How To Control Weight Gain When Prescribing Antidepressants

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WeCastbMeetingof the Mindsp SYCHIATRYAsk Dr. Schwartz about managingweight gain from antidepressant therapy.For details, see page 54How to control weight gainwhen prescribing antidepressantsIgnoring this side effectcan increase medical risk,treatment nonadherenceiaedMhltea yHnenldoweight gain occurs with most antidepressantseos Dubut is frequently overlooked,perhaps be-nalthsormetacause clinicians are focusedonyriginsteadepporC and moodbolic effects of antipsychoticsPaFostabilizers.tients taking antidepressants often complain of weightgain, however, and many of the drugs’ FDA-approvedpackage inserts acknowledge this effect.Two-thirds of patients with major depressionpresent with weight loss, and gaining weight can beassociated with successful treatment. Weight gain isof concern—and likely to be drug-induced—if it exceeds the disease-induced weight loss and continuesafter depressive symptoms improve.Weight may change early or late during antidepressant treatment, and gaining in the first weeks usuallypredicts future gains.1 Patients who are overweightwhen treatment begins are especially at risk if givenweight-promoting agents. This article: compares antidepressant effects on patient weight discusses mechanisms by which antidepressantsmay cause weight gain outlines a plan to prevent excess weight gain whenpatients start antidepressant therapy recommends diet, exercise, cognitive-behavioraltherapy (CBT), and medications for overweight patients on long-term antidepressant treatment. 2007 GERARD ROBERTSWThomas L. Schwartz, MDAssociate professorZsuzsa S. Meszaros, MD, PhDClinical assistant instructorRahat Khan, MDClinical externNikhil Nihalani, MDClinical assistant professorDepartment of psychiatrySUNY Upstate Medical UniversitySyracuse, NYWeight-gain potential by classUnlike antipsychotics, antidepressants have not beenassociated in clinical trials with causing metabolic syn-For mass reproduction, content licensing and permissions contact Dowden Health Media.Current PsychiatryVol. 6, No. 543

ies with the drug used. Inthis trial, 284 patients withLong-term effects of antidepressantsmajor depressive disorderon body weight, by class*were randomly assignedClassEffect (gain, loss, or neutral)to double-blind treatmentMAOIsModerate gain overallwith paroxetine, sertraline,Phenelzine: greatest gain in MAOI classor fluoxetine:Transdermal selegiline: appears neutral More of those takingNovel antidepressants Bupropion: weight loss4paroxetine gained 7% inMirtazapine: greatest potential for gainweight from baseline, andamong antidepressants5their weight gain was staNefazodone: neutral6tistically significant.Trazodone: modest gain7 Sertraline-treatedSSRIsCitalopram: modest gain8patientshad modest, nonEscitalopram: modest gain910significant weight gain.Fluoxetine: modest loss acutely Fluoxetine-treatedFluvoxamine: neutral11Paroxetine: greatest gain in SSRI class10patients had modest, nonSertraline: modest gain10significant weight loss.SNRIsDuloxetine: modest gain12Using paroxetine withVenlafaxine: modest gain (controversial)13an antipsychotic can beespeciallyproblematic.TCAsAmitriptyline: gain14Imipramine: gain15Fukowi and Murai17 deNortriptyline: neutral16scribed 2 cases in which* Information is a general representation of available literature, gathered from manyadding paroxetine to risstudies with differing designs. Consult original reports for specific data on dosing, patientperidone caused severepopulations, treatment durations, and weigh changes.MAOIs: monoamine oxidase inhibitors; SNRIs: serotonin-norepinephrine reuptakeweight gain (13.5 kg toinhibitors; SSRIs: selective serotonin reuptake inhibitors; TCAs: tricyclic antidepressants 14 kg) in 4 to 5 months.Citalopram may causedrome and diabetes. Even so, certain antidea 1- to 1.5-kg weight gain over 1 year,8pressants can cause clinically significant andwhereas fluvoxamine has been shown notperhaps more insidious weight gain whento affect weight in obese patients.11 Citalopram (like TCAs) can cause carbohydratecompared with some second-generation ancraving and early weight gain.18 Escitalotipsychotics (SGAs). For example, SGAs onpram caused a modest (0.5 kg) weightaverage may cause 2.3 kg/month weightgain in elderly patients during an 8-weekgain during the first 12 weeks of treatment,trial.13and mirtazapine caused 3 kg weight gain in2,3a recent 6-week trial.Initial weight loss followed by overallTricyclic antidepressants (TCAs) andweight gain after 1 year of SSRI treatmentmonoamine oxidase inhibitors (MAOIs)is a common clinical finding that was notmay pose a greater weight-gain risk thannoted in initial acute SSRI drug trials. In anewer antidepressants, but selective serocomparison of fluoxetine’s acute and longtonin reuptake inhibitors (SSRIs) and serterm effects,19 839 patients experiencing aotonin-norepinephrine reuptake inhibimajor depressive episode were first treatedtors (SNRIs) have been clinically noted towith open-label fluoxetine, 20 mg/d. Aftercause weight gain over time (Table 1).4-1612 weeks, 395 patients who met criteria forSSRIs. Weight gain associated with longremission were randomly assigned to conterm SSRI use seems clinically apparent,tinue with placebo or fluoxetine, 20 mg/d,but the evidence is preliminary.for 14, 38, or 50 weeks.Paroxetine seems to be the SSRI mostIn the acute phase, a small but statisticallylikely to cause weight gain. A 26- to 32-weeksignificant weight loss (mean 0.35 kg, P 0.01)comparison trial by Fava et al10 showed thatwas noted. In the continuation phase, statistiweight gain risk with SSRI therapy varcally significant weight gain occurred amongTable 1Weight gainClinical PointParoxetine seemsto be the SSRImost likely tocause weight gain,especially whenused with anantipsychotic44Current PsychiatryMay 2007

all patients. Mean absoluteweight changes were: 1.1 kg at 26 weeks(P 0.001) 2.2 kg at 38 weeks(P 0.001) 3.1 kg at 50 weeks(P 0.001).The authors concludedthat the weight gain—similar with fluoxetine or placebo—was probably associated with recovery fromdepression rather thanfluoxetine treatment, although this was not a controlled variable in the study.Table 2p SYCHIATRYAntidepressants’ relative long-termeffects on body ssBupropion,4 fluoxetine10GainModest: citalopram,8 duloxetine,12escitalopram,9 sertraline,10 trazodone,7venlafaxine13Relatively more: amitriptyline,14 imipramine,15mirtazapine,5 paroxetine,10 phenelzineNeutralFluvoxamine,11 nefazodone,6 nortriptyline16Information is a general representation of available literature, gathered from many studieswith differing designs. Consult original reports for specific data on dosing, patientpopulations, treatment durations, and weight changes.Tricyclics block differing ratios of nor-Clinical PointSerotonin. Appetite is controlled by cultural, psychological, neurochemical, and metabolic factors. Among neurochemical factors,serotonin helps regulate appetite and is theneurotransmitter most often manipulatedin depression treatment.Serotonin receptor agonists such as fenfluramine and dexfenfluramine have anacute anorexigenic effect. In rats, 5-HT2creceptor agonism decreases eating behavior, and mice lacking 5-HT2c receptors areobese.20 This may explain why SGAs or antidepressants that block 5-HT2c pose thegreatest risk of weight gain.SSRI or SNRI treatment might increaseserotonin in the synaptic cleft, allowing5-HT2c receptor down-regulation that isslower than—but similar in effect to—theacute 5-HT2c blockade caused by theSGAs.21 Weight gain from SSRI use reflectson these medications’ multiple serotonergic mechanisms. Serotonin appears to regulate carbohydrate intake and can increasefood intake.22epinephrine and serotonin reuptakepumps, resulting in postsynaptic serotonergic and adrenergic receptor desensitization and, later, down-regulation.TCAs with higher serotonin reuptakeblockade may increase weight throughthis desensitization.TCAs also affect appetite by blockinghistaminergic (H1) pathways. Drugs withhigh affinity for blocking H1 receptorshave been associated with carbohydratecraving18 and low satiety rates that allowincreased calorie intake. TCAs have antimuscarinic, antihistaminic, and alpha adrenoceptor-blocking actions, all of whichmay contribute to weight gain.In theory, beta-3 adrenergic receptors in adipose tissue may play a rolein weight control by converting fat intoheat and energy, especially in response tonorepinephrine. TCAs or SNRIs that favor a noradrenergic profile may promoteweight loss or neutrality. The relativelyweight-neutral selegiline patch, whichavoids first-pass metabolism and activeadverse metabolites, also may use thismechanism.23Serotonin helpsregulate appetite andcarbohydrate intakeand is the mostoften manipulatedneurotransmitter indepression treatmentNefazodone and trazodone block 5HT2aMirtazapine blocks presynaptic alpha-receptors potently, and the norepinephrine(nefazodone only) and serotonin reuptakepumps (both agents) less potently. Differences in their mechanism (nefazodoneincreases norepinephrine) and lack of 5HT2c blockade might be responsible fortheir reported weight neutrality.2 and postsynaptic 5HT2a, 5HT2c, and5HT3 serotonin receptors as well as H1histamine receptors. Both 5HT2c andH1 blockade result in weight gain, thedrug’s most apparent adverse effect. Thismechanism is similar to that of the SGAolanzapine.Causes of weight gaincontinuedCurrent PsychiatryVol. 6, No. 545

Table 3Using antidepressants in patients at metabolic risk for weight gain Warn patients before they begin antidepressant treatment about the risks of weight gain andworsening or onset of comorbid medical conditions Obtain and document family medical history in addition to the usual family psychiatric historyWeight gain Discuss and initiate a diet and exercise plan to prevent or treat weight gain before medicallysignificant weight gain occurs Choose a weight-neutral or weight-negative antidepressant for patients with existing obesity,hypertension, hyperglycemia, or hypercholesterolemia or family history of these comorbidities Discuss the risks and benefits with your patient if antidepressants that cause weight gain areneeded for better efficacy, and document this conversation Monitor patients’ weight as long as they continue taking drugs that may increase weightClinical PointInstruct patients toweigh themselvesat home at leastweekly in themorning andto report gains 5 pounds46Current PsychiatryMay 2007TNF-α. Obese persons have increased plasma levels of TNF-α and its soluble receptor(sTNF-R p75), which may induce insulinresistance. Activation of the TNF-α system,such as by amitriptyline or mirtazapine,may promote weight gain.24Preventing weight gainEarly intervention is key to preventing drugrelated weight gain and treating obesity.Provide informed consent and psychoeducation when prescribing antidepressants. Inpatients at metabolic risk, consider usingweight-neutral or weight-loss agents (Table2, page 45), 4-16 and monitor for weight gain(Table 3). At-risk patients have: abdominal obesity (waist circumference 40 inches [102 cm] in men, 35 inches[88 cm] in women, or waist-to-hip ratio 0.9 in women and 1.0 in men) hyperlipidemia elevated body mass index (BMI [overweight BMI 25 to 30 kg/m2 , obesity BMI 30 kg/m2 ]) hypertension diabetes mellitus or impaired glucosetolerance history of stroke or cardiovasculardisease family history of obesity, hypertension, diabetes, or hyperlipidemia.Use SGA guidelines? Consider followingmodified American Diabetes Associationguidelines for metabolic monitoring ofpatients treated with SGAs.25 We suggestthat you follow SGA guidelines as a de-fault when using mirtazapine—which ispharmacodynamically the most similar toSGAs—and TCAs. For patients taking otherantidepressants, we recommend that you: measure blood pressure and weight,and calculate BMI often instruct patients to weigh themselvesat home at least weekly in the morningand to report gains 5 lbs.An overall 10-lb weight gain is clinicallysignificant in most patients and calls for amanagement plan. Abdominal girth oftenincreases as part of metabolic syndrome.If you choose to measure this variable andare uncomfortable reaching around patients while measuring, allow patients toapply the tape measure themselves.Lab tests. Obtain fasting glucose and lipidlevels at baseline for most patients and thenquarterly in those with initial weight gain,medical comorbidities, or family history ofhypertension, hypercholesterolemia, or diabetes. Many clinicians also screen for hypothyroidism and anemia, and these testsmay be added. For patients without metabolic risk factors taking SSRIs and SNRIs,start quarterly draws if weight increasesrapidly by 5 lbs or if BMI approaches 30kg/m2. Tracking fasting triglycerides canserve as a sentinel for metabolic syndrome,which sometimes occurs before substantialweight gain or hyperglycemia.Dietary measuresIf weight gain has occurred, a safe initialgoal for patients is to lose 0.5% to 1% initialcontinued on page 51

continued from page 46Table 4p SYCHIATRYMedications indicated for treating obesityEvidence ofefficacy, safetyCommentObesity(5 to 20 mg/d)î10% to 15%of body weight in1 year;29 safety,efficacy beyond1 year undeterminedî triglycerides, total cholesterol,LDL cholesterolì HDL cholesterolMonitor for serotonin syndrome whenused with serotonergic psychotropicsOrlistat(inhibits gastric andpancreatic lipasesby binding to theseenzymes in the gut)Obesity (120 mg tidwith meals; takeother drugs 1 hourpre- or post-orlistat)î9% to 10% of bodyweight in 1 year;30safety, efficacybeyond 2 yearsundeterminedî triglycerides, total cholesterol,LDL cholesterolì HDL cholesterolLower risk of drug interactionsthan with sibutramine; GI sideeffects; multivitamin requiredRimonabant(investigational,pending FDAapproval; selectivetype 1 cannabinoidreceptor blocker)Obesity (20 mg/d)(pending approval)Reduced weight,improved heartdisease risk factorsin obese patientswith metabolicsyndrome or 1cardiovascular riskfactors (1-2 years)31Generally well-tolerated; mild nauseamost common side ympathomimetic;serotonergic,noradrenergicreuptake inhibitor)* 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.GI: gastrointestinal; HDL: high-density lipoprotein; LDL: low-density lipoproteinbody weight per week—or 5% to 10% ofweight across several months. Diet and exercise produce maximal benefit but requirecommitment and motivation, which areoften difficult or impossible for depressedpatients. Encouraging the patient’s effortsis worthwhile; if intervention is postponeduntil remission is achieved, weight gainmay be substantially higher and more difficult to treat.Cutting fat and calories. The first stepin losing weight is to restrict high-fat andhigh-calorie foods and eat smaller portions. If this fails, then switch the patient toa low- or very-low-calorie diet, which provides a quick initial weight loss. This canmotivate the patient but should be triedonly under a physician’s supervision.Many patients benefit from structuredcommercial weight-loss programs, but thelikelihood of regaining the weight is highif stopped. These programs typically recommend 1,200 kcal/day for women and1,800 kcal/day for men, with 55% of calories from carbohydrates, about 25% to 35%from protein, and 10% to 25% from fat.In a study of 100 patients, those on 2 liq-uid meal replacements per day plus snacksand 1 low-fat meal (approximately 1,200 to1,500 kcal/day) lost considerable weightin the first 3 months but regained someweight later. Many maintained weight losson 1 liquid meal replacement per day plussnacks and 2 low-fat meals.26Low- and very-low-calorie diets are indicated for patients with BMI 35 kg/m2: in whom conservative treatment (aportion-controlled, low-fat diet) hasfailed and who are willing to maintain atleast 1 year of treatment and majorlifestyle changes.A low-calorie diet provides 1,000 kcal/day; very low-calorie diets may provide 800 kcal/day and rely mostly on liquidmeal replacements. This semi-starvationcan produce fatigue, weakness, lightheadedness, and changes in vital signs, including blood pressure, heart rate, and respiratory rate. For this reason, extreme dietsrequire a team approach with the primarycare clinician and a dietitian.Among mentally healthy patients following very-low-calorie diets in clinicaltrials, 90% lose 10 kg and 50% lose 20currentpsychiatry.comClinical PointEating habits canbe changed withCBT; behaviormodification alonecan generate aweight loss of 0.5to 0.7 kg per weekCurrent PsychiatryVol. 6, No. 551

Table 5Medications used ‘off label’ for treating obesityWeight gainClinical PointReserve antiobesitydrugs for patientswith BMI 30 kg/m2 ( 27 kg/m2 inthose with diabetes,hyperlipidemia,or heart disease)Evidence ofefficacy, dine(antiviral agent;may potentiatedopaminergicfunction)Influenza Aprophylaxis andParkinson’s disease(300 mg/d, witholanzapine)î3.5 kg over 3 to 6months (study of 12patients)32Patients had gained a mean7.3 kg during olanzapine treatmentNizatidine(histamine-2receptor antagonist)Duodenal ulcer;GERD (600 mg/das prophylaxis witholanzapine)î2.5 kg withnizatidine; ì5.5 kgwith placebo33(16-week RCT)Unknown effectiveness whenused as prophylaxis withantidepressants; can causedelirium, especially in older patientsNaltrexone(opioid antagonist;decreases cravingfor sweet, fattyfoods caused byTCAs and lithium)Alcohol, narcoticsaddiction (50 mg/d)TCA-induced weightgain reversed, thenresumed after drugwas stopped(8-patient trial)34Small mean weight loss comparedwith previous drug-inducedweight gain; no adverse effects seenon depressive symptomsTopiramate(anticonvulsant)Epilepsy, migraine(100 to 400 mg/das adjunct toantipsychotics)î10 to 15 lbs in33% to 55% ofbipolar disorderpatients35May serve dual purpose in treatingobese patients with affectivedisorders; fatigue, cognitive dulling,ataxia, glaucoma, oligohydrosis,acidosis are possibleMetformin(biguanideantihyperglycemic)Type 2 diabetes(500 mg tid asadjunct toantipsychotics)15 of 19 patientsSporadic diarrhea in some patients;who gained 10% in risk of lactic acidosis (testsbody weight taking unremarkable in this small trial)36SGAs lost weightwith add-onmetformin (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 reflux disease; RCT: randomized, double-blind, placebo-controlled trial; SGAs: second-generationantipsychotics; TCAs: tricyclic antidepressantskg in the first 4 to 6 months.27 Most weightloss occurs in the first 12 to 16 weeks, after which an ad libitum low-fat, high-fiberdiet can be used.Exercise has physiologic and psychological benefits, including inhibiting food intake and promoting a sense of self-control.Physical exercise increases insulin sensitivity and reduces the risk of secondarymedical problems, such as heart disease.Walking 40 minutes daily produces maximal benefit, but walking even 30 minutes 3times a week can help maintain weight.behavior change leads to healthier eatinghabits, exercise, and weight loss. Behaviormodification alone can generate a weightloss of 0.5 kg to 0.7 kg per week.28A study of 6 schizophrenia patients(mean age 37) examined CBT effects onweight gain associated with clozapine(n 4) or olanzapine (n 2). Mean BMI decreased from 29.6 kg/m2 to 25.1 kg/m2after 7 to 9 sessions of individual CBT, followed by 16 biweekly group sessions thatfocused on weight reduction and weightmaintenance. A dietician provided detailed counseling.28CBT. Eating habits can be changed through52Current PsychiatryMay 2007identifying lifestyle behaviors to be modified, setting goals, modifying triggers ofexcessive eating, and reinforcing desiredbehavior with CBT. Gradual but consistentUsing medications for weight lossSwitching. To avoid polypharmacy, consider switching the patient to a weightneutral or weight-losing antidepressant,

such as bupropion. Keep in mind whenswitching medications, however, that thenext agent with less weight-gain potentialmight not deliver comparable antidepressant efficacy.Antiobesity drugs. Short of switching, anantiobesity drug (Table 4, page 51)29-31 oroff-label intervention (Table 5)32-36 may bewarranted. Antiobesity drugs should notbe used as primary therapy for obesity.Their use may be warranted, however, forpsychiatric patients who: are unable to fully participate in dietand exercise programs because of symptoms (such as cognitive impairment or severe negative symptoms) lack social support (such as reflectedby financial problems, homelessness, orpoor compliance with treatment recommendations).Generally, we reserve antiobesity drugsfor patients with BMI 30 kg/m2 (or 27kg/m2 in patients with diabetes, hyperlipidemia, or cardiovascular disease). Before adding these agents to a psychotropicregimen, however, review the relative risksand benefits with the patient and his or herprimary care physician.The goal of pharmacotherapy is for thepatient to lose 5% to 10% of baseline weightin 3 to 6 months. Failure to achieve this goalis an indication to stop the medication. Aplateau in weight loss after 6 to 9 monthsis expected and is not cause for discontinuation. If successful, drug treatment may becontinued indefinitely, and both physicianand patient must understand the intentionto treat long-term. Most patients regainweight upon discontinuation.References1. Himmerich H, Schuld A, Haack M, et al. Early predictionof changes in weight during six weeks of treatment withantidepressants. J Psychiatr Res 2004;38(5):485-9.2. Wetterling T. Bodyweight gain with atypical antipsychotics. Acomparative review. Drug Saf 2001;24(1):59-73.3. Laimer M, Kramer-Reinstadler K, Rauchenzauner M, et al.Effect of mirtazapine treatment on body composition andmetabolism. J Clin Psychiatry 2006;67(3):421-4.Related Resourcesp SYCHIATRY Centers for Disease Control and Prevention.Overweight and obesity: contributing ing Mathur R. What causes obesity? weight loss/page2.htm.Drug Brand NamesAmantadine SymmetrelAmitriptyline ElavilBupropion WellbutrinCitalopram CelexaDuloxetine CymbaltaEscitalopram LexaproFluoxetine ProzacFluvoxamine LuvoxImipramine TofranilMetformin GlucophageMirtazapine RemeronNaltrexone ReViaNefazodone SerzoneNizatidine AxidNortriptyline PamelorOlanzapine ZyprexaOrlistat XenicalParoxetine PaxilPhenelzine NardilSelegiline (transdermal) EMSAMSertraline ZoloftSibutramine MeridianTopiramate TopamaxTrazodone DesyrelVenlafaxine EffexorDisclosuresDr. Schwartz has received grants from or served as aconsultant to AstraZeneca, Bristol-Myers Squibb, Cephalon,Cyberonics, Forest Pharmaceuticals, GlaxoSmithKline,Jazz Pharmaceuticals, Pfizer Inc., and Wyeth.Other authors report no financial relationship withany companies whose products are mentioned in thisarticle or with manufacturers of competing products.7. Weisler RH, Johnston JA, Lineberry CG, et al. Comparisonof bupropion and trazodone for the treatment of majordepression. J Clin Psychiatry 1994;14:170-9.Clinical PointWeight gain may besubstantially greaterand more difficult totreat if you postponeintervention untilafter depressionremission is achieved8. Leinonen E, Skarstein J, Behnke K, et al, for the NordicAntidepressant Study Group. Efficacy and tolerability ofmirtazapine versus citalopram: a double blind, randomizedstudy in patients with major depressive disorder. Int ClinPsychopharm 1999;14(6):329-37.9. Kasper S, Lemming OM, de Swart H. Escitalopram in thelong-term treatment of major depressive disorder in elderlypatients. Neuropsychobiology 2006;54(3):152-9.10. Fava M, Judge R, Hoog SL, et al. Fluoxetine versus sertralineand paroxetine in major depressive disorder: changes in weightwith long term treatment. J Clin Psychiatry 2000;61(11):863-7.11. Abell CA, Farquhar DL, Galloway SM, et al. Placebocontrolled, double-blind trial of fluvoxamine maleate in theobese. J Psychosomat Res 1986;30:143-6.12. Wise TN, Perahia DG, Pangallo BA, et al. Effects of theantidepressant duloxetine on body weight: analyses of10 clinical studies. Prim Care Companion J Clin Psychiatry2006;8(5):269-78.13. Silverstone PH, Ravindran A. Once daily velafaxineextended release compared with fluoxetine in outpatientswith depression and anxiety. J Clin Psychiatry 2000;61(suppl2):20-5.14. Zetin M, Frost NR, Brumfield D, et al. Amitriptylinestimulates weight gain in hemodialysis patients. Clin Nephrol1982;18:79-82.15. Fernstrom MH, Krowinski RL, Kupfer DJ. Chronic imipraminetreatment and weight gain. Psychiatr Res 1986;17:269-73.16. Prince JB, Wilens TE, Biederman J, et al. A controlled study ofnortriptyline in children and adolescents with attention deficithyperactivity disorder. J Am Acad Child Adolesc Psychiatry2000;10:193-204.4. Chouinard G. Bupropion and amitriptyline in the treatment ofdepressed patients. J Clin Psychiatry 1983;44:121-9.17. Fukui H, Murai T. Severe weight gain induced bycombination treatment with risperidone and paroxetine. ClinNeuropharmacol 2002;25(5):269-71.5. Ribeiro L, Busnello JV, Kauer-Sant’Anna M, et al. Mirtazapineversus fluoxetine in the treatment of panic disorder. Brazil JMed Biol Res 2001;34:1303-7.18. Bouwer CD, Harvey BH. Phasic craving for carbohydrateobserved with citalopram. Int Clin Psychopharmacol 1996;11:273-8.6. Davis R, Whittington R, Bryson HM. Nefazodone. A review ofits pharmacology and clinical efficacy in the management ofmajor depression. Drugs 1997;54:186-7.19. Michelson D, Amsterdam J, Quitkin FM, et al. Changes inweight during a 1-year trial of fluoxetine. Am J Psychiatry1999;156(8):1170-6.continuedCurrent PsychiatryVol. 6, No. 553

20. Curzon G, Gibson EL, Oluyomi AO. Appetite suppression bycommonly used drugs depends on 5HT availability. TrendsPharmacol Sci 1998;13:12-25.21. De Vry J, Schreiber R. Effects of selected serotonin 5-HT1and 5-HT2 receptor agonists on feeding behavior: possiblemechanisms of action. Neurosci Biobehav Rev 2000;24:341-53.22. Bickerdike HJ, Vickers SP, Dourish CT. 5HT2c receptormodulation and the treatment of obesity. Diabetes ObesMetab 1999;1:207-14.23. Strosberg AD, Pietri-Rouxel F. Function and regulation ofbeta-3 adrenoceptor. Trends Pharmacol Sci 1996;17:373-81.Weight gain24. Kraus T, Haack M, Schuld A, et al. Body weight, the tumornecrosis factor system, and leptin production duringtreatment with mirtazapine or venlafaxine. Pharmacopsychiatry2002;35(6):220-5.25. American Diabetes Association, American PsychiatricAssociation,AmericanAssociation of Clinical Endocrinologists,North American Association for the Study of Obesity.Consensus development conference on antipsychotic drugsand obesity and diabetes. Diabetes Care 2004;27:596-601.26. Ditschuneit HH, Flechtner-Mors M, Johnson TD, et al.Metabolic and weight-loss effects of a long-term dietaryintervention in obese patients. Am J Clinical Nutrition 1999;69:198-204.Clinical PointConsider stoppingan antiobesity drugif the patient doesnot lose 5% to 10%of baseline weightin 3 to 6 months27. Wadden TA. Evidence for success of calorie restriction inweight control; summary data from clinical research studies.In: Scannell SM, ed. Methods for voluntary weight loss andcontrol. Bethesda, MD: U.S. Department of Health and HumanServices 1992;64-74.28. Umbricht D, Flury H, Bridler R. Cognitive behavior therapyfor weight gain. Am J Psychiatry 2001;158:971-2.29. Bray GA, Blackburn GL, Ferguson JM, et al. Sibutramineproduces dose-related weight loss. Obes Res 1999;7(2):189-98.30. Van Gaal LF, Broom JI, Enzi G, et al. Efficacy and tolerabilityof orlistat in the treatment of obesity: a 6-month dose-rangingstudy. Eur J Clin Pharmacol 1998;54:125-32.31. Kakafika AI, Mikhailidis DP, Karagiannis A, et al. The role ofendocannabinoid system blockade in the treatment of metabolicsyndrome. J Clin Pharmacol [serial online]. March 28, 2007.32. Floris M, Lejeune J, Deberdt W. Effect of amantadine on weightgain during olanzapine treatment. Eur Neuropsychopharmacol2001;11(6):181-2.33. Breier A, Tanaka Y, Roychowdhury S, et al. Nizatidine for theprevention of weight gain during olanzapine treatment inschizophrenia and related disorders: a randomised controlleddouble-blind study. Presented at: Meeting of the Colleges ofPsychiatric and Neurologic Pharmacists; March 23-26, 2001;San Antonio, TX.34. Zimmermann U, Rechlin T, Plaskacewicz GJ. Effect ofnaltrexone on weight gain and food craving induced bytricyclic antidepressants and lithium: an open study. BiolPsychiatry 1997;41(6):747-9.35. Vieta E, Torrent C, Garcia-Ribas G, et al. Use of topiramatein treatment-resistant bipolar spectrum disorders. J ClinPsychiatry 2002;22(4):431-5.36. Morrison JA, Cottingham EM, Barton BA. Metformin forweight loss in pediatric patients taking psychotropic drugs.Am J Psychiatry 2002;159:655-7.Bottom LineAntidepressants may contribute to weight gain, although this effect varies amongagents. Pre-existing obesity and metabolic factors increase the weight gain risk.Routinely educate patients, monitor weight and metabolic factors, and encouragediet and exercise management. Consider antiobesity medication, when indicated.JOIN THE LIVE WEBCAST!Meetingof theMindsControlling weight gainfrom antidepressantsThomas Schwartz, MDAssociate Professor of PsychiatrySUNY Upstate Medical University, Syracuse, NYLearn more about how to prevent excessiveweight gain after patients start antidepressant therapy.Interactive Q-and-A to followHosted by Dr. Henry NasrallahEdit

cause weight gain over time (Table 1).4-16 SSRIs. Weight gain associated with long-term SSRI use seems clinically apparent, but the evidence is preliminary. Paroxetine seems to be the SSRI most likely to cause weight gain. A 26- to 32-week comparison trial by Fava et al10 showed that weight gain risk with SSRI therapy var-ies with the drug used. In

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