Extrapyramidal Symptoms During Risperidone Maintenance Treatment in Schizophrenia

Abstract

The risperidone maintenance treatment in schizophrenia study was designed to identify the duration of maintenance treatment required with an initial therapeutic dose in contrast to reducing the dose over time. This study investigated extrapyramidal symptoms (EPSs) in different risperidone maintenance treatment paradigms over 1 year. Clinically stabilized patients with schizophrenia (n = 374) were randomized to a no-dose-reduction group and 4-week and 26-week reduction groups, in which the dose was gradually reduced by 50% over 8 weeks and maintained. Extrapyramidal symptoms were assessed at baseline and monthly for 6 months, followed by every 2 months. The Simpson-Angus Scale of Extrapyramidal Symptoms-Chinese version assessed EPS severity. Data were analyzed by a generalized linear mixed model (GLMM). The frequency of EPS at baseline was 23.2%, 20.0%, and 21.3% in the 4-week, 26-week, and no-dose-reduction groups, respectively. Risperidone dosage, positive symptoms, and disorganized thoughts at baseline predicted development of EPS. The GLMM indicated that a significant decrease in EPS was maintained, and different trajectories occurred over time across groups. In the 235 patients who continued treatment after 1 year, the incidence of EPS decreased to 4.1%, 2.8%, and 10.0% in the 4-week, 26-week, and no-dose-reduction groups, respectively, whereas the numbers of dropouts because of intolerable EPS were not significantly different (4.8%, 6.7%, and 6.2%, respectively). These novel findings indicate EPSs were tolerable and differentially decreased depending on the dose paradigm during the 1-year treatment period. Future studies should implement a GLMM to investigate antipsychotic adverse effects during long-term treatment.

Mutual activation of glutamatergic mGlu4 and muscarinic M4 receptors reverses schizophrenia-related changes in rodents

“…The most treatment-resistant symptoms of schizophrenia are negative and cognitive symptoms, which simultaneously have a greater contribution to a poor quality of life and functional disability than the positive symptoms (Velligan et al 2009 ; Kane and Mayerhoff 1989 ). The efficacy of typical neuroleptics towards positive symptoms of schizophrenia is relatively good, although typical antipsychotics induce a variety of adverse effects due to the blockade of D 2 receptors in the striatum, including extrapyramidal motor effects (Corripio et al 2012 ; Bo et al 2016 ).…”

Into a Deeper Understanding of CYP2D6’s Role in Risperidone Monotherapy and the Potential Side Effects in Schizophrenia Spectrum Disorders

“…Another considerable risk in the treatment with risperidone is the possibility of extrapyramidal side effects (EPS), such as dystonia, parkinsonism, akathisia, and tardive dyskinesia. Although the appearance of EPS may be a sign of therapeutic levels’ achievement [ 20 ], they decrease the quality of life [ 21 ], and seem to occur more often in patients treated with risperidone than other second-generation antipsychotics [ 22 ], but less than in those treated with the conventional ones [ 23 ]. Several studies have tried to shed light on the different aspects of risperidone treatment in schizophrenia spectrum disorders, stressing the role of pharmacogenetics in obtaining better outcomes and a more personalized approach [ 24 , 25 ].…”

Prolactin related symptoms during risperidone maintenance treatment: results from a prospective, multicenter study of schizophrenia

“…The main results of the study were published in 2010 [21], and specific issues, such as sex differences [22], cigarette smoking [22], weight changes [23], socio-demographic and clinical profiles of paranoid and nonparanoid schizophrenia [24], predictors of relapse [25], and extrapyramidal symptoms [26], have been addressed in subsequent papers. Regarding PRS, the initial analysis analyzed the presence of prolactin-related adverse events at 4 weeks and the end of the study, regardless of the other time points.…”