Pimavanserin for the treatment of Parkinson's disease psychosis: number needed to treat, number needed to harm, and likelihood to be helped or harmed

CNS Spectr. 2018 Jun;23(3):228-238. doi: 10.1017/S1092852917000736. Epub 2017 Nov 3.

Abstract

Objective: Our aim was to describe the efficacy and tolerability of pimavanserin, a highly selective serotonin 5-HT2A receptor inverse agonist/antagonist indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP), using the metrics of number needed to treat (NNT) and number needed to harm (NNH).

Methods: Categorical efficacy and tolerability data were extracted from the clinical trial databases of the double-blind placebo-controlled studies of pimavanserin in persons with PDP. NNT and NNH values were calculated with their respective 95% confidence intervals. The likelihood to be helped or harmed (LHH) was then calculated contrasting therapeutic response versus discontinuation because of an adverse event.

Results: NNT values for pimavanserin 34 mg/d versus placebo for several definitions of clinical response are 10, and/or are not statistically significant, and/or show an advantage for pimavanserin over placebo (such as for postural hypotension). In terms of LHH, pimavanserin 34 mg/d is about five times more likely to result in clinical response (as measured by a ≥3 point decrease from baseline on the Scale for the Assessment of Positive Symptoms adapted for Parkinson's disease) versus discontinuation due to an adverse event.

Conclusions: Using the metrics of NNT, NNH, and LHH, pimavanserin 34 mg/d for the treatment of PDP appears to have a compelling benefit/risk profile.

Keywords: Efficacy; Parkinson’s disease psychosis; number needed to harm; number needed to treat; pimavanserin; tolerability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Clinical Trials as Topic / methods*
  • Clinical Trials as Topic / standards
  • Humans
  • Numbers Needed To Treat*
  • Parkinson Disease / complications
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / psychology
  • Piperidines / administration & dosage
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Psychotic Disorders / drug therapy*
  • Psychotic Disorders / etiology
  • Serotonin 5-HT2 Receptor Antagonists / administration & dosage
  • Serotonin 5-HT2 Receptor Antagonists / adverse effects
  • Serotonin 5-HT2 Receptor Antagonists / therapeutic use*
  • Urea / administration & dosage
  • Urea / adverse effects
  • Urea / analogs & derivatives*
  • Urea / therapeutic use

Substances

  • Piperidines
  • Serotonin 5-HT2 Receptor Antagonists
  • Urea
  • pimavanserin