Title Researcher

: Effectiveness of Adjunctive Antidepressant Treatment for Bipolar Depression : Gary S. Sachs, M.D., Andrew A. Nierenberg, M.D., Joseph R. Calabrese, M.D., Lauren B. Marangell, M.D., Stephen R.
Wisniewski, Ph.D., Laszlo Gyulai, M.D., Edward S. Friedman, M.D., Charles L. Bowden, M.D.,Mark D. Fossey, M.D., Michael J. Ostacher, M.D., M.P.H., Terence A. Ketter, M.D., Jayendra Patel, M.D.,Peter Hauser, M.D., Daniel Rapport, M.D., James M. Martinez, M.D., Michael H. Allen, M.D.,David J. Miklowitz, Ph.D., Michael W. Otto, Ph.D., Ellen B. Dennehy, Ph.D., and Michael E. Thase, M.D.

A. Are the result of the trial valid? Screening question 1. Did the trial address a clearly focused issue? An issue can be focused in terms of The population studied Ya. Subjek penelitian yang digunakan dalam penelitian ini adalah pasien dengan gangguan bipolar episode depresi. Hal ini dapat diketahui dari jurnal di bagian Methods paragraf 3 tentang jenis subjects .Study subjects were at least 18 years old and met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) (Hal.1712) The intervention given Ya. Yes Cant tell No

Pasien dengan gangguan bipolar episode depresi diberikan terapi mood satabilizer plus anti depresan dibandingkan dengan mood stabilizer saja, hal ini dapat dilihat pada bab Methods, Subjects were assigned to double-blind treatment with a mood stabilizer plus an adjunctive anti-depressant or a mood stabilizer plus a matching placebo with the use of an equipoise-stratified randomization method

(Hal.1713) The comparator given Ya. Pada penelitian ini terdapat pembandingnya yaitu berupa kelompok kontrol. Hal ini dapat diketahui di bagian Methods mengenai jenis kontrol yang digunakanSubjects were assigned to double-blind treatment with a mood stabilizer plus an adjunctive antidepressant or a mood stabilizer plus a matching placebo with the use of an equipoise-stratified randomization method.. (Hal.1713)

The outcomes considered

Ya. Dalam penelitian ini, tujuan dari penelitian adalah untuk mengeksplorasi efektifitas penggunaan antidepresan

adjunctive pada penderita bipolar episode depresi di bandingkan dengan pemberian mood stabelizer dosis tunggal. Hal ini dapat diketahui dari jurnal di pendahuluan to determine whether adjunctive antide-pressant therapy reduces symptoms of bipolar depression without increasing the risk of mania. (Hal 1711) 2. Was the assignment of patients to treatments randomized? Yes Pasien dikelompokkan menjadi 2 kelompok, yaitu kelompok penelitian dan kontrol yang dipilih secara acak dan double blind. Hal ini terdapat pada bagian methods tentang pembagian intervensi Subjects were assigned to double-blind treatment with a mood stabilizer plus an adjunctive anti-depressant or a mood stabilizer plus a Cant tell No

matching placebo with the use of an equipoise-stratified randomization method.. (Hal.1713).... 3. Where all of the patients who entered the trial properly accounted for at its conclusion? Was follow up complete? Yes Dijelaskan. Pada jurnal ini dijelaskan follow up complete terhadap kelompok penilitian. Hal ini dijelaskan dalam bab intervensi pada paragraf ...Four follow-up assessments were scheduled over the first 6 week.. (Hal 1713) Were patient analysed in the groups to Ya. which they were randomized? Dalam jurnal ini pasien dianalisis secara acak setiap kelompoknya. Hal ini dijelaskan dalam bagian methods tentang....This method enabled treating psychiatrists to choose from three randomization. (Hal 1713) Cant tell No

Detailed Question 4. Were patients, health workers and study personnel Yes Cant tell No

blind to treatment? 5. Were the patients Were the health worker Were the study personnel

Dijelaskan. Dalam jurnal penelitian ini dijelaskan bahwa peneliti double blind Yes Cant tell No

Were the groups similar at the start of trial?

In terms of other factors that might effect the Ya. outcome such as age, sex, social class Kelompok pasien memiliki karakteristik yang sama sesuai diagnosis bipolar denagn episode depresi. Hal ini dijelaskan dalam selections of subjectStudy subjects were at least 18 years old and met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), for a major depressive episode associated with bipolar I or bipolar II disorder. The diagnosis of bipolar disorder was confirmed at entry into STEP-BD by using an affective disorder evaluation form adapted from the Structured Clinical Interview for DSM-IV and by the independent

administration of the Mini-International Neuropsychiatric Interview... (Hal 1713) 6. Aside from the experimental intervention, were the groups treated equally Yes Dijelaskan. Dalam jurnal penelitian ini dijelaskan bagaimana perlakuan yang dilakukan kepada kelompok penilitian diluar intervensi yaitu berupa terapi psikososial Cant tell No

B. What are the result? 7. How large was the treatment effect? What outcomes are measured? Hal ini dapat dilihat dibagian hasil dan pembahasan There were no significant differences between the two groups in the percent-age of subjects meeting the criteria for any effectiveness outcome.... (Hal.1716) Similar percentages of subjects in each group did not have even a single week of euthymia over the first 16 weeks and were classified as having no response to an adequate.... (Hal.1716)

The augmentation of drug therapy with brief or in tensive psychotherapy carried no significant benefit..... (Hal.1717) The primary outcome of 8 consecutive weeks of euthymia, however, reflects a considerably longer period than do the cross-sectional outcomes (response or remission) used in typical efficacy studies... (Hal.871)

8.

How precise was the estimate of the treatment Analysis of results that were adjusted for acceptance effect? What are its confidence limits? or rejection of enrollment into the STEP-BD randomized psychosocial treatment study showed no significant differences between the two groups (adjusted P = 0.25 for the primary outcome)....(Hal 1717) For the subgroup of 130 subjects who re -jected random assignment to a protocol-specified psychotherapy, rates of recovery were 17.9% (12 of 67 subjects) in the group receiving a mood stabilizer plus an antidepressant and 30.2% (19 of 63 subjects) in the group receiving a mood stabilizer plus placebo (P = 0.15); for the subgroup

of 106 subjects who underwent brief psychoeducation, 20.0% (11 of 55 subjects) and 19.6% (10 of 51 subjects), respectively (P = 0.99); and for the subgroup of 130 subjects who underwent intensive psychotherapy, 33.3% (19 of 57 subjects) and 30.1% (22 of 73 subjects), respectively (P = 0.71). Furthermore, there was no significant interaction between the augmentation of drug therapy with psychotherapy and the type of psychosocial intervention used (P = 0.28)... (Hal 1719)

C. Will the result help locally? 9. Can the results be applied to the local population? Yes Cant tell No

Do you think that the patients covered by the trial YA are similar enough to your population? Tidak ada perbedaan antara pasien yang ada di penelitian dengan pasien yang ada di setting kita karena memeliki karasteristik yang sama. 10. Were all clinically important outcomes considered? Yes If not, does this affect the decision? Secara klinis penelitian ini penting untuk No

dipertimbangkan sebagai penelitian selanjutnya karena untuk mengetahui efektifitas pemberian antidepresan terhadap pasien bipolar episode depresi untuk mengurangi dissabilitas dari pasien akibat episode depresi tersebut 11. Are the benefits worth the harms and costs? Yes No This is unlikely to be addresses by the trial. But Penelitian ini penting sebagai awal penelitian selanjutnya, what do you think? walaupun pada penelitian ini tidak didapatkan effektifitas yang bermakna antara pemberian obat tambahan

antidepresan dengan terapi tunggal mood stabilizer

terhadap gangguan yang dialami oleh pasien. Sehingga pada penggunaan klinis masih belum dapat diaplikasikan kepada pasien tetapi diharapkan selanjutnya dapat dilakukan penelitian dengan metode penilitian yang lebih baik dari penelitian sebelumnya sehingga bisa diketahui secara pasti efektifitas penggunaan terapi tambahan antidepresan pada pasien bipolar episode mania sehingga dapata menurunkan angka dissabiolitas yang disebabkan oleh episode tersebut.