A double-blind, randomized study comparing the efficacy and safety of sertindole
and risperidone in patients with treatment-resistant schizophrenia.
Author(s): Kane JM, Potkin SG, Daniel DG, Buckley PF.
Affiliation(s): Department of Psychiatry, The Zucker Hillside Hospital, 75-59 263rd St, Glen
Oaks, NY 11004, USA. psychiatry@lij.edu
Publication date & source: 2011, J Clin Psychiatry. , 72(2):194-204
OBJECTIVE: The comparative efficacy of second-generation antipsychotics has yet
to be fully elucidated in patients with treatment-resistant schizophrenia. The
objective of this study was to examine the efficacy and safety of sertindole,
compared to risperidone, in this patient population.
METHOD: In this multicenter, phase 3, randomized, double-blind, parallel-group
study, only patients with DSM-IV schizophrenia who had failed an adequate
antipsychotic treatment within the previous 6 months and who had not responded
positively to haloperidol during screening were eligible for enrollment. The
primary efficacy variable was change in Positive and Negative Syndrome Scale
(PANSS) from baseline to final assessment. Weekly assessments included the PANSS,
the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of
Negative Symptoms (SANS), and the Clinical Global Impressions (CGI) scale. The
study was conducted between June 1996 and April 1998.
RESULTS: Of the 321 patients randomly assigned to double-blind treatment, 217
patients completed the study (sertindole, n/n = 142/216 [66%]; risperidone, n/n =
75/105 [71%]). The main reason for withdrawal in both groups was ineffective
therapy. The between-group difference in PANSS total score was not statistically
significant and both groups showed improvement, with mean changes of -18.6 in the
sertindole group and -20.9 in the risperidone group based on observed cases and
-12.0 and -19.0, respectively, based on the last-observation-carried-forward
method for inputing missing data. There were no statistically significant
differences between the groups in any of the secondary end points: PANSS positive
and negative subscales, CGI scores, BPRS total scores and positive symptom
subscale scores, and SANS total scores. Patients reported similar levels of
adverse events and treatment-emergent adverse events (TEAEs), except for
extrapyramidal syndrome-related TEAEs, which were more common in the
risperidone-treated group. Prolongation of the QTc interval was observed
significantly more frequently with sertindole treatment.
CONCLUSIONS: Sertindole and risperidone are effective and well-tolerated in
patients with treatment-resistant schizophrenia. Sertindole offers an alternative
treatment option for refractory patients in Europe given its good EPS profile,
favorable metabolic profile, and comparable efficacy to risperidone.
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