Uso de psicofármacos durante la gestación: necesidad vs seguridad / Use of psychotropic drugs during pregnancy: necessity vs Safety

Resumen La seguridad de los psicofármacos durante el embarazo es un tema crucial en la práctica clínica. En esta revisión, se hace un breve recorrido sobre los cambios en el embarazo que impactan en la farmacodinamia de los medicamentos, además, se analizan los principales grupos farmacológicos en psiquiatría y sus efectos durante el embarazo. Se identifican tres períodos críticos durante el embarazo. El período de las primeras dos semanas se asocia con un mayor riesgo de aborto espontáneo. El período de la segunda a la décima semana es el más riesgoso, ya que pueden ocurrir alteraciones teratogénicas que afectan el desarrollo fetal. El período posterior a la décima semana se caracteriza por alteraciones en el crecimiento y desarrollo funcional del feto, pero suelen ser menos graves. Los antidepresivos, especialmente los inhibidores selectivos de la receptación de serotonina (ISRS) y los antipsicóticos de segunda generación se consideran los más seguros, pero estos últimos pueden estar asociados con síndrome metabólico, cardiopatías congénitas y trastornos del neurodesarrollo. El litio se ha asociado con efectos teratogénicos y malformaciones cardíacas, mientras que el valproato está relacionado con defectos congénitos importantes. Las benzodiacepinas pueden tener efectos tóxicos y causar síndrome de abstinencia en el recién nacido. La seguridad de los psicofármacos durante el embarazo requiere una evaluación individualizada de los beneficios y riesgos. Aunque algunos grupos de psicofármacos se consideran relativamente seguros, es necesario tener precaución y considerar las posibles complicaciones asociadas con su uso durante el embarazo.

Abstract: The safety of psychoactive drugs during pregnancy is a crucial issue in clinical practice. In this review, a brief overview of the changes in pregnancy that impact the pharmacodynamics of drugs is made; in addition, the main pharmacological groups in psychiatry and their effects during pregnancy are analyzed. Three critical periods during pregnancy are identified. The period of the first two weeks is associated with an increased risk of miscarriage. The period from the second to the tenth week is the most at risk , since teratogenic effects that affect fetal development can take place. The period after the tenth week is characterized by alterations in fetal growth and functional development , however ,less severe defects. Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), and second-generation antipsychotics are considered the safest, but the latter may be associated with metabolic syndrome, congenital heart disease, and neurodevelopmental disorders. Lithium has been associated with teratogenic effects and cardiac malformations, while valproate is associated with major birth defects. Benzodiazepines can have toxic effects and cause Neonatal Withdrawal Syndrome . The safety of psychotropic drugs during pregnancy requires an individualized assesment of the benefits and risks. Although some groups of psychiatric drugs are considered relatively safe, caution is needed when considering the potential complications associated with their use during pregnancy.

Dosing levels of antipsychotics and mood stabilizers in bipolar disorder: A Nationwide cohort study on relapse risk and treatment safety.

BACKGROUND: Finding effective treatment regimens for bipolar disorder is challenging, as many patients suffer from significant symptoms despite treatment. This study investigated the risk of relapse (psychiatric hospitalization) and treatment safety (non-psychiatric hospitalization) associated with different doses of antipsychotics and mood stabilizers in persons with bipolar disorder. METHODS: Individuals aged 15-65 with bipolar disorder were identified from Finnish national health registers in 1996-2018. Studied antipsychotics included olanzapine, risperidone, quetiapine, aripiprazole; mood stabilizers lithium, valproic acid, lamotrigine, and carbamazepine. Medication use was divided into three time-varying dose categories: low, standard, and high. The studied outcomes were risk of psychiatric hospitalization (relapse) and the risk of non-psychiatric hospitalization (treatment safety). Stratified Cox regression in within-individual design was used. RESULTS: The cohort included 60,045 individuals (mean age 41.7 years, SD 15.8; 56.4% female). Mean follow-up was 8.3 years (SD 5.8). Of antipsychotics, olanzapine and aripiprazole were associated with a decreased risk of relapse in low and standard doses, and risperidone in low dose. The lowest adjusted hazard ratio (aHR) was observed for standard dose aripiprazole (aHR 0.68, 95% CI 0.57-0.82). Quetiapine was not associated with a decreased risk of relapse at any dose. Mood stabilizers were associated with a decreased risk of relapse in low and standard doses; lowest aHR was observed for standard dose lithium (aHR 0.61, 95% CI 0.56-0.65). Apart from lithium, high doses of antipsychotics and mood stabilizers were associated with an increased risk of non-psychiatric hospitalization. Lithium was associated with a decreased risk of non-psychiatric hospitalization in low (aHR 0.88, 95% CI 0.84-0.93) and standard doses (aHR 0.81, 95% CI 0.74-0.88). CONCLUSIONS: Standard doses of lithium and aripiprazole were associated with the lowest risk of relapse, and standard dose of lithium with the lowest risk of non-psychiatric hospitalization. Quetiapine was not associated with decreased risk of relapse at any dose.

Psychiatrists effect on positive symptom severity and daily functioning during pharmacotherapy for first-episode psychosis patients.

Clinical outcomes after a first-episode of psychosis (FEP) are heterogeneous. Many patient-related factors such as gender and comorbidity have been studied to predict symptomatic outcomes. However, psychiatrist-related factors such as prescription behaviour and gender have received little attention. We assessed the relationship between patients' psychiatrists, psychosis severity and daily functioning in 201 patients remitted from an FEP for a duration of one year, treated by 18 different psychiatrists. We controlled for baseline severity, dose and type of antipsychotic medication, frequency of visits, and patients' education. Symptom severity, daily functioning, and antipsychotic drug use were assessed at baseline and at 3, 6, and, 12 months follow-up. We found that psychiatrists accounted for 9.1% of the explained variance in patients' symptom severity and 10.1% of the explained variance in daily functioning.These effects persisted even when controlling for factors such as baseline severity and the prescribed dose. The effect of prescribed dose on symptom severity and daily functioning differed between psychiatrists. Treatment centre, session frequency, and medication nonadherence were not related to symptom severity. Our results emphasize the importance of individual psychiatrist factors in symptomatic outcomes after an FEP. Further identification of psychiatrist-related factors such as the quality of therapeutic alliances and shared decision-making, may optimize psychiatrists' training with the goal of improving patient outcomes.

Comparative Effects of Stimulant and Antipsychotic Medications on Eating Behaviors and Weight in Children with Attention Deficit Hyperactivity Disorder.

BACKGROUND/OBJECTIVES: Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with an increased risk of obesity and disordered eating behaviors. This study compared weight status and eating behaviors among drug-naïve ADHD children, those on stimulant monotherapy, those on combined stimulant and antipsychotic treatment, and healthy controls. METHODS: This cross-sectional study included 547 children aged 6-12 years from four Turkish provinces: 361 with ADHD (152 drug-naïve, 156 on stimulants, and 53 on combined therapy), and 186 healthy controls. Anthropometric measurements, psychiatric assessments, and eating behavior evaluations were conducted using standardized tools. RESULTS: Drug-naïve ADHD children had the highest obesity rate (13.8%), while those on stimulant monotherapy had the lowest (4.5%) compared to controls. Combined treatment group obesity rates were similar to controls (7.5% vs. 8.6%). The drug-naïve and combined treatment groups showed increased food approach behavior and desire to drink, with the combined treatment group also showing increased emotional overeating. CONCLUSIONS: This study reveals a complex relationship between ADHD, its pharmacological management, and the risk of obesity. Stimulant monotherapy may mitigate the risk of obesity, while combined stimulant and antipsychotic treatment may lead to problematic eating behaviors. These findings emphasize the importance of monitoring weight status and eating behaviors in ADHD children, especially those receiving pharmacological interventions.

Clinical Reasoning in the Use of Long-acting Aripiprazole in Psychosis in Bilateral Nephrectomy on Hemodialysis.

Psychiatric disorders are common in patients on hemodialysis. To the best of our knowledge there are no reported cases of psychosis developing in hemodialysis patients in the context of nephrectomy, and there is limited data on the use of long-acting antipsychotics in hemodialysis, which are generally not recommended in chronic kidney disease. We present the case of a 40-year-old lady with bilateral nephrectomy receiving hemodialysis who developed psychosis that resulted in her refusing to continue hemodialysis and was irregularly compliant with oral antipsychotics, necessitating the use of a long-acting injection. We report on the approach to clinical reasoning in the choice of aripiprazole and the need for a long-acting injection. Based on its pharmacological and pharmacokinetic properties oral aripiprazole 20 mg was commenced and after establishing tolerability and response, the patient was switched to long-acting aripiprazole 400 mg monthly achieving full remission of psychotic symptoms after 6 months with maintained improvement after 12 months. Based on its properties, aripiprazole may be a reasonable option in the treatment of psychosis in patients on hemodialysis with nephrectomy and can be considered even as a long-acting injection in these patients.

The Real-world Effect of Long-acting Injectable Antipsychotics on Annual Medical Costs of Korean Schizophrenia Patients.

Objective: Schizophrenia is a severe and chronic mental disorder that significantly impacts cognitive, social, and occupational functions, leading to substantial economic burdens. Long-acting injectable (LAI) antipsychotics have been introduced to improve treatment adherence and outcomes, yet their economic impact remains debated. We aim to analyze the impact of LAIs on the medical costs of Korean schizophrenia patients. Methods: A retrospective analysis of 164 schizophrenia patients treated with LAI antipsychotics, paliperidone palmitate, and aripiprazole monohydrate at Korea University Guro Hospital between January 2017 and July 2022 was performed. Comparisons of inpatient department (IPD) and outpatient department (OPD) healthcare expenditures one year before and after LAI initiation were conducted. Results: LAIs led to an increase in annual OPD costs (1,437.44 ± 1,127.60 to 4,015.42 ± 1,204.59; units: 1,000 KRW) but significantly reduced IPD admission associated costs (3,826.06 ± 5,500.63 to 698.06 ± 3,619.38; units: 1,000 KRW). After LAI administration, there was an overall reduction in total annual healthcare costs (5,263.49 ± 5,333.11 to 4,713.48 ± 3,625.89; units: 1,000 KRW), but it was not statistically significant. Conclusion: Although the use of LAIs did not significantly lower the first-year medical costs of schizophrenia patients, they offer beneficial economic impacts over time by reducing hospitalization-associated costs. Future research should focus on long-term cost analyses and the impacts of newer LAI formulations.

Assessing the Risk of QT Prolongation in a Psychiatric Inpatient Cohort: A Retrospective Cross-Sectional Study.

BACKGROUND: QT prolongation is a potential serious adverse drug reaction, and assessing the risk of QT-prolonging drugs is routinely included in psychotropic medication reviews. However, the actual clinical benefits of such assessments are unknown. We investigate whether QT prolongation (QTc value > 480 ms) manifests in psychiatric inpatients at risk of QT prolongation as identified by assessing drug regimens. Secondly, we test the predictive value of well-known risk factors for QT prolongation. RESULTS: The median patient age was 49 years (IQR 34-64) for patients treated with a median of nine drugs (IQR 6-12) and a median QT-prolonging drug sum of three daily defined dosages (IQR 1.88-4.76). We extracted 290 ECGs for patients where pharmacist-led-medication reviews (PMRs) identified an increased risk of QT prolongation and 190 ECGs for patients with no such risk, identifying 33 cases of verified QT prolongation equally distributed between groups. Unadjusted regression analysis revealed that advanced age (OR 3.27 CI 95% 1.60-6.84) and cardiovascular comorbidity (OR 3.53 CI 95% 1.71-7.29) were associated with manifest QT prolongation, while the QT-prolonging drug load was not. METHODS: We reviewed electronic health records (EHRs) of 799 psychiatric inpatients exposed to PMRs made from 1 September 2016 to 31 December 2018 in Region Zealand Denmark. CONCLUSIONS: Patients at risk of QT prolongation as identified by drug reviews rarely manifests with actual QT prolongation. Non-pharmacological risk factors seem to be better predictors for identifying patients with QT prolongation.

Advances in synthesis of novel annulated azecines and their unique pharmacological properties.

Annulated azecines, mostly partially saturated benzo[d]azecine and dibenzo[c,g]azecine fusion isomers, constitute a unique class of alkaloids and nature-inspired azaheterocyclic compounds with interesting reactivity, physicochemical and biological properties. Due to difficulties associated with the synthesis of the benzazecine (or bioisosteric) scaffold they are not the focus of organic and medicinal chemists' consideration, whereas it is worth noting the range of their pharmacological activities and their potential application in medicinal chemistry. Herein, we reviewed the synthetic methodologies of arene-fused azecine derivatives known up to date and reported about the progress in disclosing their potential in drug discovery. Indeed, their conformational restriction or liberation drives their selectivity towards diverse biological targets, making them versatile scaffolds for developing drugs, including antipsychotic and anticancer drugs, but also small molecules with potential for anti-neurodegenerative treatments, as the recent literature shows.

A retrospective review of intramuscular olanzapine and parenteral benzodiazepine coadministration in the emergency department.

Introduction: Acute agitation is a common presenting symptom in medical and mental health emergencies that may require pharmacologic intervention. There is a manufacturer recommendation against intramuscular coadministration of olanzapine with parenteral (intramuscular or intravenous) benzodiazepines despite a deficiency of high-quality evidence. The purpose of this study was to contribute to available literature regarding intramuscular olanzapine and parenteral benzodiazepine use in acutely agitated patients in the emergency department (ED). Methods: This was a single-center retrospective chart review of adult ED patients who received intramuscular olanzapine and a parenteral benzodiazepine within 2 hours. The composite primary endpoint evaluated the occurrence of cardiac or respiratory compromise within 2 hours of medication administration. Secondary endpoints mirrored the primary endpoint within 30 minutes and evaluated the occurrence of cardiac arrest or desaturation in the ED outside the 2-hour window. Results: One hundred eleven patients were included in the analysis, 64 (57.7%) of whom had documented vitals or oxygen status within 2 hours of medication administration. The composite primary endpoint occurred in 8 patients (12.5%), with only 1 patient requiring intervention with intravenous fluids. The secondary composite endpoint occurred in 2 (9.5%) of 21 patients with documented vitals or oxygen status within 30 minutes of treatment, neither of which required intervention. There were no identified events of intubation or significant cardiac events. Discussion: Until better evidence is available, this combination therapy should, at minimum, include appropriate patient monitoring. Future studies should investigate risk factors for serious adverse effects.

Clozapine may consistently protect from suicidal behaviors while other antipsychotics may lack a specific protective effect: a comprehensive VigiBase study interpreted in the context of the prior literature.

BACKGROUND: In the United States, clozapine was first approved for treatment-resistant schizophrenia and then for suicidality in schizophrenia psychoses. Systematic reviews support clozapine's anti-suicidal effect, but the forensic literature stresses its lethality during overdoses. RESEARCH DESIGN AND METHODS: Clozapine reports to the international pharmacovigilance database (VigiBase) were analyzed for suicidal ideation, suicide attempts, intentional overdose, and completed suicides from introduction to 1 January 2024. VigiBase uses the information component (IC) as a disproportionality analysis. RESULTS: The clozapine ICs (range: other antipsychotics) were: 1) suicidal ideation IC = 0.570 with IC025 = 0.454 to IC975 = 0.680 (IC = 3.568 for aripiprazole and 1.729 for risperidone), 2) suicide attempt IC = 1.428 with IC025 = 1.323 to IC975 = 1.529 (IC = 4.150 for quetiapine and 2.968 for risperidone), 3) intentional overdose: IC = 0.995 with IC025 = 0.864 to IC975 = 1.120 (IC = 4.080 for quetiapine and 1.957 for aripiprazole), and 4) completed suicide IC = 1.133 with IC025 = 1.026 to IC975 = 1.235 (IC = 4.648 for quetiapine and 2.160 for risperidone). In summary, all clozapine ICs were significantly lower. We found 2391 clozapine-treated patients on the suicidality spectrum (627 cases with suicidal ideation, 752 with suicide attempt, 488 with intentional overdose, and 731 with completed suicide) but many were taking other antipsychotics. The most frequent reporting countries were the United States, the United Kingdom, and Croatia. CONCLUSION: This pharmacovigilance study, with all its inherent limitations, provides independent proof, not overlapping with prior literature, that clozapine may have specific strong anti-suicidal effects that do not appear to be present in other antipsychotics. Further VigiBase studies are needed to compare the lethality of an intentional overdose of clozapine (14.3%) with other antipsychotics.

The Risk of Venous Thromboembolism Events Resulting in Hospitalization following Exposure to Antipsychotic Medication in Pre-Disposed Adult Patients.

Introduction: The primary objective of this study was to compare the incidence of antipsychotic use in those with venous thromboembolism (VTE) resulting in hospital admission. This study expands upon current knowledge regarding VTE risk and antipsychotic use and investigates potential risk factors and lab values that may precede antipsychotic-induced coagulopathy. Methods: This retrospective, case-control, chart review investigated patients admitted to an acute care hospital with either a VTE or non-VTE diagnosis. Primary outcome analysis compared the presence of an antipsychotic medication in patients who had a VTE versus those who did not. Secondary analysis included: 1) the duration, class, dose, frequency, and route of antipsychotic and 2) coagulation parameters, patient characteristics, and VTE risk factors. Results: Analysis included 400 participants with 200 participants in each group (VTE and non-VTE). Of the 51 patients who received an antipsychotic, 29 (56.9%) developed or presented with a VTE. However, there was no significant difference in VTE development between groups when controlled for antipsychotic use (OR 1.37, 95% CI 0.76-2.50, P-value=0.30). Conclusion: While primary study findings were not statistically significant, results support a weak association of exposure to antipsychotic(s) in VTE groups compared to control (non-VTE). Obesity significantly increased the odds of VTE whereas a history of type 2 diabetes significantly decreased the odds of VTE.

Metabolic Monitoring for Adults Living with a Serious Mental Illness on a Second-Generation Antipsychotic Agent: A Scoping Review.

Premature mortality in people living with a severe mental illness (SMI) is often attributed to multiple factors including the use of medicines such as antipsychotics. Second-generation antipsychotics (SGAs) are known to cause metabolic syndrome which can increase the risk of cardiovascular disease. Practice guidelines have recommended regular physical health monitoring, particularly of metabolic parameters, however, metabolic monitoring for people living with SMI using antipsychotics remains suboptimal. Therefore, highlighting the need for ongoing research. This scoping review aimed to provide an overview of current metabolic monitoring practices. We anticipate that this information will assist clinicians and policymakers and inform future research. The following databases were searched: MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), the Cochrane Database of Systemic Reviews (Wiley), APA PsycInfo (Ovid) and Scopus (Elsevier Science Publishers). The target group was adults (aged ≥ 18) diagnosed with SMI (including bipolar disorder, major depressive disorder and psychotic disorders) and taking SGAs. In total, 44 studies from 14 countries were retrieved. Our findings highlighted that most studies conducted in hospitals did not report on metabolic monitoring practices. Additionally, the roles and responsibilities of healthcare professionals in metabolic monitoring for SMI were infrequently described and parameters such as waist circumference and BMI were often poorly monitored. The scoping review highlights that no streamlined approach towards metabolic monitoring currently exists. There is a need to stipulate and define the roles and responsibilities of all health professionals involved in metabolic monitoring in SMI to optimise care for these individuals. Moreover, there is a need for ongoing research, particularly in the community setting, to promote increased accessibility to metabolic monitoring for SMI.

Constipation-associated factors in outpatients with schizophrenia: A multicenter questionnaire survey.

Constipation is a prevalent gastrointestinal disorder that affects people globally, decreasing their quality of life and life expectancy. Individuals with schizophrenia often suffer from constipation, which could be a result of the illness itself or the side effects of psychotropic medications. However, little research has been conducted on factors contributing to constipation in individuals with schizophrenia. To address this issue, we conducted a survey using self-administered questionnaires and medical records to identify factors associated with constipation in psychiatric outpatients. This study included 399 patients with schizophrenia, resulting in a high prevalence of constipation (43.4%). The analysis suggested that female gender, the doses of antiparkinsonian medications, and benzodiazepine sleeping pills may be associated with constipation.

Kufor-Rakeb syndrome-associated psychosis: a novel loss-of-function ATP13A2 variant and response to antipsychotic therapy.

Biallelic (autosomal recessive) pathogenic variants in ATP13A2 cause a form of juvenile-onset parkinsonism, termed Kufor-Rakeb syndrome. In addition to motor symptoms, a variety of other neurological and psychiatric symptoms may occur in affected individuals, including supranuclear gaze palsy and cognitive decline. Although psychotic symptoms are often reported, response to antipsychotic therapy is not well described in previous case reports/series. As such, we describe treatment response in an individual with Kufor-Rakeb syndrome-associated psychosis. His disease was caused by a homozygous novel loss-of-function ATP13A2 variant (NM_022089.4, c.1970_1975del) that was characterized in this study. Our patient exhibited a good response to quetiapine monotherapy, which he has so far tolerated well. We also reviewed the literature and summarized all previous descriptions of antipsychotic treatment response. Although its use has infrequently been described in Kufor-Rakeb syndrome, quetiapine is commonly used in other degenerative parkinsonian disorders, given its lower propensity to cause extrapyramidal symptoms. As such, quetiapine should be considered in the treatment of Kufor-Rakeb syndrome-associated psychosis when antipsychotic therapy is deemed necessary.

Stevens-Johnson syndrome-toxic epidermal necrolysis overlap in a patient taking quetiapine and famotidine: a case report.

BACKGROUND: Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TNE) overlap is a rare skin disorder characterized by erythema, blisters, extensive exfoliation, epidermal detachment, the involvement of multiple mucosae, and positive Nikolsky's sign. SJS-TEN has a high mortality rate. Our case involves a rare occurrence of drug-induced Stevens-Johnson syndrome-toxic epidermal necrolysis overlap with a delayed onset in the setting of quetiapine and famotidine therapy. CASE PRESENTATION: An 82-year-old Taiwanese female was admitted to our hospital for decreased urine output, generalized edema, and multiple skin blisters and bedsores. With further spread of the lesions, multiple ruptured bullae with shallow erosions on the face, trunk, and limbs and mucosal involvement affected 20% of the total body surface area. Nikolsky's sign was positive. A diagnosis of Steven-Johnson syndrome was highly suspected. One month prior, she had started famotidine and quetiapine. Intravenous methylprednisolone treatment was initiated, which ameliorated the skin lesions after 3 days. However, new lesions developed after only 1 day of methylprednisolone tapering. The patient died 12 days after admission. CONCLUSION: Stevens-Johnson syndrome-toxic epidermal necrolysis is a rare skin disorder. Although it is mainly acute and has a high mortality rate, delayed onset can still occur. Quetiapine and famotidine are generally safe and effective for treating geriatric and gastrointestinal problems, but rare drug hypersensitivity reactions can lead to debilitating consequences. Therefore, increased clinical awareness and the initiation of supportive care are imperative. Optimal management guidelines are still lacking, and confirmation of developed guidelines through randomized controlled trials is needed. Collaboration for better management strategies is warranted.

Effect of Lurasidone on Life Engagement in Schizophrenia: Post-Hoc Analysis of the JEWEL Study.

Purpose: To evaluate the effect of lurasidone on a new, patient Life Engagement scale in schizophrenia. Patients and Methods: This post-hoc analysis included participants (ages 18 to 74) diagnosed with schizophrenia who were randomized to lurasidone (40 mg/day) or placebo in a 6-week double-blind efficacy study and those who continued in a subsequent 12-week open-label extension study during which patients received either 40 or 80/mg day lurasidone (flexibly dosed). Change in life engagement was measured using the Positive and Negative Syndrome Scale (PANSS) 11-item Life Engagement subscale score, and individual subscale items, at week 6 during the double-blind phase and extension phase week 12 during the open-label extension phase. Results: Analysis focused on 478 subjects randomized to lurasidone or placebo during the 6-week trial, and 146 who received lurasidone during the extension phase. During the 6-week trial, there was a significantly greater change on the PANSS11 Life Engagement subscale score from baseline to week 6 in the lurasidone group compared to the placebo group (mean changes of -6.4 and -4.8, respectively, p = 0.006; effect size = 0.27). Further improvement was evident during the extension phase for patients who received lurasidone in both phases, with a mean change from double-blind baseline to week 12 of the open-label treatment phase of -10.1 on in PANSS11 Life Engagement subscale. Conclusion: This post-hoc analysis suggests that lurasidone may improve life engagement in patients with schizophrenia, a meaningful outcome from patients' perspective. Further studies are needed to confirm this effect. Eudract Number: Trial registration: EudraCT Numbers: 2016-000060-42; 2016-000061-23.

A hybrid model for predicting response to risperidone after first episode of psychosis.

Patient response to antipsychotic drugs varies and may be related to clinical and genetic heterogeneity. This study aimed to determine the performance of clinical, genetic, and hybrid models to predict the response of first episode of psychosis (FEP). patients to the antipsychotic risperidone. We evaluated 141 antipsychotic-naïve FEP patients before and after 10 weeks of risperidone treatment. Patients who had a response rate equal to or higher than 50% on the Positive and Negative Syndrome Scale were considered responders (n = 72; 51%). Analyses were performed using a support vector machine (SVM), k-nearest neighbors (kNN), and random forests (RF). Clinical and genetic (with single-nucleotide variants [SNVs]) models were created separately. Hybrid models (clinical+genetic factors) with and without feature selection were created. Clinical models presented greater balanced accuracy 63.3% (confidence interval [CI] 0.46-0.69) with the SVM algorithm than the genetic models (balanced accuracy: 58.5% [CI 0.41-0.76] - kNN algorithm). The hybrid model, which included duration of untreated psychosis, Clinical Global Impression-Severity scale scores, age, cannabis use, and 406 SNVs, showed the best performance (balanced accuracy: 72.9% [CI 0.62-0.84] - RF algorithm). A hybrid model, including clinical and genetic predictors, can provide enhanced predictions of response to antipsychotic treatment.

A Pharmacovigilance Study on Clozapine in the Food and Drug Administration Adverse Event Reporting System: A Regional Comparative Analysis.

Objective: This pharmacovigilance study evaluated the profile of clozapine-related adverse events by region using the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We categorized each case into five regions (America, Europe/West Asia, Oceania, Asia, and Africa) based on the reporting country information in the FAERS database. The number of clozapine-related adverse events reported in each region was aggregated according to the preferred term (PT) and the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ). Results: A total of 101,872 clozapine-related adverse events were registered in the FAERS database. In America and Europe, leukocyte or neutrophil count abnormalities accounted for half of the top 10 PTs by relative reporting rate. However, Asia had higher relative reporting rates of pyrexia and salivary hypersecretion (13.91% and 10.85%, respectively). Regarding the SMQ, the relative reporting rates of infective pneumonia, convulsions, extrapyramidal syndrome, gastrointestinal obstruction, and hyperglycaemia/new onset diabetes mellitus were higher in Asia than in other regions (5.26%, 9.72%, 12.65%, 5.13%, and 8.26%, respectively), with significant differences even after adjusting for confounding factors using multivariate logistic regression analysis. Conclusion: Spontaneous reports of adverse events associated with clozapine show regional disparities, particularly in Asia, where concentration-dependent adverse events are more frequently reported. However, the spontaneous reporting system has several limitations, requiring further research for validation.