Movement disorders Parkinson's disease PD neuropsychiatry

Is lumateperone good for psychosis in Parkinson disease?

Lumateperone is a new drug recently approved by the FDA for treatment of schizophrenia. The key clinical trial was just published and includes data on motor side effects of the drug. The sponsor, Intra-Cellular Therapies, Inc., may have data on use in Parkinson disease (PD), but I don’t think any of it is public. So here’s what I glean from the study report.

  1. This was done in people with schizophrenia, mean age 42 years (range, 18-60). Obviously a different population.
  2. A neurological exam was done at each visit. Then again, the sites may have differed in the sensitivity of the examiner to motor signs.
  3. Dystonia, akathisia, parkinsonism and TD were prospectively assessed at each visit using standard rating scales. There was little difference between drug and placebo groups (see eTable 8 in Supplement 2 to the paper cited below).
  4. Rescue drugs (benztropine and propranolol) were available for dystonia, akathisia, or parkinsonism, and were rarely used (see eTable 9).
  5. Akathisia, dystonia or dyskinesia were noted as a treatment-emergent adverse event in only 6 of 150 patients assigned to the 42mg/d effective dose (see eTable 7).
  6. A prior PET study with this drug suggested that at effective doses it occupies only about 40% of dopamine D2 receptors, much lower than for most antipsychotics. I haven’t looked up this paper yet to compare doses, though.

Summary: Lumateperone looks really good as far as motor side effects. These data are better than I would expect for most antipsychotics. But until it is tried in PD it is hard to say. It may be worth a try in patients who are hospitalized for psychosis, or who have failed pimavanserin and/or clozapine (ziprasidone may also be an option in those cases).

Patients treated with a lower dose (28mg rather than 42mg) had only marginal improvement in schizophrenia, and a higher dose (84mg) was not effective in a previous study. So 42 or possibly 28mg may be the place to start for PD. Then again, clozapine is usually dosed at 300-800mg/d in schizophrenia, but at 12.5-150mg/d in PD. So if it’s not tolerated in PD, a lower dose may be very reasonable.

Reference: Correll CU, Davis RE, Weingart M, et al. Efficacy and Safety of Lumateperone for Treatment of Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. Published online January 08, 2020. doi:10.1001/jamapsychiatry.2019.4379

This post is not meant to provide treatment advice to any patient. Individual circumstances vary and your physician is better placed to identify good treatment choices.

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