Journal of Clinical Psychopharmacology Volume 20(2), April 2000, pp 272-273 Naturalistic Study of the Weight Effects of Amitriptyline, Fluoxetine, and Sertraline in an Outpatient Medical Setting [Letters To The Editors] Sansone, Randy A. MD; Wiederman, Michael W. PhD; & Shrader, John A. MD ---------------------------------------------- With the possible exception of protriptyline,1 a clinical concern with the administration of tricyclic antidepressants has been weight gain.2, 3 In contrast, the prescription of selective serotonin reuptake inhibitors (SSRIs) may result in either weight loss 4-7 or weight gain.8-12 Most studies exploring appetite or weight effects with SSRIs have been short term (i.e., days to weeks). However, time effects may be important, because weight loss with fluoxetine may occur at the beginning of treatment, but may not continue to a meaningful degree.7, 13 This study was undertaken to retrospectively explore in an ambulatory clinic the naturalistic weight effects over a several-month period of treatment with amitriptyline, fluoxetine, and sertraline. Methods In an ambulatory internal medicine clinic, all patients receiving amitriptyline, fluoxetine, or sertraline, the most commonly prescribed antidepressants in this practice setting, were identified using a computerized office practice management system.14 Only those patients with a recorded weight at antidepressant initiation (seen from July 1, 1984, through October 14, 1997) were selected for the study. Data reviewed included age, sex, weight, and antidepressant type, duration, and dose. The most recent weight in the electronic record during the period in which subjects were being prescribed the antidepressant, as well as the number of months between the drug-initiation weight (time 1) and the last weight (time 2), were coded (less than 1 month was coded as 0). Weight change was calculated by subtracting the weight at time 1 (drug initiation) from the weight at time 2 (i.e., positive values represent weight gain, whereas negative values represent weight loss). When varying doses of antidepressant were prescribed over the study period, the highest dose was coded. Because of the retrospective nature of this study, it was not possible to control for several variables that might have influenced body weight in individual cases (e.g., prescribed weight loss, or weight changes resulting from mood disorder, severity of psychopathology, medical conditions, and adjunctive medications). Results The final sample consisted of 544 patients. The descriptive data are presented in Table 1 as a function of the prescribed antidepressant. Amitriptyline was the most commonly prescribed antidepressant (N = 284), followed by sertraline (N = 180) and fluoxetine (N = 80). Equal proportions of patients in each antidepressant group were female. Patients in each category did not differ with regard to mean age or mean weight change. However, post hoc Scheffe tests revealed that, with regard to starting weight, patients prescribed amitriptyline weighed significantly less than did patients prescribed fluoxetine. With regard to the mean number of months receiving antidepressant treatment, patients prescribed amitriptyline continued treatment for a greater length of time compared with patients prescribed sertraline. Doses most prescribed were 25 mg (47.4%) or 50 mg (31.3%) of amitriptyline; 20 mg (77.5%) of fluoxetine; or 50 mg (73.1%) or 100 mg (20.6%) of sertraline. ---------------------------------------------- Table 1. Descriptive data as a function of antidepressant treatment (N = 544) ---------------------------------------------- The three study cells did not differ with regard to mean weight gained or lost during the study period. However, we calculated the proportion in each group that evidenced some degree of weight gain, which was identical for amitriptyline and fluoxetine groups (52.5%) and significantly higher than for the sertraline group (40.0%) ([chi]2 [2, N = 544] = 7.50, p r = 0.01), fluoxetine (r = 0.13), and sertraline (r = -0.09). When considering only those patients who gained weight during their course of treatment (N = 263), there were no differences between the three antidepressants with regard to the number of pounds gained, body weight at the start of treatment, age at start of treatment, number of months on treatment, or proportion of patients who were female. Discussion The mean weight change while receiving antidepressant treatment was minimal and did not differ as a function of antidepressant type. The proportion of patients who gained weight was significantly higher among patients given amitriptyline and fluoxetine compared with those given sertraline. For those who gained weight, the amount was not significantly different among the antidepressant groups and was not related to dosage. Several important limitations must be noted for this study. First, this study was retrospective in nature (e.g., some potential candidates had to be eliminated at the outset because there was no body weight recorded at the initiation of antidepressant treatment). Second, there are a variety of potentially confounding variables relating to medical conditions and the prescription of other medications that may have influenced weight changes in this sample. Third, there were several differences between study groups (e.g., antidepressant doses were not comparable among study groups; the fluoxetine group was heavier in terms of initial mean weight, perhaps related to anticipation of weight-loss effects; the amitriptyline group had a longer mean duration of treatment, possibly related to treatment of chronic disorders such as fibromyalgia). Finally, the mean age of participants was approximately 50 years, and therefore the findings may not be applicable to younger or geriatric age groups. With each antidepressant type, some patients lost weight, others maintained their weight, and still others gained weight, with no significant overall mean weight change between groups. These observations mask a great degree of variation across patients. Further research is needed to understand why particular individuals gain weight while others maintain or lose weight when taking antidepressants. Randy A. Sansone, MD Department of Psychiatry; Wright State University School of Medicine and Kettering Medical Center; Dayton, OH Michael W. Wiederman, PhD Department of Psychological Sciences; Ball State University; Muncie, IN John A. Shrader, MD Internal Medicine Program and the Transitional Year Program; Kettering Medical Center; Department of Medicine; Wright State University School of Medicine; Dayton, OH References 1. Box J, Arnold LE, Smeltzer DJ. Protriptyline weight loss in compulsive eaters: a placebo-controlled study. J Psychiatr Treat Eval 1983;5:387-91. 2. Fernstrom MH, Kupfer DJ. Antidepressant-induced weight gain: a comparison study of four medications. Psychiatry Res 1988;26:265-71. Full Text Bibliographic Links Document Delivery 3. Fernstrom MH. Drugs that cause weight gain. Obes Res 1995;3:435S-439S. Bibliographic Links Document Delivery 4. Ferguson JM. Fluoxetine-induced weight loss in overweight, nondepressed subjects [letter]. Am J Psychiatry 1986;143:1496. 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