Agomelatine reversal of escitalopram-induced apathy: A case report


IT HAS BEEN reported that apathy may be a potential adverse effect of selective serotonin reuptake inhibitors (SSRI).[1] We herein report a case of a patient who developed apathy with escitalopram reversed by agomelatine.

A 70-year-old male patient, with the recurrence of a major depressive episode, was taking escitalopram 10 mg/day for 6 months with some improvement. Consultation was requested due to prominent loss of drive and motivation lasting for 2 months without worsening of depression. He did not display depressive symptoms, but he obtained a score of 62 on the Apathy Evaluation Scale, Clinician version (AES-C). Comprehensive physical examinations and laboratory testing, including brain computed tomography, were normal.

Agomelatine 25 mg/day at bedtime was prescribed in addition to escitalopram and after 2 weeks of treatment his wife noted that the patient seemed more motivated (AES-C score of 51). After another 3 weeks, a significant decline in symptomatology was observed (AES-C score of 40). Two weeks later, the patient reported a further improvement (AES-C score of 29). After another 2 weeks of constant improvement, escitalopram was discontinued without negative effects on symptomatology.

In the present case report, agomelatine remarkably reversed escitalopram-induced apathy and this effect was unrelated to improvement of depression. Moreover, the patient did not report major life changes or stressors that may have confounded the findings.

It has been suggested that SSRI-induced apathy may be due to a hypodopaminergic and/or hyponoradrenergic state, possibly via 5-HT2a post-synaptic stimulation at the mesocorticolimbic level.[2] Agomelatine's observed anti-apathy properties may be due to its action in the 5-HT2c receptors in the frontal cortex.[3] In fact, agomelatine may increase dopamine and noradrenaline levels in the frontal cortex, mainly through the blockade of 5-HT2c receptors' inhibitory input to cortical dopaminergic and adrenergic pathways, explaining the positive outcome observed in this case.[4] This warrants replication in double-blind, controlled studies on larger samples.