Vortioxetine is a new antidepressant (AD) recently introduced in Europe. With an action profile that extends beyond traditional serotonin (5-HT) reuptake blockade, it is considered a 5-HT_3A, 5-HT₇, and 5HT_1D receptor antagonist, 5-HT_1B partial agonist, 5-HT_1A agonist, and inhibitor of the serotonin transporter.¹

Data on the safety of vortioxetine for treatment of depressive episodes in patients with bipolar disorder (BD) are still lacking. We found only one report of manic mood switch² and an episode of hypomania in a patient with unknown diagnosis of BD in an analysis of randomized placebo-controlled trials and open-label extension studies.³

We report a patient with previously undiagnosed BD who experienced a manic switch (MS) after initiating AD treatment with vortioxetine.

A 41-year-old male with at least two previous depressive episodes and paternal psychiatric family history of puerperal psychosis and recurrent depressive disorder developed a severe depressive episode. Vortioxetine (10 mg/day) was introduced with trazodone (50 mg/day) as a sleep inducer. One week later, the patient developed a MS consisting of elated mood, racing thoughts, disinhibition, irritability, and paranoid and grandeur delusions. Due to marked behavioral changes and lack of insight, the patient was involuntary admitted and AD treatment was discontinued. At admission, he scored 46 on the Young Mania Rating Scale and 13 on the Hamilton Depression Rating Scale. Blood tests including toxicological and serological screening were negative, and pharmacological treatment with olanzapine (20 mg/day) and valproic acid (1,000 mg/day) was initiated; the patient attained a provisional response after 17 days (scores reduced to 7 and 4, respectively) and was discharged to outpatient treatment with a diagnosis of BD – severe manic episode with psychotic features. At the time of writing, the patient had developed a depressive switch and been started on outpatient treatment with lithium (800 mg/day).

Even though low doses of trazodone are considered safe in BD,⁴ a synergistic effect of its combination with vortioxetine inducing MS cannot be excluded. While vortioxetine appears promising as a second-line AD option, additional long-term data are still lacking,⁵ and clinicians need to be aware of the possible risks of MS when prescribing this AD in monotherapy or in combination to patients with BD.