Drugs That Cause Weight Gain

Abstract

Among drugs which cause weight gain, the tricyclic antidepressant medications are a drug class producing persistent andproblematic bodyweight gaininmanytreated patients. Major depressive illness is often associated with reductions in appetiteandbodyweight,andtreatmentwith antidepressants effectively restores mood,appetite andweight. However, afrequent complaint of patients treated with tricyclic drugs is of excessive and unwanted weight gain, oftentimes resulting in medication noncompliance. The incidence of weight gain during acuteandchronic treatmentwith different, frequently prescribed antidepressant drugs will be reviewed, as will the possible mechanisms by which such drugs alter caloric intake and expenditure, contributing to drug-induced weight gain. Key words: antidepressants, ingestive behavior, obesity, depressionTricyclic Antidepressants and Weight Gain: Defining the Problem Change in body weight is a frequent symptom of major depression, likely secondary to alterations in appetite. Patientstypicallylose weight (12,13,15), althoughsomedo gain weight during a depressive episode (12,17,18). As a pharmacologic treatment, the tricyclic antidepressants remain, even after almost 40 years, the first choice of medication for the treatment of severe major depression throughout the world (16). Althoughvery effective agents for restoration of normal mood, there are numerous side effects associated with this drug treatment, particularly unwanted and excessive weight gain. Previously, weight gain during antidepressant treatment had been interpreted as a positive sign of improvement, so prevalent and predictable was the effect. Such weight gain is of concern to both patient and clinician, as this is the reason often cited for medication non-compliance. Over the past 15 years, severalnewer medications of a different drug class, the selective serotonin reuptake inhibitors (SSRk), have become available. These drugs are effective as antidepressants, without the side effect of weight The use of two frequently prescribed tricyclic drugs, amitriptyline (4,8,10,14) and imipramine (1,4,5) havemost often been associated with increasing body weight during treatment (Table 1). Moreover, withinthe tricyclic drug class, amitriptyline appears to promote weight gain to a much greater degreethanthe others (Table 1). In contrast, zimelidine, (which is no longer prescribed but belongs in the category of selective serotonin reuptake inhibitors) did not promote weight gain. Importantly, in our own studies, no relationship between clinical response and weight gain was observed (4,5,10). In fact, weight change during drug treatment was not negatively correlated with that occurring at disease onset; that is, weight gain was not simply areflection of weight lost during the depressive episode. These results suggest that drug-induced changes in weight likely result from a pharmacologic action of the drug independent of its effect on mood. The mechanism(s) by which tricyclic antidepressants promote weight gain are not well understood and can r...

Obesity: What Mental Health Professionals Need to Know

“…Several classes of psychotropic medications are associated with unwanted weight gain, including antipsychotics, antidepressants, mood stabilizers, and, to a lesser degree, anxiolytics (68)(69)(70). Weight gain could theoretically be due to increased energy intake, decreased energy expenditure, or a combination of the two; in most cases, we have too little information to distinguish among these possibilities.…”

“…However, as reviewed by Ackerman and Nolan (68), more recent studies have reported relatively modest mean weight gains, even over the long term, and much larger increases in a relatively small number of patients. Of the tricyclics, amitriptyline is thought to induce the most weight gain (67,69). The mechanism of tricyclic antidepressant-induced weight gain appears to involve decreased basal metabolic energy expenditure and diet-induced thermogenesis.…”

“…The mechanism of tricyclic antidepressant-induced weight gain appears to involve decreased basal metabolic energy expenditure and diet-induced thermogenesis. Shifts in food preference toward calorically dense foods occur in a minority of patients but do not seem to be associated with significant weight gain (69). Among the MAOIs, the reversible inhibitors of MAO A such as moclobemide (not yet available in this country) appear to be least likely to induce weight gain (77).…”

“…Why do SSRIs differ from tricyclic antidepressants and MAOIs in their effects on weight? Proposed mechanisms include SSRI-induced increases in metabolic rate (69) or serotonin-mediated effects on appetite and food intake. However, although the SSRI fluoxetine is known to decrease binge eating in patients with bulimia nervosa (80) and to decrease meal size but not frequency in overweight women (81), the effects of SSRIs on food intake have not yet been well characterized.…”

Weight development over time in parous women—The SPAWN study—15 years follow-up

“…1 Body weight at one age is strongly correlated with body weight decades later, which suggests a strong genetic influence on body weight. 2,3 However, the genotypical body weight development depends upon environmental influences such as lifestyle, 4,5 and various life events, for example, illness, 6 long-term medication 7 and pregnancy, 8 can alter the genetically programmed weight development trajectory.…”