Early response or nonresponse at week 2 and week 3 predict ultimate response or nonresponse in adolescents with schizophrenia treated with olanzapine: results from a 6-week randomized, placebo-controlled trial

Stentebjerg-Olesen, Marie; Ganocy, Stephen J.; Findling, Robert L.; Chang, Kiki; DelBello, Melissa P.; Kane, John M.; Tohen, Mauricio; Jeppesen, Pia; Correll, Christoph U.

doi:10.1007/s00787-015-0725-1

Cited by 20 publications

(18 citation statements)

References 48 publications

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“…These findings demonstrate that in schizophrenic patients treated by olanzapine, risperidone and paliperidone, early non-responders have a very high chance, more than 90%, to become non-responders. Previously, studies on second-generation antipsychotics also found that early improvement of psychotic symptom at Week 2 could predict subsequent treatment responses [ 1 , 2 , 5 , 7 , 9 , 11 , 16 , 18 – 21 ]. It has been suggested that a lack of response to antipsychotic agents in the early course can serve as a marker for response defects in patients undergoing treatment [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Early predictors of poor treatment response in patients with schizophrenia treated with atypical antipsychotics

Chen

Chiu

et al. 2018

BMC Psychiatry

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BackgroundThe aims of this study were to explore the relationship between early reduction in psychotic symptoms and the ultimate response in patients with schizophrenia treated by atypical antipsychotics, and to determine the best time to switch or maitain the regimen. We also explore the possible predictors for the clinical response.MethodsOne hundred eleven inpatients with acutely exacerbated schizophrenia were randomized to give optimal therapy of olanzapine, risperidone, and paliperidone in one-week run-in period and 12 weeks’ intervention. All participants were assessed using Positive and Negative Syndrome Scale (PANSS). Early Response, defined as reduction of 25% in PANSS score, was examined at weeks 1, 2, 3, 4 and 8, and these ratings were used to predict ultimate response (25% PANSS reduction) at week 12. We hypothesized that early treatment response at Week 1 or 2 could predict Week 12’s treatment outcome.ResultsThe early treatment response at Week 2 had a greater negative prediction value (NPV, 93.6%) than did the response at Week 1 (NPV, 69.7%), Week 3 (NPV, 91.5%), Week 4 (NPV, 90.7%) and Week 8 (NPV, 87.2%). The positive predictive value became more acceptable (65%) until Week 4. There was no any other potential predictors, including types of antipsychotics medication and treatment dosage, were associated with ultimate response in this study.ConclusionThe treatment non-response at Week 2 optimally predicted the ultimate (Week 12) non-response, in terms of negative predictive value (NPV). These finding suggests that the revision of treatment strategy should be considered t if patients with schizophrenia was not responsive to them after 2 weeks’ treatment, and for those who are responders at Week 2, another two weeks are needed to further evaluate whether they will be continuously responsive.Trial registrationNCT03730857 at ClinicalTrial.gov. Date of registration: 30/Oct/2018.

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Section: Discussionmentioning

confidence: 99%

Early predictors of poor treatment response in patients with schizophrenia treated with atypical antipsychotics

Chen

Chiu

et al. 2018

BMC Psychiatry

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“…Each file was reviewed by 2 child and adolescent psychiatry consultants (CJB, MH) with extensive expertise in the treatment of EOS, who reappraised and confirmed the diagnoses and the adequacy of treatment episodes. An adequate antipsychotic treatment episode was defined as an antipsychotic trial in sufficient dosage for at least 2 weeks with one of the following substances: amisul-pride, aripiprazole, benperidol, chlorpromazin, chlorprothixen, flupentixol, haloperidol, olanzapine, perazine, perphenazin, pimozide, pipamperone, quetiapine, risperidone, sulpiride, thioridazine, tiapride, ziprasidone, or zuclopenthixol [30,31]. The adequacy of dosage was determined according to the German version of the Clinical Handbook of Psychotropic Drugs for Children & Adolescents [32].…”

Section: ▼ Patientsmentioning

confidence: 99%

“…Information regarding the variables IQ, BMI, and positive family history of schizophrenia was not available for all patients, which limits the validity of our findings regarding possible influencing factors. As we counted treatment episodes ≥ 2 weeks duration as adequate in length [30,31], comparability with studies employing other (e. g., treatment trials of 6 weeks duration [26]) or no time criteria at all [22] is hampered. The same holds true for the definition of adequate dosage, which had to be judged by 2 experienced consultants, as in Germany no defined therapeutic dose range for antipsychotics in children and adolescents exists.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Time to Initiation of Clozapine Treatment in Children and Adolescents with Early-Onset Schizophrenia

et al. 2016

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Early-onset schizophrenia (EOS) has a poor prognosis and is difficult to treat, which often leads to the initiation of clozapine treatment. Studies in adults have shown that the initiation of clozapine treatment is often delayed. There is a lack of studies concerning the initiation of clozapine in children and adolescents with EOS. The aim of this study was to investigate the time span from first EOS-related psychiatric hospitalization to clozapine initiation. We retrospectively studied a consecutive cohort of children and adolescents with EOS and first-time clozapine prescriptions from a tertiary care child and adolescent psychiatric center in Germany. Clinical records with data on clozapine initiation were available for 112 patients (35.7% females, mean age: 15.2±1.6 years). The mean time from first EOS-related hospitalization to clozapine initiation was 1.1 (±1.0) years, with an average of 2.3 (±1.1) prior antipsychotic treatment episodes. Higher age and higher IQ predicted earlier clozapine initiation. At the time of clozapine initiation, 40.2% of patients received antipsychotic polypharmacy. Prior to clozapine, 33.9% of patients had received 3 or more antipsychotic treatment episodes. In our study, clozapine treatment was initiated markedly earlier than in the few existing studies, which may partly be due to the expected poor prognosis of EOS. The significant portion of patients undergoing 3 or more antipsychotic trials or antipsychotic polypharmacy prior to clozapine may indicate a need for improved dissemination of knowledge on the effectiveness of clozapine in treatment-resistant schizophrenia in order to promote timely clozapine prescriptions in these cases.

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“…Participants were not included in the study if they had a medical condition affecting the central nervous system, alcohol or substance abuse in the last 6 months, mental retardation and traumatic brain injury causing a loss of consciousness for more than 5 minutes. Forty-two schizophrenic patients were evaluated and eventually 27 patients with schizophrenia (in-and out-patients) diagnosed according to the DSM-IV criteria were included in the study 23 . As we intended to predict the antipsychotic response, we included patients who were moderately-to-severely ill. Moderatelyto-severely ill patients were defined as folllows: baseline PANSS total score ≥75, with at least "moderate" level of severity (score ≥4) on at least 2 of the 4 Brief Psychiatric Rating Scale (BPRS) psychotic cluster items (i.e.…”

Section: Participantsmentioning

confidence: 99%

Prediction of Response to Antipsychotic Drugs in Schizophrenia Patients within the Early Phase of Treatment

Yıldız

Yazıcı

Yağcıoğlu

et al. 2015

Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychophar

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Objective: Currently, schizophrenia guidelines recommend waiting for 3 to 6 weeks before considering a patient as non-responder. However, recent studies indicate that the response to antipsychotic medications starts within the first two weeks of treatment. The aim of this study is to determine the predictive value of early improvement at 2 or 4 weeks for non-response at 6 weeks.Methods: Twenty seven in-and out-patients with a diagnosis of schizophrenia according to DSM-IV, between the ages of 18 to 65 years, who were moderately-to-severely ill (baseline Positive and Negative Syndrome Scale (PANSS) total score ≥ 75, with at least "moderate" level of severity / score>4 on at least 2 of the 4 Brief Psychiatric Rating Scale (BPRS) psychotic cluster items) were included. Ten patients were receiving antipsychotic treatment for the first time, and 17 patients' treatment was changed due to nonresponse to prior antipsychotic treatment. The patients were evaluated with the PANSS and the Clinical Global Impression-Severity (CGI-S) scale at 0, 2, 4 and 6 weeks of antipsychotic treatment. Non-response at endpoint was defined in 3 different ways to reflect the variations in the level of response to medication:"not minimally improved", "not much improved" and "not remitted". As previously described, "not minimally improved" and "not much improved" were defined as less than 28% and 53% improvement in the PANSS total scores, respectively. "Not remitted" was defined according to the criteria developed by "The Remission in Schizophrenia Working Group" without the time criterion. Signal detection methods using receiver operating characteristics (ROC) curves were implemented to detect the optimal threshold of early nonresponse at 2 and 4 weeks. Total accuracy, sensitivity, specificity and positive and negative predictive value of cut-off points were calculated for predicting "not minimally improved", "not much improved" and "not remitted" at endpoint. Results:The early response threshold for predicting "not minimally improved' was less than 15.3% reduction in PANSS total score at week 2, less than 15.5% reduction at week 4. The early response threshold for predicting "not much improved" was less than 22.1% reduction at week 2 and less than 44.3% reduction at week 4; for "not remitted" was less than 17.5% reduction at week 2 and less than 23.2% reduction at week 4. Specific thresholds of "much improvement" and "remission" were not identified at week 2, whereas thresholds calculated for week 4 had good discriminative power. Conclusion:The findings of this study did not support the findings of earlier studies indicating that nonresponse at 2 weeks accurately predicts subsequent lack of response in patients with schizophrenia. Instead, the findings revealed that non-response could best be predicted at 4 weeks as in some other previous studies. The question of which time point for early prediction of response could be best predicted in schizophrenia patients needs to be further addressed in subsequent studies with larger sample size.

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Early response or nonresponse at week 2 and week 3 predict ultimate response or nonresponse in adolescents with schizophrenia treated with olanzapine: results from a 6-week randomized, placebo-controlled trial

Cited by 20 publications

References 48 publications

Early predictors of poor treatment response in patients with schizophrenia treated with atypical antipsychotics

Early predictors of poor treatment response in patients with schizophrenia treated with atypical antipsychotics

Time to Initiation of Clozapine Treatment in Children and Adolescents with Early-Onset Schizophrenia

Prediction of Response to Antipsychotic Drugs in Schizophrenia Patients within the Early Phase of Treatment

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