Clinical Edge

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Adjunctive pimavanserin improves sexual function in patients with MDD

Key clinical point: The addition of pimavanserin to ongoing treatment improves sexual function in patients with major depressive disorder (MDD).

Major finding: Pimavanserin vs. placebo significantly improved the Massachusetts General Hospital Sexual Functioning Index mean scores from baseline to week 5 (least square mean difference, −0.634; P = .0002). Item 14 scores (sexual interest) on the 17-item Hamilton Depression Rating Scale improved significantly with pimavanserin vs. placebo (P less than .05).

Study details: This secondary analysis of the CLARITY study included 203 patients with MDD randomly assigned to either pimavanserin (n = 51) or placebo (n = 152) in addition to their current treatment.

Disclosures: This study was funded by ACADIA Pharmaceuticals, Inc. Dr. Marlene Freeman: Investigator Initiated Trials/Research: Takeda, JayMac, Sage; Advisory boards: Otsuka, Alkermes, Janssen, Sage; Sunovion; Independent Data Safety and Monitoring Committee: Janssen (Johnson & Johnson); Medical Editing: GOED newsletter. Speaking/honoraria: U.S. Psychiatric Congress, Medscape. He is an employee of Massachusetts General Hospital.


“This study by Freeman et al. reviewed data from their study where pimavanserin, a novel antipsychotic approved for use in Parkinson’s disease related psychosis, was being used as an antidepressant augmentation treatment in major depressive disorder. This drug is a 5HT-2a receptor antagonist and inverse agonist mechanistically. Patients treated with this had improved sexual functioning either in that their lessened depression symptoms allowed better functioning or that pimavanserin may pharmacodynamically undo SSRI/SNRI drug induced sexual dysfunction as an antidote. Interestingly, the antidepressant nefazodone employs 5HT-2a antagonism and improves sexual functioning as well. The remaining sedating antidepressants (trazodone and mirtazapine) tend to show less sexual side effect generation compared to the SSRI and SNRI classes in regulatory trials. Mechanistically, it is felt that the SSRI and SNRIs by way of increasing synaptic serotonin levels robustly likely over stimulate 5HT-2A receptors causes sexual dysfunction at the level of the spinal cord in the descending serotonin pathways. In this manner, pimavanserin seems effective in lowering this stimulation and either avoids the onset of induced sexual dysfunction or possibly may improve it de novo.”

Thomas L. Schwartz, MD
Senior Associate Dean of Education, Interim Chair/Professor of Psychiatry
SUNY Upstate Medical University


Freeman MP et al. Depress Anxiety. 2020 Apr 17. doi: 10.1002/da.23017.