Printable Version

Home > Abstracts of Current Literature > Weight Gain Associated With SSRI's in OCD Treatment

Weight Gain During Long-Term Treatment of Obsessive-Compulsive Disorder: A Prospective Comparison Between Serotonin Reuptake Inhibitors

Background: Weight gain during antidepressant treatment has been studied mainly in patients with depression; however, this issue has not been addressed specifically in patients with obsessive-compulsive disorder (OCD).

Objective: The aim of this study was to establish whether long-term pharmacotherapy of OCD could lead to an increase in weight, and whether this weight gain is to be considered clinically significant. The study also wanted to verify whether patients taking different antiobsessive drugs experience weight gain differently.

Methods: In this study, patients were first entered into a 6-month acute treatment phase. Patients who met the criteria for treatment response were then entered into a 2-year extension. Both phases were prospective, naturalistic, parallel-group, open-label studies with non-random assignment based on clinical decisions. All patients had to meet DSM-IV criteria for OCD. To be included in the 2-year extension, patients had to meet the criteria for response (a decrease of at least 35% in Yale-Brown Obsessive Compulsive Scale [YBOCS] total score) at the end of the 6-month acute treatment phase. Exclusion criteria were pregnancy; lactation; a current or past diagnosis of eating disorder, schizophrenia, or other psychotic disorders; substance use disorders; an organic mental disorder; a medical illness that would contraindicate the use of serotonin reuptake inhibitors (SRIs); patients currently meeting diagnostic criteria for a major depressive episode or having a 17-item Hamilton Rating Scale for Depression (HAM-D) total score of at least 15 at the screening visit. The original sample contained 292 patients. During the 2-year follow-up period, dosages varied within each treatment group according to tolerability and response; however, daily dosages were within the following ranges at any time during the follow-up: clomipramine 150-250 mg (N=23), citalopram 40-80 mg (N=21), fluoxetine 40-80 mg (N=23), fluvoxamine 200-300 mg (N=28), paroxetine 40-80 mg (N=21), and sertraline 150-200 mg (N=22). Patients were consecutively recruited and followed from May 1998 to March 2003 and were maintained on drug treatment for at least 2.5 years. Primary outcome measures included mean weight changes in kilograms across time among the different treatment groups for all patients who completed the follow-up period, mean percentage change in weight across time among SRIs, and the number of patients who experienced at least a 7% or greater increase in weight. Power was not addressed, and a safety analysis was not performed. Exclusion-of-subjects analysis was the data handling method utilized in this trial.

Results: From the original sample of 292 patients, 267 (91.4%) completed the 6-month acute treatment phase. A total of 149 (55.8%) met the criteria for response and were entered into the 2-year extension. Eleven patients were lost to follow-up. Thus, 138 patients completed the 2-year follow-up. At the end of the 2.5-year study period, patients had gained a mean of 2.5% of body weight with respect to baseline, equal to 1.58 kg. When considering “extreme” weight gain, 14.5% of the total sample experienced at least a 7% increase in weight at the end of the study period. Within each but the fluoxetine group, a significant increase in weight (kg) from baseline to final visit was reported (clomipramine, p<0.001; citalopram, p=0.002; fluoxetine, p=0.303; fluvoxamine, p<0.001; paroxetine, p=0.001; sertraline, p=0.010). There was a significant difference in weight gain between treatment groups after 2.5 years (p=0.009), with clomipramine being associated with the highest mean increase in weight and fluoxetine and sertraline with the lowest. A higher proportion of clomipramine-treated patients (34.8%) gained at least 7% in weight as compared with sertraline and fluoxetine, which accounted for the lowest percentage of patients with a significant weight gain (4.5% and 8.7%, respectively. When patients were categorized by gender, female patients (N=70) experienced a higher mean final increase in weight than male patients (N=68) (3.25±4.56% vs. 1.77±2.44% of body weight; p=0.019). The authors concluded that risk of weight gain during extended SRI treatment for OCD differs depending on which drug is used, and the differences among antiobsessive drugs may affect compliance with medication and health risks.

Strengths: Authors had no conflicting affiliations. “Extreme” weight gain threshold of at least 7% was used in other clinical trials. Baseline patient characteristics were similar. It was beneficial to compare a variety of medications.

Weaknesses: Confidence intervals were not reported (CI would show the range of true population while SD only shows variance of sample population). There was a lack of power, and the small number of patients in each group could lead to type II error. The study compared a TCA to SSRI with respect to side effects. The study was open-label which could introduce. There was an absence of a placebo arm to establish if the observed weight gain was truly related to the pharmacologic effects of the drugs. Non-random assignment was based on clinical decisions, and compliance was not addressed. Also, doses of the agents used varied and could have affected the results.

Conclusion: The authors concluded that antidepressant-induced weight gain during long-term OCD treatment can be regarded as a true medication side effect. However, even the authors recognized that the absence of a placebo arm makes it difficult to establish if the observed weight gain was strictly due to the pharmacologic effect of the drugs. I believe that there are too many limitations in this study for it to have a direct impact in clinical practice. However, I believe that this study should raise awareness of possible weight gain with these drugs in OCD patients, especially with clomipramine and women. Further, randomized controlled trials are needed to validate these results.

Jason Gevanosky, PharmD. Candidate