The most common adverse events were somnolence, insomnia, and headache in the directs-witch group (all 11%), and somnolence (15%), headache (9%), insomnia (7%), and increased appetite (7%) in the cross-titration group. Differences in these percentages were not statistically significant.
EPS and akathisia improved significantly in both groups (p< 0.01) after switching to olanzapine. Thirteen (24%) patients in the direct-switch group and 17 (32%) in the cross-titration taper group required at least one dose of benztropine. Use of concomitant medications was similar.
Quetiapine can be abruptly discontinued with minimal risk of adverse events when initiating another antipsychotic.
Cutler et al6 switched 50 stable patients who had been treated with risperidone, thioridazine, haloperidol, or haloperidol plus benztropine. The original antipsychotics were abruptly discontinued, and quetiapine was initiated in a doseescalating fashion and then maintained at 300 mg/d for 12 days. After that, quetiapine was abruptly discontinued and patients were assessed for side effects, including EPS.
Most patients’ BPRS or CGI-Severity of Illness scores did not change significantly. Two patients (4%) experienced psychotic relapse during the switch. The authors speculated that these relapses might have been related to subtherapeutic quetiapine dosing. Transient nausea and vomiting were reported after quetiapine was discontinued.
Ziprasidone. When switching from another antipsychotic to ziprasidone, all three strategies appear well tolerated and maintain symptom control.
Using randomized, open-label trials, Weiden et al7 investigated strategies for switching patients to ziprasidone from olanzapine, risperidone, and traditional antipsychotics. All participants were diagnosed with schizophrenia or schizoaffective disorder and had experienced partial or inadequate response or side effects with their original antipsychotics.
Patients were assigned to one of three switching strategies:
- abruptly discontinue the initial antipsychotic
- decrease the initial antipsychotic’s dosage by 50% for 1 week, then discontinue it
- gradually taper the initial antipsychotic, so that subjects received 100% for 3 days of ziprasidone treatment, 50% for the next 4 days, and none thereafter.
For all three strategies, ziprasidone was started at 80 mg/d for 2 days, with dosing adjusted as needed to 40 to 160 mg/d.
All patients’ total score and positive and negative PANSS subscale scores improved significantly (p<0.01) across 6 weeks, although these data represent symptom changes after switching to ziprasidone. No efficacy or safety data were reported during switching. The authors concluded that patients could switch successfully to ziprasidone over a relatively short period using a variety of methods.
In another study, Stip8 switched 54 patients to ziprasidone from haloperidol. All received ziprasidone, 40 mg bid for 2 days and then 80 mg bid. Haloperidol was discontinued:
- immediately on day 1
- after the dosage was decreased by 50% for 7 days
- or after continuing the full dosage for 2 days, then taking 50% of the initial dosage for 5 days.
All patients maintained symptom control while switching, and 40 of 54 completed the trial. Among responders, BPRS and CGI scores improved significantly across 6 weeks, and EPS improved as expected.
Aripiprazole. Direct-switch and cross-titration tapering methods appear to be effective and welltolerated when switching stable patients to aripiprazole.
In an 8-week, randomized, open-label trial, Casey et al9 switched 311 outpatients with schizophrenia or schizoaffective disorder to aripiprazole. The patients—who had been taking stable dosages of haloperidol, chlorpromazine, risperidone, or olanzapine for at least 1 month—were randomly assigned to three groups:
- group 1 immediately discontinued the previous antipsychotic and started aripiprazole, 30 mg/d
- group 2 started aripiprazole, 30 mg/d, and discontinued the previous antipsychotic across 2 weeks
- group 3 started aripiprazole (10 mg/d in week 1, 20 mg/d in week 2, and 30 mg/d in week 3) and tapered the previous antipsychotic (50% less in week 1, another 50% less in week 2, then discontinued).
Investigators assessed treatment efficacy using the PANSS and CGI at baseline and weeks 4 and 8. They questioned patients about adverse events at each follow-up visit.
Nearly three-fourths (72%) of patients completed the trial. Discontinuation rates were 31% in group 1, 34% in group 2, and 19% in group 3. Efficacy, safety, tolerability, and incidence of discontinuation because of worsening psychosis were comparable across groups.
Similar percentages of patients in each group reported one or more adverse event (89%, 89%, and 81% for groups 1, 2, and 3, respectively). Most adverse events were described as mild to moderate. Insomnia was reported most frequently. Other adverse effects that occurred in >10% of subjects included nausea, akathisia, anxiety, psychosis, headache (groups 2 and 3), somnolence, lightheadedness (groups 1 and 2) vomiting (group 2 only), agitation (group 3 only), and diarrhea (group 2 only).
Seven patients were hospitalized for serious adverse events—usually worsening psychosis. Hospitalization rates were comparable among the three groups.