ORIGINAL RESEARCH/(",eyWords: psychotropic drugs, weight loss, carbohydrate craving, "beslty, antidepressants, weight gain, antipsy-chotic drugs

The Effect of a Nov~l DietaryInterventiOn on Weight Loss in

Psychotropic Drug-Induced ObesityBy Judith J. Wurtman, PhD, Janine M McDermott,

M.A.,Philip Levendusky, PhD, Karen"Duca, PhD,and Richard Wurtman, MD

" .

.ABS7'R4CT - Weight gain 6SS«iatd fDith the use of psychotropie drugs may he related to"

their hlochu/e of serp"'kzill receptors wbidJ mediate satiety. Ohese illaif1i4uals ~hose

'Weight gaill jonofid psy.chotropk drug use, or etmIrol1lfJ1Uirug-treatea ohese sulJjeds,

'WeTetreated with a 12-fDld 'fDlight loss program that illduded a carhohydrate-rich,

proteill-pODr hlf)erage thought to .mrease haill serotD1l.1I.The 38 psychotropic drug

treated females lost slightly more 'fDlight thall their 60 1I0000rug-treatea controb, ie.

13.4~.8 pounds 'UemIS 12.1~.1 poutUls. The eight drug-treated ma/es.Jost26~4.1

pounds and their 12 1ID1lIirug-treated tlJ1Itrob lost 22.2~.2 poUtlds. Weight loss 'Was

signifiant'll all groups (aUP<.OOl).A treatment program that induded a high carbo-

hydrate dietary supp/emmt tJZUSedas much weight loss among patients OIlpsychotropie

drugs as amollg control dbesepatients, fDithout blowlIg the drugs' therapeutic effic/s.

Psych<>pharmacology BuJIetin. 2002;36(3):55-59

INTRODUCTION

Patients chronically treated with psychotropic medications including atypicalantipsychotic agents and the selectiveserotonin reuptake inhibitors (SSRIs) maygain substantial amounts of weight,1-' at least partly because they overconsumesweet and starchy foods.'" This change in eating behavior may result from block-ade by the drugs7-10of the serotoneigic 5-~2c receptors that "regulate proteinand carboh~te intab; and mediate satie~u.u Since t4ese same receptors areinvolved in the drugs' therapeutic effects, use of the drugs is not infrequentlylinked to the unfortunate consequence of destabi11'T.ingweight. ReverSing the

. resulting weight gain by the use of anorectic agents that activate these receptors

Dr. J. Wurtmanis director and Ms. McDennottis research coordinatorat the TRIADWeightManagementCenter at Mclean Hospitalin Belmont,Mass. Dr.Levenduskyis directorof thePsychologyDepartmentof McleanHospital.Dr;Ducais assistant professorinthe DepartmentofElectricalEngineeringand ComputerSciences at Tufts Universityin Medford,Mass. Dr. R.Wurtmanis professor in the Departmentof Brainand CognitiveSciencesand GeneralClinicalResearchCenterat the MassachusettsInstituteofTechnologyinCambridge. "

To whom cOrrespondence should be addressed: Jucfrth J. Wurtman, PhD; TRIADWeightManagement Center Mclean Hospital, 115 Mill St., Belmont. MA 02478; Tel: 617-855-2960;Fax: 617~5-2961; E-mail: frieda@mit.edu" .

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might.not be advisable,since su~ agents could interfere with the ther-apeutic effects of the psychOtropICdrugs.

We conducted a study to see whether increasing brain serotonin pro-duction through the twice daily consumption of a carbohydrate-rich,protein-poor beverage could reverse the obeSity caused by the psy-chotropic drugs without diminishing their therapeutic effects. Weightloss was compared with that in a Similarly treated population whoseobesity was not related to psychotropic drug use.

METHODS

The' stu<iYwas conducted at the nuAD Weight ManagementCenter at McLean Hospital in Belmont, Massachusetts. Patients camefrom the greater Boston area.The 12-week weight I~ssprogram pro-vided six nutritional education and counseling sessions,and six individ-1J~11'7,ed.exercise sessions. The 1,8<>O-caloriefood plan for men and'1,400 calorie plan for w<?menincluded three meals and two carbohy-drate-rich, protein-poor .supplements.The supplement contained 45grams of food-derived, high-glycemic-index carbohydrates, and wasconsumed an hour before lunch and dinner. The drink.contained suffi-

cient carbohydrate to elevate the ratio of the plasma tryptophan con-centration to the summed concentrations of five other large neutralamino acids (the "plasma tryptophan ratio") within 30 minutes of itsconsumption, 13 thus leading to increased brain serotonin synthesis.11.14

Weight change over the 12-week period was analyzed for subjectswho were concurrently receivingpsychotropic drugs, and for those whowere medication free. (As the clinic population consist~ of individuals

. who were paying for their weight-loss treatment, it was not possible tohave a control sample that was not also receiving a nutritional interven-tion to eJevateb~ serotonin). A paired t-test was used to compare ini-tial and week 12 body mass indices and weight.

RESULTS -The subject population included 38 females and 8 males who had

been treated with psychotropic drugs for at least 1 year and were stillreceiving those drugs. The control sample consisted of 60 females and13 males who enrolled in th~ weight losscenter over the same periOdoftime. The mean ages and body mass indexes of the two groups did notdiffer significantl~ (Table 1).

The female patients on psychotropic drugs and the control femaleslost similar amounts of weight. Femaleswith drug induced obesity lostan average of 13.4:1:1.1pounds and control females 10st 12.1:1:1.1

.'

. -.-_.-

WEIGHT Loss IN PsycHOTROPIC DRUG-INDUCED OBESITY

pounds (Tables2 and 3). Males with drug-induced obesity lost an aver-age of 26:!:4.1pounds; control males lost 22.2:!:3.2pounds.

Twenty-four females and six males were being treated with a singleantidepressant; the others were on combinations of antidepressantsand/or other psychotropic drUgs(Tables 4 and 5). No relatioD:shipwasobserved between type of drug treatment and weight loss. Five females

o. who were on psychotropicdrugs known to cause substantialweightgain (lithium, thioridazine, moIindone, risperidOI~e,valproate, quetiap-ine) lost between 22 and 37 pounds in 3 months; five of the eight malepatients on antidepressant drugs associated with weight gain lost 30 ormore pounds.

None of the drug-~ted patients reported a decrease in the efficacyof their medications temporally associated with consnminJ! the carbo-hydrate-rich supplement.- -PROFILEOF PATIENTSWrrH DRUG-INDuCED OBESI1YDRUG-INDUCEDOBESnv FEMALES MALES

384621-72~6.235.1:tO.9

"8

4128=49300.7:1:2740.6:1:2.9

Wurtman,u.McDcrmottJM.LevmduslyP,Duo K,WurtmanR.~ BuDdin.Vol 36.No. 3. 2002.

PRonu: o~ PATIENTSWrm NONDRuc-lNDuCED OBESITYNONDRUG-INDUCEDOBESITY FEMALES MALES

NumberMean

604716=75212.6:t5.235.9:tO.8

13473S=6S264:1:2541.1:t3.9

Wurtman,U.McDcnnottJM.LevmduslyP,Due. K,Wurtmm R.P1ythop~ BuDdin.VoL36.No.3.2002.

FEMAlES

13.4:tl.812.1:t1.1

MALES°

25.8:t4.122.2:t3.2

Wurtman,U. McDcrmottJM, Levmdusly P, Due. K, Wartman R. P1ythop/xmntJaJ/ogyBuDdin. Vol 36.No. 3. 2002.

....

WEIGHT Loss IN PSYCHOTROPIC DRUG=1NDUCED_OBESlTY

. linel10:

0.0

.

X..17.9

.e

nortriDtvline

*Represents >1 patient.Wurtman.H. Mc:DcnnottJM. Leva1dusky P, Due. K. Wartman R. Ps]chop~ BIIOdin. VoL 36.No.3. 2002. o.

THREE-MoNnl WEIGHT Loss AMONG EIGHT MAI.E PATIENTSONPsYcHOTROPIC MEDICATIONS

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Citatopram.Citato~oxetineF1uoxetineAmi

.tn

Paroxetine

Nefazodone, bupropionValDroatelrisoeridone

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WEIGHT CHANGE IPOUNDS)

39.234.716.233.231.514.530'1

-Represents >1 patient.Wurtman.H.McDcrmottJM.LeveodusItyP,Due. K.WurtmanR.~ BulIdin.VoL36.No.3.2002. -:-

WEIGHT Loss IN PSYCHOTROPIC DRUG-INDUCED OBESITY

CoNCLUSION

These data show that obese individuals whose weight gain is associ-ated with psychotropic drug treatment are able to lose substantialamounts of weight with a treatment that increases serotonin synthesis.Their weight loss is as'gOO(ras that of obese individualswhose weightgain was not associated with ongoing psychotropic drug treatment. 4-

ACKNOWLEDGMENT .

This work was supported by a grant from the Center for BrainSciencesand MetabolismCharitableTrost, Cambridge,Mass.

REFERENCES

1.ZajecbJM. CJiaicalissuesin Joog-bib treatmcDtwithantidepressants]CIin~ ~61:20-2S.2.EImslieJL,MannJl, SilvastmDeon Williams8M,RomaasSE.DctcrmiDantsofoverweightand0be-

sityin patientswithbipolar~] CIin~ 2001;62:486-491.3.AIJisonDB, MeotorcJL, Hco M, et 81.~ w6jht pin: a ~ aesem:h

Ipdhesis.Am]~ 1999-,156:1686-1696 .4.Mic:beIsooD.AmstadamJD. QpitkinF,et 81.Chauga inwaght duringal-,ear trialof flnomioe.Am

]~ 1999;156:1170-1176.5. SussmanN. GiosbeIg D. Weight gain ISSOCiatedwith SSRIs. Prim4t] 1'1ychUztrJ.1998;7:28-37.6. Fan M.Judge R, Hoog sr.. NiJssonME. KoJa:sc. Fh~ YCI'SUSsertaIine and pamzdinC in ID2j~

~ discmfcr.cbanges in wcigbtwith Ioag teaD tte2tIDeDt.]C/inPIJcItUzIrJ.2000;61:863-867.7.MdtzerH. TheroJeoflt&~in~drugIldioa.N~ 1999-.21:1065-1155.8.MajJ.BijakM.Dzjedzkb-WasyIewsbM,et 81.Theeft"eds ofpuaxetincgivcn ~oa the5-Hr

m:eptor sub-popuIatioas in the at brain.~ (Ber/).1996;127:78-82.9. Wong])"f, TJueJkdd PG. Robertson DW..Aftinitics offlu~ its eoantiomcrs.and other.inhibitors

of ecrotoniDupakc foe subtypes of ICIOtoDinrea;pt1m.~ 1991;5:43-47.10. Gingrich]A. Hen R. DisscctiDgthe roL:of the ICIOtODinsymm in acumpsydUatricdisonJca using

knoc:Icoutmice.Psychop~ 2001;155:1-10. .11. BluaddlJ. Scmtonin JD2DipuIationsand the strw:turcoffecclingbchaviour.Appma.I986;7:39-S6.12. Spcddiog M. Ouvry C. MiDan M, DuhauIt}, Dacquct C. Wurtmao RJ. Neural control of dieting.

Nllhln.l996-,380:488. .13. Martin-Du-Pan RC. Wurtman RJ. Role de fa1ima1tation dans Ja I)'Dtbcsc des ~ of ct

dans Jcs fonctions CCRbaJcs: w.pIiatioas dioiqucs. &IrrDei%Mea WDt'&nstln:1981:111:1422-1434.

14. FcmstromJD, Wurtman RJ. Bnin ICIOtoDinconteDt:physioJogic:al~ by plasmaueutra1amino.ads. &im«.1972;178:155-167.

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