Sleep disturbances. Disrupted sleep— another hallmark of depression—appears to be a risk factor for weight gain.10 Although the basis for this relationship is still under investigation, one possibility is that some patients with insomnia get up to eat more often than those without sleep disturbances. Research has shown that when sleep is curtailed in a sleep laboratory, patients consume approximately 20% more calories from snacks (1,086 calories) than non-sleep-deprived patients (866 calories).11 Although this 220-calorie increase may seem small, it would amount to approximately 2 lbs of additional weight per month.
Appetite. Although weight loss is a cardinal sign of MDD, increased appetite and weight gain can be seen in many depressed patients who do not meet diagnostic criteria for MDD as well as those with seasonal affective disorder and metabolic syndrome, a condition characterized by insulin resistance, glucose intolerance, atherogenic dyslipidemia, visceral adiposity, hypercoagulation, chronic inflammation, oxidative stress, and hypertension.12
Emerging information about the neuroendocrinology of appetite regulation may lead to a better understanding of weight management in OW/OB-D patients. Leptin, a hormone released by adipose tissue, increases when fat stores are high, leading to reduced appetite and fat stores. Conversely, when fat stores are low, plasma leptin levels decrease, producing increased appetite and reduced energy expenditure.13
Researchers have suggested that leptin insufficiency and/or leptin resistance may contribute to vulnerability to depression, and leptin may have antidepressant effects.14 Lawson et al15 found that leptin levels were inversely associated with Hamilton Depression Rating Scale scores in normal-weight (BMI ≤25) women.
Leptin levels also are significantly associated with comorbid depressed mood and sleep disturbance.16 In healthy volunteers, shortening sleep duration to 4 hours produced an approximately 20% reduction in leptin release compared with normal sleep duration.17 Because of the relationship between sleep disorders and depression, leptin may act on sleep regulatory mechanisms, depressogenic pathways, or both. But studies of leptin’s role in obesity, depression, and sleep have not yet found a single role for leptin that ties all 3 conditions to this hormone’s known physiological functions.
Nonadherence. Compared with non-depressed patients, depressed patients are 76% more likely to not adhere to treatment.18 Patients may report that they are not interested in the treatment program or lack hope that it will be successful. Furthermore, OW/OB-D patients may consider exercise programs to be too strenuous and diet programs too depriving.19
OW/OB-D patients may require special care in monitoring adherence. The presence of depression in patients enrolled in weight loss programs may prompt the treatment staff to modify the usual protocol by including the patient in an active depression treatment module.20
Effects of pharmacologic agents
Many antidepressant agents are associated with weight gain.21Tables 1 and 2 summarize the effects antidepressants and adjunctive medications used to treat depression have on weight.22,23 SGAs such as clozapine and olanzapine, which frequently are used as augmenting agents in patients with treatment-resistant depression (TRD), are associated with weight gain.22 Lamotrigine also is an effective adjunctive medication for TRD and is not associated with significant weight gain.24
Bupropion has antidepressant and weight-loss effects and may be a suitable primary medication for OW/OB-D patients.
Early weight gain with olanzapine/fluoxetine combination may be a strong indicator of substantial weight gain with longer-term treatment. A weight gain of >2 kg (4.4 lbs) during the first 2 weeks of treatment is a strong predictor of weight gain of ≥10 kg (22 lbs) at 26 weeks.25
Antidepressants may be associated with an increased risk of obesity, and strategies to offset this risk may be useful in clinical practice, particularly patient education on the risks of weight gain and early introduction of a diet and exercise program.
Evidence suggests that depression and obesity are associated with alterations in immune activity (Box). This suggests that anti-inflammatory agents might have a role in treating depression by reducing the release of cytokines that may lead to depressive symptoms.
Table 1
Pharmacotherapy and weight gain: Antidepressants
| Agent | Effect on weight |
|---|---|
| SSRIs | |
| Paroxetine | Moderate gain |
| Fluoxetine | Early: weight loss Long-term: moderate gain |
| SNRIs | |
| Duloxetine | Minimal gain |
| Escitalopram | Moderate gain |
| Other agents | |
| Imipramine (TCA) | Moderate gain |
| Selegiline (MAOI) | Moderate gain |
| Trazodone (tetracyclic) | Moderate gain |
| Bupropion (atypical) | Moderate loss |
| MAOI: monoamine oxidase inhibitor; SNRIs: serotonin-norepinephrine reuptake inhibitors; SSRIs: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressant Source: References 22,23 | |