Pharmacopsychiatry 2011; 44(3): 109-113
DOI: 10.1055/s-0031-1271688
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

An Open Randomized Pilot Trial on the Differential Effects of Aripiprazole versus Risperidone on Anhedonia and Subjective Well-Being

E. Liemburg1 , A. Aleman1 , J. Bous2 , K. Hollander1 , H. Knegtering1 , 3 , 4
  • 1Department of Neuroscience, University Medical Center Groningen, and BCN – NeuroImaging Center, University of Groningen, Groningen, The Netherlands
  • 2University Center of Psychiatry, University Medical Center Groningen, University of Groningen, The Netherlands
  • 3Rob Giel Research Center, University of Groningen, Groningen, The Netherlands
  • 4Lentis, Center for Mental Healthcare Groningen, Groningen, The Netherlands
Further Information

Publication History

received 01.10.2010 revised 01.12.2010

accepted 02.12.2010

Publication Date:
22 March 2011 (online)

Abstract

Introduction: Negative symptoms of schizophrenia often predict an unfavorable clinical outcome. Disturbed dopamine transmission in different brain parts may underlie different aspects of negative symptoms, and the effect of antipsychotics on them may also differ. This pilot study investigated the potentially therapeutic effects of the partial dopamine agonist aripiprazole on different negative symptoms.

Methods: This pilot study randomly assigned patients with schizophrenia (N=40) to either aripiprazole or risperidone. After 6 weeks of treatment, the severity of negative symptoms was determined by the PANSS. Subscales of self-report questionnaires were used to assess differences in initiative, anhedonia, social functioning and subjective well-being.

Results: Patients treated with aripiprazole showed a significant improvement on measures for anhedonia and subjective wellbeing. Negative symptoms in general, lack of initiative and social inhibition were also lower in the aripiprazole treated group, but without reaching statistical significance.

Discussion: According to this pilot study, aripiprazole appears to specifically improve anhedonia and subjective wellbeing compared to risperidone. This may be caused by a specific effect of aripiprazole on the limbic branch of the dopamine system. Future studies should replicate this finding with a larger sample size.

References

  • 1 Mueser KT, McGurk SR. Schizophrenia.  Lancet. 2004;  363 (9426) 2063-2072
  • 2 Andreasen NC. Negative symptoms in schizophrenia. Definition and reliability.  Arch Gen Psychiatry. 1982;  39 784-788
  • 3 Gold JM, Carpenter C, Randolph TE. et al . Auditory working memory and Wisconsin card sorting test performance in schizophrenia.  Arch Gen Psychiatry. 1997;  54 159-165
  • 4 Grace AA. Gating of information flow within the limbic system and the pathophysiology of schizophrenia.  Brain Res Rev. 2000;  31 330-341
  • 5 Abi-Dargham A, Moore H. Prefrontal DA transmission at D1 receptors and the pathology of schizophrenia.  Neuroscientist. 2003;  9 404-416
  • 6 Jarskog LF, Miyamoto S, Lieberman JA. Schizophrenia: new pathological insights and therapies.  Ann Rev Med. 2007;  58 49-61
  • 7 Goldman-Rakic PS. Working memory dysfunction in schizophrenia.  J Neuropsychiatry Clin Neurosci. 1994;  6 348-357
  • 8 Gur RE, Loughhead J, Kohler CG. et al . Limbic activation associated with misidentification of fearful faces and flat affect in schizophrenia.  Arch Gen Psychiatry. 2007;  64 1356-1366
  • 9 Juckel G, Schlagenhauf F, Koslowski M. et al . Dysfunction of ventral striatal reward prediction in schizophrenia.  NeuroImage. 2006;  29 409-416
  • 10 Chan HY, Lin WW, Lin SK. et al . Efficacy and safety of aripiprazole in the acute treatment of schizophrenia in Chinese patients with risperidone as an active control: a randomized trial.  J Clin Psychiatry. 2007;  68 29-36
  • 11 Lambert M, Schimmelmann BG, Karow A. et al . Subjective well-being and initial dysphoric reaction under antipsychotic drugs – concepts, measurement and clinical relevance.  Pharmacopsychiatry. 2010;  36 (suppl 3) 181-190
  • 12 Bortolozzi A, Díaz-Mataix L, Toth M. et al . In vivo actions of aripiprazole on serotonergic and dopaminergic systems in rodent brain.  Psychopharmacology. 2007;  191 745-758
  • 13 Jordan S, Koprivika V, Dunn R. et al . In vivo effects of aripiprazole on cortical and striatal dopaminergic and serotonergic function.  Eur J Pharmacol. 2004;  483 45-53
  • 14 de Haan L, Booij J, Lavalye J. et al . Occupancy of dopamine D2 receptors by antipsychotic drugs is related to nicotine addiction in young patients with schizophrenia.  Psychopharmacology. 2006;  183 500-505
  • 15 Brown ES, Nejtek VA, Perantie DC. et al . Cocaine and amphetamine use in patients with psychiatric illness: a randomized trial of typical antipsychotic continuation or discontinuation.  J Clin Psychopharmacol. 2009;  23 384-388
  • 16 Abi-Dargham A, Laruelle M. Mechanisms of action of second generation antipsychotic drugs in schizophrenia: insights from brain imaging studies.  Eur Psychiatry. 2005;  20 15-21
  • 17 Lee MA, Thompson PA, Meltzer HY. Effects of clozapine on cognitive function in schizophrenia.  J Clin Pharmacol. 1994;  55 (9 suppl B) 82-87
  • 18 da Silva Alves F, Figee M, van Amelsvoort T. et al . The revised dopamine hypothesis of schizophrenia: evidence from pharmacological MRI studies with atypical antipsychotic medication.  Psychopharmacolog Bull. 2008;  41 121-132
  • 19 Kapur S, Zipursky RB, Jones C. et al . A positron emission tomography study of quetiapine in schizophrenia.  Arch Gen Psychiatry. 2009;  57 553-559
  • 20 Green AI, Zimmet SV, Strous RD. et al . Clozapine for comorbid substance use disorder and schizophrenia: do patients with schizophrenia have a reward-deficiency syndrome that can be ameliorated by clozapine?.  Harvard Rev Psychiatry. 1999;  6 287-296
  • 21 Lambert M, Schimmelmann B, Karow A. et al . Subjective well-being and initial dysphoric reaction under antipsychotic drugs – concepts, measurement and clinical relevance.  Pharmacopsychiatry. 2003;  36 (suppl 3) S181-S190
  • 22 van Nimwegen LJ, de Haan L, van Beveren NJM. et al . Effect of olanzapine and risperidone on subjective well-being and craving for cannabis in patients with schizophrenia or related disorders: a double-blind randomized controlled trial.  Can J Psychiatry. 2008;  53 400-405
  • 23 McGravin JK, Goa KL. Aripiprazole.  Adis New Drug Profile. 2002;  16 779-786
  • 24 Lieberman JA. Dopamine partial agonists: a new class of antipsychotic 13.  CNS Drugs. 2004;  18 251-267
  • 25 Semba J, Watanabe A, Kito S. et al . Behavioural and neurochemical effects of OPC-14597, a novel antipsychotic drug, on dopaminergic mechanisms in rat brain.  Neuropharmacology. 1995;  34 785-791
  • 26 Janicak P, Glick I, Marder S. et al . The acute efficacy of aripiprazole across the symptom spectrum of schizophrenia: a pooled post-hoc analysis from 5 short-term studies.  J Clin Psychiatry. 2009;  70 25-35
  • 27 Kane JM, Meltzer HY, Carson WH. et al . Aripiprazole for treatment-resistant schizophrenia: results of a multicenter, randomized, double-blind, comparison study versus perphenazine.  J Clin Psychiatry. 2007;  68 213-223
  • 28 Riedel M, Schennach-Wolff R, Musil R. et al . Neurocognition and its influencing factors in the treatment of schizophrenia – effects of aripiprazole, olanzapine, quetiapine and risperidone.  Hum Psychopharmacol. 2010;  25 116-125
  • 29 Riedel M, Spellman I, Schennach-Wolff R. et al . Effect of aripiprazole on cognition in the treatment of patients with schizophrenia.  Pharmacopsychiatry. 2010;  43 50-57
  • 30 Kane JM. Comparative utility of aripiprazole and haloperidol in schizophrenia: Post-hoc analysis of 52-week, randomized, controlled trials.  Appl Health Econ Health Policy. 2010;  7 109-119
  • 31 de Boer MK, Wiersma D, Bous J. et al . A randomized open-label comparison of the impact of aripiprazole versus risperidone on sexual functioning.  J Clin Psychopharmacol. 2010;  in press
  • 32 Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale of schizophrenia.  Schizophrenia Bull. 1987;  13 271-276
  • 33 Naber D, Moritz S, Lambert M. et al . Improvement of schizophrenic patients’ subjective well-being under atypical antipsychotic drugs.  Schizophrenia Res. 2001;  50 79-88
  • 34 Wolters HA, Knegtering H, van de Bosch R. et al . Effects and side effects of antipsychotic treatment in schizophrenia: pros and cons of available self-rating scales.  Schizophrenia Res. 2009;  112 114-118
  • 35 Wolters H, Knegtering H, Wiersma D. et al . The spectrum of subjective effects of antipsychotic medication.  Acta Neuropsychiatrica. 2003;  15 274-279
  • 36 van der Gaag M, Hoffman T, Remijsen M. et al . The five-factor model of the positive and negative syndrome scale II: A ten-fold cross-validation of a revised model.  Schizophrenia Res. 2006;  85 280-287
  • 37 Li Z, Ichikawa J, Dai J. et al . Aripiprazole, a novel antipsychotic drug, preferentially increases dopamine release in the prefrontal cortex and hippocampus in rat brain.  Eur J Pharmacol. 2004;  493 75-83
  • 38 Mizrhahi R, Marno D, Rusjan P. et al . The relationship between subjective well-being and dopamine D2 receptors in patients treated with a dopamine partial agonist and full antagonist antipsychotics.  Int J Neuropsychopharmacol. 2009;  1-7
  • 39 McIntyre RS. Aripiprazole for the maintenance treatment of bipolar I disorder: A review.  Clin Therapeut. 2010;  32 S32-S38
  • 40 Pae C-U, Serretti A, Patkar AA. et al . Aripiprazole in the treatment of depressive and anxiety disorders.  CNS Drugs. 2008;  22 367-388
  • 41 Hertel P. Comparing sertindole to other new generation antipsychotics on preferential dopamine output in limbic versus striatal projection regions: mechanism of action.  Synapse. 2006;  60 543-552
  • 42 Han M, Hang XF, Deng C. Aripiprazole differentially affects mesolimbic and nigrostriatal dopaminergic transmission: implications for long-term drug efficacy and low extrapyramidal side-effects.  Int J Neuropsychopharmacol. 2009;  12 941-952

Correspondence

E. LiemburgMSc 

Department of Neuroscience

University Medical Center

Groningen

University of Groningen

Antonius Deusinglaan 2

P.O. Box 196

9700 AD Groningen

The Netherlands

Phone: +31/50/363 8999

Fax: +31/50/363 8875

Email: E.J.Liemburg@med.umcg.nl

    >