sign in sign up
<<
Home , Anorectic, Vilazodone

Web audio at CurrentPsychiatry.com Dr. Schwartz: Strategies to help patients maintain healthy weight during treatment How to control weight gain when prescribing 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 . 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 . 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, could have caused the excessive gain. This is considered a side effect, or iatro- genic weight gain, and should not be considered normal or clinically acceptable. Patients who are overweight or obese when beginning 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 • 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 . 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. 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 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 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) (, ) 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. , The researchers’ goal was to use blood pres- a selective 5-HT2c receptor , 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 might have hypothalamus. less weight gain potential. These medica- Among SSRIs and SNRIs, tions are not used frequently for treating might be one of the worst for provoking depression, but is used as an long-term weight gain; a study showed an adjunctive agent for . 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 and a decline in appe- . 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. 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 antidepressants noradrenergic tone, 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 has receptor-blocking effects TCAs block H1 (amitriptyline, , in appetite on noradrenergic α-2 and serotonergic ), 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 (, , what is seen with some SGAs. H1 antago- ) 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 by 1.74 kg (P < .0001) in the first 4 heterogeneity among these studies, and the to 12 weeks of mirtazapine treatment, with possibility of publication bias (Egger test, greater variability in periods >4 months.6 P < .0001). In the same meta-analysis, the Among the more novel antidepressants even the more noradrenergic nortriptyline released since the era of tricyclic antidepres- was associated with an increase of 2.0 kg on sants (TCAs) or monoamine oxidase inhibi- average over baseline during acute treat- tor, mirtazapine might have the greatest ment, with that number dropping to 1.24 kg weight gain potential. over baseline at ≥4 months.6

Trazodone and block 5-HT2a and 5-HT2c receptors, as well as serotonin Newer antidepressants reuptake transporters. Compared with Vilazodone is a weak SSRI that aggres- trazodone, nefazodone has a more potent sively partially agonizes pre-synaptic and effect on 5-HT2a receptor antagonism and a post-synaptic 5-HT1a receptors in the CNS. Current Psychiatry less potent effect on 5-HT2c receptors, and This dual site 5-HT1a action is somewhat Vol. 15, No. 6 35 unique among antidepressants. This type in combination with medication. Some of agent sometimes is called multimodal,8 patients might ask about extreme weight- or could be considered an “SSRI +” antide- loss measures, such as low-calorie diets pressant. These are SSRIs at the core combined with intense exercise programs but have additional 5-HT receptor modu- that have been popularized in the media. lating capabilities. Vilazodone has a favor- Although the motivation to initiate and able weight gain profile, as suggested in a maintain meaningful weight loss should Weight gain with 52-week trial reporting 1.7 kg gain over 52 be encouraged, doing so in a more gradual antidepressants weeks, compared with an average of 6.8 to manner should be the goal. 10 kg for long-term SSRI therapy.9 Addressing portion size is a good approach in the early stages of managing is a stronger SSRI that also obesity. Restaurants often serve portions partially agonizes presynaptic 5-HT1a that have more calories than should be con- receptors. In addition, it antagonizes sumed in one meal. Visual cues can influ- 5-HT1d, 5-HT3, and 5-HT7 receptors, giv- ence this trend; using smaller plates can ing it a unique pharmacodynamic profile.10 help reduce caloric intake.15 Clinical Point Vortioxetine also had minimal impact on Exercise, sustained for at least 45 minutes, Eating smaller drug-induced weight gain in 52-week stud- can have long-lasting effects, with a small ies, with data from 2 trials indicating either study showing an increase in metabolic rate portions, combined minimal weight gain in 6.1% of patients of 190 ± 71.4 kcal (P < .001) above baseline with restricting foods (mean increase of 0.41 kg over 52 weeks)11 or for 14 hours after exercise.16 Endurance exer- high in calories and gain that was not statistically significant.12 cise training is associated with a significant fat, should be the first decrease in total cholesterol, triglycerides, Levomilnacipran is unique in that it has the and low-density lipoprotein cholesterol, as step in managing most aggressive norepinephrine reuptake well as an increase in the high-density lipo- weight gain inhibition of all SNRIs.13 Again, increased protein level over a 24-week period.17 noradrenergic tone might curb appetite Encouraging an exercise regimen that and caloric intake. Many SNRIs cause low- is appropriate for your patient can help grade nausea, which could account for maintain weight loss. In small trials,18,19 decreased appetite. Long-term, 52-week high-intensity exercise was shown to help data for this drug also shows minimal pro- suppress appetite and decrease 24-hour clivity for weight gain, with the trial partici- caloric consumption by 6% to 11%.18 pants reporting a slight decrease of 4.34 kg on average from baseline.14 Psychotherapy can become an important intervention for initiating and maintaining weight loss. CBT can help patients recog- Addressing weight gain nize and modify lifestyle components, and Lifestyle modification. Eating smaller por- reinforce behaviors that promote weight tions, combined with restricting foods high loss. This can come from setting realistic in calories and fat, should be the first step. weight loss goals; preventing triggering A simple suggestion to a patient to eat the factors that lead to overeating; encouraging same foods, but remove 20% of the por- portion control during meals; and promot- tion, is a simple intervention akin to that ing exercise habits. of suggesting sleep hygiene practices for In a small, randomized controlled trial insomnia management. Under medical (RCT) examining weight loss in obese supervision or with referral to a dietician or women, those who underwent CBT and nutritionist, more rigid caloric restrictions psychoeducation for 2 hours a week for 10 could be employed. weeks in addition to dietary changes and Commercial weight-loss programs, exercise showed an average weight loss of such as Weight Watchers or Curves, can 10.4 kg at 18-month follow-up, compared be helpful; some insurers will only cover with weight gain of 2.3 kg in the control medications for weight loss if one of group.20 The short duration of treatment in Current Psychiatry 36 June 2016 these programs have been tried or is used this study might be desirable to reduce cost continued on page 38 continued from page 36

Table 1 FDA-approved medications for treating obesity Evidence of efficacy Drug (mechanism of action) Dosage and safety Adverse effects Comments - (NDRI curbs appetite Bupropion, ↓5.2% baseline body mass in first Nausea, Consider if a patient is stopping via DA and NA activation of POMC; μ- 90 mg-naltrexone, year22; safety and efficacy beyond , smoking; contraindicated in receptor antagonist dampens reward pathway 8 mg, 2 tablets 1 year is undetermined22,23 constipation patients with , a history of Weight gain with and removes endogenous POMC activation taken twice a day seizures, or are taking antidepressants negative feedback ligand) Lorcaserin (selective 5-HT2c receptor agonist, 10 mg, twice ↓3 kg from baseline in first year; safety Nausea, vomiting, Theoretical risk of serotonin causing anorectic effect via POMC neurons a day and efficacy beyond 1 year is syndrome (avoid serotonergic activation in the hypothalamus) undetermined24 medications); contraindicated during - ER (topiramate Phentermine, For 7.5/46 mg or 15/92 mg: ↓6.8% Xerostomia, Evaluate after 12 weeks to inhibits appetite stimulation via ↑ GABA and 7.5 mg-topiramate, or 8.8% baseline body mass in first constipation, discontinue or to increase ↓ glutamate release, which ↓↓ NPY and AgRP 46 mg, or year, respectively25 and in second dosage (can gradually increase to pathway; phentermine then ↑ POMC via DAT phentermine, year ↓7.8% or 8.7% respectively26; phentermine, 15 mg-topiramate, and NET inhibition, to ↓↓ appetite further) 15 mg-topiramate, safety and efficacy beyond 2 years 92 mg). Raise or discontinue Clinical Point 92 mg is undetermined25 gradually. Pregnancy category X (congenital malformation risk). CBT can help Use cautiously in patient with history of kidney stones patients recognize (GLP-1 receptor agonist, causes 3 mg/d ↓5.4 kg average in first year; safety Nausea, vomiting, Avoid in patients with personal and modify lifestyle more insulin to be released and suppression of subcutaneous and efficacy beyond 1 year diarrhea, anorexia, or family history of MEN type 2, glucagon; results in decreased appetite, less is undetermined27 hypoglycemia; or medullary thyroid cancer components, and energy storage) rare risk of reinforce behaviors (reversible direct pancreatic and gastric 60 to 120 mg, with ↓3 kg in 1 year28; safety and efficacy Largely GI ↓triglycerides, cholesterol (total that promote enzyme inhibitor, preventing fat breakdown and meals beyond 4 years is undetermined29 (diarrhea, fecal and LDL) ↑ HDL cholesterol. weight loss absorption) urgency) Supplement with multivitamin AgRP: agouti-related protein; DA: ; DAT: ; GABA: γ-aminobutyric acid; GI: gastrointestinal; GLP-1: glucagon like peptide-1; HDL: high-density lipoprotein; LDL: low-density lipoprotein; MEN: multiple endocrine neoplasia; NA: noradrenaline; NDRI: norepinephrine dopamine ; NE: norepinephrine; NET: norepinephrine transporter; NPY: Y; POMC: proopiomelanocortin

and utilization of services. Group formats treating medication-associated weight gain. also could be employed. It is important to obtain any family his- Motivational interviewing is a useful tory of obesity, diabetes, , and tool in addiction psychiatry and shows hyperlipidemia. This will likely indicate a promise for treating obesity and over- patient’s risk for weight gain before initiat- eating as well. The approach may dif- ing medication. fer slightly because weight-loss therapy Obtain vital signs at every visit, includ- involves behavior modification rather ing blood pressure. Monitoring weight at than behavior cessation. In a meta-analysis every clinical visit can be used to calculate of data from RCTs exploring motivational and monitor BMI, while also asking the interviewing and its use as an intervention patient to maintain a log of weight mea- for weight loss, those in the intervention surements obtained at home. Measuring groups experienced significant weight loss abdominal girth is important to watch for as indicated by BMI decreasing a standard- metabolic syndrome, although often this is ized mean difference of −0.51, compared the least measured variable. with control groups.21 Laboratory testing is helpful. Obtaining a baseline lipid panel and a fasting glu- cose level (consider measuring hemoglobin

Medical management A1c in patients with diabetes) is warranted. considerations Including thyroid markers, such as thyroid- . Recognition and early inter- stimulating hormone and thyroxine (free T4), Current Psychiatry Diagnostics 38 June 2016 vention are instrumental in successfully might be important considerations, because Table 1 vortioxetine, and levomilnacipran, might FDA-approved medications for treating obesity have less propensity to cause weight gain. In patients with severe depression, augment- Evidence of efficacy ing with medications containing amphet- Drug (mechanism of action) Dosage and safety Adverse effects Comments amine or could cause Bupropion-naltrexone (NDRI curbs appetite Bupropion, ↓5.2% baseline body mass in first Nausea, Consider if a patient is stopping via DA and NA activation of POMC; μ-opioid 90 mg-naltrexone, year22; safety and efficacy beyond headaches, smoking; contraindicated in some weight loss, but greater care should be receptor antagonist dampens reward pathway 8 mg, 2 tablets 1 year is undetermined22,23 constipation patients with anorexia, a history of taken because of cardiovascular effects and and removes endogenous POMC activation taken twice a day seizures, or are taking opioids dependency issues. negative feedback ligand) Discussing with your patient the pos- Lorcaserin (selective 5-HT2c receptor agonist, 10 mg, twice ↓3 kg from baseline in first year; safety Nausea, vomiting, Theoretical risk of serotonin causing anorectic effect via POMC neurons a day and efficacy beyond 1 year is diarrhea syndrome (avoid serotonergic sibility of changing or worsening depres- activation in the hypothalamus) undetermined24 medications); contraindicated sive symptoms when adding or switching during pregnancy medications allows them to be aware and Phentermine-topiramate ER (topiramate Phentermine, For 7.5/46 mg or 15/92 mg: ↓6.8% Xerostomia, Evaluate after 12 weeks to engaged in the process and can encour- inhibits appetite stimulation via GABA and 7.5 mg-topiramate, or 8.8% baseline body mass in first constipation, discontinue or to increase ↑ age them to notice and report changes. ↓ glutamate release, which ↓↓ NPY and AgRP 46 mg, or year, respectively25 and in second paresthesias dosage (can gradually increase to pathway; phentermine then ↑ POMC via DAT phentermine, year ↓7.8% or 8.7% respectively26; phentermine, 15 mg-topiramate, Developing a sensible schedule to taper and NET inhibition, to ↓↓ appetite further) 15 mg-topiramate, safety and efficacy beyond 2 years 92 mg). Raise or discontinue an existing medication slowly over several 25 92 mg is undetermined gradually. Pregnancy category X weeks and allowing a new one to build up Clinical Point (congenital malformation risk). Use cautiously in patient with gradually to a therapeutic level can help Recognition and history of kidney stones minimize adverse effects or a discontinua- early intervention Liraglutide (GLP-1 receptor agonist, causes 3 mg/d ↓5.4 kg average in first year; safety Nausea, vomiting, Avoid in patients with personal tion syndrome. more insulin to be released and suppression of subcutaneous and efficacy beyond 1 year diarrhea, anorexia, or family history of MEN type 2, If switching antidepressants is not pos- are instrumental glucagon; results in decreased appetite, less is undetermined27 hypoglycemia; or medullary thyroid cancer energy storage) rare risk of sible, or is ineffective, an anti-obesity in successfully pancreatitis medication (Table 122-29) can be considered. treating medication- Orlistat (reversible direct pancreatic and gastric 60 to 120 mg, with ↓3 kg in 1 year28; safety and efficacy Largely GI ↓triglycerides, cholesterol (total These medications should not be consid- 29 associated weight enzyme inhibitor, preventing fat breakdown and meals beyond 4 years is undetermined (diarrhea, fecal and LDL) ↑ HDL cholesterol. ered first-line in weight loss management, absorption) urgency) Supplement with multivitamin but reserved for more difficult or refractory gain AgRP: agouti-related protein; DA: dopamine; DAT: dopamine transporter; GABA: γ-aminobutyric acid; GI: gastrointestinal; GLP-1: glucagon like peptide-1; HDL: high-density lipoprotein; LDL: low-density lipoprotein; MEN: multiple endocrine neoplasia; weight loss challenges and in patients who NA: noradrenaline; NDRI: norepinephrine dopamine reuptake inhibitor; NE: norepinephrine; NET: norepinephrine transporter; are not able to participate in weight loss or NPY: neuropeptide Y; POMC: proopiomelanocortin dieting programs because of cognitive disor- ders, a history of nonadherance, financial or travel limitations, or in those with poor social inadequate management of hypothyroidism support systems such as homelessness. can complicate the clinical picture. Some of these medications are not reim- Follow-up testing should be ordered bursed by insurance companies; therefore, every 3 to 12 months to monitor progress consider the financial burden to the patient if your patient is showing signs of rapid and their capacity for adherence to ther- weight gain, or if BMI nears ≥30 kg/m². apy, and discuss this challenge before initi- These guidelines generally are assigned ating treatment. There is some evidence for for prescribing of SGAs, but can be applied using medications off-label to treat obesity when using any psychotropic with weight (Table 2,30-34 page 47). gain potential. Anti-obesity medications typically are considered for patients with a BMI >30 or in any overweight patient with diabetes, Medications to consider hyperlipidemia, or cardiovascular disease. When considering the medication regimen As always, discuss with patients and their as an intervention point, consider changing primary care provider the potential ben- the antidepressant to one that is not associ- efits and risks of adding any of these or ated with significant weight gain. Although other medications to an existing treatment not specifically indicated as a monotherapy regimen. for weight loss, switching to or augmenting If weight loss goals are not met, con- therapy with bupropion could aid weight sider discontinuing anti-obesity therapy. loss through appetite suppression.20 Some Patients and physicians should be cognizant Current Psychiatry newer antidepressants, such as vilazodone, of the need to continue long-term mainte- Vol. 15, No. 6 39 continued on page 47 continued from page 39

Table 2 Medications used off-label to treat obesity FDA-approved Evidence Drug (mechanism indication and of efficacy Adverse of action) dosage and safety effects Comments Type 2 diabetes ↓2 kg in 1 year30; Risk Weight loss is (biguanide mellitus (850 mg, safety and efficacy of lactic modest antihyperglycemic) twice a day) beyond 10 years is acidosis undetermined31 Exenatide (GLP-1 Type 2 diabetes ↓2.49 kg in Nausea Requires injection receptor agonist; mellitus (10 μg 35 weeks; twice daily. Avoid in causes more insulin subcutaneous longer efficacy those with personal to be released and injection, before is undetermined; or family history suppression of breakfast and safety longer of MEN type 2, or glucagon. Results in dinner) than 3 years is medullary thyroid decreased appetite, undetermined32 cancer; small trial less energy storage) size Partial seizures ↓3.3 kg greater than , Moderate weight () (400 mg/d) diet and lifestyle nausea, loss, but high Clinical Point intervention; vomiting adverse effect rate safety and efficacy If switching beyond 1 year is undetermined33 antidepressants is Pramlintide Types 1 and 2 ↓2.27 kg in first Nausea, Those randomized not possible, or is (synthetic human diabetes mellitus year; safety headache, to drug in trial ineffective, an anti- amylin analogue) (120 to 360 mcg, and efficacy anorexia had ↑ 1.8 times twice or 3 times beyond 1 year is likely to report obesity medication a day34) undetermined34 nausea. Requires subcutaneous can be considered injection twice daily GLP-1: glucagon like peptide-1; MEN: multiple endocrine neoplasia

nance on these medications after successful 8. Schwartz TL, Siddiqui UA, Stahl SM. Vilazodone: a brief pharmacological and clinical review of the novel treatment—perhaps indefinitely, because serotonin and reuptake inhibitor. Ther Adv patients frequently regain weight after medi- Psychopharmacol. 2011;1(3):81-87. 9. Robinson DS, Kajdasz DK, Gallipoli S, et al. A 1-year, cation is discontinued. open-label study assessing the safety and tolerability of vilazodone in patients with major depressive disorder. J Clin Psychopharmacol. 2011;31(5):643-646. References 10. Stahl SM. Modes and nodes explain the mechanism of 1. Ogden CL, Carroll MD, Kit BK, et al. Prevalence of action of vortioxetine, a multimodal agent (MMA): actions childhood and adult obesity in the United States, 2011-2012. at serotonin receptors may enhance downstream release JAMA. 2014;311(8):806-814. of four pro-cognitive neurotransmitters. CNS Spectr. 2015; 2. Vandenberghe F, Gholam-Rezaee M, Saigí-Morgui N, et al. 20(6):515-519. Importance of early weight changes to predict long-term 11. Jacobsen PL, Harper L, Chrones L, et al. Safety and weight gain during psychotropic drug treatment. J Clin tolerability of vortioxetine (15 and 20 mg) in patients with Psychiatry. 2015;76(11):e1417-e1423. major depressive disorder: results of an open-label, flexible- 3. Grade Definitions. Electronic Preventive Services Selector dose, 52-week extension study. Int Clin Psychopharmacol. (ePSS). http://epss.ahrq.gov/ePSS/gradedef.jsp. Accessed 2015;30(5):255-264. May 2, 2016. 12. Boulenger JP, Loft H, Olsen CK. Efficacy and safety 4. Tomiyama AJ, JM, Nguyen-Cuu J, et al. of vortioxetine (Lu AA21004), 15 and 20 mg/day: a Misclassification of cardiometabolic health when using body randomized, double-blind, placebo-controlled, - mass index categories in NHANES 2005-2012 [published referenced study in the acute treatment of adult patients online February 4, 2016]. Int J Obes (Lond). doi: 10.1038/ with major depressive disorder. Int Clin Psychopharmacol. ijo.2016.17. 2014;29(3):138-149. 5. Berglund ED, Liu C, Sohn J, et al. Serotonin receptors 13. Grady MM, Stahl SM. Novel agents in development for the in pro-opiomelanocortin neurons regulate energy treatment of depression. CNS Spectr. 2013;18(suppl 1):37-40; and glucose homeostasis. J Clin Invest. 2013;123(12): quiz 41. 5061-5070. 14. Mago R, Forero G, Greenberg WM, et al. Safety and 6. Serretti A, Mandelli L. Antidepressants and body weight: a tolerability of levomilnacipran ER in major depressive comprehensive review and meta-anaylsis. J Clin Psychiatry. disorder: results from an open-label, 48-week extension 2010;71(10):1259-1272. study. Clin Drug Investig. 2013;33(10):761-771. 7. Mago R, Forero G, Greenberg WM, et al. Safety and 15. Hollands GJ, Shemilt I, Marteau TM, et al. Portion, package tolerability of levomilnacipran ER in major depressive or tableware size for changing selection and consumption disorder: results from an open-label, 48-week extension of food, and tobacco. Cochrane Database Syst Rev. Current Psychiatry study. Clin Drug Investig. 2013;33(10):761-771. 2015;9:CD011045. Vol. 15, No. 6 47 continued 22. Apovian CM, Aronne L, Rubino D, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight Related Resource and obesity-related risk factors (COR-II). Obesity (Silver • Crayton JW. How to manage depression in overweight or Springs). 2013;21(5):935-943. obese patients. Current Psychiatry. 2012;11(7):33-39,A. 23. Greenway FL, Fujioka K, Plodkowski RA, et al. Effect of naltrexone plus bupropion on weight loss in overweight Drug Brand Names and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. Amitriptyline • Elavil Nefazodone • Serzone 2010;376(9741):595-605. Bupropion • Wellbutrin, Zyban Nortriptyline • Pamelor 24. Fidler MC, Sanchez M, Raether B, et al; BLOSSOM Clinical Clomipramine • Anafranil Olanzapine • Zyprexa Trial Group. A one-year randomized trial of lorcaserin for Desipramine • Norpramin Orlistat • Xenical Weight gain with weight loss in obese and overweight adults: the BLOSSOM Exenatide • Byetta, Bydureon Paroxetine • Paxil trial. J Clin Endocrinol Metab. 2011;96(10):3067-3077. antidepressants Imipramine • Tofranil Phentermine/topiramate 25. Gadde KM, Allison DB, Ryan DH, et al. Effects of low- Levomilnacipran • Fetzima • Qsymia dose, controlled-release, phentermine plus topiramate Liraglutide • Victoza, Saxenda Pramlintide • Symlin combination on weight and associated comorbidities in Lorcaserin • Belviq Protriptyline • Vivactil overweight and obese adults (CONQUER): a randomised, Metformin • Glucophage Quetiapine • Seroquel placebo-controlled, phase 3 trial [Erratum in Lancet. Methylphenidate • Ritalin, Trazodone • Desyrel, Oleptro 2011;377(9776):1494]. Lancet. 2011;377(9774):1341-1352. Methylin Vilazodone • Viibryd 26. Garvey WT, Ryan DH, Look M, et al. Two-year sustained Mirtazapine • Remeron Vortioxetine • Trintellix weight loss and metabolic benefits with controlled-release Naltrexone/bupropion Zonisamide • Zonegran phentermine/topiramate in obese and overweight adults • Contrave (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr. 2012;95(2):297-308. 27. Pi-Sunyer X, Astrup A, Fujioka K, et al; SCALE Obesity and Clinical Point Prediabetes NN8022-1839 Study Group. A randomized, controlled trial of 3.0 mg of liraglutide in weight Some newer management. N Engl J Med. 2015;373(1):11-22. 28. Leblanc ES, O’Connor E, Whitlock EP, et al. Effectiveness antidepressants, of primary care-relevant treatments for obesity in adults: a 16. Knab AM, Shanely RA, Corbin KD, et al. A 45-minute systematic evidence review for the U.S. Preventive Services such as vilazodone, vigorous exercise bout increases metabolic rate for 14 hours. Task Force. Ann Intern Med. 2011;155(7):434-447. Med Sci Sports Exerc. 2011;43(9):1643-1648. 29. Torgerson JS, Hauptman J, Boldrin MN, et al. XENical in the vortioxetine, and 17. Halverstadt A, Phares DA, Wilund KR, et al. Endurance prevention of diabetes in obese subjects (XENDOS) study: exercise training raises high-density lipoprotein a randomized study of orlistat as an adjunct to lifestyle levomilnacipran, cholesterol and lowers small low-density lipoprotein changes for the prevention of type 2 diabetes in obese and very low-density lipoprotein independent of body patients. Diabetes Care. 2004;27(1):155-161. might be less likely to fat phenotypes in older men and women. Metabolism. 2007;56(4):444-450. 30. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention cause weight gain 18. Thivel D, Isacco L, Montaurier C, et al. The 24-h energy or metformin. N Engl J Med. 2002;346(6):393-403. intake of obese adolescents is spontaneously reduced after intensive exercise: a randomized controlled trial 31. McDonagh MS, Selph S, Ozpinar A, et al. Systematic review in calorimetric chambers [published online January 17, of the benefits and risks of metformin in treating obesity 2012]. PLoS One. 2012;7(1):e29840. doi: 10.1371/journal. in children aged 18 years and younger. JAMA Pediatr. pone.0029840. 2014;168(2):178-184. 19. Sim AY, Wallman KE, Fairchild TJ, et al. High-intensity 32. Dushay J, Gao C, Gopalakrishnan GS, et al. Short-term intermittent exercise attenuates ad-libitum energy intake. exenatide treatment leads to significant weight loss in a Int J Obes (Lond). 2014;38(3):417-422. subset of obese women without diabetes. Diabetes Care. 2012;35(1):4-11. 20. Stahre L, Tärnell B, Håkanson CE, et al. A randomized controlled trial of two weight-reducing short-term group 33. Gadde KM, Kopping MF, Wagner HR 2nd, et al. Zonisamide treatment programs for obesity with an 18-month follow- for weight reduction in obese adults: a 1-year randomized up. Int J Behav Med. 2007;14(1):48-55. controlled trial. Arch Intern Med. 2012;172(20):1557-1564. 21. Armstrong MJ, Mottershead TA, Ronksley PE, et al. 34. Singh-Franco D, Perez A, Harrington C. The effect of Motivational interviewing to improve weight loss in pramlintide acetate on glycemic control and weight in overweight and/or obese patients: a systematic review and patients with type 2 diabetes mellitus and in obese patients meta-analysis of randomized controlled trials. Obes Rev. without diabetes: a systematic review and meta-analysis. 2011;12(9):709-723. Diabetes Obes Metab. 2011;13(2):169-180.

Bottom Line Many antidepressants are known to increase the risk of excessive weight gain, although risk of weigh gain varies among antidepressant classes. First, advise changes in diet and exercise; next, initiate psychotherapy as indicated, and then consider referral to a nutritionist. Consider switching to an antidepressant with less potential for causing weight gain or adding bupropion, which could lead to weight loss, if your patient can tolerate it. If these strategies are unsuccessful, consider an Current Psychiatry 48 June 2016 anti-obesity medication.