Search Results (208)

Background: Aripiprazole is an atypical antipsychotic that acts as a partial agonist on the dopamine receptor D2 while also displaying agonistic activity on the 5-HT1A and antagonistic activity on the 5-HT2A receptors. As a partial agonist, aripiprazole stabilizes the activity of the D2 receptor, preventing overactivation. Case presentation: Within our deprescribing activity, we came across the case of a 30-year-old antipsychotic-naïve patient treated with the depot formulation of aripiprazole for bipolar disorder and acute mania, possibly developing hypersexuality due to an overdose that impacted negatively and heavily on his personal life. Results: The patient developed a peculiar subset of hypersexuality, changing his sexual orientation. Of interest, one month after discontinuing aripiprazole and switching to paliperidone, all the sexual-related symptoms and impulse control disorders resolved. Conclusions: We suggest stronger communication among the clinical teams involved in the patient’s care and screening patients for impulse control disorder prior to the administration of aripiprazole and monitoring them during treatment. Full article

Background and Clinical Significance: Wilson disease is a rare autosomal recessive disorder of copper metabolism that can initially present with psychiatric symptoms, leading to delays in accurate diagnosis and treatment. Adult-onset cases may be misdiagnosed as primary psychiatric disorders, particularly when hepatic signs are subtle or absent. Early recognition is critical to prevent irreversible neurological and hepatic damage. Case Presentation: A 48-year-old Hispanic male developed persecutory delusions, cognitive decline, and ultimately catatonia over a three-year period. He was initially diagnosed with a primary psychiatric disorder and treated with antipsychotics, which caused severe extrapyramidal side effects. Further evaluation revealed markedly abnormal liver function tests, low serum ceruloplasmin, and elevated 24 h urinary copper excretion. Brain MRI showed characteristic findings of Wilson disease, and liver biopsy confirmed the diagnosis. The patient was started on trientine and zinc sulfate, but progressive hepatic dysfunction necessitated liver transplantation. Following a successful transplant, the patient experienced significant neurological and psychiatric recovery. Conclusions: This case underscores the importance of considering Wilson disease in patients presenting with atypical or treatment-resistant psychiatric symptoms, particularly when accompanied by abnormal liver function or intolerance to antipsychotics. Timely, multidisciplinary evaluation is essential to avoid misdiagnosis and initiate appropriate therapy. Early intervention can significantly improve both psychiatric and medical outcomes in Wilson disease. Full article

Background and Objectives: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social communication deficits, restricted interests, and repetitive behaviors. At present, there is no pharmacological intervention that reliably targets the core symptoms of ASD; instead, medications are primarily used to manage associated or concurrent symptoms such as irritability, aggression, anxiety, attention difficulties, and sleep disturbances. This review summarizes the current evidence for pharmacological treatments in ASD, emphasizing how these interventions are used in a symptom-focused, adjunctive manner, and highlighting efficacy, mechanisms, limitations, and emerging therapeutic targets. Methods: A comprehensive literature review was conducted across PubMed, Cochrane Library, and Embase to identify clinical trials, systematic reviews, meta-analyses, and preclinical studies on pharmacological interventions for ASD. Seventy-seven references were integrated to reflect the current state of evidence. Results: Established pharmacological strategies include atypical antipsychotics for severe irritability and aggression, as well as antidepressants, stimulants and non-stimulant agents, mood stabilizers, and anxiolytics for selected comorbid symptoms, although efficacy is often modest and variable, and side effects can be significant. Adjunctive and investigational approaches targeting glutamatergic and GABAergic neurotransmission, monoaminergic systems, and neuroinflammatory and oxidative stress pathways show preliminary promise but remain experimental. Across all categories, pharmacological treatments are most effective when embedded in individualized, multimodal care plans that integrate behavioral, rehabilitative, and psychological interventions. Conclusions: This review maps pharmacologic strategies in ASD onto their underlying neurobiological mechanisms and clarifies how evidence strength differs across drug classes and symptom domains. Ongoing advances in genetics, synaptic and circuit-level neuroscience, and neuroimmune signaling are expected to yield more specific, mechanism-based pharmacological approaches for autistic behaviors, with the potential to improve long-term functioning and quality of life when combined with comprehensive psychosocial care. Full article

Objectives: To evaluate reports of diabetic ketoacidosis (DKA) associated with antipsychotic drug (APD) use submitted to the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS). Methods: A retrospective pharmacovigilance analysis was conducted using FAERS data from January 2000 to December 2022. DKA cases were identified using the MedDRA preferred term “diabetic ketoacidosis” in reports listing antipsychotic drugs as suspect medications. Disproportionality analyses, including the proportional reporting ratio (PRR) and empirical Bayes geometric mean (EBGM), were used to assess reporting patterns. Multiple analyses were performed, including those restricted to primary suspect listed drugs only, expanded to incorporate secondary suspect drugs, and sensitivity analyses excluding reports submitted by legal professionals. Results: Among 19,961 DKA reports in FAERS, 2489 (12.5%) listed atypical antipsychotics as the primary suspect drug, whereas reports involving typical APDs were rare. The majority of reports were submitted by healthcare professionals (74.1%), and nearly half originated from the United States (45.4%). Hospitalization was a frequent outcome, reported in 74.3% of cases. Quetiapine and olanzapine were the most frequently reported atypical APDs, with disproportionality analyses demonstrating strong safety signals when compared to all other drugs in FAERS: olanzapine PRR 13.2 (95% CI: 12.4–14.2) and quetiapine PRR 11.8 (95% CI: 11.1–12.5). The findings remained consistent across multiple sensitivity analyses, including incorporating secondary suspect drugs, when the comparator group was restricted to only psychotropic drugs, and excluding reports submitted by lawyers. Conclusions: This pharmacovigilance analysis highlights a potential safety signal for DKA with atypical antipsychotic drugs, notably quetiapine and olanzapine. While these findings do not establish causality, they underscore the need for further investigation using clinical and epidemiological data. Full article

Adolescent-onset schizophrenia (AOS; onset between ages 13 and 18) represents a rare but severe subtype of schizophrenia that disrupts crucial neurodevelopmental and psychosocial milestones. Marked by prominent cognitive deficits, negative symptoms, and poor long-term outcomes, AOS poses unique diagnostic and therapeutic challenges distinct from adult-onset cases. A comprehensive search of PubMed/MEDLINE (January 2003–February 2025) and reference lists of prior reviews identified twenty-four primary studies addressing pharmacological, psychosocial, and neurobiological aspects of AOS. Synthesis of this evidence highlights atypical antipsychotics such as aripiprazole and brexpiprazole as well-tolerated first-line options for positive symptom reduction, while clozapine remains the most effective treatment for resistant AOS. High-dose olanzapine offers comparable efficacy but carries greater metabolic risk. Psychosocial approaches—including cognitive behavioral therapy (CBT) and motivational enhancement therapy (MET)—enhance adherence, insight, and functional recovery when integrated with pharmacotherapy. Converging neuroimaging and biomarker data reveal persistent neuroinflammatory and glutamatergic dysregulation, characterized by elevated interleukin-6 (IL-6), C-C motif chemokine ligand 11 (CCL11), and dorsomedial prefrontal hypoglutamatergia, suggesting immune-mediated and developmental mechanisms underlying symptom persistence. Emerging research on neuromodulation and N-methyl-D-aspartate (NMDA)-targeted strategies further broadens the therapeutic landscape. Collectively, these findings highlight the importance of early, developmentally informed, and multidisciplinary interventions tailored to adolescents. Strengthening longitudinal, biomarker-guided, and neuromodulation-inclusive studies will be critical for refining precision treatment models and informing future clinical and policy frameworks for adolescent psychosis care. Full article

Atypical antipsychotics (AAPs) remain the most effective treatment to control irritability associated with autism spectrum disorder (ASD). Although there is no pharmaceutical treatment to target the core symptoms of ASD, AAPs reduce their severity. However, AAPs have been reported to be associated with severe adverse drug reactions (ADRs) that may lead to long-term conditions such as diabetes mellitus and heart disease. Their prevalence varies depending on the type of AAP prescribed, age, ethnicity, gender, healthcare systems, and the severity of the ASD. Current ADR monitoring guidelines exist, but they are broad in scope and do not fully account for these factors. Therefore, the need to develop ADR monitoring guidelines considering these factors has increased with the expanded use of AAPs in paediatrics with ASD. This gap in knowledge and clinical practice highlights the ongoing need for research to explore these factors and how they can inform the creation of tailored guidelines for monitoring ADRs in this population. Full article

Copay accumulator (CA) and copay maximizer (CM) programs in the United States, which prevent manufacturer copay assistance from counting toward deductibles or out-of-pocket (OOP) maximums, are increasingly used, raising concerns about costs and outcomes for patients with major depressive disorder (MDD) or bipolar disorder (BPD) treated with branded atypical antipsychotics (AAPs) and/or antidepressants (ADs). This retrospective claims study used Kythera commercial data (2020–2024) in the United States to identify adults with MDD or BPD who had at least 1 diagnosis and one branded AAP or AD prescription between 2021 and 2023, requiring 12 months’ continuous enrollment pre- (2020–2021) and post-index (2023–2024) and at least three months of post-index branded medication use. This retrospective claims study used Kythera commercial data (2020–2024) to identify adults with MDD or BPD who had at least one diagnosis and one branded AAP or AD prescription between 2021 and 2023, requiring 12 months’ continuous enrollment pre- and post-index and at least 3 months of post-index branded medication use. Patients were stratified into CA, CM, or standard copay plan (SCP) cohorts, and propensity score matching was used to compare treatment patterns and costs. Both CA and CM groups had significantly higher median OOP costs than SCPs (e.g., $75/$60 vs. $16 for MDD+AAP; p < 0.0001), and higher pharmacy costs among adherent patients. CA patients had poorer adherence and persistence, shorter treatment duration, and higher discontinuation and abandonment rates than SCPs. These findings highlight higher OOP burden and adherence challenges with CA and CM programs, underscoring the need for careful benefit design for US mental health patients. Full article

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by challenges in social and communication skills and restricted interests. It is associated with behavioural symptoms and/or comorbidities (e.g., attention deficit hyperactivity disorder (ADHD)). Developing effective treatments for ASD remains a challenge because its pathophysiology is not fully understood. Multiple treatment options are used for ASD with varying levels of effectiveness and safety profiles. Atypical antipsychotics (AAPs), particularly risperidone and aripiprazole, provide superiority over other drug classes of pharmacological interventions. However, they are linked to adverse drug reactions (ADRs), specifically metabolic and endocrine ADRs. These ADRs may lead to chronic diseases such as diabetes and cardiovascular conditions, adding strain to healthcare systems beyond the original treatment of ASD. This narrative review enhances our understanding of ASD and highlights a gap in current knowledge about the evaluation of the effectiveness and safety of pharmacological treatments, especially AAPs for ASD in paediatric patients. Full article

Atypical antipsychotics (AAP), including clozapine (Clo), aripiprazole (Ari), and risperidone (Ris), are widely used in psychiatry but can lead to kidney damage due to oxidative stress. This study investigated whether dietary supplementation with selected antioxidants—ellagic acid, vitamin C, zinc, and seleno-methionine (SeMet) in fish oil, formulated as the composite product “ProCloSupp” (PCS)—can mitigate the oxidative damage induced by subchronic administration of AAP. Rats were treated with each antipsychotic for 28 days, with PCS added in the last 14 days. The kidney tissue was examined histologically and by determining the activities of antioxidant enzymes (copper, zinc and manganese superoxide dismutase—CuZn SOD and Mn SOD, catalase—CAT, glutathione peroxidase—GPx, glutathione reductase—GR, glutathione S-transferase—GST). All AAPs caused discrete to moderate renal damage and significant changes in enzyme profiles, which were most pronounced with Ari. Clo and Ari significantly decreased CuZn SOD and Mn SOD activity, while Ris only affected Mn SOD. Clo additionally increased CAT activity, while Ari increased GPx activity. Antioxidant-related protein levels increased only in the Ris group. PCS supplementation increased CuZn SOD and GPx activities and was associated with less pronounced histopathological changes than antipsychotic treatment alone. In conclusion, subchronic Clo, Ari, and Ris exposure induces oxidative renal damage in rats, while PCS supplementation enhances antioxidant defences and attenuates tissue damage. These results support PCS as a potential nephroprotective strategy in antipsychotic therapy. Full article

Oxidative stress observed in schizophrenia and other psychiatric disorders can induce neuronal damage and modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis. The aim of this study was to estimate in vitro the possible antioxidant properties of curcumin, the natural polyphenolic antioxidant, and its protective effects against lipid peroxidation induced by the atypical antipsychotic Ziprasidone. Curcumin (5 µg/mL, 12.5 µg/mL, 25 µg/mL, 50 µg/mL) was added to human plasma and incubated for 1 and 24 h, alone and in the presence of Ziprasidone (40 ng/mL, 139 ng/mL, 250 ng/mL). Control plasma samples were incubated for 1 and 24 h. The concentration of thiobarbituric acid-reactive substances (TBARSs; lipid peroxidation marker) was determined by the spectrophotometric method according to Rice-Evans. Curcumin at the tested concentrations significantly inhibited lipid peroxidation in human plasma by about 60%. Ziprasidone (40 ng/mL, 139 ng/mL, 250 ng/mL) significantly increased TBARS levels, but in the presence of the studied curcumin concentrations, its pro-oxidative effects were reduced by about 56%. Our results confirm that Ziprasidone in vitro may induce lipid peroxidation in human plasma, whereas curcumin protects against lipid peroxidation in human plasma caused by the antipsychotic Ziprasidone. Full article

Background/Objectives: The objective of this study is to investigate the patterns and characteristics of medication errors (MEs) associated with antipsychotic medication use in hospitals affiliated with the Ministry of Health (MOH) in Saudi Arabia and to identify areas for improvement. Methods: A retrospective descriptive analysis of MEs associated with antipsychotic use was conducted using data collected from MOH-affiliated hospitals between April 2020 and September 2022. The data were analyzed descriptively to identify the factors underpinning unsafe antipsychotic use. Results: The sample period produced 35,077 reported MEs. Reports from the Western region contributed the highest error percentage, and MEs were reported more frequently in male (76.1%, n = 26,705) and adult (97.7%, n = 34,275) patients. Pharmacists reported MEs more often than other healthcare professionals (66.5%, n = 23,312). Most MEs (89.9%, n = 31,524) originated in the prescribing stage, with missing prescription information being the most frequently reported ME type (40.5%, n = 14,206). Atypical antipsychotics accounted for the greatest proportion of reports (79.3%, n = 27,811) compared to typical antipsychotics (20.7%, n = 7262). Most ME outcomes fell into Category B: The error occurred but did not reach the patient (56.4%, n = 19,794). Factors related to staffing or workflow accounted for 21.3% (n = 7467) of the reported errors, followed by a lack of policies in relation to antipsychotics prescribing and monitoring (20.5%; n = 7195). Conclusions: MEs in hospitals in Saudi Arabia frequently involve antipsychotic medications. This study identified important targets that may help reduce such risks in the future. Full article

Background/Objectives: Therapeutic drug monitoring (TDM) of antipsychotic medications plays an important role in optimizing treatment efficacy, reducing adverse effects, and supporting adherence. While Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry (UHPLC–MS/MS) has long been the gold standard for antipsychotic quantification, recent advances in automated platforms and microsampling raise questions about its current clinical practicality. This systematic review evaluated the clinical applicability and analytical performance of UHPLC-based methods for monitoring antipsychotic drugs, focusing on precision, recovery, matrix effects, and suitability across various biological matrices. Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted for studies published between 2013 and 2024 involving UHPLC-based quantification of antipsychotics in clinical samples from adult patients. Data on analytical parameters, sample matrices, and study characteristics were extracted. A custom quality checklist was used to assess methodological rigor. In addition to qualitative synthesis, non-traditional quantitative approaches were applied, including descriptive aggregation of recovery, matrix effects, and precision across studies, as well as correlation analyses to explore relationships among performance parameters. Results: Twelve studies were included, spanning a range of typical and atypical antipsychotics and metabolites. Plasma and serum demonstrated the highest analytical reliability (recovery >90%, minimal matrix effects), while dried blood spots (DBSs), whole blood, and oral fluid showed greater variability. Clinically, UHPLC–MS/MS enabled more accurate dose adjustments and identification of non-adherence, outperforming immunoassays in sensitivity, specificity, and metabolite detection. Microsampling methods showed promise for outpatient and decentralized care but require further clinical validation. Conclusions: UHPLC–MS/MS remains the most robust and reliable method for TDM of antipsychotics, especially when quantification of active metabolites is required. While logistical barriers remain, technological advances may enhance feasibility and support broader integration into routine psychiatric care. Full article

Objective: Schizophrenia is a chronic psychiatric disorder associated with increased oxidative stress. We aimed to investigate serum myeloperoxidase (MPO), catalase (CAT), and malondialdehyde (MDA) levels and their diagnostic value in schizophrenia. Methods: Sixty patients with schizophrenia, diagnosed according to DSM-V criteria, and 65 age- and sex-matched healthy controls were enrolled. Clinical severity was assessed with the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI). Serum MPO and CAT were measured using ELISA, and MDA levels were determined spectrophotometrically. Receiver operating characteristic (ROC) analysis was performed to assess diagnostic performance. Results: Compared with controls, schizophrenia patients demonstrated significantly higher serum MDA (5.64 vs. 3.42 pg/mL, p < 0.001), MPO (77.25 vs. 31.42 ng/mL, p < 0.001), and CAT (22.06 vs. 6.58 ng/mL, p < 0.001) levels. Subgroup analysis revealed consistently increased values across patients receiving typical, atypical, or combined antipsychotics. ROC analysis indicated good diagnostic accuracy: AUC = 0.884 for MDA (cut-off: 3.79 pg/mL), AUC = 0.882 for MPO (cut-off: 34.56 ng/mL), and AUC = 0.875 for CAT (cut-off: 9.38 ng/mL), all p < 0.001. Combined analysis of MPO, CAT, and MDA yielded superior diagnostic performance (AUC = 0.995; sensitivity = 98.3%). MPO was positively correlated with PANSS-N scores (r = 0.275, p = 0.033), and both MPO and CAT were correlated with CGI severity scores. Conclusions: Elevated MPO, CAT, and MDA levels indicate increased oxidative stress in schizophrenia. MPO may also be associated with negative symptom severity. These findings suggest potential utility of oxidative stress biomarkers as adjunctive diagnostic tools, although results should be considered preliminary and validated in larger, drug-naïve, and longitudinal samples. Full article

Background: Schizophrenia is a chronic disorder requiring long-term pharmacological treatment. Many patients experience inadequate response and adverse effects, often leading to poor adherence and need for antipsychotic switch or polypharmacotherapy. In this context, brexpiprazole, an atypical antipsychotic with favorable tolerability profile, may offer clinical benefits following previous treatment failure or intolerance. However, real-world evidence after treatment switch remains limited. Methods: This retrospective, observational study included 50 outpatients with schizophrenia switched to brexpiprazole (2–4 mg/day) via cross-titration and evaluated over 12 weeks. Primary outcomes were changes in Patient Life Engagement, assessed through a 14-item subset of the Positive and Negative Syndrome Scale (PANSS), along with response/remission rates. Secondary outcomes included changes in subjective well-being, quality of life, sexual functioning (based on Subjective Well-being under Neuroleptics—Short Form [SWN-S], WHO-5 Well-Being Index [WHO-5], and Arizona Sexual Experience Scale [ASEX] scores, respectively), metabolic parameters, and prolactin levels. Results: Life engagement improved significantly (p < 0.001) across all domains, and clinical response was achieved in 40% of patients. Significant improvements were observed in SWN-S and WHO-5 scores (both p < 0.001). Weight and BMI significantly decreased (–2.64 kg, p = 0.013, and –0.91 kg/m², p = 0.006, respectively). Numerical non-significant reductions were found in ASEX (p = 0.067) and prolactin levels (–30.7 ng/mL, p = 0.077). Overall, treatment was well-tolerated. Conclusions: Switching to brexpiprazole was associated with improvements in psychopathological, functional, and physical health domains. These findings support its potential role in real-world, personalized therapeutic strategies for patients with schizophrenia following suboptimal outcomes with prior antipsychotic treatments. Full article

Background: Delirium is a rare but clinically significant complication of opioid withdrawal that remains poorly characterized in the literature. While classical withdrawal symptoms are well recognized, atypical presentations such as delirium are less frequently reported and often challenging to diagnose due to symptom overlap and heterogeneity of withdrawal syndromes. Methods: In this systematic review, we systematically analyzed available case reports and case series describing delirium precipitated by spontaneous opioid withdrawal, tapering, or antagonist-induced withdrawal. Twelve papers met inclusion criteria, comprising a total of fifteen case reports. Results: Most patients (n = 15) developed delirium within hours to days of withdrawal onset, often with fluctuating consciousness, disorientation, perceptual disturbances, and psychomotor changes. Reported risk factors included psychiatric comorbidity (major depressive disorder, anxiety disorder), concomitant use of psychotropic medication, rapid detoxification protocols, and potential exposure to adulterated substances. Management strategies varied but generally involved supportive care, benzodiazepines, antipsychotics, or reinstatement of opioid agonists. Conclusions: The findings highlight the need for heightened clinical awareness, careful differentiation from other withdrawal-related neuropsychiatric states, and systematic exclusion of organic etiologies. Despite the increasing number of patients affected by OWS, the knowledge available to date is based on case reports and a small case series, making it impossible to critically assess the prevalence or identify risk factors. Future research should aim to identify risk factors, optimize treatment, and explore novel diagnostic approaches, including AI-driven monitoring and connectomic analyses, to improve early detection and therapeutic outcomes in opioid withdrawal-associated delirium. Full article