Augmentation with ramelteon to achieve remission in geriatric major depression


THE MELATONERGIC SYSTEM may be associated with the pathophysiology of depression.1 MT1 receptors acutely inhibit firing in the suprachiasmatic nucleus while MT2 receptors contribute to phase shifting.1 Ramelteon is a synthetic analog of melatonin that acts specifically on MT1/MT2 melatonin receptors.2 Ramelteon has a longer half-life and greater affinity to MT1/MT2 receptors than melatonin.3 This case report presents the successful use of ramelteon as augmentation treatment in geriatric major depression without any side-effects. To our knowledge, this is the first published report of such an intervention. The present patient provided informed consent for the publication of this case.

A 77-year-old man was brought to hospital in December 2010. On initial evaluation he reported a number of depressive symptoms including depressive mood, decreased sleep, loss of appetite, poor concentration and low energy. He had been diagnosed with major depressive disorder according to DSM-IV and another physician had prescribed two kinds of hypnotics 1 month previously. Unfortunately, he had a traffic accident due to drowsiness in November 2010, which was the reason for the hospital presentation. At the time of consultation, he was taking brotizolam 0.25 mg/day, and zolpidem 5 mg/day, but he still had severe insomnia. The initial Hamilton Rating Scale for Depression (HAM-D) score was 23, with a significant complaint of sleep disturbance. The zolpidem was continued, but the brotizolam was stopped because of daytime sleepiness. Instead, the patient was treated with 50 mg sertraline twice a day. After 2 weeks treatment of treatment there was almost no change in his mental condition, including severe insomnia. Therefore, we proposed to retain sertraline and change zolpidem to 8 mg ramelteon at bedtime, which he consented to. In January 2011, 2 weeks after the change, he reported that his sleep quality had improved, which was obviously noticeable in his calm facial expression, within a few days. The HAM-D score had declined to 13, and, 4 weeks later, the HAM-D score was 6. Six months later, the patient was still in remission on ramelteon and sertraline treatment.

Because of the very beneficial effect of serotonin re-uptake inhibitors in most depressed patients, decreased serotonin availability is almost certainly important in those patients. Whether this has anything to do with the role of melatonin, however, is not clear; in fact a decrease in serotonin availability may not involve effects on production of melatonin. Although a single case report should be interpreted with caution, we propose that ramelteon may be an effective and easily tolerated supplementary treatment for geriatric major depression. Further studies in a more controlled manner are warranted to determine the effectiveness of ramelteon in addition to antidepressants.