Pimavanserin in psychiatry- novel facts vs fiction

Dear Editor, Parkinson's disease (PD) is characterized by gradual neural degeneration in the substantia nigra, a region of the midbrain, which results in motor abnormalities, e.g., bradykinesia, resting tremor, cogwheel rigidity, and postural instability. The neuropsychiatric symptoms can include depression, dementia, apathy, hallucinations, and delusions (1). Some 20% to 50% of PD patients develop psychosis, with hallucinations and/ or delusions being the most prevalent symptoms (2). Pimavanserin (Nuplazid; Acadia Pharmaceuticals Inc., San Diego, CA, USA) is a 5-HT2A receptor antagonist. It differs from other antipsychotic medications commonly used in Parkinson’s disease psychosis (PDP) due to the selectivity for 5-HT2 receptors, a lower binding-affinity at the serotonin-2C receptor and the sigma 1 receptor, and because it spares dopamine post-synaptic receptors. It was approved by the US Federal Drug Administration in 2016 to treat Parkinson’s-related delusions and hallucinations (1). Development of the drug as a treatment for schizophrenia was attracted researchers and pimavanserin is currently in phase 3 clinical trials for the treatment of schizophrenia (2,3).

___

1. Bozymski KM, Lowe DK, Pasternak KM, Gatesman TL, Crouse EL. Pimavanserin: a novel antipsychotic for Parkinson’s disease psychosis. Ann Pharmacother. 2017;51(6):479–87.

2. Markham A. Pimavanserin: first global approval. Drugs. 2016;76(10):1053–7.

3. ACADIA Pharmaceuticals Inc. Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia (ADVANCE-2). https://clinicaltrials. gov/ct2/show/NCT04531982. Accessed October 25, 2021.

4. Combs BL, Cox AG. Update on the treatment of Parkinson’s disease psychosis: role of pimavanserin. Neuropsychiatr Dis Treat 2017; 13:737-744.

5. Kitten AK, Hallowell SA, Saklad SR, Evoy KE. Pimavanserin: a novel drug approved to treat Parkinson’s disease psychosis. Innov Clin Neurosci 2018; 15:16-22.

6. Yasue I, Matsunaga S, Kishi T, Fujita K, Iwata N. Serotonin 2A receptor inverse agonist as a treatment for Parkinson’s disease psychosis: a systematic review and meta-analysis of serotonin 2A receptor negative modulators. J Alzheimers Dis 2016; 50:733-740.

7. Ballard C, Banister C, Khan Z, Cummings J, Demos G, Coate B, et al. Evaluation of the safety, tolerability, and efficacy of pimavanserin versus placebo in patients with Alzheimer’s disease psychosis: a phase 2, randomised, placebo-controlled, doubleblind study. Lancet Neurol 2018; 17:213-222.

8. Hacksell U, Burstein ES, McFarland K, Mills RG, Williams H. On the discovery and development of pimavanserin: a novel drug candidate for Parkinson's psychosis. Neurochem Res 2014; 39:2008-2017.

9. Black KJ, Nasrallah H, Isaacson S, Stacy M, Pahwa R, Adler CH, et al. Guidance for switching from off-label antipsychotics to pimavanserin for Parkinson’s disease psychosis: an expert consensus. CNS Spectr 2018; 23:402-413.

10. Bugarski-Kirola D, Arango C, Fava M, Nasrallah H, Liu IY, Abbs B, et al (editors). Advance: Phase 2, Randomised, DoubleBlind, Placebo-Controlled Study of Adjunctive Pimavanserin in Patients with Negative Symptoms of Schizophrenia. In European Neuropsychopharmacology. Amsterdam: Elsevier Radarweg, 2020, 328-329.

11. Nasrallah HA, Fedora R, Morton R. Successful treatment of clozapine-nonresponsive refractory hallucinations and delusions with pimavanserin, a serotonin 5HT-2A receptor inverse agonist. Schizophr Res 2019; 208:217-220.

12. Fava M, Dirks B, Freeman MP, Papakostas GI, Shelton RC, Thase ME, et al. A Phase 2, randomized, double-blind, placebocontrolled study of adjunctive pimavanserin in patients with major depressive disorder and an ınadequate response to therapy (CLARITY). J Clin Psychiatry 2019; 80:19m12928.

13. Shelton RC, Fava M, Freeman MP, Thase ME, Papakostas GI, Jha MK, 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
Düşünen Adam - Psikiyatri ve Nörolojik Bilimler Dergisi-Cover
  • ISSN: 1018-8681
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 1984
  • Yayıncı: Kare Yayıncılık
Sayıdaki Diğer Makaleler

Pimavanserin in psychiatry- novel facts vs fiction

Sheikh SHOIB, Alaa BAIOU, Sana JAVAD, Dom nica Nathaly CEVALLOS-ROBALİNO, Fahimeh SAEED

The moderating role of perceived social support on early maladaptive schemas and well-being for primary caregivers of dementia patients

Elçin YORULMAZ, Özlem BOZO

YouTube as a source of information: How good is the quality and reliability of videos related to obsessive compulsive disorder?

Hasan KAYA, Aybeniz CİVAN KAHVE, Alper BÜLBÜL

Prenatal attachment in the COVID-19 pandemic: A cluster analysis

Zeynep Seda ALBAYRAK, Sefa COŞGUN, Eralp BULUTLAR, Tuğçe ÖNCÜ, Gizem Berfin ULUUTKU

The mediating role of cognitive flexibility in therelationship between metacognition andpsychological health: A study in a non-clinical sample

Hande KAYNAK, Oyku AYDIN

The relation between resilience and problematic Internet use among youth

Mehmet DİNC, Feyza TOPCU

24-hour mobile phone helpline service for women discharged from mother-baby psychiatry unit (MBU): Is it enough?

Sheikh SHOIB, Seshadri Sekhar CHATTERJEE, Soumitra DAS, Irfan ULLAH, Renato de FİLİPPİS

Autistic traits, emotional recognition and empathy in adolescents with gender dysphoria

Kübra Bercem KAHRAMAN, Zilan TOPCU, Duygu YAVUZ, Erten DİRENC, Ayşe Burcu ERDOĞDU

Evaluation of the procedures of people applying to the psychiatry outpatient clinics to remove their past diagnosis

Sare AYDIN, Esma AKPINAR ASLAN, Sedat BATMAZ, Zekiye ÇELİKBAŞ

The effect of childhood trauma on alcohol and non alcohol substance use in a Turkish sample ofuniversity students: The mediating role ofdissociative experiences

Murat YALÇIN, Batuhan HOKTEM, Hakan KARAS