Multicenter Study

. 2023 May;25(3):233-244.

doi: 10.1111/bdi.13296. Epub 2023 Jan 18.

Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment-resistant depression

Giovanni Martinotti^{1

2}, Bernardo Dell'Osso³, Giorgio Di Lorenzo^{4

5}, Giuseppe Maina⁶, Alessandro Bertolino⁷, Massimo Clerici⁸, Stefano Barlati^{9

10}, Gianluca Rosso⁶, Marco Di Nicola^{11

12}, Matteo Marcatili⁸, Giacomo d'Andrea¹, Clara Cavallotto¹, Stefania Chiappini^{1

2}, Sergio De Filippis¹³, Giuseppe Nicolò¹⁴, Pasquale De Fazio¹⁵, Ileana Andriola⁷, Raffaella Zanardi^{16

17}, Domenica Nucifora¹⁸, Stefania Di Mauro¹⁹, Roberta Bassetti²⁰, Mauro Pettorruso¹, Roger S McIntyre^{21

22

23

24

25}, Stefano L Sensi¹, Massimo di Giannantonio¹, Antonio Vita^{9

10}; REAL-ESK Study Group

Collaborators, Affiliations

Affiliations

¹ Department of Neurosciences, Imaging and Clinical Sciences, Università degli Studi G. D'Annunzio, Chieti, Italy.
² Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK.
³ Department of Biomedical and Clinical Sciences Luigi Sacco and Aldo Ravelli Center for Neurotechnology and Brain Therapeutic, University of Milan, Milano, Italy.
⁴ Chair of Psychiatry, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
⁵ IRCCS Fondazione Santa Lucia, Rome, Italy.
⁶ Department of Neurosciences Rita Levi Montalcini, University of Torino, Turin, Italy.
⁷ Università degli Studi di Bari Aldo Moro, Italy.
⁸ Department of Mental Health and Addiction, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
⁹ Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
¹⁰ Department of Mental Health and Addiction Services, ASST Spedali Civili of Brescia, Italy.
¹¹ Section of Psychiatry, Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.
¹² Department of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
¹³ Neuropsychiatric Clinic, Villa Von Siebenthal, Genzano di Roma, Italy.
¹⁴ Department of Mental Health and Addiction, ASL Roma 5, Rome, Italy.
¹⁵ Psychiatry Unit, Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy.
¹⁶ Mood Disorder Unit, Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹⁷ Department of Clinical Neurosciences, University Vita-Salute San Raffaele, Milan, Italy.
¹⁸ MDSMA Taormina-Messina Sud ASP di Messina, Messina, Italy.
¹⁹ SPDC Frosinone - ASL Frosinone, Frosinone, Italy.
²⁰ Department of Mental Health and Addiction Services, Niguarda Hospital, Milan, Italy.
²¹ Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, ON, Toronto, Canada.
²² Department of Pharmacology and Toxicology, University of Toronto, ON, Toronto, Canada.
²³ Canadian Rapid Treatment Center of Excellence, ON, Mississauga, Canada.
²⁴ Brain and Cognition Discovery Foundation, ON, Toronto, Canada.
²⁵ Department of Psychiatry, University of Toronto, ON, Toronto, Canada.

PMID: 36636839
DOI: 10.1111/bdi.13296

Free article

Multicenter Study

Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment-resistant depression

Giovanni Martinotti et al. Bipolar Disord. 2023 May.

Free article

. 2023 May;25(3):233-244.

doi: 10.1111/bdi.13296. Epub 2023 Jan 18.

Authors

Affiliations

¹ Department of Neurosciences, Imaging and Clinical Sciences, Università degli Studi G. D'Annunzio, Chieti, Italy.
² Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK.
³ Department of Biomedical and Clinical Sciences Luigi Sacco and Aldo Ravelli Center for Neurotechnology and Brain Therapeutic, University of Milan, Milano, Italy.
⁴ Chair of Psychiatry, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
⁵ IRCCS Fondazione Santa Lucia, Rome, Italy.
⁶ Department of Neurosciences Rita Levi Montalcini, University of Torino, Turin, Italy.
⁷ Università degli Studi di Bari Aldo Moro, Italy.
⁸ Department of Mental Health and Addiction, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
⁹ Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
¹⁰ Department of Mental Health and Addiction Services, ASST Spedali Civili of Brescia, Italy.
¹¹ Section of Psychiatry, Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.
¹² Department of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
¹³ Neuropsychiatric Clinic, Villa Von Siebenthal, Genzano di Roma, Italy.
¹⁴ Department of Mental Health and Addiction, ASL Roma 5, Rome, Italy.
¹⁵ Psychiatry Unit, Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy.
¹⁶ Mood Disorder Unit, Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹⁷ Department of Clinical Neurosciences, University Vita-Salute San Raffaele, Milan, Italy.
¹⁸ MDSMA Taormina-Messina Sud ASP di Messina, Messina, Italy.
¹⁹ SPDC Frosinone - ASL Frosinone, Frosinone, Italy.
²⁰ Department of Mental Health and Addiction Services, Niguarda Hospital, Milan, Italy.
²¹ Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, ON, Toronto, Canada.
²² Department of Pharmacology and Toxicology, University of Toronto, ON, Toronto, Canada.
²³ Canadian Rapid Treatment Center of Excellence, ON, Mississauga, Canada.
²⁴ Brain and Cognition Discovery Foundation, ON, Toronto, Canada.
²⁵ Department of Psychiatry, University of Toronto, ON, Toronto, Canada.

PMID: 36636839
DOI: 10.1111/bdi.13296

Abstract

Background: Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first-line therapeutic options, resulting in treatment-resistant bipolar depression (B-TRD). Esketamine, the S-enantiomer of ketamine, has recently been approved for treatment-resistant depression (TRD), but no data are available on its use in B-TRD.

Objectives: To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B-TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B-TRD, focusing on the average risk of an affective switch.

Methods: Thirty-five B-TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery-Asberg Depression Rating Scale/MADRS, Hamilton-depression scale/HAM-D, Hamilton-anxiety scale/HAM-A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up.

Results: A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B-TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B-TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment-emergent affective switch.

Conclusions: Our results supported the effectiveness and tolerability of esketamine in a real-world population of subjects with B-TRD. The low risk of manic switch in B-TRD patients confirmed the safety of this treatment.

Keywords: TRD; bipolar depression; esketamine; glutamate; mood disorders; pharmacological treatment; rapid-acting antidepressant; real-world study; treatment-resistant depression.

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Comment in

Giovanni Martinotti: Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine and bipolar × unipolar treatment resistant depression.
Gonçalves MAS, Leite TRA, Júnior EAB, Araújo GAC, Bisol LW, Gomes de Matos E Souza F. Gonçalves MAS, et al. Bipolar Disord. 2023 Aug;25(5):429-430. doi: 10.1111/bdi.13359. Epub 2023 Jun 8. Bipolar Disord. 2023. PMID: 37291727 No abstract available.

References

REFERENCES

1. McIntyre RS, Berk M, Brietzke E, et al. Bipolar disorders. Lancet (London, England). 2020;396(10265):1841-1856. doi:10.1016/S0140-6736(20)31544-0
1. McIntyre RS, Calabrese JR. Bipolar depression: the clinical characteristics and unmet needs of a complex disorder. Curr Med Res Opin. 2019;35(11):1993-2005. doi:10.1080/03007995.2019.1636017
1. Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007;356(17):1711-1722. doi:10.1056/NEJMoa064135
1. Levenberg K, Cordner ZA. Bipolar depression: a review of treatment options. Gen Psychiatry. 2022;35(4):e100760. doi:10.1136/gpsych-2022-100760
1. Bahji A, Hawken ER, Sepehry AA, Cabrera CA, Vazquez G. ECT beyond unipolar major depression: systematic review and meta-analysis of electroconvulsive therapy in bipolar depression. Acta Psychiatr Scand. 2019;139(3):214-226. doi:10.1111/acps.12994

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Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment-resistant depression

Collaborators

Affiliations

Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment-resistant depression

Authors

Collaborators

Affiliations

Abstract

Comment in

References

REFERENCES

Publication types

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Substances

LinkOut - more resources

Full Text Sources

Medical