No Response to Lurasidone at 2 Weeks? Study Suggests Dose Escalation May Help

Despite the fact that early nonresponse to antipsychotic therapy in patients with schizophrenia is known to predict future poor response, there is limited evidence available to guide clinicians for addressing early nonresponse in this patient population. A study in the Journal of Clinical Psychiatry that examined nonresponse to a standard dose of lurasidone at two weeks suggests that escalating the dose of the medication early may lead to symptom improvements.

Antony Loebel, M.D., of Sunovion Pharmaceuticals Inc., and colleagues randomly assigned patients with acute schizophrenia (Positive and Negative Syndrome Scale [PANSS] total score equal to or greater than 80) to lurasidone 80 mg/d (n=199) or placebo (n=112) for two weeks. After two weeks of treatment with lurasidone 80 mg/d, the researchers classified 98 patients (49.5%) as early nonresponders (less than 20% improvement in PANSS total score) and re-randomized these patients to either continue treatment with lurasidone at 80 mg/d or lurasidone at 160 mg/d. 

In patients classified as early nonresponders at week 2, mean change from week 2 to week 6 in PANSS total score was significantly greater for patients whose lurasidone dose was increased to 160 mg/d compared with that for patients who continued receiving 80 mg/d (-16.6 versus -8.9). While a comparable magnitude of improvement was observed in Clinical Global Impression-Severity (CGI-S) score from week 2 to week 6 for early nonresponders re-randomized to lurasidone 160 mg/d versus 80 mg/d, the difference was not statistically significant. Treatment response (defined as equal or greater than 20% decrease in PANSS total score from study baseline to week 6) was demonstrated by 74.4% and 59.6% of early nonresponders re-randomized to lurasidone 160 mg/d and 80 mg/d, respectively. 

Early nonresponders whose dose was increased to lurasidone 160 mg/d reported a greater incidence of anxiety, abdominal discomfort, akathisia, insomnia, and somnolence compared with patients who continued on lurasidone 80 mg/d.

“[T]he increased probability of response in early nonresponders after dose escalation to lurasidone 160 mg/d should be considered in the context of the risk-versus-benefit findings associated with this strategy,” the authors wrote. “These considerations include a modest increase in the frequency of certain adverse events and the clinical need to enhance the rate of response.”

William Carpenter, M.D., a professor of psychiatry at the University of Maryland School of Medicine and an expert on schizophrenia, told Psychiatric News that “the initial response predicting later outcome has been documented in several datasets, but the dose escalation benefit observed with lurasidone should not be generalized to other antipsychotic medications, where adverse effects may outweigh benefit. It is natural for clinicians to seek new options if you don't see a treatment response at two weeks, but there is scant evidence supporting common practices such as dose increase or addition of another drug.”

Added Carpenter, who was not involved in the study, “Clinicians who prescribe lurasidone should also consider if the real message of these findings is that they should start patients at 160 mg/day. And, if so, should the higher dose be reduced once remission is achieved?” 

This study was sponsored by Sunovion Pharmaceuticals Inc.