Pimavanserin Effective for Depression in Parkinson Disease, Major Depressive Disorder

Parkinsonian tremor
Researchers conducted an 8-week, open-label, single-arm study and a subsequent 2-stage, sequential, parallel comparison study to assess the use of pimavanserin among patients with Parkinson disease and major depressive disorder.
(HealthDay News) — A day after his inauguration, President Joe Biden plans to unveil a new, far-reaching pandemic response plan. He will also issue executive orders that aim to ramp up the production and distribution of COVID-19 tests and vaccines, make schools and travel safer, and help states fight the spread of COVID-19.

Biden has repeatedly promised to get 100 million COVID-19 shots into the arms of the American people by his 100th day in office; he has already directed the Federal Emergency Management Agency to begin constructing federally supported community vaccination centers, with the goal of having 100 centers in operation within the next month.

On Wednesday, Biden signed three executive orders relating to the COVID-19 pandemic shortly after taking office, The New York Times reported. They require mask wearing and social distancing on federal property and under other limited circumstances; halting the Trump administration’s withdrawal from the World Health Organization; and recreating a White House unit on global health security and biodefense that was disbanded a few years ago, the newspaper said.

For travel, the president plans to sign an executive order requiring masks to be worn in airports and international travelers to show proof of a negative COVID-19 test before boarding planes to the United States, The Times said.

The New York Times Article

Pimavanserin, a selective 5-HT2A receptor antagonist/inverse agonist, was reported to successfully treat depression among patients with Parkinson disease (PD) and major depressive disorder (MDD). These findings, from a pooled analysis of 2 trials, were presented during Psych Congress 2020 Virtual Experience, held online from September 11 to 13, 2020.

In an 8-week, open-label, single arm study, patients (N=47) with PD and depressive symptoms, as defined by a Hamilton Depression Rating Scale (HAMD-17) score ³15, were randomly assigned to receive pimavanserin 34 mg alone or in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). Participants were assessed by the HAMD-17, Clinical Global Impression-Severity scale (CGI-S), CGI-Improvement scale (CGI-I), EuroQol-5 Dimensions-5 Levels Proxy (EQ-5D-5L), and the Movement Disorder Society Unified PD Rating Scale Part III (MDS-UPDRS III).

In a 2-stage, sequential, parallel comparison study, patients (N=155) with MDD, as defined by a CGI-S score ³4 and a Montgomery-Åsberg Depression Rating Scale score >20, who were being treated with an SSRI or SNRI were randomly assigned in a 3:1 ratio to receive pimavanserin 34 mg in addition to their current medication or a placebo for 5 weeks. At week 5, placebo recipients and nonresponders were reassigned in a 1:1 ratio to receive treatment or placebo for 5 additional weeks. Patients were again assessed using the HAMD-17, CGI-S, CGI-I, and the Sheehan Disability Scale (SDS).

At baseline, patients with PD had symptoms of moderate depression (HAMD-17, 19.2; standard deviation [SD], 3.1). Clinical improvement in their depression was observed as early as 2 weeks following treatment initiation. Throughout the study duration patients in the monotherapy and dual therapy groups showed similar responses. At 8 weeks, the participants exhibited an overall improvement (least squared difference [LS], -10.8; SD, 0.63; 95% CI, -12.0 to -9.5; P <.0001), and 44.4% of participants reached clinical remission of their depression symptoms. Patients exhibited significant improvement in their CGI-S (P <.0001), EQ-5D-5L (P =.0068), and MDS-UPDRS III (P =.007) scores.

At baseline, patients with MDD had HAMD-17 scores of 22.8 (SD, 4.6) among the treatment group and 22.0 (SD, 4.2) among the placebo group. Patients in the treatment group had greater decreases in HAMD-17 scores (LS, -11.5; SD, 0.94 vs LS, -7.5; SD, 0.55; P =.0003). Similar to the observation among patients with PD, after 5 weeks of treatment 23.5% of the treatment group reached clinical remission. Patients in the treatment group reported significantly greater improvement in CGI-S (P =.0001), CGI-I (P =.001), and function (P =.0036) scores.

A limitation of this study was the low sample sizes, especially among patients with PD. Further studies with larger sample sizes are needed to confirm these findings.

The study authors concluded that pimavanserin was well tolerated, did not incur adverse effects with regard to motor skills or function, and significantly improved symptoms of depression among patients with PD and MDD. The similar response of participants in the open-label and the placebo-controlled studies was a strong indicator that pimavanserin had the potential to treat symptoms of depression.

Disclosure: An author of the study declared affiliations with industry. Please refer to the original abstract for a full list of disclosures.

(HealthDay News) — For patients with symptomatic, radiographically confirmed osteolysis undergoing revision total hip arthroplasty surgery, a single dose of denosumab results in a reduction in osteoclast numbers, according to a study published online Jan. 11 in The Lancet Rheumatology.

Mohit M. Mahatma, from the University of Sheffield in the United Kingdom, and colleagues conducted a phase 2 randomized, proof-of-concept superiority trial involving patients aged 30 years or older and scheduled for revision total hip arthroplasty surgery for symptomatic, radiographically confirmed osteolysis. Participants were randomly assigned to either subcutaneous denosumab or placebo. The between-group difference in osteoclast number per millimeter of bone surface of biopsies taken from the osteolytic membrane-bone interface at surgery eight weeks later was assessed as the primary outcome.

Ten patients in the denosumab group and 12 in the placebo group were assessed for the primary outcome. The researchers found that compared with the placebo group, in the denosumab group, there were 83 percent fewer osteoclasts at the osteolysis membrane-bone interface (median, 0.05 versus 0.30 per mm). There were no deaths or treatment-related serious adverse events reported.

“The results of this proof-of-concept clinical trial indicate that denosumab is effective at reducing bone resorption activity within osteolytic lesion tissue and is well tolerated within the limitations of the single dose used here,” the authors write.

The study was funded by Amgen. Amgen provided denosumab and placebo free of charge.

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DeKarske D, Jacobi L, Nunez R, et al. Depression in Parkinson’s disease: investigation of pimavanserin, a selective 5-HT2A receptor antagonist/inverse agonist. Presented at: Psych Congress 2020 Virtual Experience; September 10-13, 2020. Poster 131.

This article originally appeared on Psychiatry Advisor