How to Control Weight Gain When Prescribing Antidepressants

Web audio at CurrentPsychiatry.com Dr. Schwartz: Strategies to help patients maintain healthy weight during treatment How to control weight gain when prescribing antidepressants Address diet and exercise first, then consider switching antidepressants or prescribing an adjunctive agent Jeffrey S. MacDaniels, MD he prevalence of undesired weight gain in the United States has Clinical Assistant Instructor reached an all-time high, with 68.5% of adults identified as over- Thomas L. Schwartz, MD weight (body mass index [BMI] ≥25) or obese (BMI ≥30), 34.5% Professor T 1 considered obese, and 6.4% considered extremely obese (BMI ≥40). • • • • Reasons for weight gain include various physical and nutritional factors Department of Psychiatry in a patient’s life, but sometimes weight gain is iatrogenic. Many medi- SUNY Upstate Medical University cations we prescribe are associated with weight gain, including most Syracuse, New York antidepressants and atypical antipsychotics. Clinicians might minimize Disclosures or overlook the risk of weight gain when prescribing antidepressants. The authors report no financial relationship with any company whose products are mentioned in this article Patients with major depression often have associated weight loss. or with manufacturers of competing products. Regaining weight can be seen as sign of successful treatment of depres- sive symptoms. If weight gain after treatment exceeds the amount of weight loss attributed to depression, however, medication could have caused the excessive gain. This is considered a side effect, or iatrogenic weight gain, and should not be considered normal or clinically acceptable. Patients who are overweight or obese when beginning antidepressant treatment might be at greater medical risk when placed on a medication that can cause additional weight gain. The time to onset of weight gain during treatment can predict weight gain patterns; those affected in the first month are most at risk of future excessive weight gain.2 In this article, we discuss: • considerations when prescribing antidepressants • ways to approach weight gain • medications available to assist in weight loss. continued Current Psychiatry ©CLARK DUNBAR/CORBIS Vol. 15, No. 6 31 Our general recommendations as surrogate markers of health, and then Screen. The United States Preventive statistically compare results with patients’ Services Task Force maintains a Class-B corresponding BMI. Their findings showed recommendation for screening all patients that approximately one-half of people who for obesity. This means that the Task Force’s are overweight and 29% of obese people review panel determined that such screen- can be considered healthy.4 ing is at least moderately or substantially Weight gain with beneficial.3 Screening is important in a set- antidepressants ting of potential weight gain in patients tak- Potential causes of weight gain ing an antidepressant. There may be more than one reason for weight gain during depression treatment, Educate and treat. Provide at least some so a multifactorial management approach education and encouragement about eat- might be necessary, depending on the ing a healthy diet and exercising, or refer patient’s medication regimen. Appetite the patient to a nutritionist or dietician. might be influenced by physical (chemi- Next, initiate psychotherapy (motivational cal, metabolic) and psychological (cultural, Clinical Point interviewing, cognitive-behavioral therapy familial) factors. The following sections Provide education [CBT]) as needed. Reserve anti-obesity focus on specific antidepressant classes and medications for those who do not respond their proclivity for weight gain. and encouragement to weight loss efforts or who might be tak- about eating ing an antidepressant for the long term. a healthy diet and The need for medical management of Serotonergic antidepressants exercising, or refer weight gain has given rise to specialists Many patients with depression are treated who treat this complicated, multifactorial with medications that alter serotonin levels the patient to condition. Whether psychiatrists should be in the body, such as selective serotonin a nutritionist seen as a substitution for their specialty is reuptake inhibitors (SSRIs) or serotonin- not the purpose of this review; rather, how norepinephrine reuptake inhibitors (SNRIs). we might more effectively (1) work on our This neurotransmitter often is affected patients’ behalf to mitigate potential weight through depression treatment, and therefore gain from the treatments that we prescribe might be a factor contributing to unintended and (2) participate in consultations that weight gain. In mice bred to lack serotonin we’ve provided on their behalf. 5-HT2c receptors in proopiomelanocortin (POMC) neurons, the expected anorec- tic reaction to serotonergic agents often is BMI is not an absolute marker reversed, causing a robust increase in hyper- of health phagia and obesity.5 This effect indicates that BMI likely should not be viewed as a marker 5-HT2c receptor stimulation might control with absolute prognostic certainty of overall appetite and feeding. health of an overweight or obese person: An After SSRI or SNRI treatment, accumula- overweight person considered healthy from tion of serotonin over time in the synaptic a cardiovascular and metabolic perspective cleft is thought to result in down-regulation could still benefit from preventing further of 5-HT2c receptors. This may cause a rela- weight gain. tive absence of 5-HT2c receptors, similar Tomiyama et al4 concluded that BMI to what is seen in mice who lack them bio- itself was insufficient to stratify health in logically. The loss of these receptors or their Discuss this article at a meaningful way—and that such a focus activity often will result in excessive weight www.facebook.com/ would lead to overweight and obese people gain. Some sedating antidepressants (mir- CurrentPsychiatry in otherwise good health being penalized tazapine) and some second-generation anti- unfairly through higher health insurance psychotics (SGAs) (olanzapine, quetiapine) premiums, and would divert focus on those directly block 5-HT2c receptors and might with less optimal health but a normal BMI. cause more rapid weight gain. Lorcaserin, The researchers’ goal was to use blood pres- a selective 5-HT2c receptor agonist, theo- Current Psychiatry 32 June 2016 sure, lipid levels, and glycemic markers retically could reverse this proposed weight continued on page 35 continued from page 32 gain mechanism and suppress appetite also mildly inhibits uptake of norepineph- by activating the POMC pathway in the rine—meaning that this drug might have hypothalamus. less weight gain potential. These medica- Among SSRIs and SNRIs, paroxetine tions are not used frequently for treating might be one of the worst for provoking depression, but trazodone is used as an long-term weight gain; a study showed an adjunctive agent for insomnia. Used even average increase of 2.73 kg over a 4-month at off-label low dosages, trazodone exerts period.6 H1-histaminic and α-1 adrenergic antago- Theoretically, SNRIs have the ability to nistic properties, decreasing the level of increase noradrenergic tone. This might be consciousness and allowing sedation and associated with nausea and a decline in appe- somnolence. Because of its fast onset and tite or it might generally curb appetite. These relatively short duration of action, it can agents likely will cause less future weight improve depression symptoms by pro- gain. SNRIs typically induce more norad- moting restful sleep as well as by facilitat- renergic tone at increasingly higher dosages. ing monoamine neurotransmission. It also There may be a dose-response curve in this might add to weight gain because of its manner. Levomilnacipran likely is the most pharmacodynamic receptor profile. Clinical Point noradrenergic of the SNRIs; recent regula- SNRIs can increase tory studies suggest no statistically signifi- cant weight gain over the long term.7 Tricyclic antidepressants noradrenergic tone, Amitriptyline can be associated with release which might be of tumor necrosis factor-alpha, which is associated with Sedating antidepressants implicated in causing weight gain. Many nausea and a decline Mirtazapine has receptor-blocking effects TCAs block H1 (amitriptyline, imipramine, in appetite on noradrenergic α-2 and serotonergic clomipramine), likely causing weight gain. 5-HT2a and 5-HT2c receptors. Additionally, Most TCAs antagonize muscarinic receptors histamine blocking of H1 receptors can con- as well. The more noradrenergic TCAs could tribute to additional weight gain, similar to curb appetite (nortriptyline, desipramine, what is seen with some SGAs. H1 antago- protriptyline) similar to SNRIs, therefore nism dampens satiety response, resulting in countering some of the weight gain drive. increased caloric intake. In that case, or when As an example, in a meta-analysis exam- specific SGAs are used for managing depres- ining weight gain with antidepressants, sion, appetite increases (H1 antagonism) and amitriptyline was associated with weight metabolism slows (possibly 5-HT2c antago- gain of 1.52 kg above baseline in the acute nism, muscarinic receptor antagonism, etc.), period (4 to 12 weeks) and 2.24 kg above thus allowing for greater adipose tissue baseline at 4 to 7 months.6 These results growth and leptin insensitivity. of the acute phase should be viewed cau- In a meta-analysis, mean weight tiously because the authors reported high increased

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