We independently inspected citations and, where possible abstracts; ordered papers for re-inspection and quality assessment and independently extracted data. For homogeneous dichotomous data, we calculated the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) or number needed to harm (NNH) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We inspected all data for heterogeneity.
MAIN RESULTS: Currently the review includes three studies with a total of 1,104 participants. One was a medium term (eight weeks) placebo controlled study that examined three different doses of
sertindole (8, 12 and 20mg/day). The remaining two studies compared the use of
sertindole with
haloperidol (10mg/day). One was a short term study (six weeks) that looked at four different doses of
sertindole (8, 16, 20, 24mg/day) and the other was a long term study (one year) that evaluated the use of
sertindole 24mg/day in participants attending outpatients. We excluded two large important studies because they did not report any usable data. (Both had greater than 50% loss to follow-up and data on 'leaving the study early' was inadequately reported).
SERTINDOLE VERSUS PLACEBO:
Sertindole at 20mg/day was found to be more effective than placebo in terms of BPRS total scores (1 study, n=78, MD 6.2, CI -11.8 to -0.6) and CGI total end point scores (1 study, n=78, MD -0.9, CI -1.6 to -0.2). A marginally statistically significantly greater number of participants that were treated with 20 mg of
sertindole were reported to have been 'very much improved' as compared to those taking placebo (1 study, n=102, RR 7.6, CI 1.0 to 57.9, NNT 7.9, CI 4.3 to 41.1). There was no statistically significant difference between
sertindole at 8 or 12 mg/day and placebo for these three outcome measures. There were no statistically significant differences between
sertindole (8, 12 or 20 mg) and placebo for the incidence of extrapyramidal symptoms, extrapyramidal related events or use of medication to avoid extrapyramidal symptoms. There were no statistically significant differences found between
sertindole and placebo for the
movement disorders akathisia,
cogwheel rigidity, hypertonia and
tremor or
somnolence. At eight weeks a statistically significant difference between placebo and all
sertindole groups (8, 12 and 20 mg) for mean change from baseline in the QT and QTc intervals were observed (p values and SD were not reported). There was a statistically significant greater mean
weight gain among participants taking
sertindole (20 mg, mean
weight gain of 3.3 kg) as compared to placebo (mean
weight gain of 0.8 kg; p<0.05).
SERTINDOLE VERSUS
HALOPERIDOL: At one year, a greater number of participants who were treated with
haloperidol as compared to
sertindole (24mg/day) were leaving the study early due to any reason (1 study, n=282, RR 0.6, CI 0.4 to 1.0, NNH 8.8, CI 4.7 to 74.0) or non-compliance (1 study, n=282, RR 0.2, CI 0.0 to 0.7, NNH 12.8, CI 7.7 to 37.8). However, at six weeks, there was no statistically significant difference between
sertindole (at 8, 16, 20, or 24mg) and
haloperidol for this latter outcome. The incidence of EPS was higher among those treated with
haloperidol than
sertindole at 8, 16, 20 or 24mg/day (8mg: 1 study, n=245, RR 0.1, CI 0.0 to 0.7, NNH 11.4, CI 7.1 to 29.8; 16mg: 1 study, n=252, RR 0.3, CI 0.1 to 1.0, NNH 15.5, CI 8.0 to 217.9; and 20mg: 1 study, n=253, RR 0.2, CI 0.1 to 0.8, NNH 13.7, CI 7.7 to 68.3; 24mg: 2 studies, n=524, RR 0.6, CI 0.4 to 0.8, NNH 8.7, CI 5.4 to 23.0). More participants treated with
haloperidol experienced
akathisia,
tremor and hypertonia than those treated with
sertindole (
Akathisia - 8mg: 1 study, n=245, RR 0.2, CI 0.1 to 0.5, NNH 6.0, CI 4.1 to 11.2; 16mg: 1 study, n=252, RR 0.1, CI 0.0 to 0.3, NNH 5.4, CI 3.9 9.0; 20mg: 1 study, n=253, RR 0.3, CI 0.2 to 0.7, NNH 7.3, CI 4.6 to 17.9; 24mg: 2 studies, n=524, RR 0.5, CI 0.3 to 0.7, NNH 8.6, CI 5.6 to 18.3.
Tremor - 8mg: 1 study, n=245, RR 0.3, CI 0.1 to 0.7, NNH 8.5, CI 5.2 to 24.0; 16mg: 1 study, n=252, RR 0.2, CI 0.1 to 0.5, NNH 7.3, 4.8 to 15.6; 20mg: 1 study, n=253, RR 0.2, CI 0.1 to 0.6, NNH 7.8, CI 4.9 to 18.1; 24mg: 2 studies, n=524, RR 0.4, CI 0.2 to 0.6, NNH 8.2, CI 5.6 to 15.3. For Hypertonic - 24mg: 2 studies, n=524, RR 0.5, CI 0.3 to 0.8, NNH 12.4, CI 7.5 to 35.0; for
sertindole 8, 16 and 20mg there was no statistically significant differences between the treatment groups). One study reported that at six weeks, there was a statistically significant greater increase from baseline to final value in mean QTc interval in the
sertindole 16, 20 and 24mg groups (20, 26, and 24msec, respectively) than in the
haloperidol group (0msec; p value was not reported), but no SD or any other measure of variance for the effect sizes were reported. For one long term study only one participant from the
sertindole group (24mg) had a QT interval that exceeded 500msec (1 study, n=282, RR 3.0 CI 0.1 to 73.0), but 11participants treated with
Sertindole had QTc intervals of at least 500msec, compared to none in the
haloperidol treated group (1 study, n=282, RR 23.0, CI 1.4 to 386.6, NNH 12.8, CI 8.2 to 29.6). At six weeks, fewer participants treated with
sertindole at 8mg or 24mg were affected by
somnolence than those treated with
haloperidol (
sertindole 8mg: 1 study, n=245, RR 0.1, CI 0.0 to 0.7, NNH 11.4, CI 7.1 to 29.8; 24mg: 2 studies, n=524, RR 0.6, CI 0.4 to 1.0, NNH 14.8, CI 7.7 to 205.2). The incidence of
rhinitis was found to be statistically significantly higher among those taking
sertindole at 16 or 24mg as compared to
haloperidol (16mg: 1 study, n=252, RR 10.8, CI 1.4 to 82.6, NNH 12.7, CI 7.7 to 36.7; 24mg: 2 studies, n= 524, RR 2.1, CI 1.4 to 3.1, NNH 8.7, CI 5.6 to 18.6). At one year, 33 participants treated with
sertindole (24mg) had experienced the sexual adverse event of decreased ejaculatory volume, compared with six participants treated with
haloperidol. However the number of included male participants was not reported and therefore the RR could not be calculated. At one year, more participants taking
sertindole (24mg/day) had put on weight compared to those taking
haloperidol (1 study, n=282, RR 6.3, CI 1.9 to 20.9, NNH 8.8, CI 5.7 to 19.1). At six weeks, all of the
sertindole groups showed an increase in
body weight from baseline to final evaluation ranging from 1.3kg to 1.9kg, all of which represented a statistically significantly different weight change than that recorded for the
haloperidol treatment group (-0.1Kg). However, the actual
weight gain for each
sertindole dosage group was not reported and no SD or any other measure of variance was given.
AUTHORS' CONCLUSIONS: