Agomelatine-associated manic switch in bipolar depression: A case report

To the Editor

The potential for antidepressants from a number of classes to precipitate manic switch in unipolar and bipolar depression has been well described and reviewed (Tondo et al., 2010).

We describe here a 31-year-old female sales assistant who became anxious, avoidant, socially withdrawn and depressed following an assault. She was initially managed by her regular GP and a counsellor. Sertraline was trialled, but when she developed intolerable nausea, this was changed to the melatonergic antidepressant agomelatine at a dose of 25mg nocte. Approximately two months later she was referred to mental health services by her counsellor, who was concerned by her mental state. At this time she demonstrated abundant confidence, pressure of speech, episodic irritability, an irregular eating pattern, and reduction in sleep to four hours per night. She had begun to engage in excessive cleaning and spending behaviours. At presentation no overt psychotic phenomenology was elicited. A diagnosis of antidepressant-induced hypomania was made. Agomelatine was ceased, and she was commenced on quetiapine 25mg nocte with gradual improvement in her symptoms over the following three weeks. Some months later however, she presented with an episode of overt mania in the absence of antidepressant therapy, supporting an underlying diagnosis of bipolar disorder.

Risk factors for progression to manic switch include underlying Axis I mood disorder and younger age at the time of antidepressant introduction, with a higher risk of switch in bipolar disorder compared to major depressive disorder (Tondo et al., 2010). The timeframe for emergence of symptoms of hypomania or mania is variable. In the Systematic Treatment Enhancement Program for Bipolar Disorder, a longitudinal cohort study, Perlis et al. (2010) found that amongst patients who transition from a depressive state directly to a manic, hypomanic, or mixed state, the median time to transition was 74 days. The role of antidepressants in bipolar depression remains a contentious issue and the subject of much debate. Tondo et al. (2010) noted that antidepressant-induced manic switch has been well reported with a number of antidepressant classes, including tricyclics, SSRIs, SNRIs, and MAOIs. The present case report suggests that agomelatine may also have the potential to precipitate manic switching. We suggest that, as with other antidepressants, all patients should be closely monitored during therapy for evidence of emerging hypomania or mania, particularly in the setting of bipolar disorder and during the first few months of therapy initiation.