Efficacy and tolerability of quetiapine versus haloperidol in first-episode schizophrenia: a randomized clinical trial

Abstract

BackgroundSchizophrenia is a chronic disease of global importance. The second-generation antipsychotic quetiapine has a favorable side-effect profile, however, its clinical effectiveness has been called into question when compared with first-generation antipsychotics such as haloperidol. This study evaluates the efficacy and tolerability of quetiapine versus haloperidol for first-episode schizophrenia in the outpatient setting.Methods156 adult patients with first-episode schizophrenia participated in an outpatient clinical trial and were randomized to quetiapine (200 mg/d; n = 78) or haloperidol (5 mg/d; n = 78). The study medications were titrated to a mean daily dose of 705 mg for quetiapeine and 14 mg for haloperidol. The patients were assessed at baseline, six weeks, and twelve weeks. The primary outcome measures were positive and negative scores of the Positive and Negative Syndrome Scale (PANSS). Secondary measures were Global Assessment of Functioning (GAF) scale for overall psychosocial functioning, and Simpson-Angus Scale (SAS) for extra-pyramidal symptoms.ResultsAt twelve weeks, the quetiapine group had a greater decrease in PANSS positive (18.9 vs. 15.3, p = 0.013) and negative scores (15.5 vs. 11.6, p = 0.012), however, haloperidol showed a greater decrease in general psychopathology score (23.8 vs. 27.7, p = 0.012). No significant difference between groups were found for total PANSS (58.3 vs. 54.8, p = 0.24) and GAF (45.7 vs. 46.2, p = 0.79).ANOVA identified significant group interactions on PANSS positive (F = 18.72, df = 1.6,52.4, p < 0.0001), negative (F = 5.20, df = 1.1,35.7, p < 0.0001), depression/anxiety (F = 106.49, df = 1.14,37.8, p < 0.0001), and total scores (F = 7.51, df = 1.4,45.6, p = 0.001).SAS (8.62 vs. 0.26, p < 0.0001) and adverse events of akathisia (78% vs. 0%, p = 0.000), parkinsonism (66.6% vs. 0%, p < 0.0001), and fatigue (84.6% vs. 66.6%, p = 0.009) were greater in haloperidol compared to quetiapine, whereas headache was more common in quetiapine treated patients (11.5% vs. 35.9%, p < 0.0001).ConclusionsQuetiapine has greater efficacy for positive and negative symptoms with less extra-pyramidal symptoms than haloperidol when used for first-episode schizophrenia in the outpatient setting.

Updating the Comparative Evidence on Second‐Generation Antipsychotic Use With Schizophrenia

“…We included a total of 278 RCTs (see flow diagram in the online supplement); one systematic review of 138 trials (N=47,189) ( 17 ) and 24 additional trials (N=6,672) ( 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ) for SGAs versus other SGAs, and one systematic review of 111 trials (N=118,503) ( 45 , 46 ) and five additional trials (N=1,055) ( 35 , 47 , 48 , 49 , 50 ) for FGAs versus SGAs. The two systematic reviews also included 33 cohort studies (N =652,505) ( 17 , 45 , 46 ).…”

“…All‐cause discontinuation of treatment was not reported in the systematic review of FGAs versus SGAs ( 45 ). However, withdrawals due to adverse events were significantly higher with haloperidol use compared with aripi‐prazole (eight RCTs, RR=1.25), olanzapine (24 RCTs, RR=1.89), risperidone (25 RCTs, RR=1.32), and ziprasidone (27 RCTs, RR=1.68) ( 35 , 45 , 47 , 48 , 49 ). There were no differences in withdrawal due to adverse events in comparisons of haloperidol and clozapine (five RCTs) or quetiapine (10 RCTs).…”

“…Results of a network meta-analysis (90 RCTs, N¼29,678) revealed significantly lower withdrawals because of adverse events with risperidone LAI than with clozapine (OR¼0.27, 95% CI¼0.10 to 0.71), lurasidone (OR¼0.39, 95% CI¼0. 18 (35,45,(47)(48)(49). There were no differences in withdrawal due to adverse events in comparisons of haloperidol and clozapine (five RCTs) or quetiapine (10 RCTs).…”

Superior effects of quetiapine compared with aripiprazole and iloperidone on MK-801-induced olfactory memory impairment in female mice

“…Recent clinical studies indicated that second generation atypical antipsychotic agents (clozapine, ziprasidone, quetiapine and olanzapine) improve cognitive impairment, whereas typical agents, such as haloperidol, exerted no effect (6,7). The cognitive tests of the atypical antipsychotics in preclinical studies demonstrate normal cognitive functions, which is in contrast to the classical antipsychotics.…”

Three Cases of Schizoaffective Disorder: Different Pharmacological Interventions

“…It seldom causes EPS and is a prolactin-sparing antipsychotic drug. It causes metabolic and cardiac adverse effects like risperidone [10]. The patient in case report 2 was treated with quetiapine, and the psychotic and affective symptoms were improved very much.…”