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 Table of Contents  
Year : 2021  |  Volume : 8  |  Issue : 1  |  Page : 58-59

Vortioxetine-induced switch - New drug with emerging old problems

1 Department of Psychiatry, Viswabharathi Medical College, Kurnool, Andhra Pradesh, India
2 Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India

Date of Submission14-Jun-2021
Date of Acceptance26-Jun-2021
Date of Web Publication05-Aug-2021

Correspondence Address:
Dr. Shiva Shanker Reddy Mukku
Department of Psychiatry, Viswabharathi Medical College, Kurnool, Andhra Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jgmh.jgmh_27_21

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How to cite this article:
Reddy Mukku SS, Nadella RK. Vortioxetine-induced switch - New drug with emerging old problems. J Geriatr Ment Health 2021;8:58-9

How to cite this URL:
Reddy Mukku SS, Nadella RK. Vortioxetine-induced switch - New drug with emerging old problems. J Geriatr Ment Health [serial online] 2021 [cited 2022 May 23];8:58-9. Available from:


Vortioxetine is a recent addition to the list of existing antidepressants. It received FDA approval in 2013 for the treatment of unipolar depression. Even though it is a selective serotonin reuptake inhibitor (SSRI), it has wide spectrum binding to serotonin receptors and serotonin transporter, which is slightly different compared to the existing SSRIs. It acts as an antagonist at 5-HT3, 5-HT1D, and 5-HT7 receptors, agonist at 5-HT1A (autoreceptors), and partial agonist at 5-HT1B (autoreceptors). In addition to its depression-ameliorating affect, it also improves cognitive functions in patients with depression.[1] This effect on cognitive functions makes it an attractive choice for geriatric depression where cognitive deficits are more common.

Vortioxetine has shown good efficacy and tolerability in unipolar depression. Recently, there are reports of extending its use in cases of treatment-resistant depression, depression in latent bipolar, and bipolar depression. This therapeutic exploration of vortioxetine is also providing us information on safety and tolerance and one such emerging adverse effect is drug induced switch. As the studies related to efficacy of vortioxetine are awaited in bipolar depression, in this article, we have reviewed the case studies on vortioxetine-induced switch. We found four cases in the literature which reported on vortioxetine-induced hypomanic/manic switch [Table 1].
Table 1: Case reports on vortioxetine-induced hypomanic/manic switch

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Among these four cases, three had diagnosis of recurrent depressive disorder [2, 4, 5] and the other had bipolar affective disorder, currently in severe depression.[3] Three patients had treatment resistance to at least one antidepressant trial. There was a history of manic switch to SSRI in report by Maud, 2016. In all these patients, vortioxetine is chosen as the second-line drug for depression. The dose of vortioxetine was 5 mg in one patient and 10 mg in three patients. In these reported cases, there was switch to mania in two patients, one patient had mixed episode, and other had hypomania. In all the cases, there was a switch within 7–10 days [Table 1].

Studies have reported manic switch rates in the short term as 40% with tricyclic antidepressants (TCAs) and 20% with newer antidepressants.[6] Among the newer antidepressants, serotonin norepinephrine reuptake inhibitors (venlafaxine) have higher risk compared to SSRI (sertraline), and the lowest was reported with bupropion.[7] Among the risk factors for antidepressant-induced switch, female gender, higher number of depressive episodes, family history of bipolar illness, endocrine abnormalities, and higher dose of antidepressants were reported.[8] Some of the risk factors for antidepressant-induced switch in the cases described are past history of SSRI-induced manic switch in one case and family history of puerperal depression in one case.

Considering the cases with Recurrent Depressive disorder (RDD), only there are few features which need attention; first, exposure to SSRI/SNRI before initiation of vortioxetine has not produced any switch. Second is longstanding depressive illness with fewer episodes which decreases the probability of underlying bipolarity. Third is the absence of comorbidity (substance use, personality disorder). All these factors suggest that there are no useful predictors of switch with vortioxetine. The explanations for the switch with antidepressants use are: it could be a natural course of bipolar illness with spontaneous episode of hypomania/mania, second is a subgroup of patient's bipolar depression showing transition to mania, hypomania, or mixed state before finally remitting, and other explanation is the emergence of hypomanic symptoms during the antidepressant withdrawal phase. [9,10]

One of the proposed hypotheses for manic switch in bipolar illness is increased postsynaptic receptor sensitivity interacting with high levels of catecholamines.[11] Studies have shown that drugs that increase dopamine and norepinephrine level at synaptic level can increase the risk of antidepressant-induced switch. This is evident from the fact that TCA and SNRI which have higher risk of manic switch compared to SSRI also cause increase in urinary dopamine and norepinephrine level. Vortioxetine with slightly unique action is known to increase dopamine, norepinephrine, serotonin, acetylcholine, and histamine in animal studies.[1] This propensity to increase multiple neurotransmitters might be the reason for vortioxetine-induced manic switch. However, the recent meta-analysis did not report manic switch with vortioxetine in depression.[12] It is suggestible for mental health professionals to monitor while using vortioxetine, especially in older adult patients with bipolar depression or latent bipolar depression.

In the cases reported so far with vortioxetine-induced switch, 50% are geriatric age group. Vortioxetine with its procognitive profile is more likely to be preferred in older adults due to their cerebral morbidity by clinicians. Hence, it is advisable to monitor for this adverse effect while using vortioxetine at least in the first 2 weeks. However, there is need for larger studies to better inform about the predictor of switch with vortioxetine.

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Conflicts of interest

There are no conflicts of interest.

  References Top

D'Agostino A, English CD, Rey JA. Vortioxetine (brintellix): A new serotonergic antidepressant. P T 2015;40:36-40.  Back to cited text no. 1
Pirdoğan Aydın E, Dalkıran M, Özer ÖA, Karamustafalıoğlu KO. Hypomanic switch during vortioxetine treatment: A case report. Psychiatry Clin Psychopharmacol 2019;29:114-6.  Back to cited text no. 2
Maud C. Vortioxetine in bipolar depression induces a mixed/manic switch. Australas Psychiatry 2016;24:206-7.  Back to cited text no. 3
D'Andrea G, De Ronchi D, Giaccotto L, Albert U. Vortioxetine Treatment-Emergent Mania in the Elderly: A Case Report. Vol. 27. Australasian Psychiatry: SAGE Publications Inc; 2019. p. 413.  Back to cited text no. 4
Sobreira G, Oliveira J, Brissos S. Vortioxetine-induced manic mood switch in patient with previously unknown bipolar disorder. Braz J Psychiatry 2017;39:86.  Back to cited text no. 5
Ghaemi SN, Hsu DJ, Soldani F, Goodwin FK. Antidepressants in bipolar disorder: The case for caution. Bipolar Disord 2003;5:421-33.  Back to cited text no. 6
Leverich GS, Altshuler LL, Frye MA, Suppes T, McElroy SL, Keck PE Jr, et al. Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers. Am J Psychiatry 2006;163:232-9.  Back to cited text no. 7
Valentí M, Pacchiarotti I, Bonnín CM, Rosa AR, Popovic D, Nivoli AM, et al. Risk factors for antidepressant-related switch to mania. J Clin Psychiatry 2012;73:e271-6.  Back to cited text no. 8
Goldstein TR, Frye MA, Denicoff KD, Smith-Jackson E, Leverich GS, Bryan AL, et al. Antidepressant discontinuation-related mania: Critical prospective observation and theoretical implications in bipolar disorder. J Clin Psychiatry 1999;60:563-7.  Back to cited text no. 9
Perlis RH, Ostacher MJ, Goldberg JF, Miklowitz DJ, Friedman E, Calabrese J, et al. Transition to mania during treatment of bipolar depression. Neuropsychopharmacology 2010;35:2545-52.  Back to cited text no. 10
Salvadore G, Quiroz JA, Machado-Vieira R, Henter ID, Manji HK, Zarate CA Jr. The neurobiology of the switch process in bipolar disorder: A review. J Clin Psychiatry 2010;71:1488-501.  Back to cited text no. 11
Pae CU, Wang SM, Han C, Lee SJ, Patkar AA, Masand PS, et al. Vortioxetine: A meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder. J Psychiatry Neurosci 2015;40:174-86.  Back to cited text no. 12


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