General Information

Nuplazid (pimavanserin) is an atypical antipsychotic.

Nuplazid is specifically indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease.

Nuplazid is supplied as tablets and capsules for oral administration. The recommended dose is 34 mg, taken orally as two 17 mg tablets once daily, without titration. The tablets can be taken with or without food.

Mechanism of Action

The mechanism of action of pimavanserin in the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis is unclear. However, the effect of pimavanserin could be mediated through a combination of inverse agonist and antagonist activity at serotonin 5-HT2A receptors and to a lesser extent at serotonin 5-HT2C receptors.

Side Effects

Adverse effects associated with the use of Nuplazid may include, but are  not limited to, the following:

• peripheral edema
• confusional state

Nuplazid comes with the following Black Box Warning: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Nuplazid is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson’s disease psychosis.

Clinical Trial Results

The FDA approval of Nuplazid was based on a 6-week, randomized, placebo-controlled, parallel-group study. In this outpatient study, 199 patients were randomized in a 1:1 ratio to Nuplazid 34 mg or placebo once daily. Subjects (male or female and aged 40 years or older) had a diagnosis of Parkinson’s disease (PD) established at least 1 year prior to study entry and had psychotic symptoms (hallucinations and/or delusions) that started after the PD diagnosis and that were severe and frequent enough to warrant treatment with an antipsychotic. At entry, subjects were required to have a Mini-Mental State Examination (MMSE) score ≥21 and to be able to self-report symptoms. The PD-adapted Scale for the Assessment of Positive Symptoms (SAPS-PD) was used to evaluate the efficacy of Nuplazid. A negative change in score indicates improvement. Primary efficacy was evaluated based on change from baseline to Week 6 in SAPS-PD total score. Nuplazid 34 mg was statistically significantly superior to placebo in decreasing the frequency and/or severity of hallucinations and delusions in patients with PDP as measured by central, independent, and blinded raters using the SAPS-PD scale. An effect was seen on both the hallucinations and delusions components of the SAPS-PD.