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Combined treatment with

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

Latar Belakang
Treatment optimal untuk depresi pd remaja
saat ini masih belum jelasbbrp studi ttg
efikasi & safety obat2 antidepressan dan
terapi psikologis sdh mulai diteliti
NICE 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 Penelitian
A. Search Method
B. Selection Criteria
C. Validity Assesment
D. Data Extraction
E. Quantitative Data Synthesis

A. Search Method
Database dari PsycINFO,Medline, Cochrane dg
terminologi : depressive disorders, Cognitive
behavioural treatment, antidepressant
treatment, randomised controlled trials
Jurnal dan publikasi yg relevan
Penulis/pengarang artikel
Artikel Penelitian diambil dari Januari 1980Maret 2009 yg sudah dipublikasikan dalam
bahasa Inggris

B. Selection Criteria
Randomised controlled trials (RCTs),
sebagian besar termasuk remaja umur 1118 tahun dengan DSM-IV episode depresi
dg terapi CBT yang dikombinasi dg newergeneration antidepressant dan
dibandingkan dg pengobatan antidepresan
saja tanpa kombinasi CBT.
Principle outcomes : depression and
impairment scores, overall improvement,
suicidality and adverse events.

C. Validity Assesment
Metode 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 Extraction
Ad 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 Synthesis


Quantitative outcome measure CDRSR, HRSD, MFQ, RADS, BDI, CES-D, CGAS,
HoNOSCA, Kiddie-SADS-PL, SIQ-Jr
Pengukuran odds ratio : Mantel-Haenszel
method, DerSimonian-Laird estimate.

Hasil Penelitian
A. Literature search
B. Quality of trials
C. Study characteristics
D. CBT intervention
E. Antidepressant treatment
F. Adjunct treatment
G. Depression outcome
H. Other adverse events

A. Literature search
Ada 5 studi penelitian RCT yg terpilih untuk dianalisis
1. ADAPT
2. TORDIA
3. TADS
4. Melvin et al trial
5. Clarke et al trial
3 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 characteristics
Total 1206 adolescent, rata-rata
umur 15 tahun
Sampel 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 ADAPT
ADAPT 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 intervention
480 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 Treatment
Fluoxetine or sertraline were selected as principle
antidepressants in three studies; two studies did
not specify a particular antidepressant, and the
TORDIA trial also used venlafaxine
Dosis pengobatan diantara ke 5 studi hampir
samatidak berbeda secara signifikan
Fewer sessions were offered in the medication
alone arms than for CBT

F. Adjunct Treatment
Two studies permitted treatment as
usual alongside study treatment
two 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 26to36 week outcomes

Depression outcome
con't
Self-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 betweenstudy 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)

Suicidality
a. 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.

Discussion
No 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
outcomes
Depression outcomes
Impairment outcomes
only TADS reported a significant benefit combined
treatment (CGAS, but not HoNOSCA)
Improvement
TORDIA (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.
Suicidality
all found a decrease with no significant differences
between arms after acute treatment.
Adverse event

Strengths and limitations


the difficulties of running
psychological treatment trials in this
field
The 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

Kesimpulan
CBT 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

TERIMAKASIH