Effectiveness of Cognitive Behavioral Therapy and Selective Serotonin Reuptake Inhibitors in Adolescents with Depression Megan Boose, PA-S Evidence Based Medicine Spring 2009

PICO Question Patient – adolescents aged 13-18Patient – adolescents aged Intervention – Cognitive Behavioral Therapy (CBT) plus a Selective Serotonin Reuptake Inhibitor (SSRI)Intervention – Cognitive Behavioral Therapy (CBT) plus a Selective Serotonin Reuptake Inhibitor (SSRI) Comparison – SSRI (sertraline, paroxetine, citalopram, or fluoxetine)Comparison – SSRI (sertraline, paroxetine, citalopram, or fluoxetine) Outcome – Effectiveness at relieving symptoms of major depression using the Children’s Depression Rating Scale-Revised (CDRS-R) and the Clinical Global Impressions Improvement score (CDI)Outcome – Effectiveness at relieving symptoms of major depression using the Children’s Depression Rating Scale-Revised (CDRS-R) and the Clinical Global Impressions Improvement score (CDI)

PICO Question In adolescents aged 13-18, is CBT plus an SSRI more effective than an SSRI alone at relieving symptoms of major depression using the CDRS-R and the CGI score?

Impact of Depression Prevalence: 4-8% of adolescents Up to 70% of adolescents are inadequately treated 40-90% have comorbid disorders: –Anxiety –Attention Deficit Hyperactive Disorder –Substance Abuse –Bipolar Disorder

Impact of Depression High morbidity and mortality including: –Suicidal behavior –Completed suicide –Substance abuse –Behavioral problems –Poor academic performance –Difficulties with relationships –Legal Problems –Early Pregnancy –Physical Illness

Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV): Criteria for Major Depressive Disorder A. Five (or more) of the following symptoms have been present for two weeks; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.A. Five (or more) of the following symptoms have been present for two weeks; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.

DSM-IV Criteria continued (1) Depressed mood (2) Diminished interest or pleasure in activities (3) Weight loss or weight gain (4) Insomnia or hypersomnia (5) Psychomotor agitation or retardation

DSM-IV Criteria continued (6) Fatigue or loss of energy (7) Feelings of worthlessness or guilt (8) Diminished ability to think or concentrate (9) Recurrent thoughts of death, suicidal ideation with or without a plan, or a suicide attempt

Cognitive Behavioral Therapy (CBT) Depression is caused by depressive thoughts and poor positive reinforcement Treatment includes individual and family sessions lasting minutes: –Education –Goal setting –Monitoring mood –Social problem solving

Mechanism of Action of SSRIs

CGI Scale 1.Very much improved 2.Much improved 3.Minimally Improved 4.No change 5.Minimally worse 6.Much worse 7.Very much worse

CDRS-R 17 depressive symptoms17 depressive symptoms –14 symptoms are based on child or adult response –3 symptoms are assessed by the clinician Symptoms are rated on a 5 or 7 point scaleSymptoms are rated on a 5 or 7 point scale Score ranges from Score ranges from

Study 1 Selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in children and adolescents

SSRI compared with Placebo for Depression in Adolescents ParoxetineSertralineCitalopramFluoxetine CDRS-R CGI 49-67% 69% 69% 36-46% 36-46% 41-61% 41-61%

SSRI compared with Placebo for Depression in Adolescents Paroxetine (Paxil)Paroxetine (Paxil) –No statistical significant decrease in depressive symptoms Decreased CDRS-R by 2.55 Decreased CDRS-R by 2.55 –No statistically significant decrease response rate 49-67% treatment versus 46-58% placebo49-67% treatment versus 46-58% placebo

SSRI compared with Placebo for Depression in Adolescents Citalopram (Celexa)Citalopram (Celexa) –No statistical significant decrease in depressive symptoms Decreased CDRS-R by 2.13Decreased CDRS-R by 2.13 –Statistically significant increase in response rate 36-46% treatment versus 24-38% placebo36-46% treatment versus 24-38% placebo

SSRI compared with Placebo for Depression in Adolescents Sertraline (Zoloft)Sertraline (Zoloft) –Statistically significant decrease in depressive symptoms Decreased CDRS-R by 4.56Decreased CDRS-R by 4.56 –No statistically significant increase in response rate 69% treatment versus 59% placebo69% treatment versus 59% placebo

SSRI compared with Placebo for Depression in Adolescents Fluoxetine (Prozac)Fluoxetine (Prozac) –Statistically significant decrease in depressive symptoms Decreased CDRS-R by 5.63Decreased CDRS-R by 5.63 –Statistically significant increase in response rate 41-61% treatment versus 20-35% placebo41-61% treatment versus 20-35% placebo

Study 2 Fluoxetine, Cognitive-Behavioral Therapy, and Their Combination for Adolescents with Depression

Fluoxetine, CBT, and Combination Fluoxetine AloneFluoxetine Alone –Decreased CDRS-R from to –Baseline CGI was 4.66 with a 60.6% response rate CBT AloneCBT Alone –Decrease the baseline CDRS-R from to –Baseline CGI was 4.77 with a 43.2% response rate

Fluoxetine, CBT, and Combination Placebo AlonePlacebo Alone –Decreased CDRS-R from to –Baseline CGI was 4.84 with a 34.8% response rate CBT plus FluoxetineCBT plus Fluoxetine –Decreased CDRS-R from to –Baseline CGI was 4.79 with a 71.0% response rate

Fluoxetine, CBT, and Combination

Study 3 Switching to Another SSRI or to Venlafaxine With or Without Cognitive Behavioral Therapy for Adolescents with SSRI- Resistant Depression

Switching to another SSRI or to Venlafaxine with or without CBT Switching to another SSRISwitching to another SSRI –Decreased the CDRS-R from 59.8 to 37.9 –Decreased CGI from 4.5 to 2.9 with a 47.0% response rate Switching to VenlafaxineSwitching to Venlafaxine –Decreased the CDRS-R from 57.8 to 37.0 –Decreased CGI from 4.4 to 2.8 with a 48.2% response rate

Switching to another SSRI or to Venlafaxine with or without CBT Use of either SSRI or Venlafaxine without CBTUse of either SSRI or Venlafaxine without CBT –Decreased CDRS-R from 58.4 to 38.1 –Decreased CGI from 4.5 to 3.0 with a 40.5% response rate Use of either an SSRI or Venlafaxine plus CBTUse of either an SSRI or Venlafaxine plus CBT –Decreased CDRS-R from 59.2 to 36.9 –Decreased CGI from 4.5 to 2.7 with a 54.8% response rate

Switching to another SSRI or to Venlafaxine with or without CBT

Study 4 A Randomized Controlled Trial of Fluoxetine and Cognitive Behavioral Therapy in Adolescents With Major Depression, Behavioral Problems, and Substance Use Disorders

Fluoxetine and CBT in adolescents with Substance Use Disorders (SUD) and behavioral problems Fluoxetine plus CBTFluoxetine plus CBT –Decreased CDRS-R from to –Baseline CGI was 4.84 with an 84.1% response rate Placebo plus CBTPlacebo plus CBT –Decreased CDRS-R from to –Baseline CGI was 4.68 with a 77.8% response rate

Fluoxetine and CBT in adolescents with SUD and behavioral problems

Study 5 A Randomized Controlled Trial of Cognitive Behavioral Therapy in Adolescents with Major Depression Treated by Selective Serotonin Reuptake Inhibitors. The ADAPT Trial

Fluoxetine, CBT, and combination in adolescents receiving outpatient therapy Fluoxetine AloneFluoxetine Alone –Decreased CDRS-R from 59.0 to 40.0 after 12 weeks and 40.0 to 34.6 after 28 weeks with a 94% response rate –Decreased baseline HoNOSCA from 25.5 to 18.0 after 12 weeks and 18.0 to 14.5 after 28 weeks

Fluoxetine, CBT, and combination in adolescents receiving outpatient therapy Fluoxetine plus CBTFluoxetine plus CBT –Decreased CDRS-R from 58.9 to 42.5 after 12 weeks and 42.5 to 36.4 after 28 weeks with a response rate of 98% –Decreased baseline HoNOSCA from 25.1 to 17.1 after 12 weeks and 17.1 to 15.4 after 28 weeks

Fluoxetine, CBT, and combination in adolescents receiving outpatient therapy

Conclusions Fluoxetine is effective at relieving depressive symptoms in adolescents Combination therapy is effective at relieving depressive symptoms in adolescents with major depression The combination of another SSRI plus CBT may be an effective alternative for adolescents who are resistant to one SSRI

Questions?

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