Treatment with Nuplazid (pimavanserin), approved in the U.S. for treating hallucinations and delusions associated with Parkinson’s psychosis, eased depression and sleep problems in patients with Parkinson’s, according to results from a Phase 2 clinical trial.
The research, “Open-Label Study of Pimavanserin Patients With Comorbid Parkinson’s Disease and Depression,” was presented at the 2019 International Congress of Parkinson’s Disease and Movement Disorders in Nice, France.
Depression is one of the most frequent non-motor symptoms of Parkinson’s. While its severity and duration typically increase with disease progression, easing depression has been linked with greater quality of life and less disability.
An eight-week, open-label, study (NCT03482882) assessed Acadia Pharmaceuticals’ Nuplazid either as a stand-alone therapy, or as an add-on to a selective serotonin reuptake inhibitor (SSRI, a type of antidepressant) or a selective norepinephrine reuptake inhibitor (SNRI) for Parkinson’s patients with depressive symptoms. The 47 participants, all 50 or older, received two 17 mg oral tablets per day of Nuplazid.
Nuplazid is a selective serotonin inverse agonist that targets serotonin receptors called 5HT2A receptors. Inverse agonists bind to the same receptors as agonists, but induce the opposite pharmacological response. Serotonin receptors are found throughout the nervous system. Specifically, 5HT2A has been associated with mental disorders such as depression and epilepsy.
The results found significant benefits as early as week 2 assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17) — the study’s primary goal. At week 8, 60% of the participants showed an improvement of at least 50% on the HAMD-17 score, with 44.4% of patients reaching remission (HAMD-17 score up to 7).
The study also showed improvements on the Clinical Global Impression-Severity scale (a measure of disease severity) and the Clinical Global Impression-Improvement — a 0.5 lower score from week 2 to week 8, as rated by clinicians.
Sleep measures, namely the SCOPA-nighttime sleep and SCOPA-daytime sleepiness scales, also revealed benefits from week 4 to week 8. Likewise, the SCOPA-Global Sleep Quality scale showed significant improvements comparing week 8 to baseline.
“Results of this open-label study suggest that pimavanserin may be a potential treatment to be further investigated for depression associated with Parkinson’s,” Gus Alva, MD, a co-author of the study, and founder and medical director of ATP Clinical Research, said in a press release.
Treatment with Nuplazid was well-tolerated, with treatment emergent adverse events (TEAE) being in line with other studies of this therapy. Reported TEAEs included falls (8.5%), nausea (6.4%), diarrhea (4.3%), edema, or swelling (4.3%), skin abrasion (4.3%), and urinary tract infection (4%).
“Pimavanserin [Nuplazid] as adjunctive or monotherapy is associated with early sustained improvement of depressive symptoms in patients with [Parkinson’s] and is well tolerated,” the scientists wrote.
“We are pleased with the exploratory study results which show a positive treatment effect with pimavanserin [Nuplazid] for depression in patients with Parkinson’s,” said Serge Stankovic, MD, Acadia’s president.
Stankovic commented that the results are consistent with those of the 10-week CLARITY Phase 2 study (NCT03018340). Using Nuplazid as an add-on led to improved HAMD-17 scores, while also easing disability and sleepiness, and improving sexual function in patients with major depressive disorder with inadequate response to standard SSRI/SNRI treatments.
Nuplazid is currently being tested in two six-week Phase 3 studies named CLARITY-2 (NCT03968159) and CLARITY-3 (NCT03999918), each with approximately 280 patients. Patients who complete these trials will be able to participate in a 52-week open-label extension study (NCT04000009) to assess long-term safety and tolerability. These three studies are currently enrolling. (For more information, follow the links on the NCT identifiers.)
“We are committed to continued research for pimavanserin [Nuplazis] to address unmet medical needs in central nervous system disorders, including our ongoing Phase 3 clinical program in major depressive disorder,” Stankovic said.