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Aripiprazole and Cariprazine for Bipolar Disorder?

DOI: 10.4236/ojmp.2022.114019, PP. 254-273

Keywords: Bipolar Disorder, Mania, Depression, Mood Stabilizers, Clinical Trials, Problems with Current Measures

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In this article, the present author, a research psychologist and measurement expert, evaluates the major clinical trials used to support the use of aripiprazole and the chemically almost identical cariprazine for treating bipolar disorder. The main problem with the trials is that they were conducted mainly with outpatients, who on average were only moderately manic in the mania studies and only moderately depressed in the depression studies. The effectiveness of aripiprazole and cariprazine in treating moderate mania, most likely hypomania, and moderate depression, was far from encouraging. Aripiprazole produced just 7% greater reduction of mania symptoms than did placebo treatment, and just 1% greater reduction of depression symptoms than did placebo treatment when administered, as is common practice, with an SSRI or SNRI antidepressant. Cariprazine proved to be not much better because at the high dosage level of 3.0 mg/day to 12.0 mg/day, cariprazine produced only 9% greater reduction of mania symptoms than did placebo treatment, and at the typical low dosage of 1.5 to 3.0 mg/day produced just 4% greater reduction of depression symptoms than did placebo treatment. Moreover, as the pharmaceutical industry has long suspected, there is a massive placebo effect associated with these two drugs, especially for depression. These findings imply that government regulatory authorities’ approval of aripiprazole and cariprazine as mood stabilizers for treating bipolar disorder is dubious. Nevertheless, the possibility remains that the purported mood-stabilizing mechanism of these two medicines is activated only with patients presently experiencing severe mania or severe depression, a possibility that requires an in-hospital clinical trial or, at the very least, a longitudinal analysis of bipolar patients’ treatment records. Furthermore, an appendix to the present article demonstrates that the measures used in the trials, the Young Mania Rating Scale and the Montgomery-Asberg Depression Rating Scale, are deficient and that a briefer combination measure focusing only on the core symptoms of bipolar disorder should be used.


[1]  Mitchell, J.M. (2022) A Psychedelic for Trauma. Scientific American, 326, 56-61.
[2]  Insel, T.R. (2012) Next-Generation Treatments for Mental Disorders. Science Translational Medicine, 4, 1-4.
[3]  U.S. Food and Drug Administration (2021) Fact Sheet: FDA at a Glance.
[4]  Sadock, B.J. and Sadock, V.A. (2007) Kaplan & Sadock’s Synopsis of Psychiatry. 10th Edition, Lippincott Williams & Wilkins, Philadelphia, PA.
[5]  American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR). 5th Edition, American Psychiatric Association, Arlington.
[6]  Parker, G., Spoelma, M.J., Tavella, G., Alda, M., Hajek, T., Dunner, E.L., et al. (2020) The Bipolar Disorders: A Case for Their Categorically Distinct Status Based on Symptom Profiles. Journal of Affective Disorders, 277, 225-231.
[7]  Ferrari, A.J., Baxter, A.J. and Whiteford, H.A. (2011) A Systematic Review of the Global Distribution and Availability of Prevalence Data for Bipolar Disorder. Journal of Affective Disorders, 134, 1-13.
[8]  Perlis, R.M. (2005) Misdiagnosis of Bipolar Disorder. American Journal of Managed Care, 11, S271-S274.
[9]  Mitchell, P.B., Loo, C.K. and Gould, B.M. (2010) Diagnosis and Monitoring of Bipolar Disorder in General Practice. Medical Journal of Australia, 193, S10-S13.
[10]  Hirschfeld, R.M.A, Lewis, L. and Vornik, L.A. (2003) Perceptions and Impact of Bipolar Disorder: How Far Have We Really Come? Results of the National Depressive and Manic-Depressive Association 2000 Survey of Individuals with Bipolar Disorder. Journal of Clinical Psychiatry, 64, 161-174.
[11]  Zimmerman, M. (2017) Screening for Bipolar Disorder with Self-Administered Questionnaires: A Critique of the Concept and a Call to Stop Publishing Studies of Their Performance in Psychiatric Samples. Depression and Anxiety, 34, 779-785.
[12]  Parker, G., Paterson, A., McCraw, S., Friend, P. and Hong, M. (2013) Do Practitioners Managing Mood Disorders Work to a Sub-Typing or a ‘One Size Fits All’ Model? Australasian Psychiatry, 21, 17-21.
[13]  Parker, G. (2013) Personal Communication with Dr. Parker.
[14]  Allergan plc. (2019) Allergan and Gedeon Richter Receive U.S. FDA Approval for Expanded Use of VRAYLAR (Cariprazine) in the Treatment of Bipolar Depression.
[15]  Villines, Z. (2019) What Is Dopamine Deficiency? Low Dopamine Symptoms to Watch for.
[16]  Keck, P.E., Orsulak, P.J., Cutler, A.J., Sanchez, R., Torbeyns, A., Marcus, R.D., et al. (2009) Aripiprazole Monotherapy in the Treatment of Acute Bipolar I Mania: A Randomized, Double-Blind, Placebo- and Lithium-Controlled Study. Journal of Affective Disorders, 112, 36-49.
[17]  Thase, M.E., Jonas, A., Khan, A., Barron, C.L., Wu, X., McQuade, R.D., et al. (2008) Aripiprazole Monotherapy in Non-Psychotic Bipolar I Depression: Results of 2 Randomized, Placebo-Controlled Studies. Journal of Clinical Psychopharmacology, 28, 13-20.
[18]  Fava, M., Mischoulon, D., Iosifescu, D., Witte, J., Pencina, M., Flynn, M., et al. (2012) A Double-Blind, Placebo-Controlled Study of Aripiprazole Adjunctive to Antidepressant Therapy among Depressed Outpatients with Inadequate Response to Prior Antidepressant Therapy (Adapt-A Study). Psychotherapeutics and Psychosomatics, 81, 87-97.
[19]  McIntyre, R.S., Masand, P.S. and Earley, W. (2019) Cariprazine for the Treatment of Bipolar Mania with Mixed Features: A Post-Hoc Pooled Analysis of 3 Trials. Journal of Affective Disorders, 257, 600-606.
[20]  Ketter, T.A, Sachs, G.S., Durgam, S., Lu, K., Starace, A., Laszlovsky, I., et al. (2018) The Safety and Tolerability of Cariprazine in Patients with Manic or Mixed Episodes Associated with Bipolar I Disorder: A 16-Week Open-Label Study. Journal of Affective Disorders, 225, 350-356.
[21]  Durgam, S., Earley, W., Lipschitz, A., Guo, H., Laszlovsky, I., Nemeth, G., et al. (2016) An 8-Week Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of Cariprazine Patients with Bipolar I Depression. American Journal of Psychiatry, 173, 271-281.
[22]  Earley, W., Burgess, M., Rekeda, M.V., Dickinson, R., Szatmari, B., Nemeth, G., et al. (2019) Cariprazine Treatment of Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Phase 3 Study. American Journal of Psychiatry, 176, 439-448.
[23]  Wikipedia (2021) Cariprazine.
[24]  Badgaiyan, R.D. (2014) Imaging Dopamine Neurotransmission in Live Human Brain. Progress in Brain Research, 211, 165-182.
[25]  First, M.B., Williams, J.B.W., Karg, R.S. and Spitzer, R.L. (2016) Structured Clinical Interview for DSM-5® Disorders—Clinician Version (SCID-5-CV). American Psychiatric Association, Arlington.
[26]  Sheehan, D.V., Lecrubier, Y., Weiller, E., Amorim, P., Bonora, I., Harnett Sheehan, K., et al. (1997) The Mini International Neuropsychiatric Interview (MINI): A Short Diagnostic Structured Interview: Reliability and Validity According to the CIDI. European Psychiatry, 12, 224-231.
[27]  Young, R.C., Biggs, J.T., Ziegler, V.E. and Meyer, D.A. (1979) A Rating Scale for Mania: Reliability, Validity and Sensitivity. British Journal of Psychology, 133, 429-435.
[28]  Montgomery, S.A. and Asberg, M. (1979) A New Depression Scale Designed to Be Sensitive to Change. British Journal of Psychiatry, 134, 382-389.
[29]  Rossiter, J.R. (2022) The DEP-6: A Brief Multi-Diagnostic Measure of Depression. Psychology, 13, 853-871.
[30]  Australian Government, Department of Health and Ageing, Therapeutic Goods Administration (2011) Australian Public Assessment Report for Aripiprazole. 1-122.
[31]  Frances, A. (2013) Essentials of Psychiatric Diagnosis. Revised Edition, The Guilford Press, New York.
[32]  Rothschild, A.J. (2021) Why Is There No Food and Drug Administration-Approved Medication for Major Depression with Psychotic Features? Journal of Clinical Psychopharmacology, 41, 359-361.
[33]  Rossiter, J.R. (2020) A Brief Mental Disorder Screener Based on Core Symptoms. Charles Sturt University, Bathurst.
[34]  Parker, G., Tavella, G., Macqueen, G., Berk, M., Grunze, H., Deckersbach, T., et al. (2018) Revising Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Criteria for the Bipolar Disorders: Phase I of the AREDOC Project. Australian & New Zealand Journal of Psychiatry, 52, 1173-1182.


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