Rimonabant-induced depression in schizophrenia.

Sir,

Cannabinoids modulate mood probably through serotonergic neurons in medial prefrontal cortex and cannabinoid receptor (CB1) receptor antagonists may reverse these effects.[1] Rimonabant, a CB1 receptor antagonist and an anti-obesity agent has been associated with depressive and anxiety symptoms in clinical trials[2] though was initially considered to be safe.[3] We report a patient with schizophrenia developing depression possibly due to rimonabant.

Mr. A, 19-year-old male, presented to us in February 2008 with symptoms of delusions of persecution and reference, thought broadcast, 3rd person auditory hallucinations, alogia, anhedonia, amotivation since 2 years. He did not have history of mood symptoms or suicidal ideation. Using mini international neuropsychiatric inventory (MINI) and comprehensive clinical interview, he was diagnosed as having schizophrenia (DSM-IV). He was on treatment with risperidone 6 mg/day and trihexyphenidyl 4 mg and escitalopram 10 mg/day for treatment of negative symptoms since past one month and reported 60% improvement.

On scale for assessment of negative symptoms (SANS), he had a score of 95 and a score of 36 on scale for assessment of positive symptoms (SAPS). His weight was 94.5 kgs, waist circumference 104 cms, and body-mass-index- 30.85 suggestive of obesity. On appetite questionnaire,[4] he had a score of 36. Investigations showed normal fasting glucose and lipid profile, except increased triglycerides (181.9 mg%) and total cholesterol (223 mg%). He was started on Rimonabant 20 mg/day along with dietary modifications and exercise, while other medications were continued. After 1 month, he had no positive psychotic symptoms (zero on SAPS), but continued to have negative symptoms (106 on SANS). He had 4.5 kg reduction in weight (weight- 90 kgs, BMI- 29.38) and 50% reduction in appetite (17 on appetite questionnaire).

He complained of new onset pervasive sad mood, insomnia, feelings of worthlessness, psychomotor retardation, recurrent suicidal ideation, diminished ability to think in the past 2 weeks suggestive of major depressive episode (DSM IV). On Montgomery Asberg depression rating scale (MADRS), he had a score of 34. In view of new onset depressive symptoms, rimonabant was stopped, while rest of the medications continued. Within next 2 weeks, there was improvement in depressive symptoms (22 on MADRS).

The temporal correlation between rimonabant initiation and onset of depressive symptoms and improvement of depressive symptoms on withdrawal of drug points towards possibility of depressive symptoms due to rimonabant. However, post-psychotic depression is a possibility. But rapid recovery as seen in this case is uncommon in post-psychotic depression.[5] New onset of sad mood and suicidal ideation described above are indicative of depression than continuation of negative symptoms. Though patient was on escitalopram 10 mg/day, dose may not have been sufficient to prevent depression of severe intensity as seen in earlier reports.[6] In conclusion, our reports suggest rimonabant can result in new onset depression in patients with schizophrenia and one has to be cautious in initiating rimonabant though there are studies that suggest the contrary.[7]