TY - JOUR
T1 - Spotlight on pimavanserin tartrate and its therapeutic potential in the treatment of major depressive disorder
T2 - The evidence to date
AU - Soogrim, Vicki
AU - Ruberto, Valerie L.
AU - Murrough, James
AU - Jha, Manish Kumar
N1 - Publisher Copyright:
© 2021 Soogrim et al.
PY - 2021
Y1 - 2021
N2 - Major depressive disorder (MDD) is widely prevalent and one of the leading causes of disability. Treatment outcomes remain suboptimal with 1 in 3 patients with MDD responding inadequately to commonly used antidepressants. Pimavanserin, an atypical anti-psychotic that modulates serotonergic neurotransmission by selectively binding to serotonin receptor (2A and 2C) subtypes and without dopaminergic activity, may have the potential as an adjunctive treatment for MDD. In a phase 2 trial (n=203), addition of pimavanserin, as compared to placebo, to stable treatment with antidepressants was associated with greater reduction in 17-item Hamilton Depression Rating Scale score [HAMD, least square means (95% confidence interval) of −1.7 (−0.03, −3.37), p=0.039]. Furthermore, treatment with pimavanserin was associated with significantly greater improvement in specific symptoms associated with depression such as impaired sexual function, anxiety, sleepiness, and irrit-ability. However, the availability of pimavanserin for clinical care of patients with MDD remains uncertain. Top-line results of phase 3 studies (n=298) that were announced by the sponsor found similar reductions in HAMD (mean baseline-to-week-5 reduction of 9.0 and 8.1, p=0.296) and rates of adverse events (58.1% and 54.7%) with addition of pimavanserin and placebo respectively to stable treatment with antidepressants. Given the potential benefit for specific symptoms such as impaired sexual function, anxiety and sleep/wakefulness disturbances, future studies that enrich for these symptoms may be needed to clarify the utility of adjunctive pimavanserin in treatment of patients with MDD.
AB - Major depressive disorder (MDD) is widely prevalent and one of the leading causes of disability. Treatment outcomes remain suboptimal with 1 in 3 patients with MDD responding inadequately to commonly used antidepressants. Pimavanserin, an atypical anti-psychotic that modulates serotonergic neurotransmission by selectively binding to serotonin receptor (2A and 2C) subtypes and without dopaminergic activity, may have the potential as an adjunctive treatment for MDD. In a phase 2 trial (n=203), addition of pimavanserin, as compared to placebo, to stable treatment with antidepressants was associated with greater reduction in 17-item Hamilton Depression Rating Scale score [HAMD, least square means (95% confidence interval) of −1.7 (−0.03, −3.37), p=0.039]. Furthermore, treatment with pimavanserin was associated with significantly greater improvement in specific symptoms associated with depression such as impaired sexual function, anxiety, sleepiness, and irrit-ability. However, the availability of pimavanserin for clinical care of patients with MDD remains uncertain. Top-line results of phase 3 studies (n=298) that were announced by the sponsor found similar reductions in HAMD (mean baseline-to-week-5 reduction of 9.0 and 8.1, p=0.296) and rates of adverse events (58.1% and 54.7%) with addition of pimavanserin and placebo respectively to stable treatment with antidepressants. Given the potential benefit for specific symptoms such as impaired sexual function, anxiety and sleep/wakefulness disturbances, future studies that enrich for these symptoms may be needed to clarify the utility of adjunctive pimavanserin in treatment of patients with MDD.
KW - Antidepressant
KW - Depression
KW - Major depressive disorder
KW - Pimavanserin
UR - http://www.scopus.com/inward/record.url?scp=85099714005&partnerID=8YFLogxK
U2 - 10.2147/DDDT.S240862
DO - 10.2147/DDDT.S240862
M3 - Review article
C2 - 33469267
AN - SCOPUS:85099714005
SN - 1177-8881
VL - 15
SP - 151
EP - 157
JO - Drug Design, Development and Therapy
JF - Drug Design, Development and Therapy
ER -