Sir: While depression, dysthymia, and panic disorder can often be effectively treated with the selective serotonin reuptake inhibitors (SSRIs), patients are sometimes left with treatmentemergent sedation or fatigue that can itself be quite disabling. 1,2 Although Keck and McElroy 3 postulated that, for fluoxetine, this may be related to an elevated norfluoxetine/fluoxetine ratio, personal experience has shown this fatigue to be present in some cases where the tested ratio was less than one.Bupropion is an activating antidepressant 4 whose clinical efficacy is thought to be mediated through the dopamine system and which has been used to treat fluoxetine-resistant chronic fatigue syndrome, 5 fatigue due to multiple sclerosis, 6 and apathy due to organic brain syndromes. 7 Three cases where the addition of bupropion was associated with relief from SSRI-induced fatigue are presented. Case 1. Ms. A, a 50-year-old bank worker, was referred 6 years ago with a 5-year history of low energy, partial anhedonia, increased social isolation, moodiness, irritability, nervousness, feeling keyed up, poor sleep, poor concentration, trouble coping with stress, and excessive worrying. She responded favorably to fluoxetine 20 mg/day, but within 2 months had started feeling more tired during the day. Attempts to decrease the dose to 20 mg every other day resulted in partial relapse. She opted to continue with 20 mg q.d. because of the efficacy. Her 5-year bout with this fatigue ended within a week of adding bupropion 75 mg q.a.m. to her fluoxetine, and there were no adverse effects. She now feels continued relief from her dysthymia with no daytime fatigue.Case 2. Mr. B, a 46-year-old teacher, was referred 2 years ago because of a lifelong history of angry outbursts, irritability, being "too intense," occasional restless sleep, carbohydrate cravings, and obsessive-compulsive personality traits. He responded well to sequential trials of fluoxetine, sertraline, and nefazodone, but had side effects to all, including decreased sexual functioning, sweating, gassy abdominal bloating, fatigue, overeating, and weight gain. He did best on paroxetine 20 mg/day, complaining only of continued fatigue and trouble taking off extra weight. The fatigue had started to creep back the second month after starting paroxetine, and by Month 3, he felt like a "couch potato," lacking energy and motivation in addition to "sleepiness." During his previous fluoxetine trial, his target symptoms had returned when dosage reduction from 20 to 10 mg/day was attempted. Therefore, instead of reducing the paroxetine dose, bupropion was added. He noted no improvement after 1 week at 75 mg q.a.m., but when the dose was increased to 150 mg q.a.m., his daytime fatigue disappeared within a week. He continues to maintain the efficacy from the paroxetine, and there have been no new side effects attributable to the bupropion.Case 3. Ms. C, a 47-year-old teacher, was originally seen 3 years ago owing to worsening symptoms for several years, including depressed and anxious mood,...
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