Good Article Review On The Evaluation Was Done Among Groups Randomly Assigned With Fluoxetine, Cognitive Behavioral Therapy (CBT), Fluoxetine Coupled With CBT And Placebo.

Part 3A:

QUESTION 1:
March et al. were the principal investigators.

QUESTION 2:

The purpose of this study is to evaluate the effectiveness of treatment options available for major depressive disorder (MDD) in adolescent population.

QUESTION 3:
It is a double-blinded, randomized multicenter placebo based clinical trial. The study was conducted from 2000 till 2003 at 13 different academic and community clinics of the United States.

QUESTION 4:

DSM-IV diagnosed case of MDD patients, aged between 12 to 17 years who were able to receive outpatient care and had a children’s depression rate scale-revised (CDRS-R) of 45 or higher in total were included in this study. Patients must possess an IQ of greater than 80 and no history of anti-depressant must be there.
Patients with prior history of any psychiatric and mental disorder, use of drugs related to psychiatric practice, non-English speaking patients and/or parents, pregnant females. Patients who were a threat to others were considered high-risk and excluded from the study.

QUESTION 5:

Patients deemed eligible were assigned randomly to fluoxetine or CBT alone, placebo and fluoxetine in combination with CBT. Randomization was done using computerized stratified randomization and sex and site were set as variables for stratification.

QUESTION 6:

Placebo and fluoxetine were administered at an initial dose of 10mg/day which later on increased to 20mg/day in the first week. According to the need, it reached to a maximum dose of 40md/day at the end of 8th week.
50 to 60 minutes long 15 psychotherapy sessions of CBT were done in a period of initial 12 weeks. Two parent only and 1 to 3 parent and adolescent combined psychoeducation sessions were also held.

QUESTION 7:

Patients received treatment for 12 weeks with 20 to 30 minutes long six sessions of medication visits over a period of 12 weeks.
QUESTION 8:
Two primary outcomes were measured in this study using independent evaluator at 6th and 12th week. The two outcomes are scalar CDRS-R total score which is synthesized based on the interview conducted on both, the parents and the adolescents, and CGI improvement score at the end of the treatment.

Suicidal ideation was also assessed and was registered as a secondary outcome.

QUESTION 9:
Study showed that fluoxetine combined with CBT was statistically significant (p=0.001) as compared to fluoxetine and CBT alone. Further, placebo and fluoxetine showed no superiority to each other but fluoxetine alone was better than CBT alone (p=0.01). in adjusted setting, fluoxetine coupled with CBT (p=0.001) and fluoxetine alone (p=0.002) showed superiority to placebo while CBT did not (p=0.97).
Reynolds adolescent depression scale (RADS) showed significant results more or less similar to that found on CDRS-R. Further, in CDRS-R system, at least 27% of the patients showed inclination towards suicide ideation with 2% showing severe validation. But no single treatment regime showed predilection to develop suicidal ideation in any of the patients.

QUESTION 10:

The strength of this study is its large sample size. It was a well-crafted randomized controlled, double blinded trial with less chances of error. The exclusion criterion was excellent.
The limitations of the study included absence of combination group of placebo with CBT, comparison group preferably a community group, predictability of the treatment given to patients, inability to demarcate one single element of improvement and exclusion of high risk patients was not justified.

QUESTION 11:

The study showed significant improvement of outcomes of MDD treatment when fluoxetine is combined with CBT. It also reduces the chances of suicide attempts as compared to when given only fluoxetine. Also, the study showed that all cases of MDD in adolescents should be addressed seriously.

Part 3B:

March et al. conducted a double-blinded, randomized multicenter placebo based clinical trial. The study was conducted from 2000 till 2003 at 13 different academic and community clinics of the United States. The objective of the study was to find out the efficacy of four treatment modalities in adolescent patients suffering from major depressive disorder (MDD). Prior to this study, CBT alone or Selective Serotonin reuptake inhibitors (SSRIs) were given to treat MDD but their efficacy is questionable. A total of 439 patients were enrolled aged between 12 to 17 years of age diagnosed with MDD based on criterion of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). The study lasted for 12 weeks and treatment groups formed were fluoxetine alone dosage ranging from 10 to 40mg/day, CBT alone, CBT coupled with fluoxetine and placebo. Two main outcomes were studied at the end of this study which are Children’s Depression Rating Scale-Revises (CDRS-R) total score and Clinical Global Impressions (CGI) improvement score. On CDRS-R scale, fluoxetine combined with CBT showed significant result with a p=0.001 as compared to placebo group, fluoxetine alone group and CBT alone group. Similarly, fluoxetine alone is a better treatment modality as compared to CBT alone (p=0.01). On CGI scale, fluoxetine combined with CBT group and fluoxetine alone group showed significant superiority over CBT alone or placebo. The study also showed that patients taking fluoxetine are prone to develop mild to moderate intensity suicidal thoughts. All four treatment groups showed reduction in these thought with highest reduction in fluoxetine combined with CBT group (p=0.02). As an end note, it is imperative that MDD in adolescents can be associated with grave outcomes in terms of mortality and morbidity; therefore they should be addressed seriously. Also, the study concluded that while treating MDD patients, first choice should be initiation of CBT with fluoxetine for achieving therapeutic goals and minimizing the associated risk.

References

March. J. S., et al. Fluoxetine, Cognitive-Behavioral Therapy, and Their Combination for Adolescents With Depression: Treatment for Adolescents With Depression Study (TADS) Randomized Controlled Trial. JAM. 2004;292(7):807-820.