Mania,a probable adverse drug reaction of opipramol in a patient with generalized anxiety disorder

To the Editor

The drug opipramol, a tricyclic compound, which acts through dopaminergic, serotonergic, histaminic and sigma receptors, has prominent anxiolytic and antidepressant effects (Müller et al., 2004). Due to its anxiolytic properties, opipramol is effective in generalized anxiety disorder (Möller et al., 2001).

A 45-year-old married female presented with a 5-year history of persistent anxiety, worries and apprehension related to day-to-day activities; disturbed sleep; and multiple non-specific somatic symptoms (backache, headache and dyspepsia). Informed consent was obtained. She had been treated earlier, with amitriptyline (up to 50 mg/day), paroxetine (up to 25 mg/day) and clonazepam for varying periods of time, by multiple physicians. She was a hypertensive and being treated with olmesartan 40 mg/day.

Her past and family histories were not relevant, and there were no psychosocial stressors of note. Premorbidly, she was well adjusted to life. Her physical examination did not reveal any abnormality; routine hematology, renal function tests, lipid profile and thyroid function tests did not reveal any abnormality. On mental status examination, the patient was anxious; she had worries related to the future of her children and family.

On the basis of history and mental status findings, a diagnosis of Generalized Anxiety Disorder was made and she was started on opipramol 150 mg/day in three divided doses, clonazepam 0.25 mg as per need and zolpidem 10 mg, bedtime. Later on (4 weeks following treatment initiation), the dose of opipramol was increased to 300 mg/day, to which the patient had shown significant improvement. However, at follow-up, family members reported changes in her behavior in the form of increased talkativeness, cheerfulness, increased physical activity and increased religiosity. The patient was evaluated on the Naranjo Adverse Drug Reaction Probability Scale, and the score was found to be 6, which was suggestive of ‘probable’ adverse drug reaction.

Opipramol was stopped immediately and olanzapine 15 mg/day was commenced. Her symptoms responded to this medication.

There is one reported case of opipramol-induced mania in the literature (Firoz et al., 2015), our case being the second. In the first case report, the patient was suffering from Bipolar Depression and switched into mania on opipramol. The propensity of antidepressant-induced mania is lower in anxiety disorders than that in bipolar disorder treated with tricyclic compounds.

Despite being different from conventional tricyclic antidepressants (TCAs), opipramol still carries the risk of switching to mania; hence, adequate caution needs to be exercised.