoinduction, with one research paper investigating the role of β-oxidation in VPA autoinduction without a clinical case description. As shown in Table 1, VPA autoinduction in case 1 was primarily formulation-based, cases 2–4 were dose-related, and case 5 involved protein displacement reaction with co-prescribed ibuprofen. All reviewed cases were Caucasian males, with a mean age (SD) of 44.0 ± 14.88, receiving a VPA formulation with different diagnoses, including bipolar disorder, schizophrenia, tuberous sclerosis, and traumatic brain injury. All VPA levels were trough levels obtained at the steady-state and analyzed by the same laboratories for each case. This review utilizes clinical data from a few published cases to present the complexities of pharmacokinetic mechanisms underlying VPA autoinduction. Nevertheless, clinicians should consider requesting free fraction along with the total VPA levels to diagnose and manage VPA autoinduction, particularly in clinically challenging patients.

Background & Objective: Uninformed use of medications can be dangerous especially those medications that require some level of monitoring to ensure safety and tolerability and prevent misuse, such as benzodiazepines and other psychotropic medications. In most developed countries, medications (except over-the-counter medications) are not dispensed without a physician's script. This may not be true for developing countries, like Pakistan, where nearly all medications are dispensed without a script. However, the extent and nature of script-less dispensing has never been studied. This study was designed to investigate the extent and prevalence of dispensing psychotropic medications without physicians' prescriptions, and the pharmacy practices, including the staff qualifications, to not only dispense but also recommend psychotropic medications, in Karachi, Pakistan. Method: A Cross-sectional study was conducted in Karachi over three months (September 2021 to November 2021) with 200 pharmacists in various pharmacies, using a structured questionnaire in a convenient study sample. Pharmacists from registered pharmacies were included in the study. Statistical analysis was done using the Chi-Square test of association. Results: Out of 200 pharmacists working at various locations, 89.0% did not required prescriptions to dispense medications, with benzodiazepines being the most frequently dispensed medication. Surprisingly, only 9.0% had a bachelor's in pharmacy and were qualified enough to legally dispense medications. 76.0% admitted to recommending medications to the patients. Since many of the pharmacists were not qualified enough to dispense medications, 78.5% mentioned that they did not had awareness regarding the abuse potential of psychotropic medications. Conclusion: Dispensing of psychotropic medications without prescriptions and recommending such medications has been a significant issue in the past. Our study reveals this practice to be prevalent in this part of the world, posing a serious threat to the patients. Steps should be taken by the government to ensure proper dispensing of these medications having an abuse potential to prevent harm.