Newer Treatments for Schizophrenia: Benefits and Drawbacks

New treatments for patients with schizophrenia may be on the horizon, according to research presented at the annual meeting of the American Psychiatric Association (APA) in San Francisco.¹ While some of these therapies may help treat the negative and cognitive symptoms of schizophrenia, a few are associated with QTc interval prolongation.

Although about 70% of patients with schizophrenia in the United States are treated with more than 1 therapy, fewer than a third are symptom-free and able to function, according to Adrian Preda, MD, associate professor of psychiatry and human behavior at the University of California, Irvine.

Steven Potkin, MD, professor of psychiatry at the University of California, Irvine, discussed 4 of the newest compounds that have either been recently approved for the treatment of schizophrenia or are in late-stage development. Each has been demonstrated to have no effect on weight gain or increases in lipid levels, he said.

The FDA recently approved iloperidone for the treatment of schizophrenia. However, this is considered to be a second- or third-line drug because patients treated with this drug have been shown to experience QTc interval prolongation, said Dr Potkin.

The benefit of this therapy is that physicians can determine who may best respond. Studies have identified 6 genetic markers that are associated with iloperidone effectiveness and safety. Patients with 0 to 2 markers have approximately a 15% clinical response to iloperidone treatment. Those with 3 markers have approximately a 40% likelihood of improvement, and those with 4 markersare approximately 60% likely to improve. Almost all patients with 5 or 6 markers were shown to respond to treatment. “Even if you don’t know anything about a patient, there is still about a 48% chance of a clinical response to treatment, according to Potkin.

Results from recent trials of treatment of acute psychotic exacerbation in patients with schizophrenia showed that iloperidone was more effective than placebo and comparable to risperidone.² In addition, the effects of iloperidone were similar to those of haloperidol in reducing symptoms of schizophrenia.³

Studies have shown that lurasidone may be appropriate for the treatment of cognitive impairment and depressive symptoms in patients with schizophrenia. Results of phase 3 clinical trials on treatment of schizophrenia were presented at the APA conference. In a 6-week, double-blind, placebo-controlled trial, patient symptoms were assessed using the Brief Psychiatric Rating Scale (BPRSd). Patients treated with lurasidone 80 mg daily had significant improvement compared with those who received placebo, based on results using the BPRSd (-8.9 vs -4.2; P = .012).⁴

Another therapy that has been shown to cause QTc interval prolongation is sertindole, which is not yet approved for the treatment of schizophrenia. An application for approval had originally been submitted to the FDA in 1998 but was withdrawn because of QTc-related concerns. However, the therapy is once again under review by the FDA, said Potkin. A recent study showed that patients with schizophrenia who were treated with sertindole had a lower risk of death by suicide than those treated with risperidone. However, these results were not statistically significant (P = .34).⁵

Asenapine, which has not yet been approved by the FDA for the treatment of schizophrenia, has been shown to be effective in previous studies, according to Dr Potkin. However, results of a study presented at the APA meeting showed that patients treated with asenapine did not experience any advantage over second-generation antipsychotics for negative symptoms of schizophrenia.⁶

References:

References

1. Potkin S, Harvey PD, Kalali AH, Preda A. Development of new agents for the treatment of schizophrenia. Presented at: the American Psychiatric Association Annual Meeting; May 16-21, 2009; San Francisco.
2. Hamilton J, Polymeropoulos M, Feeney J, et al. Efficacy of iloperidone is comparable to risperidone in a meta-analysis of a placebo and reperidone-controlled clinical trial for schizophrenia. Presented at: the American Psychiatric Association Annual Meeting; May 16-21, 2009; San Francisco. Abstract.
3. Feeney J, Wolfgang C, Polymeropoulos M, et al. The comparative efficacy of iloperidone and haloperidol across four short-term controlled trials. Presented at: the American Psychiatric Association Annual Meeting; May 16-21, 2009; San Francisco. Abstract.
4. Cuccuaro J, Loebel A, Silva R, et al. Efficacy and safety of lurasidone in phase 2/3 acute schizophrenia trials. Presented at: the American Psychiatric Association Annual Meeting; May 16-21, 2009; San Francisco. Abstract.
5. Croca MA, Lader MH, Mittoux A, et al. Suicide in a prospective cohort of patients with schizophrenia trated with sertindole or risperidone. Presented at: the American Psychiatric Association Annual Meeting; May 16-21, 2009; San Francisco. Abstract.
6. Schooler N. Long-term treatment with asenapine versus olanzapine in subjects with predominant, persistent negative symptoms of schizophrenia. Presented at: the American Psychiatric Association Annual Meeting; May 16-21, 2009; San Francisco.