Milnacipran treatment of a terminally ill cancer patient with major depressive disorder

A significant amount of evidence supports the efficacy of tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) in patients with cancer (Berard, 2001). TCAs should be used carefully since they can produce adverse events such as orthostatic hypotension, drowsiness, dry mouth, blurred vision and constipation. Such adverse events frequently prevent patients from taking the medicine. On the other hand, though SSRIs are superior to TCAs in terms of adverse events, they are inferior to them in terms of antidepressant efficacy in inpatients (Anderson, 2000). Milnacipran, a novel selective serotonin and noradrenaline reuptake inhibitor (SNRI) (Mochizuki et al., 2002), has been shown to possess clinical antidepressant efficacy with few adverse events (Puech et al., 1997; Lopez-Ibor et al., 1996). This paper reports a terminally ill cancer patient with major depressive disorder, whose depressive symptoms rapidly improved on medication with milnacipran. A 61-year-old male was diagnosed with advanced stage lung cancer. After 3 months, he was admitted to our Department of Internal Medicine because of difficulty in breathing and severe pain. After 3 weeks of admission, he was referred to our Department of Psychiatry. He experienced loss of energy, depressed mood, anxiety, fatigue, loss of appetite, feelings of guilt and suicidal thoughts. He was diagnosed with major depressive disorder that matched the DSM-IV criteria. The severity of depression was evaluated with the Montgomery-Åsberg depression rating scale (MADRS) (Montgomery and Åsberg, 1979). The MADRS score before treatment was 36. He was administered zolpidem 10 mg/day and trazodone 50 mg/ day for sleep disturbance, an anticancer agent, morphine for pain control, an antacid and laxatives. Milnacipran 50 mg/day was added to the medical regime. After 1 week of milnacipran administration, his depressive symptoms improved partially and he began to smile. At that time, MADRS score was 18. The dosage of milnacipran was increased to 100 mg/day in order to obtain a sufficient antidepressant effect. Two weeks after the start of milnacipran therapy, he was no longer depressive. Feelings of guilt and suicidal thoughts disappeared. He was calm, composed and complained only of difficulty in breathing and pain. The MADRS score decreased to 9. He continued to take 100 mg/day of milnacipran and the symptoms did not recur under this treatment. He did not experience any adverse events. He expressed a desire to be discharged from the hospital; however, the metastasis of the cancer to the lumbar vertebrae prevented him from going home. Unfortunately, after 9 weeks of this rapid recovery from his depression, he developed bronchopneumonia and died. The prevalence rates of major depressive disorder are 2–4% in the general population, 6–14% in internal medicine inpatients, and 6–42% in cancer patients (Burvill, 1995). In cancer patients, depressive symptoms develop as a result of normal and/or morbid reactions concerned with cancer notification and fear of death. Patients frequently believe that it is natural to become depressive, and moreover, their depressive symptoms are inadequately treated. Therefore, it is difficult for clinicians to evaluate the severity of depression in cancer patients, in particular, when patients report little or no depressive symptoms. It has been reported that clinicians detect only 33% and 13% cases of mild-to-moderate and severe depression, respectively (Passik et al., 1998). In addition, Tiernan et al. (2002) have reported that depressive symptoms are commonly noted in terminally ill cancer patients, but few are treated with antidepressants. It is extremely important that clinicians adequately evaluate the severity of depressive symptoms in cancer patients and treat them with an appropriate antidepressant in order to improve their quality of life and to support their fight against the illness. In the present case, milnacipran was remarkably effective in alleviating the symptoms of depression and showed rapid improvement after 1–2 weeks