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Which patients with bipolar depression receive antidepressant augmentation? Results from an observational multicenter study

Published online by Cambridge University Press:  10 September 2021

Laura Musetti
Affiliation:
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Antonio Tundo
Affiliation:
Istituto di Psicopatologia, Rome, Italy
Erika Cambiali*
Affiliation:
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Claudia Del Grande
Affiliation:
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Rocco De Filippis
Affiliation:
Istituto di Psicopatologia, Rome, Italy
Caterina Franceschini
Affiliation:
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Luca Proietti
Affiliation:
Istituto di Psicopatologia, Rome, Italy
Sophia Betrò
Affiliation:
Istituto di Psicopatologia, Rome, Italy
Donatella Marazziti
Affiliation:
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Liliana Dell’Osso
Affiliation:
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
*
*Author for correspondence: Erika Cambiali, E-mail: erikacam@libero.it

Abstract

Background

To identify demographic and clinical characteristics of bipolar depressed patients who require antidepressant (AD) augmentation, and to evaluate the short- and long-term effectiveness and safety of this therapeutic strategy.

Methods

One hundred twenty-two bipolar depressed patients were consecutively recruited, 71.7% of them received mood stabilizers (MS)/second-generation antipsychotics (SGA) with AD-augmentation and 28.3% did not. Patients were evaluated at baseline, and after 12 weeks and 15 months of treatment.

Results

The AD-augmentation was significantly higher in patients with bipolar II compared with bipolar I diagnosis. Patients with MS/SGA + AD had often a seasonal pattern, depressive polarity onset, depressive index episode with anxious features, a low number of previous psychotic and (hypo)manic episodes and of switch. They had a low irritable premorbid temperament, a low risk of suicide attempts, and a low number of manic symptoms at baseline. After 12 weeks of treatment, 82% of patients receiving ADs improved, 58% responded and 51% remitted, 3.8% had suicidal thoughts or projects, 6.1% had (hypo)manic switch, and 4.1% needed hospitalization. During the following 12 months, 92% of them remitted from index episode, 25.5% did not relapse, and 11% needed hospitalization. Although at the start advantaged, patients with AD-augmentation, compared with those without AD-augmentation, did not significantly differ on any outcome as well on adverse events in the short- and long-term treatment.

Conclusion

Our findings indicate that ADs, combined with MS and/or SGA, are short and long term effective and safe in a specific subgroup for bipolar depressed patients.

Type
Original Research
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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Footnotes

Institution where the research was conducted: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy Istituto di Psicopatologia, Rome, Italy

References

Merikangas, KR, Akiskal, HS, Angst, J, et al. Lifetime and 12-month prevalence of bipolar spectrum disorder in the national comorbidity survey replication. Arch Gen Psychiatry. 2007;64(5):543552.CrossRefGoogle ScholarPubMed
Grande, I, Berk, M, Birmaher, B, Vieta, E. Bipolar disorder. Lancet. 2016;387(10027):15611572.CrossRefGoogle ScholarPubMed
Baldessarini, RJ, Salvatore, P, Khalsa, HMK, et al. Morbidity in 303 first-episode bipolar I disorder patients. Bipolar Disord. 2010;12(3):264270.CrossRefGoogle ScholarPubMed
Altshuler, LL, Gitlin, MJ, Mintz, J, Leight, KL, Frye, MA. Subsyndromal depression is associated with functional impairment in patients with bipolar disorder. J Clin Psychiatry. 2002;63(9):807811.CrossRefGoogle ScholarPubMed
Rosa, AR, Reinares, M, Michalak, EE, Bonnin, CM, Sole, B, Franco, C. Functional impairment and disability across mood states in bipolar disorder. Value Heal 2010;13(8):984988.CrossRefGoogle ScholarPubMed
Judd, LL, Schettler, PJ, Akiskal, HS, et al. Residual symptom recovery from major affective episodes in bipolar disorders and rapid episode relapse/recurrence. Arch Gen Psychiatry. 2008;65(4):386394.CrossRefGoogle ScholarPubMed
Liu, B, Zhang, Y, Fang, H, Liu, J, Liu, T, Li, L. Efficacy and safety of long-term antidepressant treatment for bipolar disorders—a meta-analysis of randomized controlled trials. J Affect Disord. 2017;223:4148.CrossRefGoogle ScholarPubMed
Berkol, TD, Balcioglu, YH, Kirlioglu, SS, Ozarslan, Z, Islam, S, Ozyildirim, I. Clinical characteristics of antidepressant use and related manic switch in bipolar disorder. Neurosciences. 2019;24(1):4552.CrossRefGoogle ScholarPubMed
Fountoulakis, KN, Grunze, H, Vieta, E, et al. The international college of neuro-psychopharmacology (CINP) treatment guidelines for bipolar disorder in adults (CINP-BD-2017), part 3: the clinical guidelines. Int J Neuropsychopharmacol. 2017;20(2):180195.Google ScholarPubMed
Yatham, LN, Kennedy, SH, Parikh, SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20(2):97170.CrossRefGoogle Scholar
Pacchiarotti, I, Bond, DJ, Baldessarini, RJ, et al. The International Society for bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders. Am J Psychiatry. 2013;170(11):12491262.CrossRefGoogle ScholarPubMed
Baldessarini, RJ, Leahy, L, Arcona, S, Gause, D, Zhang, W, Hennen, J. Patterns of psychotropic drug prescription for U.S. patients with diagnoses of bipolar disorders. Psychiatr Serv. 2007;58(1):8591.CrossRefGoogle ScholarPubMed
Carta, MG, Aguglia, E, Balestrieri, M, et al. The lifetime prevalence of bipolar disorders and the use of antidepressant drugs in bipolar depression in Italy. J Affect Disord. 2012;136(3):775780.CrossRefGoogle ScholarPubMed
Tundo, A, Calabrese, JR, Proietti, L, De Filippis, R. Short-term antidepressant treatment of bipolar depression: are ISBD recommendations useful in clinical practice? J Affect Disord. 2015a;171:155160.CrossRefGoogle ScholarPubMed
Rhee, TG, Olfson, M, Nierenberg, AA, Wilkinson, AT. 20-year trends in the pharmacologic treatment of bipolar disorder by psychiatrists in outpatient care settings. Am J Psychiatry. 2020;177(8):706715.CrossRefGoogle ScholarPubMed
Lyall, LM, Penades, N, Smith, DJ. Changes in prescribing for bipolar disorder between 2009 and 2016: national-level data linkage study in Scotland. Br J Psychiatry. 2019;215(1):415421.CrossRefGoogle ScholarPubMed
Joffe, RT, MacQueen, GM, Marriott, M, Young, LT. One-year outcome with antidepressant—treatment of bipolar depression. Acta Psychiatr Scand. 2005;112(2):105109.CrossRefGoogle ScholarPubMed
Altshuler, LL, Post, RM, Hellemann, G, et al. Impact of antidepressant continuation after acute positive or partial treatment response for bipolar depression: a blinded, randomized study. J Clin Psychiatry. 2009;70(4):450457.CrossRefGoogle ScholarPubMed
Grande, I, De Arce, R, Jiménez-Arriero, , et al. Patterns of pharmacological maintenance treatment in a community mental health services bipolar disorder cohort study (SIN-DEPRES). Int J Neuropsychopharmacol. 2013;16(3):513523.CrossRefGoogle Scholar
Gijsman, HJ, Geddes, JR, Rendell, JM, Nolen, WA, Goodwin, GM. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry. 2004;161(9):15371547.CrossRefGoogle ScholarPubMed
Vázquez, G, Tondo, L, Baldessarini, RJ. Comparison of antidepressant responses in patients with bipolar vs. unipolar depression: A meta-analytic review. Pharmacopsychiatry. 2011;44(1):2126.Google ScholarPubMed
Tondo, L, Baldessarini, RJ, Vázquez, G, Lepri, B, Visioli, C. Clinical responses to antidepressants among 1036 acutely depressed patients with bipolar or unipolar major affective disorders. Acta Psychiatr Scand. 2013;127(5):355364.CrossRefGoogle ScholarPubMed
Tundo, A, Musetti, L, Del Grande, C, et al. Is short-term antidepressant treatment effective and safe in bipolar depression? Results from an observational multicenter study. Hum Psychopharmacol. 2021;36(3).CrossRefGoogle ScholarPubMed
Ghaemi, SN, Rosenquist, KJ, Ko, JY, Baldassano, CF, Kontos, NJ, Baldessarini, RJ. Antidepressant treatment in bipolar versus unipolar depression. Am J Psychiatry. 2004;161(1):163165.CrossRefGoogle ScholarPubMed
Sidor, MM, MacQueen, GM. Antidepressants for the acute treatment of bipolar depression: a systematic review and meta-analysis. J Clin Psychiatry. 2011;72(2):156167.CrossRefGoogle ScholarPubMed
McGirr, A, Vöhringer, PA, Ghaemi, SN, Lam, RW, Yatham, LN. Safety and efficacy of adjunctive second-generation antidepressant therapy with a mood stabiliser or an atypical antipsychotic in acute bipolar depression: a systematic review and meta-analysis of randomised placebo-controlled trials. The Lancet Psychiatry. 2016;3(12):11381146.CrossRefGoogle ScholarPubMed
Yerevanian, BI, Choi, YM. Impact of psychotropic drugs on suicide and suicidal behaviors. Bipolar Disord. 2013;15(5):594621.CrossRefGoogle ScholarPubMed
Sachs, GS, Nierenberg, AA, Calabrese, JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007;356(17):17111722.CrossRefGoogle ScholarPubMed
Tondo, L, Vázquez, G, Baldessarini, RJ. Mania associated with antidepressant treatment: comprehensive meta-analytic review. Acta Psychiatr Scand. 2010;121(6):404414.CrossRefGoogle ScholarPubMed
Post, RM, Altshuler, LL, Leverich, GS, et al. Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline. Br J Psychiatry. 2006;189:124131.CrossRefGoogle ScholarPubMed
Bond, DJ, Noronha, MM, Kauer-Sant’Anna, M, Lam, RW, Yatham, LN. Antidepressant-associated mood elevations in bipolar II disorder compared with bipolar I disorder and major depressive disorder: a systematic review and meta-analysis. J Clin Psychiatry. 2008;69(10):15891601.CrossRefGoogle ScholarPubMed
Amsterdam, JD, Lorenzo-Luaces, L, Soeller, I, Li, SQ, Mao, JJ, DeRubeis, RJ. Safety and effectiveness of continuation antidepressant versus mood stabilizer monotherapy for relapse-prevention of bipolar II depression: a randomized, double-blind, parallel-group, prospective study. J Affect Disord. 2015;185:3137.CrossRefGoogle ScholarPubMed
Amsterdam, JD, Lorenzo-Luaces, L, Soeller, I, Li, SQ, Mao, JJ, DeRubeis, RJ. Short-term venlafaxine v. lithium monotherapy for bipolar type II major depressive episodes: effectiveness and mood conversion rate. Br J Psychiatry. 2016;208(4):359365.CrossRefGoogle ScholarPubMed
Altshuler, LL, Sugar, CA, McElroy, SL, et al. Switch rates during acute treatment for bipolar II depression with Lithium, Sertraline, or the two combined: a randomized double-blind comparison. Am J Psychiatry. 2017;174(3):266276.CrossRefGoogle ScholarPubMed
Gitlin, MJ. Antidepressants in bipolar depression: an enduring controversy. Int J Bipolar Disord. 2018;6(1):25.CrossRefGoogle ScholarPubMed
Beyer, JL. The use of antidepressants in bipolar depression. In: Handbook of Experimental Pharmacology. Vol 250. New York: Springer New York LLC; 2019:415442.Google Scholar
Rosenblat, JD, Mcintyre, RS. Treatment recommendations for DSM-5-defined mixed features. CNS Spectr. 2017;22(2):147154.CrossRefGoogle ScholarPubMed
Stahl, SM, Morrissette, DA, Faedda, G, et al. Guidelines for the recognition and management of mixed depression. CNS Spectr. 2017;22(2):203219.CrossRefGoogle ScholarPubMed
American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorder. 5th ed. Washington DC: American Psychiatric Association; 2013.Google Scholar
Hamilton, M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23(1):5662CrossRefGoogle ScholarPubMed
First, MB, Williams, JBW, Karg, RS, Spitzer, RL. Structured Clinical Interview for DSM-5 Disorders, Clinician Version (SCID-5-CV). Washington DC: Amer Psychiatric Pub Incorporated; 2015.Google Scholar
Koukopoulos, A, Koukopoulos, A. Agitated depression as a mixed state and the problem of melancholia. Psychiatr Clin North Am. 1999;22(3):547564.CrossRefGoogle ScholarPubMed
Sani, G, Vöhringer, PA, Napoletano, F, et al. Koukopoulos’ diagnostic criteria for mixed depression: a validation study. J Affect Disord. 2014;164:1418.CrossRefGoogle ScholarPubMed
Cassano, GB, Musetti, L, Perugi, G, et al. Major depression subcategories: their potentiality for clinical research. In: Diagnosis and treatment of depression. “Quo Vadis?” Symposium, Sanofi Group. 1987; 91103.Google Scholar
Erfurth, A, Gerlach, AL, Hellweg, I, Boenigk, I, Michael, N, Akiskal, HS. Studies on a German (Münster) version of the temperament auto-questionnaire TEMPS-A: construction and validation of the briefTEMPS-M. J Affect Disord. 2005;85(1–2):5369.CrossRefGoogle Scholar
Young, RC, Biggs, JT, Ziegler, VE, Meyer, DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978;133(11):429435.CrossRefGoogle ScholarPubMed
Guy, W. ECDEU Assessment Manual for Psychopharmacology. US Department of Health, Education, and Welfare Publication (ADM). Rockville, MD: National Institute of Mental Health; 1976: 218222.Google Scholar
Jones, SH, Thornicroft, G, Coffey, M, Dunn, G. A brief mental health outcome scale. Reliability and validity of the global assessment of functioning (GAF). Br J Psychiatry. 1995;166:654659.CrossRefGoogle ScholarPubMed
Yatham, LN, Kennedy, SH, Parikh, S V., et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord. 2013;15(1):144.CrossRefGoogle Scholar
Tohen, M, Frank, E, Bowden, CL, et al. The International Society for Bipolar Disorders (ISBD) Task Force report on the nomenclature of course and outcome in bipolar disorders. Bipolar Disord. 2009;11(5):453473.CrossRefGoogle ScholarPubMed
Forester, BP, Ajilore, O, Spino, C, Lehmann, S. Clinical characteristics of patients with late life bipolar disorder in the community: data from the NNDC registry. Am J Geriatr Psychiatry. 2015;23(9):977984.CrossRefGoogle ScholarPubMed
Oostervink, F, Nolen, WA, Kok, RM. Two years’ outcome of acute mania in bipolar disorder: different effects of age and age of onset. Int J Geriatr Psychiatry. 2015;30(2):201209.CrossRefGoogle ScholarPubMed
Lorenzo, LS, Vázquez, GH, Zaratiegui, RM, Tondo, L, Baldessarini, RJ. Characteristics of bipolar disorder patients given antidepressants. Hum Psychopharmacol. 2012;27(5):486491.CrossRefGoogle ScholarPubMed
Geoffroy, PA, Bellivier, F, Scott, J, Etain, B. Seasonality and bipolar disorder: a systematic review, from admission rates to seasonality of symptoms. J Affect Disord. 2014;168:210223.CrossRefGoogle ScholarPubMed
Subramanian, K, Sarkar, S, Kattimani, S. Bipolar disorder in Asia: illness course and contributing factors. Asian J Psychiatr. 2017; 29:1629.CrossRefGoogle ScholarPubMed
Tundo, A, Musetti, L, Benedetti, A, Berti, B, Massimetti, G, Dell’Osso, L. Onset polarity and illness course in bipolar I and II disorders: the predictive role of broadly defined mixed states. Compr Psychiatry. 2015b;63:1521.CrossRefGoogle ScholarPubMed
Vazquez, G, Gonda, X. Affective temperaments and mood disorders: a review of current knowledge. Curr Psychiatry Rev. 2013;9(1):2132.Google Scholar
Bowers, MB, McKay, BG, Mazure, CM. Discontinuation of antidepressants in newly admitted psychotic patients. J Neuropsychiatry Clin Neurosci. 2003;15(2):227230.CrossRefGoogle ScholarPubMed
Altshuler, L, Kiriakos, L, Calcagno, J, et al. The impact of antidepressant discontinuation versus antidepressant continuation on 1-year risk for relapse of bipolar depression: a retrospective chart review. J Clin Psychiatry. 2001;62(8):612616.CrossRefGoogle ScholarPubMed
Altshuler, L, Suppes, T, Black, D, et al. Impact of antidepressant discontinuation after acute bipolar depression remission on rates of depressive relapse at 1-year follow-up. Am J Psychiatry. 2003;160(7):12521262.CrossRefGoogle ScholarPubMed