Early improvements of individual symptoms as a predictor of treatment response to asenapine in patients with schizophrenia

Abstract

Aim It is well accepted that early improvement with antipsychotics predicts subsequent response in patients with schizophrenia. However, no study has examined the contribution of individual symptoms rather than overall symptom severity as the predictors. Thus, we aimed to detect individual symptoms whose improvements could predict subsequent response in patients with schizophrenia during treatment with asenapine and examine whether a prediction model with individual symptoms would be superior to a model using overall symptom severity. Methods This study analyzed a dataset including 532 patients with schizophrenia enrolled in a 6‐week double‐blind, placebo‐controlled, randomized trial of asenapine. Response to asenapine was defined as a ≥30% decrease in Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 6. Stepwise logistic regression analyses were performed to investigate the associations among response and PANSS total/individual item score improvements at week 1 or week 2. Results Response was associated with early improvement in the following PANSS items: disturbance of volition, active social avoidance, poor impulse control at week 1; and active social avoidance, poor attention, lack of judgment and insight at week 2. Prediction accuracy was almost compatible between the model with individual symptoms and the model with PANSS total score both at weeks 1 and 2 (Nagelkerke R 2 : .51, .42 and .55, .54, respectively). Conclusion Early improvement in negative symptoms, poor attention and impulse control, and lack of insight, in particular predicted subsequent treatment response in patients with schizophrenia during treatment with asenapine as accurately as prediction based on overall symptom severity.

Divergence of dose–response with asenapine: a cluster analysis of randomized, double-blind, and placebo control study

“…Early improvement in negative symptoms, poor attention and impulse control, and lack of insight predicted the 6-week treatment response with asenapine using the same dataset. 36 Prediction of both therapeutic response and dose-response is crucial during pharmaceutical treatment, and it may be necessary to evaluate asenapine treatment based on both aspects. In addition, from the perspective of continuous drug treatment, it is necessary to examine the dose of asenapine based on the difference in the profile of occurrence of adverse events in each cluster.…”

“…Considering dose incrementation during the early stages of treatment with asenapine, it may be helpful as a predictor of asenapine response after 6 weeks of treatment. Early improvement in negative symptoms, poor attention and impulse control, and lack of insight predicted the 6-week treatment response with asenapine using the same dataset 36 . Prediction of both therapeutic response and dose–response is crucial during pharmaceutical treatment, and it may be necessary to evaluate asenapine treatment based on both aspects.…”

Genotypic and Haplotypic Association of Catechol-O-Methyltransferase rs4680 and rs4818 Gene Polymorphisms with Particular Clinical Symptoms in Schizophrenia

“…For example, it was the fifth-most-common PANSS single symptom in firstepisode schizophrenia, reported in 65.4% of participants [67]. Moreover, the higher severity of disturbance of volition was, along with uncooperativeness, predictive of improved therapeutic benefit of paliperidone [68], but also during the initial asenapine treatment [69]. Despite being recognized as a common symptom in schizophrenia, disturbance of volition has received less attention than other PANSS items, and we were unable to find any data on the relationship between N5 item and either dopamine or COMT variants, but targeting such interactions appear as an attractive goal for future studies.…”

Molecular and neurocircuitry mechanisms of social avoidance

“…Furthermore, some experimental treatment approaches such as augmentation of exposure-based CBT with the partial NMDA receptor antagonist D-cycloserine [ 67 ] constitute promising potential novel treatment options for social anxiety. Schizophrenia-associated social avoidance was shown to improve significantly in response to treatment with antipsychotics [ 68 , 69 ]. In summary, these facts point at divergencies in the neurobiological underpinnings of pathological social avoidance with and without paranoid and psychotic symptoms and stimulate the hypothesis that the latter might be associated rather with an impaired serotonergic transmission while social avoidance with paranoid and psychotic symptoms might possibly be related to excessive dopamine signaling.…”