American journal of therapeutics最新文献

Background: Antipsychotic medications are prescribed in the pediatric population for various psychiatric conditions, such as schizophrenia, autism spectrum disorder, mood disorders, and other disruptive behaviors. However, the use of antipsychotic medications, particularly atypical antipsychotic medications, has raised concerns because of their potential to cause weight gain.

Study questions: This review aims to compare the effects of different antipsychotic medications on weight gain in children and adolescents, particularly patients with childhood-onset schizophrenia, after 6-8 weeks of antipsychotic treatment.

Study design: We searched 5 online databases. Seventeen articles were included with 1360 participants being enrolled.

Measures and outcomes: Meta-insight was used for network meta-analysis. We used body weight gain (kilogram) collected in the included studies for calculation.

Results: Olanzapine caused the most significant weight gain. The ranking of clozapine is not as high as in adult studies. In contrast, molindone may actually reduce weight. Weight gain in patients with schizophrenia is more clinically significant than in the whole participants.

Conclusions: Our study indicated the effects of different antipsychotic medications on body weight gain among children. Childhood-onset schizophrenia may represent a more vulnerable group. Future studies exploring genetic and physiologic risk factors for weight gain, and potential preventive strategies, are needed.

Background: Schizophrenia is characterized by 3 main groups of symptoms: positive, negative, and cognitive. Traditional antipsychotics primarily address positive symptoms via dopamine D2 receptor blockade but often cause side effects like movement disorders, sedation, and hormonal imbalances xanomeline/trospium, Food and Drug Administration (FDA) approved for the treatment of schizophrenia in adults, represents a novel, nondopaminergic approach to schizophrenia treatment, without being categorized as an antipsychotic. Xanomeline is a muscarinic receptor agonist (mainly M1 and M4) that reduces dopamine release in the associative striatum, a region linked to psychotic symptoms, while sparing sensorimotor regions involved in movement and endocrine regulation. M1 receptor stimulation also influences Gamma-aminobutyric acid (GABA)/glutamate pathways that modulate the ventral tegmental area, contributing to dopaminergic balance.

Pharmacodynamics and pharmacokinetics: Xanomeline binds to all 5 muscarinic receptor subtypes, exerting central effects. Trospium, a peripherally acting anticholinergic with limited blood-brain barrier penetration, mitigates xanomeline's peripheral cholinergic side effects, such as nausea, vomiting, and sweating. However, higher doses of trospium may introduce additional peripheral side effects. Xanomeline undergoes extensive liver metabolism, whereas trospium is primarily excreted unchanged in urine. The combination is contraindicated in patients with moderate to severe hepatic or renal impairment or urinary retention.

Clinical trials: EMERGENT-1 was a phase 2 trial, whereas the subsequent 2 EMERGENT trials were phase 3 studies evaluating the safety, tolerability, and efficacy of xanomeline/trospium compared with placebo in adult patients diagnosed with schizophrenia. The final 2 EMERGENT trials were 52-week, open-label studies designed to assess the long-term safety and efficacy of the drug. Xanomeline/trospium treatment significantly reduced Positive and Negative Syndrome Scale (PANSS) total score across the 2 phase 3 trials.

Therapeutic advance: Xanomeline/trospium represents an innovative drug approach, targeting the improvement in positive, cognitive, and negative symptoms in individuals with schizophrenia. This combination seeks to provide therapeutic benefits while displaying a different adverse effect profile than antipsychotic medications and potentially reducing the treatment discontinuation risk.