Underlying disease may increase mortality risk in users of atypical antipsychotics

Schizophrenia is a group of the most common types of mental illness.Commonly used antischizophrenia drugs all increase mortality to some extent.The increased risk of death in older individuals and patients with dementia using atypical antips-ychotics may be due to myocardial damage,increased mobility and increased risk of stroke.

Changes of Serum Insulin-like Growth Factor-2 Response to Negative Symptom Improvements in Schizophrenia Patients Treated with Atypical Antipsychotics

Accumulating evidence suggests that a disruption of early brain development,in which insulin-like growth factor-2(IGF-2)has a crucial role,may underlie the pathophysiology of schizophrenia.Our previous study has shown that decreased serum IGF-2 was correlated with the severity of psychopathology in patients with schizophrenia.Here we conducted a prospective observation trial to investigate the effects of atypical antipsychotics on serum IGF-2 level and its relationship with clinical improvements in schizophrenia patients.Thirty-one schizophrenia patients with acute exacerbation and 30 healthy individuals were recruited in this study.Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale(PANSS)and serum IGF-2 levels were determined using ELISA.We found that schizophrenia patients with acute exacerbation had lower serum IGF-2 levels than control individuals at baseline(P<0.05).After 2 months of atypical antipsychotic treatment,a significant improvement in each PANSS subscore and total score was observed in patients(all P<0.01),and the serum IGF-2 levels of patients were significantly increased compared with those at baseline(203.13±64.62 vs.426.99±124.26 ng/mL;t=−5.044,P<0.001).Correlation analysis revealed that the changes of serum IGF-2 levels in patients were significantly correlated with the improvements of negative symptoms(r=−0.522,P=0.006).Collectively,our findings demonstrated changes of serum IGF-2 response to improvements of negative symptoms in schizophrenia patients treated with atypical antipsychotics,suggesting that serum IGF-2 might be a treatment biomarker for schizophrenia.

Atypical Weight Loss in Two Patients with Schizophrenia Treated with Clozapine: A Case Report

Clozapine is widely recognized as an effective antipsychotic medication for treatment-resistant schizophrenia, but it is typically associated with significant weight gain. This case report presents two unusual cases of patients with schizophrenia who experienced substantial weight loss while on long-term clozapine therapy. The first case involves a 35-year-old male who lost 21.3% of his initial body weight, and the second case describes a 54-year-old female who lost 30.2% of her initial weight, despite having comorbid hypothyroidism. Both patients showed improvement in psychiatric symptoms concurrent with the weight loss. Comprehensive investigations did not reveal other clear etiologies for the weight reduction. These cases challenge the conventional understanding of clozapine’s metabolic effects and highlight the potential for atypical responses in some individuals. The report discusses possible mechanisms for this unusual phenomenon, including genetic factors and altered pharmacokinetics. It also emphasizes the need for individualized monitoring and management strategies in clozapine therapy. These findings contribute to the growing body of evidence suggesting that metabolic responses to clozapine may be more complex and varied than previously thought, underscoring the importance of personalized approaches in schizophrenia treatment.

Important clinical features of atypical antipsychotics in acute bipolar depression that inform routine clinical care: a review of pivotal studies with number needed to treat

English-language literature cited in MEDLINE from January,1980 to October 30,2014 was searched by using terms of antipsychotic,generic and brand names of atypical antipsychotics, ＂bipolar depression/bipolar disorder＂, ＂placebo＂,and ＂trial＂.The parameters of response（≥50%improvement on MADRS,Montgomery-Asberg Depression Rating Scale total score）,remission（either ≤12 or 8 on MADRS total score at endpoint）,discontinuation due to adverse events（DAEs）,somnolence,≥7%weight gain,overall extrapyramidal side-effects（EPSs）,and akathisia,were extracted from originally published primary outcome papers.The number needed to treat to benefit（NNT） for response and remission or harm（NNH） for DAEs or other side effects relative to placebo were estimated and presented with the estimate and 95%confidence interval.Olanzapine monotherapy,olanzapine-fluoxetine combination（OFC）,quetiapine-IR monotherapy,quetiapine-XR monotherapy,lurasidone monotherapy,and lurasidone adjunctive therapy were superior to placebo with NNTs for responses of 11-12,4,7-8,4,4-5,and 7,and NNTs for remission of 11-12,4,5-11,7,6-7,and 6,respectively.There was no significant difference between OFC and lamotrigine,and between aripiprazole or ziprasidone and placebo in response and remission.Olanzapine monotherapy,quetiapine-IR,quetiapine-XR,aripiprazole,and ziprasidone 120-160 mg/day had significantly increased risk for DAEs with NNHs of 24,8-14,9,12,and 10,respectively.For somnolence,quetiapine-XR had the smallest NNH of 4.For ≥7%weight gain,olanzapine monotherapy and OFC had the smallest NNHs with both of 5.For akathisia,aripiprazole had the smallest NNH of 5.These findings suggest that among the FDA-approved agents including OFC,quetiapine-IR and-XR,lurasidone monotherapy and adjunctive therapy to a mood stabilizer,the differences in the NNTs for response and remission are small,but the differences in NNHs for DAEs and common side-effects are large.Therefore,the selection of an FDA-approved atypical antipsychotic for bipolar depression should be based upon safety and tolerability.

Thirty years of scientific research on second-generation antipsychotic drugs in Japan: A bibliometric analysis

Aims:Research on second-generation antipsychotic drugs (SGAs) has experienced great development in last decades.We did a bibliometric study on the scientific publications on SGAs in Japan.Methods: With theEMBASEandMEDLINEdatabases, we chose papers published from Japan with SGA descriptors. Price’s law and Bradford’s law has been used as bibliometric indicators for quantitating production and dispersion, respectively, of published papers on SGAs. We also calculated the participation index of different countries, and correlated those bibliometric data with some social and health data from Japan (such as totalper capitaexpenditure on health and gross domestic expenditure on research and development). Results: A sum of 669 original documents were published from Japan from 1982 to 2011. Those results fulfilled Price’s law, with scientific production on SGAs showing exponential growth (correlation coefficientr= 0.9261, as against anr= 0.8709 after linear adjustment). The most studied SGAs in Japan wererisperidone (n= 192), aripiprazole (n= 109), and olanzapine (n= 106). Division of documents into Bradford zones yielded a nucleus occupied exclusively by theProgress in Neuro-Psychopharmacology and Biological Psychiatry(49 articles). Those publications were in 157 different journals. Seven of the first 10 frequently used journals had an impact factor of being greater than 3. Conclusions: The SGA publications in Japan have been through exponential growth over the studied period, without evidence of reaching a saturation point.