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


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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.

About the authors

Elena Teobaldi

Department of Neurosciences, University of Turin

Email: info@benthamscience.net

Enrico Pessina

Department of Mental Health, Community Mental Health Center

Email: info@benthamscience.net

Azzurra Martini

Department of Mental Health, Community Mental Health Center

Email: info@benthamscience.net

Carlo Cattaneo

Department of Mental Health,

Email: info@benthamscience.net

Domenico De Berardis

Department of Mental Health, Psychiatric Service for Diagnosis and Treatment, Hospital "G. Mazzini"

Email: info@benthamscience.net

Vassilis Martiadis

Department of Mental Health, ASL Napoli 1 Centro

Email: info@benthamscience.net

Giuseppe Maina

Department of Neurosciences, University of Turin

Author for correspondence.
Email: info@benthamscience.net

Gianluca Rosso

Department of Neurosciences, University of Turin

Email: info@benthamscience.net

References

  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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.2147/NDT.S100846 PMID: 27099503
  17. Stahl, S.M. Mechanism of action of cariprazine. CNS Spectr., 2016, 21(2), 123-127. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1016/j.jad.2019.11.098 PMID: 31969269

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