Trajectories of response to treatment with atypical antipsychotic medication in patients with schizophrenia pooled from 6 double-blind, randomized clinical trials

• Published in: Schizophrenia research 2011-08, Vol.130 (1), p.11-19
• Main Authors: Stauffer, Virginia, Case, Michael, Kollack-Walker, Sara, Ascher-Svanum, Haya, Ball, Tamara, Kapur, Shitij, Kinon, Bruce J
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Antipsychotic Agents - therapeutic use; Antipsychotic drugs; Biological and medical sciences; Databases, Factual - statistics & numerical data; Double-Blind Method; Female; Follow-Up Studies; Growth mixture modeling; Heterogeneity; Humans; Male; Medical sciences; Middle Aged; Multicenter Studies as Topic; Neuropharmacology; Pharmacology. Drug treatments; Psychiatric Status Rating Scales; Psychiatry; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Randomized Controlled Trials as Topic; Response patterns; Schizophrenia; Schizophrenia - drug therapy; Time Factors; Treatment Outcome
• ISSN: 0920-9964; 1573-2509
• DOI: 10.1016/j.schres.2011.03.015

Abstract Research has identified distinct trajectories of antipsychotic response in patients with chronic schizophrenia in short-duration trials (~ 12 weeks). This post-hoc analysis identified trajectories in patients with chronic schizophrenia treated for ≤ 24 weeks. We pooled data from 1990 patients with chronic schizophrenia from 6 randomized, double-blind, olanzapine-comparator trials of atypical antipsychotics. Trajectory analysis identified homogeneous subpopulations within the larger heterogeneous population. Baseline demographics were compared between the identified latent classes. Five distinct response trajectories based on Positive and Negative Syndrome Scale (PANSS) Total score were identified: Dramatic Responders (n = 47/1990, 2.4%), severely-ill patients (PANSS = 124) with rapid and sustained improvement (51%) by Week 3; Partial Responders (n = 1802/1990, 90.6%), moderately-ill (PANSS = 90) with minimal improvement (21%) by Week 4, and little further improvement; Partial Responders-Unsustained (Late) (n = 32/1990, 1.6%), markedly-ill (PANSS = 95) with minimal initial improvement followed by worsening after Week 12; Partial Responders-Unsustained (Early) (n = 28/1990, 1.4%), markedly-ill (PANSS = 102) with minimal initial improvement followed by worsening after Week 8; and Delayed Responders (n = 81/1990, 4.1%), markedly-to-severely-ill (PANSS = 113) with minimal (11%) improvement at Week 8, but noticeable improvement thereafter (49%). Significant differences were noted for several baseline characteristics (p < .05) and discontinuation rates (46%–72%). Dramatic Responders were younger and more likely to be female and Hispanic with higher baseline illness severity. Analysis of antipsychotic response over 24 weeks in a large, pooled, heterogeneous population treated for schizophrenia revealed 5 distinct trajectories. Most patients had modest and sustained improvements during atypical antipsychotic treatment, regardless of their baseline illness severity, representing a partial response to currently available treatments.