Add-On Pramipexole for the Treatment of Schizophrenia and Schizoaffective Disorder: A Randomized Controlled Trial

Linda Levi, BSc; Daisy Zamora, PhD; Igor Nastas, MD; Ilan Gonen, MD; Paull Radu, MD; Valentin Matei, MD; Adela M. Ciobanu, MD; Anatol Nacu, MD; Larisa Boronin, MD; Lusian Karakrah, MD; Michael Davidson, MD; John M. Davis, MD; Mark Weiser, MD

J Clin Psychiatry 2022;83(5):21m14233

ABSTRACT

Objective: Several small clinical trials have reported that the dopamine agonist pramipexole was beneficial in treating patients with schizophrenia. A confirmatory trial was conducted to test this hypothesis.

Methods: This 16-week, multicenter, double-blind, randomized, placebo-controlled study included 200 subjects meeting DSM-IV-TR criteria for schizophrenia or schizoaffective disorder. Patients were randomized to receive either pramipexole (0.75 mg twice daily, n = 100) or placebo (n = 100) as an add-on to their regular antipsychotic treatment. The primary outcome measure was the total score on the Positive and Negative Syndrome Scale (PANSS); secondary outcome measures included PANSS subscale and cognitive functioning scores. Recruitment was performed in 30 sites in Romania and 1 site in the Republic of Moldova between January and June 2011.

Results: Analysis of covariance models showed no significant difference between pramipexole and placebo for total PANSS (P > .99) and PANSS positive (P > .99), negative (P = .73), and general psychopathology (P = .99) subscale scores. Changes in Clinical Global Impressions–Severity of Illness scale and Brief Assessment of Cognition in Schizophrenia scores showed no significant difference between pramipexole and placebo.

Conclusions: The results of this large randomized controlled trial indicated that pramipexole was not efficacious as an add-on to antipsychotic medications for schizophrenia.

Trial Registration: ClinicalTrials.gov identifier NCT01320982

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References (26)

Guillin O, Abi-Dargham A, Laruelle M. Neurobiology of dopamine in schizophrenia. Int Rev Neurobiol. 2007;78:1–39. PubMed CrossRef
Maia TV, Frank MJ. An integrative perspective on the role of dopamine in schizophrenia. Biol Psychiatry. 2017;81(1):52–66. PubMed CrossRef
Chong TT, Husain M. The role of dopamine in the pathophysiology and treatment of apathy. Prog Brain Res. 2016;229:389–426. PubMed CrossRef
Mierau J, Schneider FJ, Ensinger HA, et al. Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors. Eur J Pharmacol. 1995;290(1):29–36. PubMed CrossRef
Kasper S, Barnas C, Heiden A, et al. Pramipexole as adjunct to haloperidol in schizophrenia: safety and efficacy. Eur Neuropsychopharmacol. 1997;7(1):65–70. PubMed CrossRef
Kelleher JP, Centorrino F, Huxley NA, et al. Pilot randomized, controlled trial of pramipexole to augment antipsychotic treatment. Eur Neuropsychopharmacol. 2012;22(6):415–418. PubMed CrossRef
Sabe M, Kirschner M, Kaiser S. Prodopaminergic drugs for treating the negative symptoms of schizophrenia: systematic review and meta-analysis of randomized controlled trials. J Clin Psychopharmacol. 2019;39(6):658–664. PubMed CrossRef
Weiser M, Levi L, Burshtein S, et al. The effect of minocycline on symptoms in schizophrenia: results from a randomized controlled trial. Schizophr Res. 2019;206:325–332. PubMed CrossRef
Weiser M, Zamora D, Levi L, et al. Adjunctive aspirin vs placebo in patients with schizophrenia: results of two randomized controlled trials. Schizophr Bull. 2021;47(4):1077–1087. PubMed CrossRef
Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261–276. PubMed CrossRef
Guy W. ECDEU Assessment Manual for Psychopharmacology, Revised CGI Clinical Global Impressions. US Department of Health; 1976:76–339.
Keefe RS, Goldberg TE, Harvey PD, et al. The Brief Assessment of Cognition in Schizophrenia: reliability, sensitivity, and comparison with a standard neurocognitive battery. Schizophr Res. 2004;68(2-3):283–297. PubMed CrossRef
Lingjaerde O, Ahlfors UG, Bech P, et al. The UKU side effect rating scale: a new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand suppl. 1987;334(s334):1–100. PubMed CrossRef
Simpson GM, Angus JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand suppl. 1970;212(S212):11–19. PubMed CrossRef
Golmirzaei J, Mahboobi H, Yazdanparast M, et al. Psychopharmacology of attention-deficit hyperactivity disorder: effects and side effects. Curr Pharm Des. 2016;22(5):590–594. PubMed CrossRef
Weng JJ, Wang LH, Zhu H, et al. Efficacy of low-dose D₂/D₃ partial agonist pramipexole on neuroleptic-induced extrapyramidal symptoms and symptoms of schizophrenia: a stage-1 open-label pilot study. Neuropsychiatr Dis Treat. 2019;15:2195–2203. PubMed CrossRef
Burdick KE, Braga RJ, Nnadi CU, et al. Placebo-controlled adjunctive trial of pramipexole in patients with bipolar disorder: targeting cognitive dysfunction. J Clin Psychiatry. 2012;73(1):103–112. PubMed CrossRef
Howes OD, McCutcheon R, Agid O, et al. Treatment-resistant schizophrenia: treatment response and resistance in psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology. Am J Psychiatry. 2017;174(3):216–229. PubMed CrossRef
Egerton A, Murphy A, Donocik J, et al. Dopamine and glutamate in antipsychotic-responsive compared with antipsychotic-nonresponsive psychosis: a multicenter positron emission tomography and magnetic resonance spectroscopy study (STRATA). Schizophr Bull. 2021;47(2):505–516. PubMed CrossRef
Fawcett J, Rush AJ, Vukelich J, et al. Clinical experience with high-dosage pramipexole in patients with treatment-resistant depressive episodes in unipolar and bipolar depression. Am J Psychiatry. 2016;173(2):107–111. PubMed CrossRef
Goldberg JF, Burdick KE, Endick CJ. Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression. Am J Psychiatry. 2004;161(3):564–566. PubMed CrossRef
Zarate CA Jr, Payne JL, Singh J, et al. Pramipexole for bipolar II depression: a placebo-controlled proof of concept study. Biol Psychiatry. 2004;56(1):54–60. PubMed CrossRef
Corrigan MH, Denahan AQ, Wright CE, et al. Comparison of pramipexole, fluoxetine, and placebo in patients with major depression. Depress Anxiety. 2000;11(2):58–65. PubMed CrossRef
Cusin C, Iovieno N, Iosifescu DV, et al. A randomized, double-blind, placebo-controlled trial of pramipexole augmentation in treatment-resistant major depressive disorder. J Clin Psychiatry. 2013;74(7):e636–e641. PubMed CrossRef
Tundo A, de Filippis R, De Crescenzo F. Pramipexole in the treatment of unipolar and bipolar depression: a systematic review and meta-analysis. Acta Psychiatr Scand. 2019;140(2):116–125. PubMed CrossRef
Volkow ND, Morales M. The brain on drugs: from reward to addiction. Cell. 2015;162(4):712–725. PubMed CrossRef