Lurasidone versus typical antipsychotics for schizophrenia

Antipsychotic drugs are the mainstay of treatment for schizophrenia. Even though several novel second-generation antipsychotics (i.e. lurasidone, iloperidone and cariprazine) have been approved in recent years, typical antipsychotics (e.g. chlorpromazine, haloperidol, and fluphenazine) remain a crucial therapeutic option for the condition around the world. Little is known about the relative risk-to-benefit ratio of the 'latest' second-generation antipsychotics compared to the typical agents of 'established stature'.

To systematically review the efficacy and safety of lurasidone versus typical antipsychotics for adults with schizophrenia or schizophrenia-related disorders.

We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials on 5 June 2019. We also ran an update search in CENTRAL, MEDLINE, Embase, and three additional databases as well as two trial registers and the US Food and Drug Administration database on 1 April 2024.

We searched for randomized controlled trials (RCTs) comparing lurasidonewith typical antipsychotic drugs (such as chlorpromazine, fluphenazine, haloperidol, loxapine, mesoridazine, molindone, perphenazine, thioridazine, thiothixene, zuclopenthixol) for adults with schizophrenia. No additional search restrictions were applied.

We followed standard Cochrane methodological procedures. We extracted information on participant characteristics, interventions, study outcomes, study design, trial methods, and funding sources. Two review authors independently extracted data and assessed the risk of bias. We assessed the certainty of evidence with GRADE for these key outcomes: change in mental state, death by suicide or natural cause, quality of life, total serious adverse events and severe adverse events (as defined by study authors).

We included two studies with a total of 308 individuals diagnosed with schizophrenia (220 men and 85 women). A total of 223 participants received lurasidone (20, 40, or 80 mg/day), and 82 received haloperidol (up to 10 mg/day) or perphenazine (up to 32 mg/day); three people did not receive any study medication. Both studies were performed in the US. The duration of the follow-up was four to six weeks. Death by suicide/natural causes and quality of life were not reported by the two included studies. The evidence is very uncertain about the effects of lurasidone on change in mental state: the Brief Psychiatric Rating Scale (BPRS) (MD 3.74, 95% CI 0.57 to 6.90; 1 RCT, 281 participants; very low-certainty evidence); and the Positive and Negative Syndrome Scale (PANSS) (MD 6.68, 95% CI 2.45 to 10.91; 1 RCT, 281 participants; very low-certainty evidence). The evidence is also very uncertain about the effects of lurasidone on total serious adverse events (RR 0.98, 95% CI 0.37 to 2.60; 2 RCTs, 303 participants; very low certainty of evidence) and on severe adverse events (RR 1.70, 95% CI 0.46 to 6.32; 1 RCT, 281 participants; very low certainty of evidence).

We are very uncertain about whether lurasidone offers benefits to the mental state, total serious adverse events, or severe adverse events when compared to typical antipsychotics for people with schizophrenia. The evidence included in this review is of very low certainty, derived from two small trials. Study limitations (risk of bias) and imprecise results impacted our confidence in the evidence. Furthermore, data on mortality (due to suicide or natural causes) or quality of life are unavailable. Further large-scale randomized studies are needed to provide clearer insights into the benefits and harms of lurasidone compared to typical antipsychotics for treating schizophrenia.