Combined treatment with cognitive-behavioural therapy in adolescent depression: meta-analysis Dubicka et al

Combined treatment with cognitive-behavioural therapy in adolescent depression: meta-analysis

Dubicka et al

Latar BelakangTreatment optimal untuk depresi pd remaja saat ini masih belum jelasbbrp studi ttg efikasi & safety obat2 antidepressan dan terapi psikologis sdh mulai ditelitiNICE SSRIs tidak diresepkan tanpa disertai dengan terapi psikologis berdasarkan temuan TADS bahwa kombinasi pengobatan (fluoxetine+CBT) >> fluoxetine saja.CBT+ fluoxetine mengurangi keinginan bunuh diri.

Data pada orang dewasa jg menunjukkan bhwa kombinasi pengobatan dg terapi psikologi memperlihatkan rerata perbaikan yang lebih tinggi.Sejak hasil ini dipublikasikan oleh NICEbbrp penelitian lanjutan dilakukan dan dipublikasikan dg hasil yang berbeda dari TADS.Hal tsb membawa pertanyaan apakah petunjuk tsb aplikabel untuk diterapkan. Artikel ini meninjau data2 yg tersedia saat ini untuk studi kombinasi CBT dan antidepresan pada depresi remaja

Metodologi PenelitianSearch MethodSelection CriteriaValidity AssesmentData ExtractionQuantitative Data Synthesis

Search MethodDatabase dari PsycINFO,Medline, Cochrane dg terminologi : depressive disorders, Cognitive behavioural treatment, antidepressant treatment, randomised controlled trialsJurnal dan publikasi yg relevanPenulis/pengarang artikel Artikel Penelitian diambil dari Januari 1980-Maret 2009 yg sudah dipublikasikan dalam bahasa Inggris

B. Selection CriteriaRandomised controlled trials (RCTs), sebagian besar termasuk remaja umur 11-18 tahun dengan DSM-IV episode depresi dg terapi CBT yang dikombinasi dg newer-generation antidepressant dan dibandingkan dg pengobatan antidepresan saja tanpa kombinasi CBT.Principle outcomes : depression and impairment scores, overall improvement, suicidality and adverse events.

C. Validity AssesmentMetode penilaian artikelSkala 0-3 (max.score 27)9 item : Randomisation, intention-to-treat analysis, masking, expectancy assessment, clarity of description of improvement, informants, dosage regimes, therapy manualisation and adherence, medication adherence

D. Data ExtractionAd hoc form didesain untuk ekstraksi data (diagnosis, gender, rerata umur, eksklusi, suicidality,comorbidity, etnik, metode rekrutmen, treatment, durasi dan follow up, jenis pengobatan, jumlah sesi, medikasi dan dosis, adverse events)

E. Quantitative Data SynthesisQuantitative outcome measure CDRS-R, HRSD, MFQ, RADS, BDI, CES-D, CGAS, HoNOSCA, Kiddie-SADS-PL, SIQ-JrPengukuran odds ratio : Mantel-Haenszel method, DerSimonian-Laird estimate.

Hasil PenelitianLiterature searchQuality of trialsStudy characteristicsCBT interventionAntidepressant treatmentAdjunct treatmentDepression outcomeOther adverse events

A. Literature searchAda 5 studi penelitian RCT yg terpilih untuk dianalisis1. ADAPT2. TORDIA3. TADS4. Melvin et al trial5. Clarke et al trial3 studi membahas ttg kombinasi CBT-antidepressan, 1 diantaranya membahas ttg resistensi pengobatan dg SSRI (randomising to either venlafaxine or an alternative SSRI, with or without CBT)2 studi menyajikan CBT with antidepressant and routine care

B. Study characteristicsTotal 1206 adolescent, rata-rata umur 15 tahunSampel klinik (4 studi), TADS (juvenile justice facilities, schools, 56% from advertisement)Responden wanita:54%-79%Laki-lakijumlahnya >>banyak pada TADS

4 studi memfokuskan pada depresi mayor, meskipun trdpt 16 kasus depresi minor dalam studi ADAPTADAPT score CGAS major dan minor depresi menunjukkan tingkatan gangguan yang sama ttapi major depresi sec.signifikan mempunyai score yang lebih tinggi menurut HoNOSCA.Melvin et al trial60% major depression, lainnya dysthymic disorder or depressive disorder not otherwise specified.

C. CBT intervention480 adolescents received individual manualised CBT.All studies parental participation, either jointly or as separate sessions.type of therapists used, three trials employed at least masters level therapists, ADAPT psychiatrists and the Melvin et al studypsychologists.

D. Antidepressant TreatmentFluoxetine or sertraline were selected as principle antidepressants in three studies; two studies did not specify a particular antidepressant, and the TORDIA trial also used venlafaxineDosis pengobatan diantara ke 5 studi hampir samatidak berbeda secara signifikanFewer sessions were offered in the medication alone arms than for CBT

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F. Adjunct TreatmentTwo studies permitted treatment as usual alongside study treatmenttwo offered some additional psychological treatment sessions one study offered additional treatment at the end of the acute phase

G. Depression outcome

All trials used interviewer-rated and self-report depression measures.Self-report depression dianalisis dengan:1. RADS (Reynolds Adolescent Depression scale)2. MFQ (Mood and Feelings Questionnaire)3. BDI (Beck Depression Inventory)4. CES-D (Centre for Epidemiological Studies)Interviewer-rated dianalisis :1. CDRS (Childrens Depression Rating scale)2. HRSD (Hamilton Rating Scale for Depression)

Figure 2 for 12 week outcome and table 1 for 26- to36 week outcomes

Depression outcomecon'tSelf-report depression outcomes- at 12 week did not show a significant difference between arms (standardised mean difference, SMD= 0.04, 95% CI 70.09 to 0.17, P= 0.56)- 26-36 weeks did not find a significant difference between arms (SMD =70.03, 95% CI 70.29 to 0.24, P= 0.84)Interviewer rated depression outcomes- at 12 weeksthere was some evidence of between-study heterogeneity (t2 = 0.0094; I = 32.3%)- At follow-upThere was little evidence of heterogeneity (t2=0.0014; I 2=5.1%) and the standardised mean difference was again small (SMD = 0.05, 95% CI 70.14 to 0.23, P= 0.64)

Impairment outcomes- CGAS showed a benefit for combined treatment as compared with an antidepressant alone (weighted mean difference, WMD=72.32, 95% CI 73.91 to 70.74, P= 0.004)- Based on three studies there was no evidence of a treatment effect (WMD=71.28, 95% CI 73.40 to 0.84, P= 0.24) at follow-up (Table 1 and Fig. 2), and no evidence of heterogeneity (t2 = 0.0, I2 = 0.0%).

Improvement CGI Scale- tabel 2- In a random effects meta-analysis the pooled odds ratio of improvement in CGII for combined treatment compared with an SSRI was which was not statistically significant (95% CI 0.951.92, P=0.09). - At follow-up, there was heterogeneity between studies (t2 = 0.11, I 2 = 43.8%), but no evidence of a treatment effect, with a corresponding pooled odds ratio of 0.97 (95% CI 0.491.92, P= 0.93)

Suicidalitya. systematic data- 3 studi (SIQ-Jr), ADAPT (Kiddie-SADS-PL) at 12 week and follow up : no evidence of heterogeneity or a significant difference between arms.

b. spontaneously reported suicidal events- TADS 12 week : 10 suicidal in the fluoxetine alone arm (8 ideation, 2 attempts), 6 events in the combined arm (2 attempts, 3 ideation, 1 self-harm), but this difference was not statistically significant .- TADS reported significantly more suicidal events in the fluoxetine alone arm at 36 weeks when compared with the combined treatment - The Melvin trial one adolescent in the combined arm v. four in the SSRI arm had high levels of suicidality.

DiscussionNo evidence of any significant additional benefit for CBT when combined with antidepressant medication for depressive symptoms, suicidality or global improvement in the short or longer term. There was, however, a statistically significant benefit in impairment scores (CGAS) after acute treatment, although the clinical implications of this are not clear. The finding of no difference at follow-up was consistent across studies and populations, suggesting no additional benefit from combining CBT with antidepressant medication for the 26- to 36-week outcomes.

Comparison of study outcomesDepression outcomesImpairment outcomes only TADS reported a significant benefit combined treatment (CGAS, but not HoNOSCA)ImprovementTORDIA (12 week) reported a significant benefit of combined treatment over medication alone on the CGII, but ADAPT and TADS did not. There were no significant differences at 28-week follow up.Suicidalityall found a decrease with no significant differences between arms after acute treatment.Adverse event

Strengths and limitationsthe difficulties of running psychological treatment trials in this fieldThe pool of available studies was smaller than the data available in adult depression, where combination treatment was deemed better than monotherapy, so there is the possibility of a type II error in this study.this meta-analysis are also limited by the varying populations and methodologies used in each study

KesimpulanCBT dianjurkan sbg terapi tambahan disamping antidepresan pada remaja dg depresi berat CBT dpt mengurangi perburukan gejala dalam waktu singkat, tetapi CBT tidak dapat mengurangi gejala depresi, suicidality atau pencapaian perbaikan secara keseluruhan.combined treatment may be differentially beneficial depending on severity and complexity.

The implications are that combined treatment with CBT may not always be necessary for all adolescents with depression who receive antidepressants.in contrast to the current advice from NICE, but it remains unclear which aspects of adjunct clinical care may be important in achieving an optimal response.further research to determine individual predictors of response and non-response, together with health economic data, in order to target treatment most effectively

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