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Abstract Objective To review the relationship between adiponectin levels and autism spectrum disorders (ASDs) in children. Background ASDs are associated with pervasive social interaction and communication abnormalities. Researchers have studied various pathophysiological mechanisms underlying ASDs to identify predictors for an early diagnosis to optimize treatment outcomes. Immune dysfunction, perhaps mediated by a decrease in anti-inflammatory adipokine, adiponectin, along with changes in other adipokines, may play a central role in increasing the risk for ASDs. However, other factors, such as low maternal vitamin D levels, atherosclerosis, diabetes, obesity, cardio-metabolic diseases, preterm delivery, and oxytocin gene polymorphism may also contribute to increased risk for ASDs. Methods Searches on the database; PubMed, Google Scholar, and Cochrane using keywords; adiponectin, adipokines, ASD, autism, autistic disorder, included English-language studies published till September 2022. Data were extracted on mean differences between adiponectin levels in children with and without ASDs. Results The search yielded six studies providing data on adiponectin levels in young patients with ASDs. As can be seen from Table 1, four of the six studies were positive for an inverse correlation between ASD and adiponectin levels. In addition, two of the four positive and one negative studies found low adiponectin levels associated with and the severity of autistic symptoms. However, results from one reviewed study were insignificant. Conclusion Most studies reviewed yielded lower adiponectin levels in children with ASDs as well as the severity of autistic symptoms.

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.

Since the mid-1950s discovery of the first effective antipsychotic medications (APM), we have only been able to improve the tolerability but not the overall efficacy of currently available APMs, as reflected by effectiveness trials in Europe and the United States. This inability to develop more effective APMs is attributable to multiple factors, including failure to create and use assessment tools to assess core symptom domains in schizophrenia, move beyond the dopaminergic hypothesis and to develop “me too” drugs, imposing ill-defined research domain criteria, and lacking federal funding for clinical trials. The classification of APMs is also confusing, including second-generation, partial agonists, and multimodal APMs in the same class of APMs, despite significant differences in their mechanisms of action. Other factors stagnating drug development include inadequate sample sizes to address heterogeneity, lack of statistical measures correlating with clinical significance, using the atheoretical basis of psychiatric diagnoses, failure to control placebo response, and high cost of newer and perhaps more tolerable APMs. Furthermore, there has been a failure to develop early predictors of antipsychotic response and various tools to optimize an APM response. Finally, some mental health providers are also responsible for the suboptimal use of APMs, by using excessive maintenance doses, often with irrational polypharmacy, further compromising effectiveness and medication adherence. However, some bright spots in antipsychotic development include improved tolerability of APMs and long-acting injectables to address the high prevalence of medication nonadherence. This review critically reviews 70 years of antipsychotic development, the reasons behind the failure to develop more effective APMs, and suggestions for future direction.

Objective: To examine the impact of antipsychotic dose adjustments (mainly reduction) on the efficacy and tolerability of antipsychotic medications (APMs) to facilitate hospital discharge in long-term hospitalized forensic patients with treatment-refractory psychosis., Methods: This was a retrospective review of the medical charts of 22 patients with psychosis who were discharged from January 2020 to August 2020 from a long-term state psychiatric facility after restoration of their competency to stand trial. Due to the lack of specific guidelines, the high-dose therapy was defined as a dose ≥ 50% above the average package insert dose. The primary outcome was discharge time after the antipsychotic dosing adjustments., Results: Sixty-eight percent of subjects, who were hospitalized for a mean ± SD total of 11.6 ± 5.3 months, were discharged after 2.3 ± 0.78 months of 44.4% antipsychotic dose reduction. Two patients, who were hospitalized for 14.5 ± 6.7 months, were discharged after 4 months of optimizing their subtherapeutic doses. Five patients, who were already receiving effective dosages, were discharged after a total hospital duration of 6.8 ± 2.17 months., Conclusions: The results from this study extend the finding of beneficial effects of antipsychotic dose reduction from prior reports to the forensic population., (© Copyright 2022 Physicians Postgraduate Press, Inc.)