10 10 th th ICBM Tokyo 2008 ICBM Tokyo 2008 PRCP Tokyo 2008 PRCP Tokyo 2008 1 1 The Findings of GLADS The Findings of GLADS Group for Longitudinal Affective Disorders Group for Longitudinal Affective Disorders Study Study and Their Clinical Relevance and Their Clinical Relevance in Japan in Japan Hiroaki Hiroaki Harai Harai , M.D. , M.D. Nagoya Mental Clinic Nagoya Mental Clinic Kikuchi National Hospital, Division of Clinical Research Kikuchi National Hospital, Division of Clinical Research
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1010thth ICBM Tokyo 2008ICBM Tokyo 2008PRCP Tokyo 2008PRCP Tokyo 2008 11
The Findings of GLADSThe Findings of GLADSGroup for Longitudinal Affective Disorders Group for Longitudinal Affective Disorders
StudyStudy
and Their Clinical Relevanceand Their Clinical Relevancein Japanin Japan
Lab, Arm chair theoriesLab, Arm chair theories–– Animals and coffeeAnimals and coffee
Clinical TrialsClinical Trials–– Drug companiesDrug companies
Cohort studiesCohort studies–– Years of dedicationYears of dedication
Community studiesCommunity studies–– Government commitmentGovernment commitment33
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GLADSGLADS
Group for Longitudinal Affective DisordersGroup for Longitudinal Affective Disorders–– Started 1991Started 1991
–– A cohort study by A cohort study by ““usus””
Naturalistic prospective cohort studyNaturalistic prospective cohort study–– Representative inception cohort of Representative inception cohort of unipolarunipolar
major depressive episodesmajor depressive episodes–– Recruited at the time of their treatment Recruited at the time of their treatment
commencementcommencement–– Followed up prospectively and serially with a Followed up prospectively and serially with a
semisemi--structured interview for 10 yearsstructured interview for 10 years
Methods make FactsMethods make Facts
Unbiased samplesUnbiased samples–– Various 23 institutions in JapanVarious 23 institutions in Japan–– Quasi randomly sampled new patients were Quasi randomly sampled new patients were
screened by PISA screened by PISA Psychiatric Initial Screening for Affective DisordersPsychiatric Initial Screening for Affective Disorders
Unbiased measurementsUnbiased measurements–– SemiSemi--structured Interview for this purposestructured Interview for this purpose
COALACOALA Comprehensive Assessment List for Affective disordersComprehensive Assessment List for Affective disorders
Developed and validatedDeveloped and validated
Dedication to continueDedication to continue–– Monthly for two years, annually thereafterMonthly for two years, annually thereafter 55
Treatment received by Treatment received by depressed patients in Japan depressed patients in Japan
and its determinants: naturalistic and its determinants: naturalistic observation from a multiobservation from a multi--center center
collaborative followcollaborative follow--up studyup study
Furukawa TA, 2000. Journal of Affective Disorders,Furukawa TA, 2000. Journal of Affective Disorders,60;3:173 60;3:173 -- 179179
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Dose of antidepressantDose of antidepressant
ImipramineImipramine equivalentequivalentAt 1 monthAt 1 month–– 85.2mg (SD = 73.2)85.2mg (SD = 73.2)–– 69% patients prescribed less than 125mg69% patients prescribed less than 125mgAt 6 monthsAt 6 months–– 67% patients prescribed less than 125mg67% patients prescribed less than 125mg
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Class of medications prescribedClass of medications prescribed
For patients with major depressive For patients with major depressive disorder in Japandisorder in Japan
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Antidepressants
Benzodiazepines
Antipsychotics
Lithium
Upon entry 81% 60% 11% 5%
1 month 82% 53% 14% 6%
6 month 81% 48% 12% 12%
Adequacy of continuation andAdequacy of continuation andmaintenance treatments for maintenance treatments for
majormajordepression in Japandepression in Japan
Fujita A, 2008, Journal of Psychopharmacology Fujita A, 2008, Journal of Psychopharmacology 22 2 15322 2 153--156156
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Dose of antidepressantDose of antidepressant
ImipramineImipramine equivalentequivalentContinuation phaseContinuation phase–– 45.1mg (SD = 64.7)45.1mg (SD = 64.7)–– 74% patients prescribed less than 75mg74% patients prescribed less than 75mgMaintenance phaseMaintenance phase–– 42.0 (SD = 74.7)42.0 (SD = 74.7)–– 83% patients prescribed less than 75mg83% patients prescribed less than 75mg
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OUTCOMESOUTCOMES
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Time to recovery of an Time to recovery of an inception cohort with hitherto inception cohort with hitherto
untreated untreated unipolarunipolar major major depressive episodes depressive episodes
Furukawa TA, 2000, British Journal of Psychiatry Furukawa TA, 2000, British Journal of Psychiatry 177: 331177: 331--335335
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Time to recovery without Time to recovery without antidepressantsantidepressants
Median time to recovery of the index Median time to recovery of the index episode after treatment commencementepisode after treatment commencement–– 3 months (95% CI 2.53 months (95% CI 2.5--3.6)3.6)Median time to recovery from the onset of Median time to recovery from the onset of the index episodethe index episode–– 7.0 months (95% CI 5.27.0 months (95% CI 5.2--8.8). 8.8).
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Cumulative probability of remaining in the index episode after tCumulative probability of remaining in the index episode after treatment reatment commencement for the 90 commencement for the 90 probandsprobands with DSMwith DSM--IV major depressive disorder not IV major depressive disorder not
superimposed on superimposed on dysthymiadysthymia. Patients who recovered within a few days after . Patients who recovered within a few days after treatment commencement were regarded as attaining recovery at 0 treatment commencement were regarded as attaining recovery at 0 month.month.
Clinical ImplicationsClinical Implications
Median time to recovery : 3.0 monthsMedian time to recovery : 3.0 months–– 26% reached minimally symptomatic by 1 26% reached minimally symptomatic by 1
month, month, –– 63% by 3 months, 63% by 3 months, Better than suggested by the literatureBetter than suggested by the literature12% remain an episode 24 months after 12% remain an episode 24 months after
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Time to recurrence after Time to recurrence after recovery from major depressive recovery from major depressive
episodes and its predictorsepisodes and its predictors
2020
Kanai T, 2003. Kanai T, 2003. PsycholPsychol Med 33:839Med 33:839––4545
31Full
Relapse
1yr 2yrs 6yrsRecurrence Recurrence
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95Inception
50Subthrehold
relapse
32Remain
39Remain48
Remain84
Recover
How many well vs. unwell days How many well vs. unwell days can you expect over 10 years, can you expect over 10 years, once you become depressed?once you become depressed?
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Furukawa TA, 2008, Furukawa TA, 2008, Acta Psychiatr Scand Acta Psychiatr Scand 11––88
10 Years10 Years
After starting treatment of their major After starting treatment of their major depressiondepression77% in 77% in euthymiaeuthymia, , 16% in 16% in subthresholdsubthreshold depressiondepression7% in major depression7% in major depression
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GLADS (n=94)
NIMH (n=431)
Cambridge (n=70)
Remitted 77% 58% 67%
Subthresholddepression 16% 27% 20%
Major depression 7% 15% 13%
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Major contributionsMajor contributions1.1. Furukawa TA, Time to recovery of an inception cohort with hitherFurukawa TA, Time to recovery of an inception cohort with hitherto to
untreated untreated unipolarunipolar major depressive episodes. Br J Psychiatrymajor depressive episodes. Br J Psychiatry2.2. Kanai T, Time to recurrence after recovery from major depressiveKanai T, Time to recurrence after recovery from major depressive
episodes and its predictors. episodes and its predictors. PsycholPsychol MedMed3.3. Furukawa TA, Definitions of recovery and outcomes of major Furukawa TA, Definitions of recovery and outcomes of major
depression: results from a 10depression: results from a 10--year followyear follow--up. up. ActaActa PsychiatrPsychiatr ScandScand4.4. Furukawa T, The comprehensive assessment list for affective Furukawa T, The comprehensive assessment list for affective
disorders (COALA): a disorders (COALA): a polydiagnosticpolydiagnostic, comprehensive, and serial , comprehensive, and serial semistructuredsemistructured interview system for affective and related disorders. interview system for affective and related disorders. ActaActa PsychiatrPsychiatr ScandScand
5.5. Furukawa TA, Treatment received by depressed patients in Japan Furukawa TA, Treatment received by depressed patients in Japan and its determinants: naturalistic observation from a multiand its determinants: naturalistic observation from a multi--center center collaborative followcollaborative follow--up study. J Affect up study. J Affect DisordDisord
6.6. Fujita A, Adequacy of continuation and maintenance treatments foFujita A, Adequacy of continuation and maintenance treatments for r major depression in Japan. J major depression in Japan. J PsychopharmacolPsychopharmacol
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AcknowledgementsAcknowledgementsGroup: GLADSGroup: GLADSPrinciple InvestigatorsPrinciple Investigators–– Prof. Takahashi. K, Prof. Kitamura T.Prof. Takahashi. K, Prof. Kitamura T.–– Prof. Furukawa, TA Prof. Furukawa, TA
Research GrantsResearch Grants–– 3A3A--6, 6A6, 6A--4, 8B4, 8B--2, 11A2, 11A--5, 14A5, 14A--3 and 17A3 and 17A--5 for 5 for
Nervous and Mental Disorders from the Ministry of Nervous and Mental Disorders from the Ministry of Health, Labor and Welfare, Japan. Health, Labor and Welfare, Japan.
Declaration of interestDeclaration of interest–– The speaker has/had research contracts with The speaker has/had research contracts with
Fujimoto, GSK, Janssen, Lily, Mochida, Fujimoto, GSK, Janssen, Lily, Mochida, ShinogiShinogi, , SolveySolvey, Suntory, UCB, and , Suntory, UCB, and WythWyth, for last 5 years., for last 5 years.
