Prevention of Relapse in Residual Depressionby Cognitive TherapyA Controlled TrialEugene S. Paykel, MD, FRCP, FRCPsych; Jan Scott, MD, FRCPsych; John D. Teasdale, PhD;Anthony L. Johnson, PhD, CStat; Anne Garland, BA(Hons), RMN; Richard Moore, PhD; Alison Jenaway, MB, MRCPsych;Peter L. Cornwall, MB, MRCPsych; Hazel Hayhurst, PhD; Rosemary Abbott, PhD; Marie Pope, MScBackground: Previous studies indicate that depressedpatients with partial remission and residual symptomsfollowing antidepressant treatment are common and havehigh rates of relapse. There is evidence that cognitivetherapy may reduce relapse rates in depression.Methods: One hundred fifty-eight patients with recentmajor depression, partially remitted with antidepressanttreatment (mean daily doses equivalent to 185 mg of ami-triptyline or 33 mg of fluoxetine) but with residual symp-toms of 2 to 18 months’ duration, were included in a con-trolled trial. Subjects were randomized to receive clinicalmanagement alone or clinical management plus cogni-tive therapy for 16 sessions during 20 weeks, with 2 sub-sequent booster sessions. Subjects were assessed regu-larly throughout the 20 weeks’ treatment and for a furtheryear. They received continuation and maintenance anti-depressants at the same dose throughout.Results: Cognitive therapy reduced relapse rates for acutemajor depression and persistent severe residual symp-toms, in both intention to treat and treated per protocolsamples. The cumulative relapse rate at 68 weeks was re-duced significantly, from 47% in the clinical manage-ment control group to 29% with cognitive therapy (haz-ard ratio 0.54; 95% confidence interval, 0.32-0.93;intention to treat analysis). Cognitive therapy also in-creased full remission rates at 20 weeks but did not sig-nificantly improve symptom ratings.Conclusion: In this difficult-to-treat group of patientswith residual depression who showed only partial re-sponse despite antidepressant treatment, cognitive therapyproduced worthwhile benefit.Arch Gen Psychiatry. 1999;56:829-835THERE IS widespread recog-nition that the long-termoutcome in depression isstill disappointing. Sub-stantial rates of relapseand recurrence have been reported in manyfollow-up studies.1-4Antidepressantcontinuation and maintenance reduce therates of relapse and recurrence comparedwith placebo, but these remain substantial.A common problem after acute treat-ment is partial remission with presence ofresidual symptoms. High relapse rates havebeen found in subjects with residual de-pression.5-12The treatment of such patients pre-sents a challenge. The incomplete remis-sion usually reflects limited response to an-tidepressants and suggests other treatmentpossibilities. A promising approach is cog-nitive therapy (CT). Follow-up studies ofacute treatment trials have found lower re-lapse rates following CT than followingmedication.10,11,13In 2 of 3 recent small-sample controlled trials using CT after com-plete or partial remission, there was also evi-dence of relapse reduction.14-16However,medication was withdrawn in these trials.We report a large randomized con-trolled trial of CT with clinical manage-ment vs clinical management alone in 158subjects with residual depressive symp-toms, who continued to receive main-tainance treatment with antidepressantsthroughout the trial.RESULTSPATIENT FLOW AND DROPOUTEighty-three patients were recruited fromCambridge and 75 from Newcastle, with 78randomized to clinical management and 80to CT. Within the clinical managementgroup, 66 subjects (85%) adhered to pro-tocol until the end of the study or relapse;within the CT group, 61 patients (76%) didso (Figure 1). The 8.4% difference was notsignificant (95% confidence interval [CI],−3.9% to 20.7%). Full or fairly complete rat-ings to relapse or end of study were ob-tained for all except 6 subjects in the clini-ORIGINAL ARTICLEFrom the Departments ofPsychiatry, University ofCambridge, Cambridge,England (Professor Paykel andDrs Moore, Jenaway, Hayhurst,and Abbott); University ofGlasgow, Glasgow, Scotland(Professor Scott); University ofNewcastle, Newcastle, England(Dr Cornwall and Mss Garlandand Pope); and MRC Cognitionand Brain Sciences Unit(Dr Teasdale) and MedicalResearch Council BiostatisticsUnit (Dr Johnson), Universityof Cambridge Institute of PublicHealth.ARCH GEN PSYCHIATRY/ VOL 56, SEP 1999829©1999 American Medical Association. All rights reserved.cal management group and 10 in the CT group. The mostcommon reasons for nonadherence to the protocol (notshown in the figure) were failure to attend (clinical man-agement group = 4, CT group = 10), withdrawal of con-sent (clinical management group = 2, CT group = 6), de-velopment of additional excluded diagnosis (clinicalmanagement group = 3, CT group = 1). One patient re-ceiving clinical management died and 1 moved away.INITIAL CHARACTERISTICSOF TREATMENT GROUPSThe 2 treatment groups were closely comparable on ini-tial variables, including stratification variables and co-variates (Table 1).Subjects were middle aged (mean age, 43 years) andabout 50% were male. Initial severity ratings lay in theSUBJECTS AND METHODSSUBJECTSSubjects were patients with unipolar depression aged 21to 65 years, recruited from psychiatric outpatient clinics,satisfying DSM-III-R17criteria for major depression withinthe last 18 months but not in the last 2 months, and whohad residual symptoms reaching at least 8 on the 17-itemHamilton Depression Rating Scale (HDRS)18and 9 on theBeck Depression Inventory (BDI)19(modified from crite-ria of Frank et al20). Residual symptoms had lasted 2 to 18months.Patients were excluded if there was a history of bipo-lar disorder, cyclothymia, schizoaffective disorder, defi-nite drug or alcohol dependence, persistent antisocial be-havior or repeated self-harm, DSM-III-R dysthymia withonset before age 20 years, borderline personality, learningdisability (estimated IQ ⬍70), organic brain damage, or anyother primary Axis I disorder at the time of the index ill-ness. Also excluded were patients currently receiving for-mal psychotherapy or those who had previously receivedCT for more than 5 sessions.Patients had to be taking a tricyclic antidepressant, se-rotonin reuptake inhibitor, atypical antidepressant, or mono-amine oxidase inhibitor for at least the previous 8 weeks,with 4 or more weeks at a daily dose at least equivalent to125 mg of amitriptyline, and higher levels unless there weredefinite current adverse effects or patient refusal to
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