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Web Meeting Cast of the Minds pSYCHIATRY Ask Dr. Schwartz about managing from therapy. For details, see page 54

How to control weight gain when prescribing

Ignoring this side eff ect can increase medical risk, treatment nonadherence

eight gain occurs with most antidepressants® Dowden Health Media but is frequently overlooked, perhaps be- Wcause clinicians are focused instead on meta- bolic effects of antipsychoticsCopyright and moodFor stabilizers. personal Pa- use only tients taking antidepressants often complain of weight gain, however, and many of the ’ FDA-approved package inserts acknowledge this effect. Two-thirds of patients with major depression present with , and gaining weight can be associated with successful treatment. Weight gain is of concern—and likely to be -induced—if it ex- ceeds the disease-induced weight loss and continues after depressive symptoms improve. ROBERTS

Weight may change early or late during antidepres- GERARD 2007

sant treatment, and gaining in the fi rst weeks usually © predicts future gains.1 Patients who are when treatment begins are especially at risk if given Thomas L. Schwartz, MD Associate professor weight-promoting agents. This article: • compares antidepressant effects on patient weight Zsuzsa S. Meszaros, MD, PhD Clinical assistant instructor • discusses mechanisms by which antidepressants Rahat Khan, MD may cause weight gain Clinical extern • outlines a plan to prevent excess weight gain when Nikhil Nihalani, MD patients start antidepressant therapy Clinical assistant professor • recommends diet, , cognitive-behavioral therapy (CBT), and for overweight pa- Department of psychiatry tients on long-term antidepressant treatment. SUNY Upstate Medical University Syracuse, NY

Weight-gain potential by class Unlike , antidepressants have not been Current Psychiatry associated in clinical trials with causing metabolic syn- Vol. 6, No. 5 43

For mass reproduction, content licensing and permissions contact Dowden Health Media. Table 1 ies with the drug used. In Long-term eff ects of antidepressants this trial, 284 patients with on body weight, by class* major depressive disorder were randomly assigned Class Effect (gain, loss, or neutral) to double-blind treatment MAOIs Moderate gain overall with , , : greatest gain in MAOI class or fl uoxetine: Transdermal : appears neutral Weight gain • More of those taking Novel antidepressants : weight loss4 paroxetine gained >7% in : greatest potential for gain weight from baseline, and among antidepressants5 : neutral6 their weight gain was sta- : modest gain7 tistically signifi cant. • Sertraline-treated SSRIs : modest gain8 : modest gain9 patients had modest, non- : modest loss acutely10 signifi cant weight gain. : neutral11 • Fluoxetine-treated Clinical Point Paroxetine: greatest gain in SSRI class10 patients had modest, non- Sertraline: modest gain10 Paroxetine seems signifi cant weight loss. SNRIs : modest gain12 Using paroxetine with to be the SSRI 13 : modest gain (controversial) an can be most likely to TCAs : gain14 especially problematic. cause weight gain, : gain15 Fukowi and Murai17 de- especially when : neutral16 scribed 2 cases in which * Information is a general representation of available literature, gathered from many adding paroxetine to ris- used with an studies with differing designs. Consult original reports for specifi c data on dosing, patient populations, treatment durations, and weigh changes. peridone caused severe antipsychotic MAOIs: monoamine oxidase inhibitors; SNRIs: - weight gain (13.5 kg to inhibitors; SSRIs: selective serotonin reuptake inhibitors; TCAs: antidepressants >14 kg) in 4 to 5 months. Citalopram may cause drome and . Even so, certain antide- a 1- to 1.5-kg weight gain over 1 year,8 pressants can cause clinically signifi cant and whereas fl uvoxamine has been shown not perhaps more insidious weight gain when to affect weight in obese patients.11 Citalo- compared with some second-generation an- pram (like TCAs) can cause carbohydrate tipsychotics (SGAs). For example, SGAs on craving and early weight gain.18 Escitalo- average may cause 2.3 kg/month weight pram caused a modest (0.5 kg) weight gain during the fi rst 12 weeks of treatment, gain in elderly patients during an 8-week and mirtazapine caused 3 kg weight gain in trial.13 a recent 6-week trial.2,3 Tricyclic antidepressants (TCAs) and Initial weight loss followed by overall monoamine oxidase inhibitors (MAOIs) weight gain after 1 year of SSRI treatment may pose a greater weight-gain risk than is a common clinical fi nding that was not newer antidepressants, but selective sero- noted in initial acute SSRI drug trials. In a tonin reuptake inhibitors (SSRIs) and ser- comparison of fl uoxetine’s acute and long- otonin-norepinephrine reuptake inhibi- term effects,19 839 patients experiencing a tors (SNRIs) have been clinically noted to major depressive episode were fi rst treated cause weight gain over time (Table 1).4-16 with open-label fl uoxetine, 20 mg/d. After 12 weeks, 395 patients who met criteria for SSRIs. Weight gain associated with long- remission were randomly assigned to con- term SSRI use seems clinically apparent, tinue with placebo or fl uoxetine, 20 mg/d, but the evidence is preliminary. for 14, 38, or 50 weeks. Paroxetine seems to be the SSRI most In the acute phase, a small but statistically likely to cause weight gain. A 26- to 32-week signifi cant weight loss (mean 0.35 kg, P<0.01) comparison trial by Fava et al10 showed that was noted. In the continuation phase, statisti- Current Psychiatry 44 May 2007 weight gain risk with SSRI therapy var- cally signifi cant weight gain occurred among all patients. Mean absolute Table 2 weight changes were: Antidepressants’ relative long-term pSYCHIATRY • 1.1 kg at 26 weeks eff ects on body weight (P <0.001) currentpsychiatry.com Effect Antidepressants • 2.2 kg at 38 weeks Loss Bupropion,4 fl uoxetine10 (P <0.001) • 3.1 kg at 50 weeks Gain Modest: citalopram,8 duloxetine,12 9 10 7 (P <0.001). escitalopram, sertraline, trazodone, venlafaxine13 The authors concluded Relatively more: amitriptyline,14 imipramine,15 that the weight gain—simi- mirtazapine,5 paroxetine,10 phenelzine lar with fl uoxetine or pla- Neutral Fluvoxamine,11 nefazodone,6 nortriptyline16 cebo—was probably asso- Information is a general representation of available literature, gathered from many studies ciated with recovery from with differing designs. Consult original reports for specifi c data on dosing, patient depression rather than populations, treatment durations, and weight changes. fl uoxetine treatment, al- though this was not a con- trolled variable in the study. block differing ratios of nor- Clinical Point epinephrine and serotonin reuptake Serotonin helps pumps, resulting in postsynaptic sero- regulate and Causes of weight gain tonergic and desen- Serotonin. Appetite is controlled by cultur- sitization and, later, down-regulation. carbohydrate intake al, psychological, neurochemical, and meta- TCAs with higher serotonin reuptake and is the most bolic factors. Among neurochemical factors, blockade may increase weight through often manipulated serotonin helps regulate appetite and is the this desensitization. neurotransmitter in neurotransmitter most often manipulated TCAs also affect appetite by blocking in depression treatment. (H1) pathways. Drugs with depression treatment Serotonin receptor such as fen- high affi nity for blocking H1 receptors fl uramine and dexfenfl uramine have an have been associated with carbohydrate acute anorexigenic effect. In rats, 5-HT2c craving18 and low satiety rates that allow receptor agonism decreases eating behav- increased calorie intake. TCAs have anti- ior, and mice lacking 5-HT2c receptors are muscarinic, antihistaminic, and alpha ad- obese.20 This may explain why SGAs or an- renoceptor-blocking actions, all of which tidepressants that block 5-HT2c pose the may contribute to weight gain. greatest risk of weight gain. In theory, beta-3 adrenergic recep- SSRI or SNRI treatment might increase tors in adipose tissue may play a role serotonin in the synaptic cleft, allowing in weight control by converting fat into 5-HT2c receptor down-regulation that is heat and energy, especially in response to slower than—but similar in effect to—the norepinephrine. TCAs or SNRIs that fa- acute 5-HT2c blockade caused by the vor a noradrenergic profi le may promote SGAs.21 Weight gain from SSRI use refl ects weight loss or neutrality. The relatively on these medications’ multiple serotoner- weight-neutral selegiline patch, which gic mechanisms. Serotonin appears to reg- avoids fi rst-pass metabolism and active ulate carbohydrate intake and can increase adverse metabolites, also may use this food intake.22 mechanism.23

Nefazodone and trazodone block 5HT2a Mirtazapine blocks presynaptic alpha- receptors potently, and the norepinephrine 2 and postsynaptic 5HT2a, 5HT2c, and (nefazodone only) and serotonin reuptake 5HT3 serotonin receptors as well as H1 pumps (both agents) less potently. Dif- receptors. Both 5HT2c and ferences in their mechanism (nefazodone H1 blockade result in weight gain, the increases norepinephrine) and lack of 5- drug’s most apparent adverse effect. This HT2c blockade might be responsible for mechanism is similar to that of the SGA Current Psychiatry their reported weight neutrality. . Vol. 6, No. 5 45 continued Table 3 Using antidepressants in patients at metabolic risk for weight gain

• Warn patients before they begin antidepressant treatment about the risks of weight gain and worsening or onset of comorbid medical conditions

• Obtain and document family medical history in addition to the usual family psychiatric history

• Discuss and initiate a diet and exercise plan to prevent or treat weight gain before medically Weight gain signifi cant weight gain occurs • Choose a weight-neutral or weight-negative antidepressant for patients with existing , , , or hypercholesterolemia or family history of these comorbidities

• Discuss the risks and benefi ts with your patient if antidepressants that cause weight gain are needed for better effi cacy, and document this conversation

• Monitor patients’ weight as long as they continue taking drugs that may increase weight

TNF-α. Obese persons have increased plas- fault when using mirtazapine—which is Clinical Point ma levels of TNF-α and its soluble receptor pharmacodynamically the most similar to Instruct patients to (sTNF-R p75), which may induce insulin SGAs—and TCAs. For patients taking other weigh themselves resistance. Activation of the TNF-α system, antidepressants, we recommend that you: such as by amitriptyline or mirtazapine, • measure and weight, at home at least may promote weight gain.24 and calculate BMI often weekly in the • instruct patients to weigh themselves morning and at home at least weekly in the morning to report gains Preventing weight gain and to report gains >5 lbs. Early intervention is key to preventing drug- An overall 10-lb weight gain is clinically >5 pounds related weight gain and treating obesity. signifi cant in most patients and calls for a Provide informed consent and psychoedu- management plan. Abdominal girth often cation when prescribing antidepressants. In increases as part of . patients at metabolic risk, consider using If you choose to measure this variable and weight-neutral or weight-loss agents (Table are uncomfortable reaching around pa- 2, page 45), 4-16 and monitor for weight gain tients while measuring, allow patients to (Table 3). At-risk patients have: apply the tape measure themselves. • (waist circumference >40 inches [102 cm] in men, >35 inches Lab tests. Obtain fasting glucose and lipid [88 cm] in women, or waist-to-hip ratio levels at baseline for most patients and then >0.9 in women and >1.0 in men) quarterly in those with initial weight gain, • hyperlipidemia medical comorbidities, or family history of • elevated (BMI [over- hypertension, hypercholesterolemia, or di- weight = BMI 25 to 30 kg/m2 , obesity abetes. Many clinicians also screen for hy- = BMI >30 kg/m2 ]) pothyroidism and anemia, and these tests • hypertension may be added. For patients without meta- • diabetes mellitus or impaired glucose bolic risk factors taking SSRIs and SNRIs, tolerance start quarterly draws if weight increases • history of or cardiovascular rapidly by >5 lbs or if BMI approaches ≥30 disease kg/m2. Tracking fasting can • family history of obesity, hyperten- serve as a sentinel for metabolic syndrome, sion, diabetes, or hyperlipidemia. which sometimes occurs before substantial weight gain or hyperglycemia. Use SGA guidelines? Consider following modifi ed American Diabetes Association guidelines for metabolic monitoring of Dietary measures patients treated with SGAs.25 We suggest If weight gain has occurred, a safe initial Current Psychiatry 46 May 2007 that you follow SGA guidelines as a de- goal for patients is to lose 0.5% to 1% initial continued on page 51 continued from page 46 Table 4 Medications indicated for treating obesity pSYCHIATRY Evidence of currentpsychiatry.com Drug/mechanism Indication/dosage effi cacy, safety Comment Obesity î10% to 15% î triglycerides, total cholesterol, (sympathomimetic; (5 to 20 mg/d) of body weight in LDL cholesterol , 1 year;29 safety, ì HDL cholesterol noradrenergic effi cacy beyond Monitor for when ) 1 year undetermined used with serotonergic psychotropics

Orlistat Obesity (120 mg tid î9% to 10% of body î triglycerides, total cholesterol, (inhibits gastric and with meals; take weight in 1 year;30 LDL cholesterol pancreatic lipases other drugs 1 hour safety, effi cacy ì HDL cholesterol by binding to these pre- or post-) beyond 2 years Lower risk of drug interactions enzymes in the gut) undetermined than with sibutramine; GI side effects; multivitamin required

Rimonabant Obesity (20 mg/d) Reduced weight, Generally well-tolerated; mild (investigational, (pending approval) improved heart most common side effect Clinical Point pending FDA disease risk factors approval; selective in obese patients Eating habits can type 1 with metabolic receptor blocker) syndrome or >1 be changed with cardiovascular risk CBT; behavior 31 factors (1-2 years) modifi cation alone * Many studies in this table were conducted in patients taking second-generation antipsychotics for or . Results may not apply to antidepressant-induced weight gain. can generate a GI: gastrointestinal; HDL: high-density lipoprotein; LDL: low-density lipoprotein weight loss of 0.5 body weight per week—or 5% to 10% of uid meal replacements per day plus snacks to 0.7 kg per week weight across several months. Diet and ex- and 1 low-fat meal (approximately 1,200 to ercise produce maximal benefi t but require 1,500 kcal/day) lost considerable weight commitment and motivation, which are in the fi rst 3 months but regained some often diffi cult or impossible for depressed weight later. Many maintained weight loss patients. Encouraging the patient’s efforts on 1 liquid meal replacement per day plus is worthwhile; if intervention is postponed snacks and 2 low-fat meals.26 until remission is achieved, weight gain Low- and very-low-calorie diets are in- may be substantially higher and more dif- dicated for patients with BMI >35 kg/m2: fi cult to treat. • in whom conservative treatment (a portion-controlled, low-fat diet) has Cutting fat and calories. The fi rst step failed in losing weight is to restrict high-fat and • and who are willing to maintain at high-calorie foods and eat smaller por- least 1 year of treatment and major tions. If this fails, then switch the patient to lifestyle changes. a low- or very-low-calorie diet, which pro- A low-calorie diet provides ≥1,000 kcal/ vides a quick initial weight loss. This can day; very low-calorie diets may provide motivate the patient but should be tried ≤800 kcal/day and rely mostly on liquid only under a physician’s supervision. meal replacements. This semi-starvation Many patients benefi t from structured can produce fatigue, weakness, lighthead- commercial weight-loss programs, but the edness, and changes in vital signs, includ- likelihood of regaining the weight is high ing blood pressure, heart rate, and respi- if stopped. These programs typically rec- ratory rate. For this reason, extreme diets ommend 1,200 kcal/day for women and require a team approach with the primary 1,800 kcal/day for men, with 55% of calo- care clinician and a dietitian. ries from carbohydrates, about 25% to 35% Among mentally healthy patients fol- from protein, and 10% to 25% from fat. lowing very-low-calorie diets in clinical Current Psychiatry In a study of 100 patients, those on 2 liq- trials, 90% lose ≥10 kg and 50% lose ≥20 Vol. 6, No. 5 51 Table 5 Medications used ‘off label’ for treating obesity Evidence of Drug/mechanism Indication/dosage effi cacy, safety Comment Infl uenza A î3.5 kg over 3 to 6 Patients had gained a mean (antiviral agent; prophylaxis and months (study of 12 7.3 kg during olanzapine treatment may potentiate Parkinson’s disease patients)32 Weight gain (300 mg/d, with function) olanzapine)

Nizatidine Duodenal ulcer; î2.5 kg with Unknown effectiveness when (histamine-2 GERD (600 mg/d ; ì5.5 kg used as prophylaxis with ) as prophylaxis with with placebo33 antidepressants; can cause olanzapine) (16-week RCT) , especially in older patients

Naltrexone , narcotics TCA-induced weight Small mean weight loss compared ( antagonist; addiction (50 mg/d) gain reversed, then with previous drug-induced decreases craving resumed after drug weight gain; no adverse effects seen Clinical Point for sweet, fatty was stopped on depressive symptoms foods caused by (8-patient trial)34 Reserve antiobesity TCAs and ) drugs for patients Epilepsy, î10 to 15 lbs in May serve dual purpose in treating () (100 to 400 mg/d 33% to 55% of obese patients with affective with BMI >30 kg/ as adjunct to bipolar disorder disorders; fatigue, cognitive dulling, m2 (>27 kg/m2 in antipsychotics) patients35 , , oligohydrosis, those with diabetes, acidosis are possible hyperlipidemia, Type 2 diabetes 15 of 19 patients Sporadic diarrhea in some patients; (biguanide (500 mg tid as who gained 10% in risk of lactic acidosis (tests or heart disease) antihyperglycemic) adjunct to body weight taking unremarkable in this small trial)36 antipsychotics) SGAs lost weight with add-on metformin (12-week, open-label trial)

* Many studies in this table were conducted in patients taking second-generation antipsychotics for schizophrenia or bipolar disorder. Results may not apply to antidepressant-induced weight gain. GERD: gastroesophageal refl ux disease; RCT: randomized, double-blind, placebo-controlled trial; SGAs: second-generation antipsychotics; TCAs: tricyclic antidepressants

kg in the fi rst 4 to 6 months.27 Most weight behavior change leads to healthier eating loss occurs in the fi rst 12 to 16 weeks, af- habits, exercise, and weight loss. Behavior ter which an ad libitum low-fat, high-fi ber modifi cation alone can generate a weight diet can be used. loss of 0.5 kg to 0.7 kg per week.28 A study of 6 schizophrenia patients Exercise has physiologic and psychologi- (mean age 37) examined CBT effects on cal benefi ts, including inhibiting food in- weight gain associated with take and promoting a sense of self-control. (n=4) or olanzapine (n=2). Mean BMI de- Physical exercise increases insulin sensi- creased from 29.6 kg/m2 to 25.1 kg/m2 tivity and reduces the risk of secondary after 7 to 9 sessions of individual CBT, fol- medical problems, such as heart disease. lowed by 16 biweekly group sessions that Walking ≥40 minutes daily produces maxi- focused on weight reduction and weight mal benefi t, but walking even 30 minutes 3 maintenance. A dietician provided de- times a week can help maintain weight. tailed counseling.28

CBT. Eating habits can be changed through identifying lifestyle behaviors to be modi- Using medications for weight loss fi ed, setting goals, modifying triggers of Switching. To avoid polypharmacy, con- excessive eating, and reinforcing desired sider switching the patient to a weight- Current Psychiatry 52 May 2007 behavior with CBT. Gradual but consistent neutral or weight-losing antidepressant, such as bupropion. Keep in mind when switching medications, however, that the Related Resources pSYCHIATRY next agent with less weight-gain potential • Centers for Disease Control and Prevention. Overweight and obesity: contributing factors. currentpsychiatry.com might not deliver comparable antidepres- www.cdc.gov/nccdphp/dnpa/obesity/ sant effi cacy. contributing_factors.htm. • Mathur R. What causes obesity? www.medicinenet. com/obesity_weight_loss/page2.htm. Antiobesity drugs. Short of switching, an antiobesity drug (Table 4, page 51)29-31 or Drug Brand Names off-label intervention (Table 5)32-36 may be Amantadine • Symmetrel Nizatidine • Axid Amitriptyline • Elavil Nortriptyline • Pamelor warranted. Antiobesity drugs should not Bupropion • Wellbutrin Olanzapine • Zyprexa be used as primary therapy for obesity. Citalopram • Celexa Orlistat • Xenical Duloxetine • Cymbalta Paroxetine • Paxil Their use may be warranted, however, for Escitalopram • Lexapro Phenelzine • Nardil psychiatric patients who: Fluoxetine • Prozac Selegiline (transdermal) • Fluvoxamine • Luvox EMSAM • are unable to fully participate in diet Imipramine • Tofranil Sertraline • Zoloft and exercise programs because of symp- Metformin• Glucophage Sibutramine • Meridian Mirtazapine • Remeron Topiramate • Topamax toms (such as cognitive impairment or se- • ReVia Trazodone • Desyrel vere negative symptoms) Nefazodone• Serzone Venlafaxine • Eff exor Clinical Point • lack social support (such as refl ected Disclosures Weight gain may be by fi nancial problems, homelessness, or Dr. Schwartz has received grants from or served as a substantially greater poor compliance with treatment recom- consultant to AstraZeneca, Bristol-Myers Squibb, Cephalon, Cyberonics, Forest Pharmaceuticals, GlaxoSmithKline, and more diffi cult to mendations). Jazz Pharmaceuticals, Pfi zer Inc., and Wyeth. Generally, we reserve antiobesity drugs Other authors report no fi nancial relationship with treat if you postpone for patients with BMI >30 kg/m2 (or >27 any companies whose products are mentioned in this intervention until 2 article or with manufacturers of competing products. kg/m in patients with diabetes, hyper- after depression lipidemia, or ). Be- 7. Weisler RH, Johnston JA, Lineberry CG, et al. Comparison remission is achieved fore adding these agents to a psychotropic of bupropion and trazodone for the treatment of major regimen, however, review the relative risks depression. J Clin Psychiatry 1994;14:170-9. 8. Leinonen E, Skarstein J, Behnke K, et al, for the Nordic and benefi ts with the patient and his or her Antidepressant Study Group. Effi cacy and tolerability of primary care physician. mirtazapine versus citalopram: a double blind, randomized study in patients with major depressive disorder. Int Clin The goal of pharmacotherapy is for the Psychopharm 1999;14(6):329-37. patient to lose 5% to 10% of baseline weight 9. Kasper S, Lemming OM, de Swart H. Escitalopram in the long-term treatment of major depressive disorder in elderly in 3 to 6 months. Failure to achieve this goal patients. Neuropsychobiology 2006;54(3):152-9. is an indication to stop the . A 10. Fava M, Judge R, Hoog SL, et al. Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight plateau in weight loss after 6 to 9 months with long term treatment. J Clin Psychiatry 2000;61(11):863-7. 11. Abell CA, Farquhar DL, Galloway SM, et al. Placebo- is expected and is not cause for discontinu- controlled, double-blind trial of fl uvoxamine maleate in the ation. If successful, drug treatment may be obese. J Psychosomat Res 1986;30:143-6. 12. Wise TN, Perahia DG, Pangallo BA, et al. Effects of the continued indefi nitely, and both physician antidepressant duloxetine on body weight: analyses of and patient must understand the intention 10 clinical studies. Prim Care Companion J Clin Psychiatry 2006;8(5):269-78. to treat long-term. Most patients regain 13. Silverstone PH, Ravindran A. Once daily velafaxine weight upon discontinuation. extended release compared with fl uoxetine in outpatients with depression and anxiety. J Clin Psychiatry 2000;61(suppl 2):20-5. References 14. Zetin M, Frost NR, Brumfi eld D, et al. Amitriptyline 1. Himmerich H, Schuld A, Haack M, et al. Early prediction stimulates weight gain in hemodialysis patients. Clin Nephrol of changes in weight during six weeks of treatment with 1982;18:79-82. antidepressants. J Psychiatr Res 2004;38(5):485-9. 15. Fernstrom MH, Krowinski RL, Kupfer DJ. Chronic imipramine 2. Wetterling T. Bodyweight gain with atypical antipsychotics. A treatment and weight gain. Psychiatr Res 1986;17:269-73. comparative review. Drug Saf 2001;24(1):59-73. 16. Prince JB, Wilens TE, Biederman J, et al. A controlled study of nortriptyline in children and adolescents with attention defi cit 3. Laimer M, Kramer-Reinstadler K, Rauchenzauner M, et al. hyperactivity disorder. J Am Acad Child Adolesc Psychiatry Effect of mirtazapine treatment on body composition and 2000;10:193-204. metabolism. J Clin Psychiatry 2006;67(3):421-4. 17. Fukui H, Murai T. Severe weight gain induced by 4. Chouinard G. Bupropion and amitriptyline in the treatment of combination treatment with and paroxetine. Clin depressed patients. J Clin Psychiatry 1983;44:121-9. Neuropharmacol 2002;25(5):269-71. 5. Ribeiro L, Busnello JV, Kauer-Sant’Anna M, et al. Mirtazapine 18. Bouwer CD, Harvey BH. Phasic craving for carbohydrate versus fl uoxetine in the treatment of panic disorder. Brazil J observed with citalopram. Int Clin Psychopharmacol 1996; Med Biol Res 2001;34:1303-7. 11:273-8. 6. Davis R, Whittington R, Bryson HM. Nefazodone. A review of 19. Michelson D, Amsterdam J, Quitkin FM, et al. Changes in its and clinical effi cacy in the management of weight during a 1-year trial of fl uoxetine. Am J Psychiatry Current Psychiatry major depression. Drugs 1997;54:186-7. 1999;156(8):1170-6. Vol. 6, No. 5 53 continued 20. Curzon G, Gibson EL, Oluyomi AO. Appetite suppression by 28. Umbricht D, Flury H, Bridler R. Cognitive behavior therapy commonly used drugs depends on 5HT availability. Trends for weight gain. Am J Psychiatry 2001;158:971-2. Pharmacol Sci 1998;13:12-25. 29. Bray GA, Blackburn GL, Ferguson JM, et al. Sibutramine 21. De Vry J, Schreiber R. Effects of selected serotonin 5-HT1 produces dose-related weight loss. Obes Res 1999;7(2):189-98. and 5-HT2 receptor agonists on feeding behavior: possible 30. Van Gaal LF, Broom JI, Enzi G, et al. Effi cacy and tolerability mechanisms of action. Neurosci Biobehav Rev 2000;24:341-53. of orlistat in the treatment of obesity: a 6-month dose-ranging 22. Bickerdike HJ, Vickers SP, Dourish CT. 5HT2c receptor study. Eur J Clin Pharmacol 1998;54:125-32. modulation and the treatment of obesity. Diabetes Obes 31. Kakafi ka AI, Mikhailidis DP, Karagiannis A, et al. The role of Metab 1999;1:207-14. blockade in the treatment of metabolic 23. Strosberg AD, Pietri-Rouxel F. Function and regulation of syndrome. J Clin Pharmacol [serial online]. March 28, 2007. beta-3 adrenoceptor. Trends Pharmacol Sci 1996;17:373-81. 32. Floris M, Lejeune J, Deberdt W. Effect of amantadine on weight Weight gain 24. Kraus T, Haack M, Schuld A, et al. Body weight, the tumor gain during olanzapine treatment. Eur Neuropsychopharmacol necrosis factor system, and leptin production during 2001;11(6):181-2. treatment with mirtazapine or venlafaxine. Pharmacopsychiatry 33. Breier A, Tanaka Y, Roychowdhury S, et al. Nizatidine for the 2002;35(6):220-5. prevention of weight gain during olanzapine treatment in 25. American Diabetes Association, American Psychiatric schizophrenia and related disorders: a randomised controlled Association, American Association of Clinical Endocrinologists, double-blind study. Presented at: Meeting of the Colleges of North American Association for the Study of Obesity. Psychiatric and Neurologic Pharmacists; March 23-26, 2001; Consensus development conference on antipsychotic drugs San Antonio, TX. and obesity and diabetes. Diabetes Care 2004;27:596-601. 34. Zimmermann U, Rechlin T, Plaskacewicz GJ. Effect of 26. Ditschuneit HH, Flechtner-Mors M, Johnson TD, et al. naltrexone on weight gain and food craving induced by Metabolic and weight-loss effects of a long-term dietary tricyclic antidepressants and lithium: an open study. Biol intervention in obese patients. Am J Clinical Nutrition 1999; Psychiatry 1997;41(6):747-9. 69:198-204. 35. Vieta E, Torrent C, Garcia-Ribas G, et al. Use of topiramate 27. Wadden TA. Evidence for success of calorie restriction in in treatment-resistant bipolar spectrum disorders. J Clin Clinical Point weight control; summary data from clinical research studies. Psychiatry 2002;22(4):431-5. In: Scannell SM, ed. Methods for voluntary weight loss and 36. Morrison JA, Cottingham EM, Barton BA. Metformin for Consider stopping control. Bethesda, MD: U.S. Department of Health and Human weight loss in pediatric patients taking psychotropic drugs. Services 1992;64-74. Am J Psychiatry 2002;159:655-7. an antiobesity drug if the patient does not lose 5% to 10% Bottom Line of baseline weight Antidepressants may contribute to weight gain, although this eff ect varies among in 3 to 6 months agents. Pre-existing obesity and metabolic factors increase the weight gain risk. Routinely educate patients, monitor weight and metabolic factors, and encourage diet and exercise management. Consider antiobesity medication, when indicated.

JOIN THE LIVE WEBCAST! Meeting of theMinds Controlling weight gain from antidepressants

Thomas Schwartz, MD When: Wednesday, June 6, 1:30 PM (EDT) Associate Professor of Psychiatry Where: CurrentPsychiatry.com SUNY Upstate Medical University, Syracuse, NY Learn more about how to prevent excessive weight gain after patients start antidepressant therapy. Download the proceedings after June 6 Interactive Q-and-A to follow To register, visit CurrentPsychiatry.com. Hosted by Dr. Henry Nasrallah Look for the ‘Meeting of the Minds’ icon Editor-in-Chief, CURRENT PSYCHIATRY