UE. Prevention of Recurrent Depression With Cognitive Behavioral Therapy Preliminary Findings Giovanni A. Fava, MD; Chiara Rafanelli, MD; Silvana Grandi, MD; Sandra Conti, MD; Piera Belluarde, PhD Background: Cognitive behavioral treatment (CBT) of residual symptoms alter successful pharmacotherapy yielded a substantially lower relapse rate than did clini- ‘eal management in patients with primary major depres- sive disorders. The aim of this study was to test the ef fectiveness of this approach in patients with recurrent depression (=3 episodes of depression) Metheds: Forty patients with recurrent major depres: sion who had been successfully treated with antidepres- ssant drugs were randomly assigned to either CBT of re sidual symptoms (supplemented by lifestyle modification and well-being therapy) or clinical management. In both ‘groups, during the 20-week experiment, antidepressant drug administration was tapered and discontinued. Residual symptoms were measured with modified version of the Paykel Clinical Interview for Depression. Two-year follow-up was undertaken, during which no antidepressant drugs were used unless a relapse ensued, Results: The CBT group had a significantly lower level of residual symptoms after discontinuation of drug therapy compared with the clinical management group. AL 2-year follow-up, CBT also resulted in a lower relapse rate (25%) than did clinical management (80%). This difference attained statistical significance by survival analysis, Conelusions: These resulls challenge the assumption that long-term drug treatment is the only tool to prevent re- lapse in patients with recurrent depression, Although maintenance pharmacotherapy seems to be necessary in some patients, CBT offers a viable alternative for other patients. Amelioration of residual symptoms may re- duce the risk of relapse in depressed patients by allect- {ng the progression of residual symptoms to prodromes, of relapse, Arch Gen Psychiatry. 1998;55:816- From the Department of Psychiatry, State University of [New York at Buffalo (Dr Fava) aan the Afetve Disorders Program and Laboratory of Experimental Psychotherapy Department of Psychology University of Bologna, Bologna (Drs Fava, Rajanlli, Grand, ‘and Cont) and the Department of Statistical Sciences, University of Padova, Padova (Dr Beluardo), aly HE CHRONIC and recurrent nature of major depressive disorders is geting increas dng attention."® The devel opment of improved main- tenance featment strategies for depressed patients with a history of recurrent epi- sodes hasthus become a cnicial clinical and rescarch issue." Substantial evidence sup- ports the eflicacy of long-term antidepees- Sintmedlication use i patients with rec rent depression.” particular, Frank et aP conducted a randomized 3-year mainte- nance tril in 128 patients with recurrent depression who had responded to com- bined short-term and continuation teat- rmcnt with imipramine hydrochloride and interpersonal psychotherapy. A.5-cell de- sign was used to determine whether inip- ramine therapy, placebo, and interper- sonal psychotherapy could play asignilicant role in the prevention of recurrence. Use of ‘mipramine hydrochloride, at an average dosige of 200 mg/d, provided the stron- gest prophylactic elfect, whereas monthly ierpersonal psychotherapy displayed a rodest protective elect, although the lt- {er was superior ta placebo and was more (©1908 American Med pronounced when the psychotherapy was of higher quality.” Extension of treatment with imipramine or placebo provided ad- ditional evidence for the prophylactic ef fect of drug treatment.* The linical conse- quence ofthis important investigation is that patients with recurrent depression merit continued antidepressant drug prophy- laxis for at least 5 years, although psycho- logical therapies also were useful Indeed, ina recent study.° 75 patients with recurrent depression were allocated 1o 3 groups: short-term and maintenance (2 years) treatment with antidepressant drugs, cognitive behaviorial treatment (CBT) in the short-term and maintenance phases, and an- Uidepressant use inthe short-term phase and CBI for maintenance. Cognitive therapy dis played sm prophyact eft oman The criterion forrecurrentdepression, (at least 1 previous episode of depression) \was diferent, however, from that endorsed by Franketal?(=3 episodes of unipolar de- pression, with the immediately precedingep- sodle being no more than 2 years before the onset of the present episode). It is dif ficult to know, thus, whether the cognitive Association, All rights reserved. ‘Downloaded From: http:/jamanetwork.com/pdfaccess.ashx?url=/data/journals/psych/S064/ om 03/28/2017PATIENTS AND METHODS PATIENTS Fory-five consecutive outpatients slsyng the citer de- scribed below who hd been refered to and treated inthe Affective Disorders Program ofthe Univers of Bologna School of Medicine Bologna ly, were enrolled inthe sty The patents dlagnowes were esiablished by the consents of A pejchlatist (GA F) and a clink pycholops (CR) n= dependently using the Schedule for AMfective Disorders nd Schizophrenia: Patents had to meet the following eter (D acirrent diagnosis of major depressive disorder accord inglo the Research Dagioste Criteria fora Selected Group of Faction Donde (2) 3 or more eplades of depression, ‘withthe inmedately preceding episode beg no more than 5a years before the onset ofthe present episode" (3) aint ‘mum 1O-week emission aconding to Research Diagnostic Citeia (22 symptoms present tno more than smal de- gree with absence of fnctonalmpairment between then dex episode and the immediatly preceding cise’ 4) 2 iminium global severity score of forthe ren episode of depression”; (5) no history of manic, hypomani. or lothyme eaures; (6) no htory of ave drug or alcohol shuse or dependence or of personaly dlsorder according a DsWrav enter (7) nohisony oanecedent dysyni (8) no active medal lines; and (0) succesful response io an- tipressant drug ministered by 3 pyar (3. and SC) acconding toa standardized protocol" The later pro- tocol involved the use of ticle antidepressant drugs with gradual increases in donages Patients who could ttle Be tricyclic antidepressant druge were aviched to slectve Serotonin reuptake inhibitors able ¥), ‘Mer dug eaten all patients were assessed by the same peychologist (CR) who had evalusted them on n- take but who di not ike pat in he treatment. Only pa tients rated as"better” of inuch better" sccording to glo- bal scale of improvement and as being ful remission” swere included in the study, Patents ao had to show no evidence of depressed mood aller treatment according to $ modified version of the Fapkel Clnial Interview for e- pression (CID). Paiens fi the eter for stage 3 (the Fesidual phase) of unipolar depression according toa sag ingsystem developed previously.” Written informed con- sent was secured front all patiens All patients were treated for 3 to 5 months with fll doses of antidepressant drugs Cable 1), after which the ‘modified version of the CID was administered by the clini Gal peychologlt, This interview covered 19 symptom ar tesa described im det elsewhere" Each tem is ated ona Ito -pointscale, with | indicating absence of symp- tome and 7! very incapactaing symptoms The sale i cludes awider range of sympioms (euch sia and phobic nate) compared with ther scales and te partici Tay suitable for asesing subclinical sympioms of alle tive disorders" alo in view of is capacity to measure small ncrements or smal changes near the normal end of thespectum."* Furthermore, thas been fully and inde= pendently validated for alin populations =" ‘TREATMENT Aller assessment with the CID, the 45 patients were randomly assigned to 1 of treatment groups:(1) pharmacotherapy and (CBT or (2) pharmacotherapy and CM. Inboth groups, treat- ‘ment consisted often 30-minute sessions once every other week. Antidepressant drug use was tapered at the rate of 25. rigofamitnpiylinehydrochloride or itsequivalent every other week, and then thedrugs were withdrawn completely inthe last 2 sessions, ll patents were drug free). Discontinuation of antidepressant drug use was not feasible for 5 paients (3 inthe CBT group and 2in the CM group),and they were ex- cluded from the study at that point, The same psychiatrist (GAF,) performed all reatments in both grou ‘Cognitive behavioral treatment consisted ofthe fol- lowing 3 main ingredients: (1) CBT of residual symptoms of major depression." Cognitive therapy was conducted Continued of next page approach wouldbeelfectivealsoina patient population char- acterized by a more severe course of llness.° In earlier studies," an alternative treatment strat- cegy for decreasing the relapse rate of major depression, ‘was developed. This strategy is based on the fact that the presence of residual symptoms ater completion of drug ‘or psychotherapeutic treatment has been correlated with, poor long-term outcome! and that some residual symp- toms of major depression may progress to prodromal ‘symptoms of relapse.'* In those studies,"*! 40 patients, ‘with primary major depressive disorder who had been successfully treated with antidepressant drugs were ran- domly assigned to either CBT of residual symptoms or standard clinical management (CM). In both types of treatment, antidepressant drugs were gradually tapered and discontinued. The CBT group had asignificantly lower level of residual symptoms alter discontinuation of drug, therapy than the CM group. Cognitive behavioral treat- ment also resulted in a significantly lower rate of re- lapse (35%) at 4-year follow-up than did CM (70%). The purpose ofthis study was to apply this therapeu Licapproach toa sample of depressed patients, whose cli cal features matched those inthe study by Prank et al’ on recurrent depression, and to compare the effectiveness of this approach with that of standard CM without the use of| CBT. In both types of treatment, antidepressant drug use was gradually tapered and discontinued. Inview ofthe con- siderable clinical challenge, CBT of residual symptoms was supplemented by relapse preventive strategies. es Forty patients (20 in each group) completed the 20- week experiment. There were no significant differences between the groups in any of the variables listed in Table Lorin severity of residual symptoms as measured by the CID (able 2). Comorbidity was considered only if it persisted alter treatment of acute depression and sats fied Research Diagnostic Criteria." A few patients were taking benzodiazepines at low doses and continued to do so throughout the study Cognitive behavioral treatment induced signili- cant improvement in residual symptoms, whereas there were no significant changes in the CM group. When the (©1908 American Med Association, All rights reserved. ‘Downloaded From: http:/jamanetwork.com/pdfaccess.ashx?url=/data/journals/psych/S064/ om 03/28/2017as describe by Hecke al The peychatist (G.A..) an Cperienced therapist, used strategies and techniques de- signed to help depresed pallens correct their distorted ‘ews and maladaptive bei, pariculrly regarding symp- toms concerned with anxiety and rally, which con- stu the bull of residual symptoms in patients with de- Pression." Whenever appropriate asin the cas of res Eymploms related to anaiety, exposure srategies were Planned withthe patient” eg inthe case of exposure to Phobic external etesin agoraphobia or social phabia (2) Ltesyle modification. Patients were instructed that de- pression is merely the consequence ofa maladie fe Fiyle, which doesnot take life stress, interpersonal (i= tion, excessive work, and inadequate rest into proper $ccount. Antidepressant drugs restore normal mood, But relapse may ensue iT inappropriate lfesiyle behaviors are Continued after dng withdrawal. Patients were encout- ‘ged to modify their schedules arangements ete, sccord- ingly. The strategies used technically derived from life style modification approaches that were effective in cinicl Cariclogical studies" (3) Well-being therapy. In the last Tor 3 session, a psychotherapeute strategy for enhane- ing wellbeing” was teed. The technique raed at change ing beliefs and ates detrimental o well-being, stim lating avarenessof personal growih and recovery from aMfectve les, and feinforcing behavior promoting well tring tis baced on Rand Singers" conceptual model of well-being a the result of self-acceptance, postive re indons with ethers autonomy, environmental mastery, pr pose ie and personal growth Clinical management consisted of monitoring medi cation tapering, reviewing he patients clinical tats and providing the patient with support and advice if neces- Ey. In Ch, spelic Interventions such sexposte strat gles, dary work, and cognitive restructuring were pro- strbed. The patent was encouraged toshare the main events that took place in the previous 3 weeks, Treatment ing ‘ty was checked by submiting randomly selected ped sessions (involving CBT and $ involving CM) to2 inde- Pendent sensors, who correctly identified all sessions “The 40 patients were reasesed with the CID, ater tweatment an! while drug fre, bythe same cinial psy chologist (¢R) who had performed the previous evalua tions and who wes tnewareof iment xigancat The patients were then assested 3,6, 9,12, 15, 1821, and 24 Thoms afer treatment They were instructed tell tmeditelytany new sjrptoin appeared and wee ge teed a renewed course of ntdepreseant drug therapy only inthe event of relapse Follow-up evaluation consisted of 2 brit update of ental nd medical statu, includingany trentment contacts or use of medications. Relapse was de fined asthe occurence ofa Research Diagnostic Criteia~ dined episode of major depression. During llow-ap (un less a relapse occurred), no patient recelved additonal antidepressant drug teanent or psjchotherapentic inte STATISTICAL METHODS The Dae ¢ test and the x? test were used to compare the 2 groupe and to evaluate changes in estdual symp- toms within cach of the treatment groups. Analyste of Covariance was used for comparing the means of the Festal symptoms scores, with adjustment for any dill nce in the fst assessment. Survival anasto” was Usd for time nl relapse into major depression. Six factors wwere investigated as possible predictors of oucome {ssignment to CBT or CM, age, sex, duration of the depressive epzode, number of previous depressive ep sodes, and jmber of residual sjmploms regardless of and Before treatment assignment. The Kaplan-Meier tmethod was use for estimating survival curves Because {elapse was the event of inlerest, survival refers to relapse free status, Each factor was dichotomized with acute joint around the median for measurement factors. The log-rank test and the Cox proportional hazards regression model were used to compare any 2 survival Aistiutions for each ofthe 6 factors considered. For all texts performed, the significance level was 05, 2-talled Restle ae expressed ar mean (SD). residual symptoms at the second assessment (alter CBT ‘or CM) of the groups were compared, with their initial measurements as covariates, «significant effect of CBT was found (P,.y = 31.54, P<.001) During the 2-year follow-up, 5 patients (25%) in the CBT group and 16 patients (80%) in he CM group relapsed. The mean survival times were 01 8 (22.4) weeks for the CBT ‘groupand 62.2 (26.6) weeks forthe CM group (t= 381, P<001). Of the 6 variables selected for survival analysis, ‘only treatment assignment (Figure) attained statistical sig- nificance (log-rank test,x', = 11.98; P<,001). Using the Cox proportional hazards regression model, CBT was highly sig- nificant in delaying recurrence (P = 003) Se This study has obvious limitations beeause of its prelimi nary nature, First, it involved a small number of patients inthe evaluation of long-termellects. Second, it had a sem naturalistic design because patients were initially treated ‘with different types of antidepressant drugs, and there was no placebo-controlled withdrawal of medication. Finally, treatment was provided by only 1 psychiatrist with exten- sive experience in allective disorders and CBT. The re- sults might have been different with multiple, less expe enced therapists. Nonetheless, the study provides new, important clinical insights regarding the treatment of recurrent, unipolar, major depressive disorder. Short-term CBT alter successful antidepressant drug therapy had a substantial effect on relapse rateafter discon- Linuation of antidepressant drugs, Patients who received CBT reporteda substantially lower relapse rate(25%) during the 2-year follow-up than those assigned to CM (80%). This difference was significant in terms of comparison of mean survival ime and survival analysis. The high relapse rate in the CM group isin line with the findings by Prank etal.” However, the patientsassigned to CM in the study by Prank etal hada much shorter survival ime than those in thisin- vestigation, This may be due to the very slow taper of ai- Lidepressant drugs that was endorsed by this study because this may affect outcomein mood disorders." For’ patients not included in the study, discontinuation of antidepres- sant drug therapy wasinol feasible, suggesting thatthe long- termoutlook of recurrent depression is grimif patients are (©1908 American Med Association, All rights reserved. ‘Downloaded From: http:/jamanetwork.com/pdfaccess.ashx?url=/data/journals/psych/S064/ om 03/28/2017‘Table 1. Sociodemographic and Clinical Characteristics of Patients Assigned fo Cognitive Behavioral Treatment (CBT) of Residual Symptoms or Clinical Management (Ct) (BT Group Oroup charterer ( (n=20) Aovatontyy 451 (103) 487 (721) Sox malfemae on ma antl sta, maredunarig saz tt Socal das, mi-uparvoring tet 18 Duration of ee, mo 217) 26(12) No.of previous depressive episodes a6(09) 35108) Comoridty ‘eneaiaed araty ort 6 4 Agoraphobia. 4 3 Sov phobia 0 1 Tietment of su eicade ‘Amie hyroclode, 150-200 mgid 7 7 Imipramine hydochorde, 150-200 mgid 5 5 Despraminehyroelre, 150.200 mpid 5 6 uote, 20-10 mia 2 2 Servalinefydochonie, 180 mld 1 0 Banzaiazopinee Onaropam, 30 mglé 2 1 Clonazopam, 1 mglé 1 1 Pratepam, 20 mod 1 0 uratpam hydrochode, 15 mol 0 1 Bromazepa, 3 mgt 0 1 Duration of esment, ik 15426) 15807) Data ge a mean (SO) and amber of patents ‘Accadig tothe asian ofcecpatins by Gotthorpe and Hop left without appropriate pharmacological support or have not received psychotherapy The restilts ofthis investigation lend support to the findings on the importance of psychotherapy in recur- rent depression by Frank etal** Spanier etal,’ and Black- burn and Moore.” Results ofthe latter study,” which had less stringent criteria for recurrent major depression, sig- {gest the possibility that both short-term and mainte- with cognitive therapy may yield better results than pharmacotherapy followed by psycho- therapy. This possibility, which is intriguing also in light of sensitization hypotheses related to antidepressant should be explored with future investigations. Cognitive behavioral treatment waselfective in decreas ing residual symptoms of depression, replicating previous results. By defrting the psychotherapeutie intervention Uunilafterpharmacotherapy, we were able to provide less imensive course of therapy (10 sessions) than is custom- ary (eg, 16-20 sessions) because psychotherapy could be concentrated only on the symptoms that did not abate af- terpharmacotherapy. Thefactthatmost ofthe residual symmp- toms of depression ate also prodromal," and that prodro- salymptomsof relapse tend to mirror those ofthe initial episode, explains the protective effect ofthis targeted teat- ment, Cognitive behavioral treatment may act om those residual symptoms of major depression that progress tobe- ‘come prodromal symptoms of relapse. ® This may partie larly apply anxiety andiretablity, which are prominent inthe prodromal phase of depression," may be covered bymood disturbances butarestil presentinthe acute phase. and are again a prominent feature of its residual phase. Substantial comorbidity concerned with anxiety disorders Table 2 urs tenet newt Depression (ClD) Before and After Cognitive Behavioral Treatment (CBT) of Residual Symptoms or Clinical Management (CM) ear yao Fata rotate! ty asa] moa ar aie mia) om om Ss oo oe Bos. \ : © Fos Ee S fe fs as. : Boe. = . 3.2) [some ox) [Ses ag OTe a aS Tee ial Proportons af epessedpaterts remain in emision 2 years ater cage behavioral terapy or cca management \wasfound in both groups. Compared with results ofthe pre- vious investigation," CBT was not targeted to decreasing, residual symptoms only. Two additional ingredients were added in view ofthe clinical challenge represented by a pa- tient population with recurrent depression, One was dé fined. lifestyle modification. Clinical experience has sg- gested that recovered depressed patients are olten unaware of the long-term consequences of a maladaptive lifestyl which does not take long-term, minor lfestress; interper™ sonal friction; excessive work (particularly in male profes- sionals 40-50 years old); and inadequate rest into proper account. Although lifestyle modification often hasbeen in- corporated in relapse preventive strategies in depression, thas been specifically addressed mainly inthe clinical car- diological arena (eg, modification oftype A behavior after ‘myocardial infarction)..* We postulated that the presence ofsubsyndromal psychiatriesymptoms' andlong-termstress exposure may cause an allostatic load, i, fluctuating and heightened neural or endocrine responses resulting from environmental challenge. * Purthermore, interventions that bring the person out of negative functioning (eg, exposure treatment in panic disorder withagoraphobia™)areone form of success, bu facilitating progression toward restoration ofthe positive isanother. *Rylland Singer suggested that the absence of well-being creates conditions of vulnerabi lay to possible future adversities. A specific psychothers- peutic strategy that enhances well-being” wasthe third main ingredient of the CBT approach. ts not possible to know fromour study whether these 2additional ingredients (ife- style modification with the ensuing sense ofcontrol and well- (©1908 American Med Association, All rights reserved. ‘Downloaded From: http:/jamanetwork.com/pdfaccess.ashx?url=/data/journals/psych/S064/ om 03/28/2017‘being therapy) yielded specific contributions to the clini- ‘alresultsobiained in ourinvestigation. Inanindependent, 2 Fa GA, Kale f.Podranal syptomsin alectve dst. Am Psych ty tah aba 30 : 13. Baer Span A agnosia Sh er tc is preliminary smallscalestudy,asigniicantadvantageot "> gonardSohue on Poehey ese tOP RIE ‘NelLbeingtherapyoverstandtd CBE ststegicsindecrea 1 SR Ein eb, Ase dose Cr Seat Gp ‘Tire Osos Sed lagok Bane esr risen ee ingtesdualsympiomsvae observed Furherreearchshould _-S¢ysamlZaents Ste toe clicidate these points 16. faa oe opi thu pnsPcold The results of studies by Franketal?Spanier etal? 22921860, 16. aia: cain, gota Sa Mae i and Kupferct a ale the ican tothe need forpro- AMER an Ain psn Sst Mut Men ‘idingmaintenance therapies to pales withrecurrentde- 1. Epa rage case on PLAES Cnn oe Po pression. Long-term, high-dose antidepresant drugsscemedl epi otc sacs. Eardley Pes fo Bethe teatinent of choice. This preliminary mvestiga- _ SUMS Sai uci gf ep nd tion, using a similar patient population, would challenge» fr Une Pes 18 such a stance and confirm the unfavorable long-term out- eFC, Levu A en . an Enso conbnane aos Come of patents not receiving pharmacotherapy or psy _- Matta saa ae ae ey eae ‘hotherapy: Long-term maintenance drug treatment" gr 2. Pay Th ine yr nna Je Oso 5085.8 aa 2 Fateh tater Sag angen ers npc cohen psychotherapy** may be necessary in several patients. How- FG ele 8 Song ec Pe ver.ourapproach (CBT alter pharmacotherapy) does mot 2. fa ae ana Pt PG Zale Maing epesn fall within the realm of maintenance strategies. Iisa 2- mand eee At eo eh 23 Fh San Sanh Ribena mages slags, sequent intensive approach that i based on the" prt nag dpi eta En chay,HETSSSE E fact that eatmentofdepression by pharmacologcalmeans 24 Fath Sauls Cra Peal rps ot wh is likely o leave a substantial amount of residual symp- toms in most patients Whether they reach the Usreshold ‘of comorbidity, these residal symptoms hinder lasting re covery. The findings of ths preliminary investigation await further large-scale, independent replications I the elfe~ tiveness of ths approach is established, the resule might have important implications forthe clinician and for eur- rent conceptualizations ofallective disorders.” Accepted for publication June 3, 1998. This work was supported in part by grants from the “Men- {al Health Project,” Istituto Superiore di Sanita (Dr Fava), and the “Ministero dell Universita edella Ricerca Scienificac Tec- nologica” (Dr Favaand Fortunato Pesarin, PRD), Rome, lal. Dr Pesarin, University of Padova, Padova, laly, pro- vided statistical advice Reprints: Giovanni A. Fava, MD, Department of Psy~ 8 6 a. 28 0 2. a 2. 2 au orga. Am.) Psat 1088145 TSE. Fea Gra’ Caesar reo? Pea Mchaiensct cuneate ‘acs wih expaue abn ef agwaaia (Act Osa 18122857 FG Sern6, Rafal © and & Caner Prod yptoms in ‘eesie-conpulse dard Pectopataiy 1096.28 10-134 Palle Rumaa Copa Maus Koo Back A Restuloymp- tos arpa omission, Poco Ma 190538: 17 1-100 Fav A, rom Barra, Berar Grand Calg © Mii MO fresion nd gastos oes dn. Geran TES 18, rns ask Cuneo A Saati Ranier Tombs Gaza Rag prion and anya astctoy nd Pychaty Md 19020969171, Faw, Hagel sero 6, Cnt Bale. Gane, Sempr So Tesi alarda Magan Nerden asta A Psyeha Send ieee " Fava GA, Son 6, Zale, Grand, Raa, Cos. Overcoming r= "lsuns a egoutin ane erdr wth geaphos, Acta Paha Send Scrassoe tn, Pav JA Fava Wh Levenson JA Inpring cognv hap and pharace ‘rayne wearar an propio epson anv approach PS ‘her Pajchoson ORK 211-218, Bk A Bush Al Shaw BF, Ear. Copii Tap of Doren New ork Muto Press 170. Br AT Enary Atty isd and Pdi. New Yr, WY: ase Books chology, University of Bologna, viale Berti Pichat ne bios 1 ology, University af Bologna, vile Bett Pichat 5, 40127 a ie42 Far, Phobia Ritual New Yor, Y: ford Urey Press Bologna, Italy Tne 987 EEE} 1. Fava GA Th cancop of ecoery in aletve dares, Pacha Psyeho- fom 0868523 Uitte A Do Resim depressive or Psych Psy- ‘hosom 1 6615-10 2. pl Matas stn cure pression. Psych era 4 Fata Ua Contin and msinnance wate of mor ete Sore: anid 19424201 28 a. 2 2. ®. 4 Liman 8. Review o pyehosaratc aspects of aos disse Psy ‘hte Psychosom 1O8850:10-187. Fave GX, tea Caza Con, Grand, Wag therapy ne yehahapeac approach or esau sympa of act are 5 hota ne 2645-00, FiO Sine Potiogeaatbang Printer Peosom 100651420 Lig EY utc Mera Susi Dats as de. New Wor WY dt ie Sons 192 uldossra fu ists ad npeons of ieeruping mantanc psjche- trope aug tay, ychober Psotosm 109852 1271 Fae GA Bo areas and anny drugs ease crit inate. ‘ie dora? Psjerader Pech, 10681 1-131, 5. Fa, Kuplr Pol Cae , Jaret DB, linger AG Thase ME, 42. FavaGA Hodge epescn, soaizatony arudapessart dus ade Netacran AB, Grochocnsh . Toeearoucones or atenanee aa Pogal exers Petter Pjchosam 1OEGe Bis in eure cepressin, Arh Gen Pye 10047103198 48, FeGA Grand, CanestariR, tar Pracamalsynetonsin primary me 6. Frat Kp 0 Wager Mctacvan AB, Gres Cea one Ioedepresse disorder Act iso 190 1010-12 ‘onl pyc se manennce sent of rcurent Sepreeson on- 44 Yan Pag MAb the canaly a reed ive m moed ores, Ear Aung tors Ach Gen Paya. 190746 158-050. ewopsjenophamacol 8022-36-04 7. Shaner Fak McEahan AB rechacshW, Kut OU. The pophy- 45, Faw eure mpl ané rar esi ess. Paya li Base Ine f pei pode nce dpraesin along dconation ‘azszt1208, tfc gy. Pye ad o06645F 78 48, TasofETaitonanatacr be Wight JH, Tas ME Bek Luge 1. ptr anit Cores Malina 8, Thase ME, MEacn| ds Cogatee ap Mrs Naw Yor Galo Press TOMAS, ‘A Grohocnh VF yaeteome ir maieanc thes in acre daprsin Arh Gan Pye, 12 4076-73. Bactbai Moore A Conta aia ton rl a come teapy Inoutpatems wh cura cpresin 87. Psyety 08771263 10, aah Grands, en Cresta, Morphy MA Cognit eka ‘amen fea spasm pinay aor eps Garde Am IPS har 100112051298, 11, Fah Grant, Zl Walaa C, Canestr A Four year etome fr ‘aga behavioral amen ores syptons nm epreasion. Ad Papen 006 153945. a. 8 2 0 Sd Akl HG Pauls MP The rl and lines egtenc of ater ‘oral depressive Symptons (S80) unipolar mar depres aaa. ‘et or 9718, iMeEnen 8S Stee anh ical Arch nen Mec. 1000153: bone 201, Tse ME Simons AD. MGeayJ, Catan, Hughes Haden Finan Reap ater copie benaar erp of een patel mpletans feronger auc of vant An Psenary 10021 1046-1082 Faw Conepua abstaces esearch pogss maecte asrds sy ‘hte Psychosom. 18756283 285, (©1908 American Medical Association, All ights reserved. ‘Downloaded From: http:/jamanetwork.com/pdfaccess.ashx?url=/data/journals/psych/S064/ om 03/28/2017