April 14, 2023
I’m Dr. Diana Zuckerman, president of the National Center for Health Research. My doctorate is in clinical psychology with a post doc in epidemiology.
Our nonprofit think tank focuses on the safety and effectiveness of medical products and we do not accept funding from companies that make those products. So we have no conflicts of interest.
What do we know about atypical antipsychotics in general and Rexulti specifically?
- There’s a Black box warning of deaths and warnings about other serious side effects for dementia patients
- FDA says that Rexulti’s “effect on mortality appears to be consistent with the known risk with other antipsychotics in elderly patients with dementia.”
- And its “mechanism of action in the treatment of AAD is unclear”
Agitation on CMAI Total Score at 12 weeks
- Not significant for low dose (1 mg)
- Usually statistically significant at 2-3 mg
- No information after 12 weeks: Does efficacy improve or is it reduced?
BUT more important: the CMAI has 29 questions about symptoms and should not have been evaluated by total scores. Self-harm, kicking and screaming are more disruptive than repetitive questions or repetitious mannerisms. We need to know which specific behaviors were reduced compared to placebo – Table 14 of the FDA review shows that most symptoms are not aggressive. Is it worth the increased risk of dying to reduce non-aggressive behaviors?
Secondary endpoint: [CGI-S] Measures Severity of mental illness
- The differences for patients on Rexulti are not significant for 1 mg or 2 mg
- Differences are statistically significant for 2 and 3 mg groups combined
- But again, we have no information about whether efficacy improves or is reduced after 12 weeks.
More important: Why not measure quality of life instead of overall mental illness? That would be more meaningful for this study
Unmet need
- There is an unmet need for effective treatments of agitation, which is currently treated off label with other atypical antipsychotics. Is the safety or efficacy of Rexulti sufficiently superior to those options to warrant FDA approval for agitation?
- Is it appropriate to approve a long-term treatment based on only 12 weeks of randomized control trial data, for a drug that can be fatal in the long-term?
Patients deserve better
- Many family members have told us that atypical antipsychotics were a “chemical straight jacket” for their loved ones. Will family members be warned of all Rexulti’s risks? And what are the rebound risks for patients that go off Rexulti?
- Since the risks of death are higher for Rexulti in the randomized trial, compared to other antipsychotics that are NOT approved for dementia patients, don’t we need larger studies before FDA approves Rexulti for dementia patients with agitation?
- My Last point: Many families tell us they were not fully informed of the risks of atypical antipsychotics. In nursing homes, decisions are often made with minimal input from patients or family members. Realistically, if this drug is FDA approved for dementia patients it will be widely prescribed for dementia patients in nursing homes, and some will die as a result.