Favorable Effect of Milnacipran on Depression Induced by Interferon-Alpha

SIR: Milnacipran is a novel serotonin and noradrenaline reuptake inhibitor. To our knowledge, this is the first report of a patient whose depressive symptoms induced by interferon ameliorated by treatment with milnacipran.

Case Report

A 71-year-old man with no history and no family history of psychiatric disorders was admitted to our hospital for renal cancer. He underwent surgery for removal of his left kidney and of a metastatic focus in a lumbar spinal process. One month after the operation, intramuscular injections of interferon-α-2a were started at a dosage of 3 million units three times weekly. One week after the start of interferon therapy, he started to complain of depressive mood, lassitude, and irritability. The dosage of interferon was reduced to 3 million units once a week, and trazodone 100 mg/day was prescribed. Four weeks after beginning the trazodone, the patient's irritability remitted and his depressive mood lessened. His lassitude remained unchanged.

The patient's depressive mood increased during the 2 or 3 days following the interferon injections, and he requested another reduction in the dosage of interferon. It was reduced to 3 million units once monthly, but the patient's depressive mood remained, and it increased during the 2 or 3 days following the injection. We suggested an increase in the dosage of trazodone, but the patient refused because of the side effect of thirst. We suggested trying a different antidepressant, namely, milnacipran, and the patient agreed. The trazodone dosage was reduced to 50 mg/day, and milnacipran 50 mg/day was started. Two weeks later, the trazodone was stopped and the milnacipran dosage was increased to 75 mg/day. One week after the start of the new prescription, the patient's thirst lessened. Four weeks afterward, his depressive mood and lassitude disappeared completely. His mood did not deteriorate during the 2 or 3 days following interferon injections. More than 1 year has passed since his operation. His cancer and depressive symptoms have not returned.

Comment

Interferons have both antiviral and antineoplastic properties that allow them to be used to treat a variety of medical conditions.¹ Symptoms of depression are frequently seen in patients receiving treatment with interferon-α,² and treatment of the depression is a matter of concern in clinical practice. Kamata et al.³ examined the effect of a single intracerebroventricular injection of interferon-α on monoamine concentrations in the rat brain. They found that the levels of serotonin and noradrenaline were reduced in a dose-dependent manner in the frontal cortex. These neurochemical changes are possible mechanisms of depression induced by interferon. In our patient, trazodone 100 mg/day was partially effective, and milnacipran 75 mg/day was completely effective. The primary pharmacological action of trazodone is a blockade of 5-HT₂ postsynaptic receptors.⁴ The primary pharmacological action of milnacipran is a dual reuptake-inhibition of serotonin and noradrenaline.⁵ Given the neurochemical changes reported by Kamata et al.,³ an antidepressant that activates both serotonin and noradrenaline neurotransmission may be more effective for depression induced by interferon-α.