Pimavanserin -induced decreased appetite and weight loss: A case report

Dear Editor,

Pimavanserin (ACP-103, PMV) is a selective inverse agonist of the 5-hydroxytryptamine 2A (5-HT2A) receptor and is used to treat patients with Parkinson’s disease psychosis (PDP). Clinical trials (Phase II and III) for PMV suggest that for the treatment of PDP, PMV is safe and efficacious and offers a significant reduction in hallucinations and delusions without affecting motor functions. Since Dopamine D2 receptor antagonists like quetiapine and clozapine can worsen motor dysfunction and present an increased risk of mortality in elderly patients with dementia-related psychosis DRP,[1] PMV is currently also being investigated for (DRP),[2] such as in Alzheimer’s and Lewy Body dementia. A trial found that patients with DRP, who benefitted from PMV had a lower risk of relapse if they continued with the drug than if they discontinued it. The trial was however stopped early for efficacy.[3] Two controlled studies have suggested PMV as a potential drug for the treatment of hallucinations in dementia.[4]

A comprehensive analysis of the adverse effects of PMV has identified major categories of adverse effects such as hallucination, death, product dose omission issue, and confusional state. Also, new potential adverse effects were identified, which affected sleep, cognition, and behavior among others.[5] There is literature available on the effect of PMV on cognitive and motor functions. PMV is generally considered safe in these areas.[6] In a study it was found that at week 12, mean change in body weight was −0·7 kg (SE 0·66) with pimavanserin and −0·1 kg (0·28) with placebo.[7]

But currently, no literature is available on the duration and reversibility of the decreased appetite and acute weight loss side effects of PMV.

In this case report, we discuss one such case of acute weight loss secondary to short-term PMV therapy.

Mr SJ, an 80-year-old Indian male, widower, and civil engineer, belonging to a nuclear family of higher socioeconomic status, living alone, exhibited signs of Lewy Body dementia (LBD). The patient’s Addenbrooke’s Cognitive Examination (ACE-III) score was 69, indicating mild cognitive impairment. He was experiencing effects of cognitive decline such as memory problems, and executive function problems related to planning and decision making. He was also experiencing Parkinsonism-like features such as slow movements, rigidity, and mild tremors. He had also started visually hallucinating, seeing people in his house that did not exist, often asking them to leave his house. He also experienced symptoms of depression. However, his baseline investigations (MRI brain - No acute intracranial abnormalities and age appropriate involutional changes, LFT, RFT, T3, T4, TSH, CBC, B12, Vit D3 and were normal) autoimmune encephalitis panel for NMDA, AMPA, GABA B AND LGi 1 antibody were negative and he weighed 65 kg.

The patient was started on tablet donepezil 5 mg. For the hallucinations, an antipsychotic also needed to be prescribed. Since he exhibited symptoms of mild tremors, starting him on dopamine antagonist antipsychotics like olanzapine, or risperidone was not considered advisable. He was hence started on tablet PMV 34 mg, once a day. He was on the same dosage for 20 days. Within 7 days, the visual hallucinations abated and depression symptoms lessened. But his appetite decreased significantly and he started eating less than usual. He was also experiencing constipation and difficulty in having a bowel movement. By the end of the twentieth day, the patient’s weight had fallen to 62 kg. We suspected that either donepezil or PMV could be contributing to the acute weight loss but we found less literature indicating that donepezil could be the cause. Hence, PMV was stopped. Over the next 6 weeks, the patient showed significant improvement in appetite, and reduction of constipation and there was no more weight loss noted after the PMV was stopped.

Despite showing results in reduction of hallucinations, we were compelled to stop PMV for the patient because of decreased appetite leading to acute weight loss. A low dose of second-generation antipsychotic, Olanzapine (2.5 mg) was started. The hallucinations continued to remain absent and the patient experienced better appetite. Naranjo Adverse Drug Reaction Probability Scale score was six, which suggests a probable adverse drug reaction. Score from 5 to 8 suggest probable link and score more than nine suggests definite adverse reaction.[8]

This case report hence suggests that regular weight monitoring is necessary with PMV because of the acute weight loss observed within a short span of time.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.