Voritoxetine induced generalised pruritus: A preventable incident

Dear Editor,

Vortioxetine is a drug approved for treating unipolar depression by Food and Drug Administration (FDA) in October 2013.[1] It causes serotonin transporter (SERT) inhibition and antagonist actions at 5HT3 and 5HT7 receptors, with agonist actions at 5HT1A receptors and weak partial agonist to antagonist actions at 5HT1B/D receptors. Vortioxetine can be used for managing major depressive disorder, cognitive symptoms seen with depression, generalized anxiety disorder, and other depressive conditions. It has high affinity to the serotonin transporter and antidepressive actions are by enhancing serotonin in the central nervous system. Some of the common adverse effects seen following vortioxetine intake include constipation, nausea, vomiting along with sexual dysfunction.[2,3] We hereby report a case of a middle-aged lady, who developed generalised severe pruritus following the intake of vortioxetine.

A 40-year-old married lady presented to the Dermatology OPD with generalised pruritus, present for the preceding three days. Mucocutaneous examination did not reveal any significant abnormality. On probing, we came to know that she is a patient in the Department of Psychiatry for low mood, frequent crying spells, decreased social interaction, inability to concentrate at work, lethargy, and decreased appetite with some obsessive—compulsive traits. She was started on vortioxetine 5 mg/day, 3 days ago. Following 6–8 hours of initiation of treatment, she developed generalised itching and prickling sensation. On meticulous history taking, we found that she had visited a government hospital 1 year back with similar complaints and had been treated with sertraline 50 mg/day, increased to 100 mg/day and later, Bupropion 50 mg was added for decreased libido, along with cognitive therapy. She followed this therapy regularly for about 6 months. She reported improvement in her mood, but complained of forgetfulness in trivial to major matters, which caused impairment in her office, and a decreased sexual urge, which caused marital conflicts. She received treatment with mirtazapine 15 mg/day, followed by venlafaxine 300 mg/day for 6 months, reporting partial response, along with weight gain. Following this there was introduction of Vortioxetine 5 mg/day, after which the patient complained of abrupt onset of itching and redness with prickling sensation all over the body. No further investigations were done. She discontinued her treatment shortly after, and visited the psychiatry out patient department (OPD) of a hospital with complaints of mood symptoms, and after adequate history taking, the patient was diagnosed with major depressive disorder (MDD) according to Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5).

In this episode, supposing that the lesions were drug related, we advised discontinuation of vortioxetine, and prescribed levocetirizine 5 mg at night for 7 days along with a calamine and pramoxine 1% combination lotion for the generalized pruritus. She was referred to Psychiatry for consideration of alternate drugs. According to Naranjo Adverse Drug Reaction Probability Scale, she was labelled as having “probable” ADR to vortioxetine. As per Hartwig’s severity assessment scale, it was a “moderate” reaction. As per The Schumock and Thornton scale, the reaction was “definitely preventable.” We have reported to incident to Pharmacovigilance Program of India (PvPI).

Adverse events following intake of vortioxetine include serotonin syndrome, bipolar switch, suicide attempt, galactorrhea and hyponatremia. Rarely, cutaneous adverse reactions have been reported, some of which include redness of the face, neck, arms, and occasionally, upper chest, red or purple spots on the skin, itching skin. Besides, edema, petechiae, ecchymoses, acneiform eruptions and purpuric rashes have been reported as well.[4,5,6] There are also reports of urticaria and angioedema following vortioxetine intake.[2] Small vessel vasculitis has also been seen occurring as an adverse effect.[7] Drug induced pruritus is itching that is triggered by medication. There are many drug eruptions that result in pruritus but the term “drug induced pruritus”[8,9] means that no primary visible rash is seen except occasional scratch marks or excoriation. The itching can begin within hours or weeks after the drug causing it has been administered. The pruritus can be localized or generalized and can last a few days to months before resolution.

The purpose of this report is to increase the awareness about the cutaneous adverse reactions to vortioxetine, among prescribing physicians. Even in this modern era of sophisticated investigations, a detailed history taking and counselling can obviate the need for unnecessary investigations and interventions. Moreover, we would like to mention that each such event must be documented properly, and reported to PvPI.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.