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

References

• HasinDS, SarvetAL, MeyersJL, et al. Epidemiology of adult DSM-5 major depressive disorder and its specifiers in the United States. JAMA Psychiatry. 2018;75(4):336–346. doi:10.1001/jamapsychiatry.2017.460229450462
   PubMed Web of Science ®Google Scholar
• VosT, AbajobirAA, AbbafatiC, AbbasKM, AbateK. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the global burden of disease study 2016. Lancet. 2017;390(10100):1211–1259.28919117
   PubMed Web of Science ®Google Scholar
• JhaMK, GreerTL, GrannemannBD, CarmodyT, RushAJ, TrivediMH. Early normalization of quality of life predicts later remission in depression: findings from the CO-MED trial. J Affect Disord. 2016;206:17–22. doi:10.1016/j.jad.2016.07.01227455354
   PubMed Web of Science ®Google Scholar
• JhaMK, MinhajuddinA, GreerTL, CarmodyT, RushAJ, TrivediMH. Early improvement in psychosocial function predicts longer-term symptomatic remission in depressed patients. PLoS One. 2016;11(12):e0167901. doi:10.1371/journal.pone.016790128030546
   PubMed Web of Science ®Google Scholar
• JhaMK, MinhajuddinA, GreerTL, CarmodyT, RushAJ, TrivediMH. Early improvement in work productivity predicts future clinical course in depressed outpatients: findings from the CO-MED trial. Am J Psychiatry. 2016;173(12):1196–1204. doi:10.1176/appi.ajp.2016.1602017627523501
   PubMed Web of Science ®Google Scholar
• JhaMK, TeerRB, MinhajuddinA, GreerTL, RushAJ, TrivediMH. Daily activity level improvement with antidepressant medications predicts long-term clinical outcomes in outpatients with major depressive disorder. Neuropsychiatr Dis Treat. 2017;13:803–813. doi:10.2147/NDT.S12840728352180
   PubMed Web of Science ®Google Scholar
• RushAJ, TrivediMH, WisniewskiSR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905–1917. doi:10.1176/ajp.2006.163.11.190517074942
   PubMed Web of Science ®Google Scholar
• RubertoVL, JhaMK, MurroughJW. Pharmacological treatments for patients with treatment-resistant depression. Pharmacy (Basel). 2020;13(6):6. doi:10.3390/ph13060116
   Google Scholar
• PapakostasGI, SalloumNC, HockRS, et al. Efficacy of esketamine augmentation in major depressive disorder: a meta-analysis. J Clin Psychiatry. 2020;81(4):4. doi:10.4088/JCP.19r12889
   Web of Science ®Google Scholar
• BoesAD, KellyMS, TrappNT, SternAP, PressDZ, Pascual-LeoneA. Noninvasive brain stimulation: challenges and opportunities for a new clinical specialty. J Neuropsychiatry Clin Neurosci. 2018;30(3):173–179. doi:10.1176/appi.neuropsych.1711026229685065
   PubMed Web of Science ®Google Scholar
• JhaMK, TrivediMH. Experimental therapies for treatment-resistant depression: “how do you decide when to go to an unproven or experimental therapy with patients that are treatment-resistant depression?”. Focus (Am Psychiatr Publ). 2018;16(3):279–284. doi:10.1176/appi.focus.2018001330147629
   PubMedGoogle Scholar
• MalhiGS, BellE, SinghA, et al. The 2020 royal Australian and New Zealand college of psychiatrists clinical practice guidelines for mood disorders: major depression summary. Bipolar Disord. 2020.
   Web of Science ®Google Scholar
• ParkLT, ZarateCA Jr., SolomonCG. Depression in the primary care setting. N Engl J Med. 2019;380(6):559–568. doi:10.1056/NEJMcp171249330726688
   PubMed Web of Science ®Google Scholar
• FavaM, DirksB, FreemanMP, et al. A phase 2, randomized, double-blind, placebo-controlled study of adjunctive pimavanserin in patients with major depressive disorder and an inadequate response to therapy (CLARITY). J Clin Psychiatry. 2019;80(6):6. doi:10.4088/JCP.19m12928
   Web of Science ®Google Scholar
• FreemanMP, FavaM, DirksB, et al. Improvement of sexual functioning during treatment of MDD with adjunctive pimavanserin: a secondary analysis. Depress Anxiety. 2020;37(5):485–495. doi:10.1002/da.2301732301591
   PubMed Web of Science ®Google Scholar
• PapakostasGI, FavaM, FreemanMP, et al. Effect of pimavanserin on anxious depression in patients with major depression and an inadequate response to previous therapy: secondary analysis of the clarity study. Int Clin Psychopharmacol. 2020;35(6):313–321. doi:10.1097/YIC.000000000000032832804742
   PubMed Web of Science ®Google Scholar
• Prescribing Information for Pimavanserin; 2019 Available from: https://www.nuplazid.com/sites/nuplazid/files/pdf/NUPLAZID_Prescribing_Information.pdf. Accessed 1101, 2020.
   Google Scholar
• HacksellU, BursteinES, McFarlandK, MillsRG, WilliamsH. On the discovery and development of pimavanserin: a novel drug candidate for Parkinson’s psychosis. Neurochem Res. 2014;39(10):2008–2017. doi:10.1007/s11064-014-1293-324682754
   PubMed Web of Science ®Google Scholar
• MeltzerHY, RothBL. Lorcaserin and pimavanserin: emerging selectivity of serotonin receptor subtype-targeted drugs. J Clin Invest. 2013;123(12):4986–4991.24292660
   PubMed Web of Science ®Google Scholar
• JhaMK, MinhajuddinA, SouthC, RushAJ, TrivediMH. Worsening anxiety, irritability, insomnia, or panic predicts poorer antidepressant treatment outcomes: clinical utility and validation of the concise associated symptom tracking (CAST) scale. Int J Neuropsychopharmacol. 2018;21(4):325–332. doi:10.1093/ijnp/pyx09729182724
   PubMed Web of Science ®Google Scholar
• VanoverKE, WeinerDM, MakhayM, et al. Pharmacological and behavioral profile of N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N’-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1) (ACP-103), a novel 5-hydroxytryptamine(2A) receptor inverse agonist. J Pharmacol Exp Ther. 2006;317(2):910–918. doi:10.1124/jpet.105.09700616469866
   PubMed Web of Science ®Google Scholar
• CummingsJ, IsaacsonS, MillsR, et al. Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet. 2014;383(9916):533–540.24183563
   PubMed Web of Science ®Google Scholar
• FrielingH, HillemacherT, ZiegenbeinM, NeundörferB, BleichS. Treating dopamimetic psychosis in Parkinson’s disease: structured review and meta-analysis. Eur Neuropsychopharmacol. 2007;17(3):165–171. doi:10.1016/j.euroneuro.2006.08.00717070675
   PubMed Web of Science ®Google Scholar
• NicholsMJ, HartleinJM, EickenMG, RacetteBA, BlackKJ. A fixed-dose randomized controlled trial of olanzapine for psychosis in Parkinson disease. F1000Research. 2013;2:150. doi:10.12688/f1000research.2-150.v124627787
   PubMedGoogle Scholar
• ZhangH, WangL, FanY, et al. Atypical antipsychotics for Parkinson’s disease psychosis: a systematic review and meta-analysis. Neuropsychiatr Dis Treat. 2019;15:2137–2149. doi:10.2147/NDT.S20102931551655
   PubMed Web of Science ®Google Scholar
• MeltzerHY, MillsR, RevellS, et al. Pimavanserin, a serotonin(2A) receptor inverse agonist, for the treatment of parkinson’s disease psychosis. Neuropsychopharmacology. 2010;35(4):881–892. doi:10.1038/npp.2009.17619907417
   PubMed Web of Science ®Google Scholar
• CastroVM, ClementsCC, MurphySN, et al. QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ. 2013;346:f288. doi:10.1136/bmj.f28823360890
   PubMed Web of Science ®Google Scholar
• MarekGJ, CarpenterLL, McDougleCJ, PriceLH. Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders. Neuropsychopharmacology. 2003;28(2):402–412. doi:10.1038/sj.npp.130005712589395
   PubMed Web of Science ®Google Scholar
• FavaM, EvinsAE, DorerDJ, SchoenfeldDA. The problem of the placebo response in clinical trials for psychiatric disorders: culprits, possible remedies, and a novel study design approach. Psychother Psychosom. 2003;72(3):115–127. doi:10.1159/00006973812707478
   PubMed Web of Science ®Google Scholar
• RybinD, DorosG, PencinaMJ, FavaM. Placebo non-response measure in sequential parallel comparison design studies. Stat Med. 2015;34(15):2281–2293. doi:10.1002/sim.649425865181
   PubMed Web of Science ®Google Scholar
• PosnerK, BrownGK, StanleyB, et al. The Columbia–suicide severity rating scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011;168(12):1266–1277. doi:10.1176/appi.ajp.2011.1011170422193671
   PubMed Web of Science ®Google Scholar
• SheltonRC, FavaM, FreemanMP, et al. Effect of adjunctive pimavanserin on suicidal ideation in patients with major depression: analysis of the CLARITY study. J Affect Disord. 2020;277:478–485. doi:10.1016/j.jad.2020.08.05132871535
   PubMed Web of Science ®Google Scholar
• PerlisRH, LajeG, SmollerJW, FavaM, RushAJ, McMahonFJ. Genetic and clinical predictors of sexual dysfunction in citalopram-treated depressed patients. Neuropsychopharmacology. 2009;34(7):1819–1828. doi:10.1038/npp.2009.419295509
   PubMed Web of Science ®Google Scholar
• ClaytonAH, El HaddadS, IluonakhamheJP, Ponce MartinezC, SchuckAE. Sexual dysfunction associated with major depressive disorder and antidepressant treatment. Expert Opin Drug Saf. 2014;13(10):1361–1374.25148932
   PubMed Web of Science ®Google Scholar
• IshakWW, ChristensenS, SayerG, et al. Sexual satisfaction and quality of life in major depressive disorder before and after treatment with citalopram in the STAR*D study. J Clin Psychiatry. 2013;74(3):256–261. doi:10.4088/JCP.12m0793323561231
   PubMed Web of Science ®Google Scholar
• FavaM, RushAJ, AlpertJE, et al. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry. 2008;165(3):342–351. doi:10.1176/appi.ajp.2007.0611186818172020
   PubMed Web of Science ®Google Scholar
• IonescuDF, NiciuMJ, HenterID, ZarateCA. Defining anxious depression: a review of the literature. CNS Spectr. 2013;18(5):252–260. doi:10.1017/S109285291300011423507190
   PubMed Web of Science ®Google Scholar
• CutlerAJ. The role of insomnia in depression and anxiety: its impact on functioning, treatment, and outcomes. J Clin Psychiatry. 2016;77(8):e1010. doi:10.4088/JCP.14076tx3c27561147
   PubMedGoogle Scholar
• NuttD, WilsonS, PatersonL. Sleep disorders as core symptoms of depression. Dialogues Clin Neurosci. 2008;10(3):329–336.18979946
   PubMedGoogle Scholar
• FavaM. Daytime sleepiness and insomnia as correlates of depression. J Clin Psychiatry. 2004;65(Suppl 16):27–32.
   PubMed Web of Science ®Google Scholar
• KaidaK, TakahashiM, AkerstedtT, et al. Validation of the karolinska sleepiness scale against performance and EEG variables. Clin Neurophysiol. 2006;117(7):1574–1581. doi:10.1016/j.clinph.2006.03.01116679057
   PubMed Web of Science ®Google Scholar
• JhaMK, FavaM, FreemanMP, et al. Effect of adjunctive pimavanserin on sleep/wakefulness in patients with major depressive disorder: secondary analysis from CLARITY. J Clin Psychiatry. 2020;82(1). doi:10.4088/JCP.20m13425.
   Web of Science ®Google Scholar
• JhaMK, MinhajuddinA, FattCC, et al. Association between irritability and suicidal ideation in three clinical trials of adults with major depressive disorder. Neuropsychopharmacology. 2020;45(13):2147–2154. doi:10.1038/s41386-020-0769-x32663842
   PubMed Web of Science ®Google Scholar
• JhaMK, MinhajuddinA, SouthC, RushAJ, TrivediMH. Irritability and its clinical utility in major depressive disorder: prediction of individual-level acute-phase outcomes using early changes in irritability and depression severity. Am J Psychiatry. 2019;176(5):358–366. doi:10.1176/appi.ajp.2018.1803035530922100
   PubMed Web of Science ®Google Scholar
• MinhajuddinA, JhaMK, Chin FattC, TrivediMH. Psychometric properties of the concise associated symptom tracking scale and validation of clinical utility in the EMBARC study. Psychiatry Res Clin Pract. 2020;appi.prcp.20190041.
   Google Scholar
• JhaMK, MinhajuddinA, Chin FattC, TrivediMH. Improvements in irritability with sertraline versus placebo: findings from the EMBARC study. J Affect Disord. 2020;275:44–47. doi:10.1016/j.jad.2020.06.02132658822
   PubMed Web of Science ®Google Scholar
• News Release; 2020 Available from: https://ir.acadia-pharm.com/news-releases/news-release-details/acadia-pharmaceuticals-announces-top-line-results-phase-3-0?field_nir_news_date_value%5Bmin%5D=. Accessed 1102, 2020.
   Google Scholar
• TrivediMH, SouthC, JhaMK, et al. A novel strategy to identify placebo responders: prediction index of clinical and biological markers in the EMBARC trial. Psychother Psychosom. 2018;87(5):285–295. doi:10.1159/00049109330110685
   PubMed Web of Science ®Google Scholar