Generic placeholder image

Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Research Article

Cariprazine Augmentation in Treatment-Resistant Bipolar Depression: Data from a Retrospective Observational Study

Author(s): Elena Teobaldi, Enrico Pessina, Azzurra Martini, Carlo Ignazio Cattaneo, Domenico De Berardis, Vassilis Martiadis, Giuseppe Maina* and Gianluca Rosso

Volume 22, Issue 10, 2024

Published on: 29 January, 2024

Page: [1742 - 1748] Pages: 7

DOI: 10.2174/1570159X22666240129095852

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Treatment-resistant bipolar depression is one of the leading problems in psychiatry with serious consequences on patients functioning, quality of life and resource utilization. Despite this, there is a lack of consensus on diagnostic criteria and treatment algorithms.

Objective: The objective of the present study is to assess the acute effectiveness and tolerability of cariprazine in the management of treatment resistant bipolar depression.

Methods: This is a four weeks retrospective multicentric observational study on patients with treatment resistant bipolar depression receiving cariprazine in augmentation to the current treatment. Cariprazine dosage changed during the follow-up period according to clinical judgment. Since data followed a non-normal distribution, non-parametric tests were used to pursue the analysis. The effectiveness of cariprazine was assessed through the mean change in Hamilton Depression rating scale (HAM-D) scores from baseline to endpoint. For missing values, a “Last Observation Carried Forward” approach was applied.

Results: Fifty-one patients were enrolled. Four patients (7.8%) discontinued cariprazine mainly due to adverse events. Mean cariprazine dose was 1.7 mg/day. The mean HAM-D score decreased significantly from baseline (T0) to week 4 (T4) at each evaluation point. Fourty-five one percent of the patients benefited of cariprazine add-on strategy: 23.5% achieved a clinical response and 21.6% were remitters. Among the completers, 70.6% experienced at least one adverse event. All side effects were mild to moderate.

Conclusion: Cariprazine seems to be an effective and well tolerated option in the management of patients with treatment resistant bipolar depression.

Keywords: Bipolar disorder, bipolar depression, treatment-resistance, TRBD, cariprazine, hamilton depression rating scale.

Graphical Abstract
[1]
Judd, L.L.; Akiskal, H.S.; Schettler, P.J.; Endicott, J.; Maser, J.; Solomon, D.A.; Leon, A.C.; Rice, J.A.; Keller, M.B. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch. Gen. Psychiatry, 2002, 59(6), 530-537.
[http://dx.doi.org/10.1001/archpsyc.59.6.530] [PMID: 12044195]
[2]
Judd, L.L.; Akiskal, H.S.; Schettler, P.J.; Coryell, W.; Endicott, J.; Maser, J.D.; Solomon, D.A.; Leon, A.C.; Keller, M.B. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch. Gen. Psychiatry, 2003, 60(3), 261-269.
[http://dx.doi.org/10.1001/archpsyc.60.3.261] [PMID: 12622659]
[3]
Colom, F.; Vieta, E.; Daban, C.; Pacchiarotti, I.; Sánchez-Moreno, J. Clinical and therapeutic implications of predominant polarity in bipolar disorder. J. Affect. Disord., 2006, 93(1-3), 13-17.
[http://dx.doi.org/10.1016/j.jad.2006.01.032] [PMID: 16650901]
[4]
McIntyre, R.S.; Suppes, T.; Earley, W.; Patel, M.; Stahl, S.M. Cariprazine efficacy in bipolar I depression with and without concurrent manic symptoms: Post hoc analysis of 3 randomized, placebo-controlled studies. CNS Spectr., 2020, 25(4), 502-510.
[http://dx.doi.org/10.1017/S1092852919001287] [PMID: 31576791]
[5]
Kupka, R.W.; Altshuler, L.L.; Nolen, W.A.; Suppes, T.; Luckenbaugh, D.A.; Leverich, G.S.; Frye, M.A.; Keck, P.E., Jr; McElroy, S.L.; Grunze, H.; Post, R.M. Three times more days depressed than manic or hypomanic in both bipolar I and bipolar II disorder. Bipolar Disord., 2007, 9(5), 531-535.
[http://dx.doi.org/10.1111/j.1399-5618.2007.00467.x] [PMID: 17680925]
[6]
Malhi, G.S.; Ivanovski, B.; Hadzi-Pavlovic, D.; Mitchell, P.B.; Vieta, E.; Sachdev, P. Neuropsychological deficits and functional impairment in bipolar depression, hypomania and euthymia. Bipolar Disord., 2007, 9(1-2), 114-125.
[http://dx.doi.org/10.1111/j.1399-5618.2007.00324.x] [PMID: 17391355]
[7]
Gutirrez-Rojas, L.; Gurpegui, M.; Ayuso-Mateos, J.L.; Gutirrez-Ariza, J.A.; Ruiz-Veguilla, M.; Jurado, D. Quality of life in bipolar disorder patients: A comparison with a general population sample. Bipolar Disord., 2008, 10(5), 625-634.
[http://dx.doi.org/10.1111/j.1399-5618.2008.00604.x] [PMID: 18657247]
[8]
Bauer, M.; Ritter, P.; Grunze, H.; Pfennig, A. Treatment options for acute depression in bipolar disorder. Bipolar Disord., 2012, 14(2), 37-50.
[http://dx.doi.org/10.1111/j.1399-5618.2012.00991.x] [PMID: 22510035]
[9]
Hidalgo-Mazzei, D.; Berk, M.; Cipriani, A.; Cleare, A.J.; Florio, A.D.; Dietch, D.; Geddes, J.R.; Goodwin, G.M.; Grunze, H.; Hayes, J.F.; Jones, I.; Kasper, S.; Macritchie, K.; McAllister-Williams, R.H.; Morriss, R.; Nayrouz, S.; Pappa, S.; Soares, J.C.; Smith, D.J.; Suppes, T.; Talbot, P.; Vieta, E.; Watson, S.; Yatham, L.N.; Young, A.H.; Stokes, P.R.A. Treatment-resistant and multi-therapy-resistant criteria for bipolar depression: Consensus definition. Br. J. Psychiatry, 2019, 214(1), 27-35.
[http://dx.doi.org/10.1192/bjp.2018.257] [PMID: 30520709]
[10]
De Fruyt, J.; Deschepper, E.; Audenaert, K.; Constant, E.; Floris, M.; Pitchot, W.; Sienaert, P.; Souery, D.; Claes, S. Second generation antipsychotics in the treatment of bipolar depression: A systematic review and meta-analysis. J. Psychopharmacol., 2012, 26(5), 603-617.
[http://dx.doi.org/10.1177/0269881111408461] [PMID: 21940761]
[11]
Geddes, J.R.; Calabrese, J.R.; Goodwin, G.M. Lamotrigine for treatment of bipolar depression: Independent meta-analysis and meta-regression of individual patient data from five randomised trials. Br. J. Psychiatry, 2009, 194(1), 4-9.
[http://dx.doi.org/10.1192/bjp.bp.107.048504] [PMID: 19118318]
[12]
Yatham, L.N.; Calabrese, J.R.; Kusumakar, V. Bipolar depression: Criteria for treatment selection, definition of refractoriness, and treatment options. Bipolar Disord., 2003, 5(2), 85-97.
[http://dx.doi.org/10.1034/j.1399-5618.2003.00019.x] [PMID: 12680897]
[13]
Sidor, M.M.; MacQueen, G.M. Antidepressants for the acute treatment of bipolar depression: A systematic review and meta-analysis. J. Clin. Psychiatry, 2011, 72(2), 156-167.
[http://dx.doi.org/10.4088/JCP.09r05385gre] [PMID: 21034686]
[14]
D’Urso, G.; Toscano, E.; Barone, A.; Palermo, M.; Dell’Osso, B.; Di Lorenzo, G.; Mantovani, A.; Martinotti, G.; Fornaro, M.; Iasevoli, F.; de Bartolomeis, A. Transcranial direct current stimulation for bipolar depression: systematic reviews of clinical evidence and biological underpinnings. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2023, 121, 110672.
[http://dx.doi.org/10.1016/j.pnpbp.2022.110672] [PMID: 36332699]
[15]
Kishi, T.; Ikuta, T.; Sakuma, K.; Hatano, M.; Matsuda, Y.; Kito, S.; Iwata, N. Repetitive transcranial magnetic stimulation for bipolar depression: A systematic review and pairwise and network meta-analysis. Mol. Psychiatry, 2023.
[http://dx.doi.org/10.1038/s41380-023-02045-8] [PMID: 37020049]
[16]
Fornaro, M.; De Berardis, D.; Koshy, A.; Perna, G.; Vancampfort, D.; Stubbs, B.; Valchera, A. Prevalence and clinical features associated with bipolar disorder polypharmacy: A systematic review. Neuropsychiatr. Dis. Treat., 2016, 12, 719-735.
[http://dx.doi.org/10.2147/NDT.S100846] [PMID: 27099503]
[17]
Stahl, S.M. Mechanism of action of cariprazine. CNS Spectr., 2016, 21(2), 123-127.
[http://dx.doi.org/10.1017/S1092852916000043] [PMID: 26956157]
[18]
Gyertyán, I.; Sághy, K.; Laszy, J.; Elekes, O.; Kedves, R.; Gémesi, L.I.; Pásztor, G.; Zájer-Balázs, M.; Kapás, M.; Ágai Csongor, É.; Domány, G.; Kiss, B.; Szombathelyi, Z. Subnanomolar dopamine D3 receptor antagonism coupled to moderate D2 affinity results in favourable antipsychotic-like activity in rodent models: II. behavioural characterisation of RG-15. Naunyn Schmiedebergs Arch. Pharmacol., 2008, 378(5), 529-539.
[http://dx.doi.org/10.1007/s00210-008-0311-x] [PMID: 18548231]
[19]
Duric, V.; Banasr, M.; Franklin, T.; Lepack, A.; Adham, N.; Kiss, B.; Gyertyán, I.; Duman, R.S. Cariprazine exhibits anxiolytic and dopamine D3 receptor-dependent antidepressant effects in the chronic stress model. Int. J. Neuropsychopharmacol., 2017, 20(10), 788-796.
[http://dx.doi.org/10.1093/ijnp/pyx038] [PMID: 28531264]
[20]
Do, A.; Keramatian, K.; Schaffer, A.; Yatham, L. Cariprazine in the treatment of bipolar disorder: Within and beyond clinical trials. Front. Psychiatry, 2021, 12, 769897.
[http://dx.doi.org/10.3389/fpsyt.2021.769897] [PMID: 34970166]
[21]
Murphy, B.L.; Babb, S.M.; Ravichandran, C.; Cohen, B.M. Oral SAMe in persistent treatment-refractory bipolar depression: A double-blind, randomized clinical trial. J. Clin. Psychopharmacol., 2014, 34(3), 413-416.
[http://dx.doi.org/10.1097/JCP.0000000000000064] [PMID: 24699040]
[22]
Martinotti, G.; Dell’Osso, B.; Di Lorenzo, G.; Maina, G.; Bertolino, A.; Clerici, M.; Barlati, S.; Rosso, G.; Di Nicola, M.; Marcatili, M.; d’Andrea, G.; Cavallotto, C.; Chiappini, S.; De Filippis, S.; Nicolò, G.; De Fazio, P.; Andriola, I.; Zanardi, R.; Nucifora, D.; Di Mauro, S.; Bassetti, R.; Pettorruso, M.; McIntyre, R.S.; Sensi, S.L.; di Giannantonio, M.; Vita, A. Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment‐resistant depression. Bipolar Disord., 2023, 25(3), 233-244.
[http://dx.doi.org/10.1111/bdi.13296] [PMID: 36636839]
[23]
Heerlein, K.; Perugi, G.; Otte, C.; Frodl, T.; Degraeve, G.; Hagedoorn, W.; Oliveira-Maia, A.J.; Perez Sola, V.; Rathod, S.; Rosso, G.; Sierra, P.; Malynn, S.; Morrens, J.; Verrijcken, C.; Gonzalez, B.; Young, A.H. Real-world evidence from a European cohort study of patients with treatment resistant depression: Treatment patterns and clinical outcomes. J. Affect. Disord., 2021, 290, 334-344.
[http://dx.doi.org/10.1016/j.jad.2021.03.073] [PMID: 34044256]
[24]
Heerlein, K; De Giorgi, S; Degraeve, G; Frodl, T; Hagedoorn, W; Oliveira-Maia, AJ; Otte, C; Perez Sola, V; Rathod, S; Rosso, G; Sierra, P; Vita, A; Morrens, J; Rive, B; Mulhern, H.S; Kambarov, Y; Young, AH Real-world evidence from a European cohort study of patients with treatment resistant depression: Healthcare resource utilization. J. Affect. Disord., 2022, 298(Pt A), 442-450.
[25]
Crown, W.H.; Finkelstein, S.; Berndt, E.R.; Ling, D.; Poret, A.W.; Rush, A.J.; Russell, J.M. The impact of treatment-resistant depression on health care utilization and costs. J. Clin. Psychiatry, 2002, 63(11), 963-971.
[http://dx.doi.org/10.4088/JCP.v63n1102] [PMID: 12444808]
[26]
Fountoulakis, K.N.; Yatham, L.N.; Grunze, H.; Vieta, E.; Young, A.H.; Blier, P.; Tohen, M.; Kasper, S.; Moeller, H.J. The CINP Guidelines on the definition and evidence-based interventions for treatment-resistant bipolar disorder. Int. J. Neuropsychopharmacol., 2020, 23(4), 230-256.
[http://dx.doi.org/10.1093/ijnp/pyz064] [PMID: 31802122]
[27]
Diaz, A.P.; Fernandes, B.S.; Quevedo, J.; Sanches, M.; Soares, J.C. Treatment-resistant bipolar depression: Concepts and challenges for novel interventions. Br. J. Psychiatry, 2022, 44(2), 178-186.
[http://dx.doi.org/10.1590/1516-4446-2020-1627] [PMID: 34037084]
[28]
Malhi, G.S.; Bell, E.; Boyce, P.; Bassett, D.; Berk, M.; Bryant, R.; Gitlin, M.; Hamilton, A.; Hazell, P.; Hopwood, M.; Lyndon, B.; McIntyre, R.S.; Morris, G.; Mulder, R.; Porter, R.; Singh, A.B.; Yatham, L.N.; Young, A.; Murray, G. The 2020 royal australian and new zealand college of psychiatrists clinical practice guidelines for mood disorders: Bipolar disorder summary. Bipolar Disord., 2020, 22(8), 805-821.
[http://dx.doi.org/10.1111/bdi.13036] [PMID: 33296123]
[29]
Blonde, L.; Khunti, K.; Harris, S.B.; Meizinger, C.; Skolnik, N.S. Interpretation and impact of real-world clinical data for the practicing clinician. Adv. Ther., 2018, 35(11), 1763-1774.
[http://dx.doi.org/10.1007/s12325-018-0805-y] [PMID: 30357570]
[30]
Román, V.; Gyertyán, I.; Sághy, K.; Kiss, B.; Szombathelyi, Z. Cariprazine (RGH-188), a D3-preferring dopamine D3/D2 receptor partial agonist antipsychotic candidate demonstrates anti-abuse potential in rats. Psychopharmacology, 2013, 226(2), 285-293.
[http://dx.doi.org/10.1007/s00213-012-2906-7] [PMID: 23138433]
[31]
Yatham, LN; Vieta, E; McIntyre, RS; Jain, R; Patel, M; Earley, W Broad efficacy of cariprazine on depressive symptoms in bipolar disorder and the clinical implications. Prim. Care. Companion. CNS. Disord., 2020, 22(5), 20m02611.
[http://dx.doi.org/10.4088/PCC.20m02611]
[32]
Ragguett, R.M.; McIntyre, R.S. Cariprazine for the treatment of bipolar depression: A review. Expert Rev. Neurother., 2019, 19(4), 317-323.
[http://dx.doi.org/10.1080/14737175.2019.1580571] [PMID: 30753085]
[33]
Joyce, J.N.; Millan, M.J. Dopamine D3 receptor antagonists as therapeutic agents. Drug Discov. Today, 2005, 10(13), 917-925.
[http://dx.doi.org/10.1016/S1359-6446(05)03491-4] [PMID: 15993811]
[34]
Citrome, L.; Yatham, L.N.; Patel, M.D.; Barabássy, Á.; Hankinson, A.; Earley, W.R. Cariprazine and akathisia, restlessness, and extrapyramidal symptoms in patients with bipolar depression. J. Affect. Disord., 2021, 288, 191-198.
[http://dx.doi.org/10.1016/j.jad.2021.03.076] [PMID: 33915374]
[35]
Earley, W.R.; Burgess, M.; Rekeda, L.; Hankinson, A.; McIntyre, R.S.; Suppes, T.; Calabrese, J.R.; Yatham, L.N. A pooled post hoc analysis evaluating the safety and tolerability of cariprazine in bipolar depression. J. Affect. Disord., 2020, 263, 386-395.
[http://dx.doi.org/10.1016/j.jad.2019.11.098] [PMID: 31969269]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy