Improvement of sexual functioning during treatment of MDD with adjunctive pimavanserin: A secondary analysis

Abstract

Background: Sexual dysfunction is common among patients with major depressive disorder (MDD). In the CLARITY study, the safety and efficacy of adjunctive pimavanserin, an inverse agonist at 5-HT 2A receptors, were demonstrated when added to existing treatment for MDD. This analysis provides a detailed assessment of the effects of pimavanserin on sexual function from the CLARITY study. Methods: Patients with a diagnosis of MDD in a depressive episode, inadequate response to ongoing antidepressant therapy, and a Montgomery-Åsberg Depression Rating Scale total score >20 were randomized to pimavanserin 34 mg/day or placebo added to ongoing treatment with an immediate revision of all selective serotonin or serotonin-norepinephrine for 5 weeks (Stage 1), and nonresponders (<50% improvement from baseline in Hamilton Depression Rating Scale [HAMD-17]) were re-randomized for an additional 5 week (Stage 2). Effects of pimavanserin on the Massachusetts General Hospital Sexual Functioning Index (MGH-SFI) and HAMD-17 Item 14 (sexual interest) were examined. Results: Among 203 patients (51 on pimavanserin; 152 on placebo), pimavanserin demonstrated significant improvement from baseline to Week 5 on the MGH-SFI (least square [LS]mean difference −0.634, 95% confidence interval [CI] [−0.964, −0.304]; p = .0002; effect size [ES], Cohen's d: .614). Across Stages 1 and 2, the weighted LSmean difference was −0.468 (95% CI [−0.720, −0.216]; p = .0003) for pimavanserin versus placebo. Mean changes from baseline to Week 5 for MGH-SFI Items 1, 2, 3, and 5 and HAMD Item 14 were significantly (p < .05) greater with pimavanserin versus placebo. Conclusions: Adjunctive pimavanserin improved sexual function in patients with MDD. Adding pimavanserin to ongoing treatment for MDD may be especially useful for patients experiencing sexual dysfunction. K E Y W O R D S adjunctive, major depressive disorder, pimavanserin, sexual function

Evaluating pimavanserin as a treatment for psychiatric disorders: A pharmacological property in search of an indication

“…Sexual dysfunction is a common side effect of MAO inhibitors and selective serotonin uptake inhibitors (SSRI), and particularly problematic for women is the inability to have an orgasm. Pimavanserin augmentation of SSRI or serotonin and norepinephrine reuptake inhibitors (SNRI) in the CLARITY study had a substantial effect in improving sexual function in stage 1 among women [24]. As measured by the MGH-SFI, interest in sex, sexual arousal, ability to have an orgasm, and overall sexual satisfaction improved (p < 0.01, effect sizes of 0.56-0.75).…”

Spotlight on Pimavanserin Tartrate and Its Therapeutic Potential in the Treatment of Major Depressive Disorder: The Evidence to Date

“…LS mean (95% CI) = −0.47 (−0.72, −0.22), p=0.0003)] 15. Furthermore, the authors found significant improvement with pimavanserin vs placebo in the sexual functioning as assessed with the single item (14th) of HAMD 15. …”

“…35 Therefore, Freeman and colleagues undertook a secondary analysis of CLARITY data to evaluate the effect of pimavanserin on sexual functioning. 15…”

“…[10][11][12][13] Pimavanserin tartrate, hereafter referred to as pimavanserin, is one such drug that has been studied for improving depression and associated symptoms in patients with MDD who have responded inadequately to one or more courses of serotonergic antidepressant. [14][15][16] Approved by the Food and Drug Administration (FDA) for treatment of hallucinations and delusions associated with Parkinson's disease psychosis, 17 pimavanserin differs from other atypical antipsychotics in having no appreciable affinity for dopaminergic receptors and from selective serotonin reuptake inhibitors in having no appreciable affinity for serotonin transporter. 18 In this regard, it represents a new class of medications that selectively targets specific serotonin receptor subtype(s).…”

“…We then review the findings of a recently-completed phase 2 double-blind randomized placebo-controlled trial of pimavanserin and specifically discuss its utility in improving symptom domains such as sexual dysfunction, anxiety and irritability that are typically unaffected or even worsened by commonly used serotonergic antidepressants. 14,15,20 Finally, we discuss the top-line results in media from the sponsor for the phase 3 studies of adjunctive pimavanserin for patients with MDD. 21 is a small molecule (freebase molecular weight of 427.6 g/mol) 17 that specifically modulates serotoninergic neurotransmission as an inverse agonist/antagonist of the 5-hydroxytryptamine2A (5-HT 2A ) and 5-HT 2C (at higher doses) receptors.…”