An early improvement threshold to predict response and remission in first-episode schizophrenia.
ABSTRACT Early improvement with treatment is thought to be important in patients with first-episode schizophrenia, yet a valid definition is still outstanding.
To develop a valid definition of early improvement and test its predictive validity regarding response and remission.
We examined 188 in-patients with first-episode schizophrenia. Early improvement was defined as improvement in Positive and Negative Syndrome Scale (PANSS) total score at week 2, response as a 40% PANSS total score improvement at end-point, and remission according to consensus criteria.
Reasonable predictive validity of early improvement was found for a 46% PANSS total score improvement at week 2 and a 50% improvement for remission (area under the curve: response 0.707, remission 0.692). Estimated confidence intervals ranged from 26 to 62% PANSS reduction for response and remission.
Patients with a first episode of schizophrenia should improve by at least 30% in PANSS total score at week 2 to achieve response and remission.
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ABSTRACT: The aim of this study was to determine whether an early improvement in depressive symptoms is a predictor of symptomatic remission in schizophrenia. Patients with DSM-IV schizophrenia diagnosis who received antipsychotic treatment but did not fulfill Andreasen’s symptomatic remission criteria were recruited. Each patient received quetiapine with a flexible dose strategy of 300–800 mg daily for 4 weeks after a 1-week washout period of previous antipsychotics. Remission was defined by Andreasen’s criteria, which includes eight items of the Positive and Negative Symptom Scale with scores of less than three in each item. Seventy-five patients completed the study. Of these, 27 (36%) achieved symptomatic remission after treatment with quetiapine. A significant improvement in depressive symptoms was found in both the remission and the nonremission groups, although the improvement was less pronounced in the nonremission group at the endpoint. Binary logistic regression analysis showed that age (β=−0.07, P=0.02) and early improvement in depressive symptoms within the first 3 days were predictive of symptomatic remission (β=−0.27, P=0.01) for the treatment of schizophrenia. Our data suggest that an early improvement in depressive symptoms in the treatment of schizophrenia is crucial for symptomatic remission.International Clinical Psychopharmacology 01/2013; 28(5):255-260. · 3.10 Impact Factor
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ABSTRACT: We investigated the efficacy and safety of aripiprazole in first-episode psychosis and explored the association between early response and later response to this medication. This was a 6-week, open-label, multicenter trial. The study population consisted of 59 patients with a DSM-IV diagnosis of a schizophreniform disorder, schizoaffective disorder, schizophrenia, or psychotic disorder not otherwise specified. The primary outcome measures were the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression-Severity scale. To assess the safety, we measured the drug-related adverse events, weight, and lipid-related variables. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the response status at weeks 2 and 3 to predict the subsequent response at week 6. Among the 59 participants, 38 were able to complete the 6-week trial. Treatment with aripiprazole resulted in significant improvement in the PANSS and Clinical Global Impression scores over time. The response rate (defined as a ≥30% decrease in the PANSS total score from baseline to the last observation) was 69.1%. The most accurate prediction of later response in terms of negative predictive value and specificity was a reduction in the PANSS total score from baseline to week 3 of at least 20%. Aripiprazole had a modest side effect burden and was characterized by a safe profile with respect to weight and metabolic side effects. These results indicate that aripiprazole is effective and safe in the treatment of first-episode psychosis. The response at week 3, rather than week 2, predicted the later response more accurately.International clinical psychopharmacology 08/2013; · 3.35 Impact Factor
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ABSTRACT: Abstract Objective: The use of early response/nonresponse (ER/ENR) to antipsychotics as a predictor for ultimate response/nonresponse (UR/UNR) may help decrease inefficacious treatment continuation. However, data have been limited to adults, and ER/ENR has only been determined using time-consuming psychopathology rating scales. In the current study, we assessed if early improvement on the Clinical Global Impressions-Improvement (CGI-I) scale predicted UR/UNR in psychiatrically ill youth started on antipsychotic treatment. Methods: Seventy-nine youth aged 6-19 years, with schizophrenia spectrum disorders, treated naturalistically with aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone and evaluated monthly, were divided into ER/ENR groups at week 4, using at least "minimally improved" on the CGI-I scale. Prediction using week 4 ER/ENR status for UR (CGI-I=at least "much improved"), effectiveness and adverse effect outcomes at 8-12 weeks were assessed. Results: At 4 weeks, 45.6% of subjects were ER and 54.4% were ENR without differences regarding baseline demographic, illness, and treatment variables, except for higher age (p=0.034) and maximum risperidone dose (p=0.0043) in ENR. ER/ENR status at 4 weeks predicted UR/UNR at week 12 significantly (p<0.0001): Sensitivity=68.9%, specificity=85.3%, positive predictive value=86.1%, negative predictive value=67.4%. At weeks 4, 8, and 12, ER patients improved significantly more on the CGI-I, CGI-Severity, and Children's Global Assessment of Functioning scales, and more ER patients reached UR compared with ENR patients (83.3% vs. 34.9%, all p<0.0001). ENR patients had more extrapyramidal side effects (EPS) at weeks 4, 8, and 12 (p=0.0019-0.0079). UR was independently associated with ER (odds ratio [OR]=18.09; 95% confidence interval [CI]=4.71-91.68, p<0.0001) and psychosis not otherwise specified (NOS) (OR=4.82 [CI: 1.31-21.41], p=0.017) (r(2)=0.273, p<0.0001). Conclusions: Older age and EPS were associated with ENR; ENR and schizophrenia were associated with UNR in naturalistically treated youth with schizophrenia spectrum disorders. Early CGI-I-based treatment decisions require further consideration and study.Journal of child and adolescent psychopharmacology 11/2013; · 2.59 Impact Factor