Low-Dose Ziprasidone in Combination with Sertraline for First-Episode Drug-Naïve Patients with Schizophrenia: a Randomized Controlled Trial.

Many patients with schizophrenia (SCZ) discontinue antipsychotics, frequently due to dose-related multiple and severe adverse effects. We hypothesized that a low-dose ziprasidone plus sertraline would reduce serious side effects without affecting treatment efficacy. Therefore, this clinical trial was designed to investigate the efficacy, safety, and tolerability of adding sertraline to ziprasidone in order to substantially reduce ziprasidone dose and potential side effects in first-episode and drug-naive (FEDN) patients with SCZ. This 24-week randomized, double-blinded, controlled clinical trial randomly allocated 452 FEDN SCZ patients to receive a usual dose of ziprasidone (control group) or half the dose of ziprasidone in combination with sertraline (ZS group). Treatment outcome included the Positive and Negative Syndrome Scale (PANSS), the Hamilton Depression Rating Scale (HAMD), CGI-Severity (CGI-S) and the Personal and Social Performance Scale (PSP) at baseline and weeks 2, 4, 8, 12, and 24. Repeated measures ANCOVA showed significant treatment by time interactions on the PANSS general psychopathology and total scores, as well as CGI-S, HAMD, and PSP scores (all p < 0.05). Furthermore, the ZS group had greater reductions in PANSS general psychopathology, total scores, HAMD, and CGI-S (all p < 0.05) and greater increases in the PSP total score (p < 0.01) than the control group. Importantly, adverse effects were lower in the ZS than control group. The reduction in PANSS, CGI-S, or HAMD scores was not correlated with the increase in PSP. Sex and duration of disease predicted PSP improvement from baseline to week 24 in the ZS group. Our FEDN patients with SCZ were effectively treated for their psychotic and depressive symptoms while experiencing significantly fewer adverse effects using half the usual ziprasidone dose when combined with sertraline. ClinicalTrials.gov, NCT04076371.