Comparison Of Drug Tx & Psycotherapy in the treatment of Depression


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Comparison Of Drug Tx & Psycotherapy in the treatment of Depression

  1. 1. Pharmacotherapy vs. Psychotherapy In the Treatment of: Depression
  2. 2. Depression - Criteria <ul><li>Major Depressive Disorder (MDD) </li></ul><ul><ul><li>History (Hx) of 1 or more MD episodes in the absence of maniac, hypomaniac, or mixed episodes </li></ul></ul><ul><ul><li>Must display at least 5 depressive symptoms (Sx): </li></ul></ul><ul><ul><ul><li>Depressed or irritable mood </li></ul></ul></ul><ul><ul><ul><li>Markedly diminished interest or pleasure in almost all activities </li></ul></ul></ul><ul><ul><ul><li>Change in appetite or weight </li></ul></ul></ul><ul><ul><ul><li>Insomnia or hypersomnia </li></ul></ul></ul><ul><ul><ul><li>Psychomotor agitation or retardation </li></ul></ul></ul><ul><ul><ul><li>Fatigue or loss of energy </li></ul></ul></ul><ul><ul><ul><li>Feelings of worthlessness or guilt </li></ul></ul></ul><ul><ul><ul><li>Impaired concentration, indecisiveness </li></ul></ul></ul><ul><ul><ul><li>Recurring thoughts of death or suicide </li></ul></ul></ul><ul><ul><li>1 of the Sx must be either depressed mood or loss of interest or pleasure that is present for most of the day, nearly every day, for at least two weeks, with the remaining symptoms present during the same period </li></ul></ul>
  3. 3. Depression - Criteria <ul><li>Major Depressive Disorder (MDD) contiued </li></ul><ul><ul><li>Sx must cause clinically significant distress or impairment </li></ul></ul><ul><ul><li>Represent a change from previous functioning </li></ul></ul><ul><ul><li>Must not be caused by: </li></ul></ul><ul><ul><ul><li>The direct effects of a substance (eg., drug abuse or medications) </li></ul></ul></ul><ul><ul><ul><li>A medical condition (eg., hypothyroidism) </li></ul></ul></ul><ul><ul><ul><li>Must not be better accounted for by bereavement. </li></ul></ul></ul>
  4. 4. Depression - Criteria <ul><li>Dysthymia </li></ul><ul><ul><li>(Atypical Depression, or Minor Depression) </li></ul></ul><ul><ul><li>2 to 4 Sx criteria are present rather than 5 or more as with major depression. </li></ul></ul>
  5. 5. Epidemiology and Clinical Course
  6. 6. Epidemiology <ul><li>MDD </li></ul><ul><ul><li>World Health Organization (WHO) ranks MDD among the most burdensome diseases in the world </li></ul></ul><ul><ul><li>National Comorbidity Survey Replication (NCS-R), conducted in the US in 2001-2002 </li></ul></ul><ul><ul><ul><li>lifetime prevalence* of major depression in the community is 16.2 percent </li></ul></ul></ul><ul><ul><li>Approximately 5 to 10 percent of primary care patients meet DSM-IV criteria for major depression </li></ul></ul><ul><ul><li>Patients with medical illnesses such as diabetes and heart disease have higher prevalences ‡ of major depression, with estimates between 10 and 20 percent. </li></ul></ul>*The percentage of a population that is affected with a particular disease over a given lifetime. ‡ The percentage of a population that is affected with a particular disease at a given time.
  7. 7. Epidemiology <ul><li>Dysthymia </li></ul><ul><ul><li>prevalence of minor depression in primary care settings is approximately twice that of major depression </li></ul></ul>
  8. 8. Clinical Course <ul><li>Clinical courses of MDD or Dysthymia are classified using 6 categories: </li></ul><ul><ul><li>Response — Significant reduction (usually >50 percent) of depressive Sx during the acute treatment phase. </li></ul></ul><ul><ul><ul><li>Response usually coincides with the onset of remission. </li></ul></ul></ul><ul><ul><ul><li>Clinical improvement typically is monitored using standardized depression rating scales as well as measures of overall psychosocial functioning </li></ul></ul></ul><ul><ul><li>Remission — A period of 2 weeks and <2 months with no clinically significant depressive Sx (e.g., depression rating scale scores and psychosocial functioning indices within normal limits). </li></ul></ul><ul><ul><li>Partial remission — A period of 2 weeks and <2 months with one or more clinically significant depressive Sx, but fewer Sx than the full syndrome. </li></ul></ul>
  9. 9. Clinical Course (continued) <ul><ul><li>Relapse — An episode of depression during the period of remission. </li></ul></ul><ul><ul><li>Recovery — An asymptomatic period of more than two months. </li></ul></ul><ul><ul><li>Recurrence — The emergence of Sx during the period of recovery (a new episode). </li></ul></ul>
  10. 10. Treatment
  11. 11. Treatment: 4 Phases of Therapy <ul><li>Acute </li></ul><ul><ul><li>Goal - improvement in Sx and return to near-baseline mood. </li></ul></ul><ul><ul><li>This usually takes from 6 to 12 weeks. </li></ul></ul><ul><li>Continuation </li></ul><ul><ul><li>Goal: to consolidate the treatment response and prevent relapse. </li></ul></ul><ul><ul><li>Limited empirical data to guide therapy during continuation treatment. </li></ul></ul><ul><ul><li>Current practice standards indicate the psychosocial or pharmacologic treatments that were used to attain remission in the acute phase should be used for continuation therapy </li></ul></ul><ul><ul><li>Pts are typically seen monthly or possibly biweekly depending upon their clinical status, functioning, support systems, stressors, motivation for treatment, and comorbid psychiatric or medical disorders </li></ul></ul>
  12. 12. Treatment: 4 Phases of Therapy <ul><li>Maintenance </li></ul><ul><ul><li>Once Pt has been asymptomatic for a period of approximately 6 to 12 months (continuation phase), the therapist/clinician determines whether maintenance is indicated. </li></ul></ul><ul><ul><li>The objective of maintenance is to prevent recurrence. </li></ul></ul><ul><ul><li>Decision to recommend maintenance is based on factors associated with increased risk for recurrence, as well as severity of the present depressive episode (e.g., suicidality, psychosis, functional impairment). </li></ul></ul>
  13. 13. Treatment: 4 Phases of Therapy <ul><li>Maintenance </li></ul><ul><ul><li>Factors associated with risk for recurrence include: </li></ul></ul><ul><ul><ul><li>History of prior depressive episodes </li></ul></ul></ul><ul><ul><ul><li>Family history of recurrent MDD </li></ul></ul></ul><ul><ul><ul><li>Family psychopathology </li></ul></ul></ul><ul><ul><ul><li>Presence of comorbid disorders </li></ul></ul></ul><ul><ul><ul><li>Environmental stressors </li></ul></ul></ul><ul><ul><ul><li>Limited social supports </li></ul></ul></ul><ul><ul><li>Duration of the maintenance phase may vary from one year to indefinitely. </li></ul></ul><ul><ul><li>Pts typically are seen monthly to every three months, depending upon clinical status. </li></ul></ul>
  14. 14. Treatment: 4 Phases of Therapy <ul><li>Discontinuation </li></ul><ul><ul><li>Single, uncomplicated episode of depression then, discontinuation (rather than maintenance) is indicated once the continuation phase is complete. </li></ul></ul><ul><ul><li>The decision to discontinue treatment should be arrived at collaboratively </li></ul></ul>
  15. 15. Choice of Therapy
  16. 16. Choice of Therapy: Psychotherapy <ul><li>Cognitive-Behavioral Therapy : </li></ul><ul><ul><li>Administered weekly (and sometimes biweekly). </li></ul></ul><ul><ul><li>Depending upon the protocol, acute or active treatment ranges from 8 to 18 weeks, with most treatments providing 12 to 15 therapy sessions. </li></ul></ul><ul><ul><li>Treatment typically includes homework assignments (e.g., self-monitoring, activity scheduling). </li></ul></ul><ul><ul><li>Throughout treatment, depressive symptoms and mastery of CBT skills are monitored by the therapist. </li></ul></ul>
  17. 17. Choice of Therapy: Psychotherapy <ul><li>Cognitive-Behavioral Therapy (continued) : </li></ul><ul><ul><li>Most treatment protocols provide for a continuation phase (eg, monthly booster treatment sessions) to maintain and/or extend gains. </li></ul></ul><ul><ul><li>The latter portion of treatment involves psychoeducation and planning for relapse/recurrence prevention. </li></ul></ul><ul><ul><li>Discontinuation typically is based on resolution of depressive symptoms (based on standardized rating scales) and the patient's sense of efficacy to maintain gains. </li></ul></ul><ul><ul><li>Once CBT is discontinued, the patient, family, and primary care physician should monitor for recurrence of depression. </li></ul></ul>
  18. 18. Choice of Therapy: Psychotherapy <ul><li>Interpersonal therapy : </li></ul><ul><ul><li>Brief psychosocial therapy </li></ul></ul><ul><ul><li>According to this treatment model, there are many possible pathways into depression, but independent of the cause, depression is associated with relationship disruptions. </li></ul></ul><ul><ul><li>Focuses on current relationship problems associated with the depression. </li></ul></ul>
  19. 19. Choice of Therapy: Psychotherapy <ul><li>Interpersonal therapy (continued) : </li></ul><ul><ul><li>Initial phase of treatment: </li></ul></ul><ul><ul><ul><li>includes exploring the relationships by conducting a relationship inventory to identify problem areas that will be the focus of treatment. </li></ul></ul></ul><ul><ul><ul><li>Typical foci of treatment include grief reactions, interpersonal conflicts (such as parent-child disputes or peer conflicts), role disputes, adjustments and transitions, interpersonal deficits, and adjustments related to single parent families in the context of divorce, separation, incarceration, death, etc. </li></ul></ul></ul>
  20. 20. Choice of Therapy: Pharmacotherapy <ul><li>Serotonin Selective Re-uptake Inhibitors (SSRI) </li></ul><ul><ul><li>Fluoxetine (Prozac), Sertraline (Zoloft), Paroxetine (Paxil) </li></ul></ul><ul><li>Heterocyclics, Tricyclic Antidepressants (TCA) </li></ul><ul><ul><li>Imipramine, Amitriptyline, Desipramine, Nortriptyline </li></ul></ul><ul><li>Monoamine oxidase inhibitors (MAOI) </li></ul><ul><ul><li>Tranylcypromine, Phenelzine, Selegiline </li></ul></ul><ul><li>Inhibitors of both serotonin and norepinephrine </li></ul><ul><ul><li>Venlafaxine (Effexor), and Duloxetine (Cymbalta) </li></ul></ul>
  21. 22. Choice of Therapy: Pharmacotherapy <ul><li>SSRIs </li></ul><ul><ul><li>Mechanism: block the action of the presynaptic serotonin reuptake pump, thereby increasing the amount of serotonin available in the synapse and increasing postsynaptic serotonin receptor occupancy. </li></ul></ul>
  22. 23. Choice of Therapy: Pharmacotherapy <ul><li>SSRIs </li></ul><ul><ul><li>While this action occurs rather quickly after SSRI therapy is started, the antidepressant effects of SSRIs may not appear for 3 to 6 weeks after initiation of treatment. </li></ul></ul><ul><ul><li>It is proposed that this delay in clinical response is due to a gradual &quot;down regulation&quot; or decrease in some postsynaptic serotonin receptor types in response to the increased amount of synaptic serotonin available. </li></ul></ul><ul><ul><ul><li>This may lead to changes in cellular protein production and to subsequent effects on neuronal protection and development. </li></ul></ul></ul>
  23. 24. Choice of Therapy: Pharmacotherapy <ul><li>SSRIs </li></ul><ul><ul><li>All share several other characteristics: </li></ul></ul><ul><ul><ul><li>They are all hepatically metabolized. </li></ul></ul></ul><ul><ul><ul><li>They have relatively little affinity for histaminic, dopaminergic, alpha-adrenergic, and cholinergic receptors. </li></ul></ul></ul><ul><ul><ul><li>They tend to have relatively mild side-effect profiles, although they can be associated with sexual dysfunction </li></ul></ul></ul><ul><ul><ul><li>They are relatively safe in overdose. </li></ul></ul></ul><ul><ul><ul><li>They all produce changes in sleep architecture (decreased REM latency and decreased total REM sleep). </li></ul></ul></ul>
  24. 25. Choice of Therapy: Pharmacotherapy <ul><li>SSRIs </li></ul><ul><ul><li>coadministration of any SSRI with an MAOI is contraindicated due to the potential for producing a sometimes fatal serotonin syndrome . </li></ul></ul><ul><ul><ul><li>Relatively rare but potentially lethal condition </li></ul></ul></ul><ul><ul><ul><li>Caused by overstimulation of central and peripheral serotonin receptors. </li></ul></ul></ul><ul><ul><ul><li>Clinical manifestations include agitation, confusion, and hyperthermia. </li></ul></ul></ul>
  25. 26. Choice of Therapy: Pharmacotherapy <ul><li>SSRI Common Side Effects </li></ul><ul><ul><li>Generally well tolerated with minimal or no side effects. </li></ul></ul><ul><ul><li>Side effects tend to be dose-dependent and most of them subside with time (one to two weeks) or dose reduction </li></ul></ul><ul><ul><li>The most common side effects include headache, abdominal pain, nausea, diarrhea, sleep changes, and jitteriness or agitation. </li></ul></ul><ul><ul><li>Less-common side effects include diaphoresis, akathisia (restlessness and inability to sit still), bruising, and changes in sexual functioning (decreased libido, delayed ejaculation, anorgasmia) </li></ul></ul>
  26. 27. Choice of Therapy: Pharmacotherapy <ul><li>SSRI Common Side Effects (continued) </li></ul><ul><ul><li>All antidepressants can induce a manic or hypomanic episode in individuals with a predisposition to bipolar illness. </li></ul></ul><ul><ul><li>There also appears to be a separate but distinct phenomenon of behavioral activation that can occur in the first few weeks of starting antidepressants. </li></ul></ul><ul><ul><ul><li>Characterized by impulsivity, silliness, agitation, and disinhibition and appears to be a direct side-effect of antidepressants unrelated to mania. </li></ul></ul></ul>
  27. 28. Choice of Therapy: Pharmacotherapy <ul><li>SSRIs differ in many regards, including potency, receptor selectivity, and pharmacokinetic properties </li></ul><ul><li>These differences determine each agent's side-effect profile and interactions with other medications </li></ul><ul><li>The overall efficacy of the different SSRIs, in terms of relieving depressive symptoms, appears to be similar </li></ul>
  28. 29. Choice of Therapy: Pharmacotherapy <ul><li>Heterocyclics, Tricyclic Antidepressants (TCA) </li></ul><ul><ul><li>TCAs are the 1 st generation Heterocyclics </li></ul></ul><ul><ul><li>Mechanisms of Action are not well understood, but are thought to involve inhibition of re-uptake of norepinephrine, dopamine, or serotonin </li></ul></ul><ul><ul><li>less commonly used as 1 st line antidepressants </li></ul></ul><ul><ul><ul><li>This is mainly due to the less benign side-effect profile of the cyclic antidepressants. </li></ul></ul></ul><ul><ul><ul><li>Most concerning is the toxicity of the cyclic antidepressants in overdose. </li></ul></ul></ul><ul><ul><ul><li>Can be fatal in doses as little as 5X the therapeutic dose. </li></ul></ul></ul><ul><ul><ul><li>Toxicity is usually due to prolongation of the QT interval, leading to arrhythmias. </li></ul></ul></ul><ul><ul><ul><li>Overdose of cyclic antidepressants can also cause anticholinergic toxicity and seizures. </li></ul></ul></ul><ul><ul><ul><li>Highly lipophilic and protein bound and are therefore not effectively removed by hemodialysis. </li></ul></ul></ul>
  29. 30. Choice of Therapy: Pharmacotherapy <ul><li>Heterocyclics, Tricyclic Antidepressants (TCA) </li></ul><ul><ul><li>Dose-related side effects such as: </li></ul></ul><ul><ul><ul><li>Anticholinergic and orthostatic effects </li></ul></ul></ul><ul><ul><ul><li>Sedation </li></ul></ul></ul><ul><ul><ul><li>Weight gain </li></ul></ul></ul><ul><ul><ul><li>Sexual dysfunction. </li></ul></ul></ul><ul><ul><ul><li>Higher risk of myocardial infarction compared with SSRI users </li></ul></ul></ul><ul><ul><ul><ul><li>Not clear whether this is due to deleterious effects of the TCAs themselves, protective effects of SSRIs, or both </li></ul></ul></ul></ul><ul><ul><ul><li>Patients on high doses of cyclic antidepressants may also be at increased risk for sudden cardiac death </li></ul></ul></ul>
  30. 31. Choice of Therapy: Pharmacotherapy <ul><li>Heterocyclics, Tricyclic Antidepressants (TCA) </li></ul><ul><ul><li>Choice of cyclic antidepressant is usually based upon side-effect profiles since these medications vary in their degree of sedative and anticholinergic effects </li></ul></ul><ul><ul><li>Blood levels of some cyclic antidepressants clearly correlate with both their efficacy and toxicity. </li></ul></ul><ul><ul><li>As with all antidepressants, the cyclic antidepressants can take up to three to 6 weeks before reaching full clinical effect. </li></ul></ul>
  31. 32. Choice of Therapy: Pharmacotherapy <ul><li>Monoamine Oxidase Inhibitors (MAOI) </li></ul><ul><ul><li>1 st class of antidepressants in clinical use. </li></ul></ul><ul><ul><ul><li>discovered in 1952 </li></ul></ul></ul><ul><ul><li>Mechanism of Action: irreversible blocking of monoamine oxidase </li></ul></ul><ul><ul><ul><li>the enzyme responsible for the oxidative deamination of neurotransmitters such as serotonin, norepinephrine, and dopamine. </li></ul></ul></ul>
  32. 33. Choice of Therapy: Pharmacotherapy <ul><li>Monoamine Oxidase Inhibitors (MAOI) </li></ul>
  33. 34. Choice of Therapy: Pharmacotherapy <ul><li>Monoamine Oxidase Inhibitors (MAOI) </li></ul><ul><ul><li>NOT considered to be 1 st line antidepressant medications because of: </li></ul></ul><ul><ul><ul><li>Dietary restrictions </li></ul></ul></ul><ul><ul><ul><li>Drug-drug interactions </li></ul></ul></ul><ul><ul><ul><li>Relatively extensive side-effect profile. </li></ul></ul></ul><ul><ul><ul><ul><li>Potent hypotensive effects, and up to 50 percent of patients experience dizziness. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Other common side effects are dry mouth, gastrointestinal upset, urinary hesitancy, headache, and myoclonic jerks. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Suppress REM sleep, but the clinical significance of this is unknown. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Afternoon fatigue is common. </li></ul></ul></ul></ul>
  34. 35. Choice of Therapy: Pharmacotherapy <ul><li>Monoamine Oxidase Inhibitors (MAOI) </li></ul><ul><ul><li>Dietary Restriction – “Cheese Reaction” </li></ul></ul><ul><ul><ul><li>MAO is distributed in tissues throughout the body. </li></ul></ul></ul><ul><ul><ul><li>The blockade of MAO in the gastrointestinal tract is responsible </li></ul></ul></ul><ul><ul><ul><li>Severe hypertensive crisis that can occur after patients on MAOIs ingest foods containing the sympathomimetic tyramine. </li></ul></ul></ul><ul><ul><ul><li>Tyramine is usually metabolized in the gastrointestinal tract, but the blockade of MAO allows it to flow into the general circulation. </li></ul></ul></ul><ul><ul><ul><li>Although the accepted &quot;MAOI diet&quot; has been liberalized in recent years, there are still several dietary restrictions to which patients on these medications must adhere. </li></ul></ul></ul>
  35. 36. Choice of Therapy: Pharmacotherapy <ul><li>Monoamine Oxidase Inhibitors (MAOI) </li></ul><ul><ul><li>Despite their side-effect profile, MAOIs can be particularly useful agents for the treatment of: </li></ul></ul><ul><ul><ul><li>&quot;atypical&quot; depression </li></ul></ul></ul><ul><ul><ul><ul><li>(e.g., depression with hyperphagia, hypersomnia, leaden paralysis, and rejection sensitivity) </li></ul></ul></ul></ul><ul><ul><ul><li>Frequently effective in treatment-resistant depressed patients. </li></ul></ul></ul>
  36. 37. Choice of Therapy: Pharmacotherapy <ul><li>Monoamine Oxidase Inhibitors (MAOI) </li></ul><ul><ul><li>Antidepressants should be stopped one week before beginning to avoid precipitating a hypertensive reaction or serotonin syndrome </li></ul></ul><ul><ul><li>Because of its longer half life, Fluoxetine (Prozac) should be stopped five weeks before using tranylcypromine. </li></ul></ul><ul><ul><li>2 weeks should elapse after stopping tranylcypromine before starting another antidepressant or stopping the MAOI diet. </li></ul></ul>
  37. 38. Choice of Therapy: Pharmacotherapy <ul><li>New Medications : </li></ul><ul><ul><li>Venlafaxine (Effexor), Duloxetine (Cymbalta), Trazodone, Nefazodone, Mirtazapine </li></ul></ul><ul><ul><li>Various mechanisms of action – not well understood </li></ul></ul><ul><ul><li>All have efficacy similar to SSRIs </li></ul></ul>
  38. 39. Choice of Therapy: Pharmacotherapy <ul><li>New Medications : </li></ul><ul><ul><li>Choice among these agents is often made on the basis of side-effect profiles. </li></ul></ul><ul><ul><li>Nefazodone, mirtazapine, and duloxetine appear to be associated with less sexual dysfunction than the SSRIs </li></ul></ul><ul><ul><li>Venlafaxine and mirtazapine have fewer drug-drug interactions than the SSRIs. </li></ul></ul><ul><ul><li>Nefazodone may cause serious liver toxicity and is no longer available in Europe. </li></ul></ul><ul><ul><li>Concerns that venlafaxine may be less safe in overdose than other newer antidepressants. </li></ul></ul>
  39. 40. Choice of Therapy: Pharmacotherapy <ul><li>Augmentation/Adjunctive Therapy </li></ul><ul><ul><li>A medication with a different mechanism of action is added to the first in treatment resistant patients. </li></ul></ul><ul><ul><li>Augmentation options include: </li></ul></ul><ul><ul><ul><li>Addition of another antidepressant </li></ul></ul></ul><ul><ul><ul><li>Mood Stabilizer (e.g. Lithium) </li></ul></ul></ul><ul><ul><ul><li>Atypical antipsychotic </li></ul></ul></ul><ul><ul><ul><li>Thyroid hormone </li></ul></ul></ul><ul><ul><ul><li>Stimulants </li></ul></ul></ul><ul><ul><ul><li>Anxiolytics </li></ul></ul></ul>
  40. 41. Choice of Therapy: Pharmacotherapy <ul><li>Follow-up </li></ul><ul><ul><li>An initial therapeutic response typically occurs within 2 to 6 weeks of antidepressant therapy. </li></ul></ul><ul><ul><li>There is little evidence to support extending an antidepressant therapy beyond eight weeks rather than considering other antidepressant therapies in patients who have shown no response </li></ul></ul><ul><ul><li>Patients who have a partial response should continue with therapy for an additional two to four weeks. </li></ul></ul><ul><ul><ul><li>If there is no response by 8 to 12 weeks at a maximum therapeutic dose, consider referral to a specialist for treatment of resistant depression </li></ul></ul></ul>
  41. 42. Choice of Therapy: Pharmacotherapy <ul><li>Follow-up (Continued) </li></ul><ul><ul><li>Pts need to check in at least every 1 to 2 weeks for 6 to 8 weeks during the initiation phase of medication treatment. </li></ul></ul><ul><ul><li>Adherence may be enhanced by the presence of telephone access to the therapist/clinician for the acute questions a patient may have about side effects. </li></ul></ul>
  42. 43. Choice of Therapy: Pharmacotherapy <ul><li>Treatment duration </li></ul><ul><ul><li>Antidepressant medication generally should be taken for at least 6 to 9 months. </li></ul></ul><ul><ul><ul><li>Some studies suggest 12 months </li></ul></ul></ul><ul><ul><li>When antidepressants are discontinued, they should be tapered over 2 to 4 weeks to minimize side effects associated with abrupt cessation of therapy. </li></ul></ul>
  43. 44. Choice of Therapy: Alternative Treatments <ul><li>St. John’s Wort </li></ul><ul><ul><li>Used in Europe for mild acute depression </li></ul></ul><ul><ul><li>Studies in the U.S. have not confirmed efficacy </li></ul></ul><ul><li>Dehydroepiandrosterone (DHEA) </li></ul><ul><ul><li>6 week randomized trial in 22 patients with major depression, most of whom were on antidepressant medications, patients who received DHEA (titrated over six weeks to 30 mg three times daily), compared to placebo, had improved depression </li></ul></ul><ul><ul><li>Not enough evidence to be recommended </li></ul></ul>
  44. 45. Choice of Therapy: Alternative Treatments <ul><li>Exercise </li></ul><ul><ul><li>Some studies showing benefit </li></ul></ul><ul><ul><ul><li>Studies are limited by confounding variables (socialization) </li></ul></ul></ul><ul><ul><ul><li>No adverse effects seen </li></ul></ul></ul><ul><li>Light Therapy </li></ul><ul><ul><li>Meta-analysis of randomized trials found that bright light therapy in nonseasonal depression was associated with a significant reduction in depression symptom severity with effect sizes similar to those in pharmacotherapy trials </li></ul></ul><ul><ul><li>Given the limitations of the underlying studies (small sample sizes, inadequate blinding and placebo groups, and inconsistencies in the timing and dose of therapy) additional research is needed with larger numbers of patients and longer follow-up. </li></ul></ul>
  45. 46. Choice of Therapy: Research and Recommendations
  46. 47. Choice of Therapy: Research and Recommendations <ul><ul><li>Adults – AHCPR* Guideline Panel (1993): </li></ul></ul><ul><ul><ul><li>Severe, Chronic (>2y), Recurrent Depression : </li></ul></ul></ul><ul><ul><ul><ul><li>Combination Therapy – Psychotherapy and Pharmacotherapy </li></ul></ul></ul></ul><ul><ul><ul><li>Mild to Moderate </li></ul></ul></ul><ul><ul><ul><ul><li>Either Psychotherapy or Pharmacotherapy </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Equally efficacious </li></ul></ul></ul></ul><ul><ul><ul><ul><li>No benefit seen with combination </li></ul></ul></ul></ul>* Depression Guideline Panel of the Agency for Health Care Policy and Research (AHCPR)
  47. 48. Choice of Therapy: Research and Recommendations <ul><li>Adult Choices of Psychotherapy: </li></ul><ul><ul><li>AHCPR (1993) efficacies when used alone in mild to moderate depression: </li></ul></ul><ul><ul><ul><li>Cognitive therapy to be 46% </li></ul></ul></ul><ul><ul><ul><li>Behavioral therapy to be 55% </li></ul></ul></ul><ul><ul><ul><li>Interpersonal therapy to be 52% </li></ul></ul></ul>
  48. 49. Choice of Therapy: Research and Recommendations <ul><li>Adolescents : </li></ul><ul><ul><li>Treatment for Adolescents with Depression Study (TADS) was launched in 1998. </li></ul></ul><ul><ul><li>Designed to evaluate short (12 week) and long-term (36 week) efficacy of treatment of MDD with: </li></ul></ul><ul><ul><ul><li>Fluoxetine (SSRI) monotherapy </li></ul></ul></ul><ul><ul><ul><li>CBT monotherapy </li></ul></ul></ul><ul><ul><ul><li>Fluoxetine plus CBT </li></ul></ul></ul><ul><ul><ul><li>Pill placebo </li></ul></ul></ul>
  49. 50. Choice of Therapy: Research and Recommendations <ul><li>Adolescents : TADS Preliminary Data </li></ul><ul><ul><li>Primary outcome measures: </li></ul></ul><ul><ul><ul><li>Children's Depression Rating Scale-Revised (CDRS-R) </li></ul></ul></ul><ul><ul><ul><li>Clinical Global Impression improvement (CGI-I) </li></ul></ul></ul>
  50. 51. Choice of Therapy: Research and Recommendations <ul><li>Adolescents : TADS Preliminary Data </li></ul><ul><ul><li>Over the course of therapy, all groups had improved scores on the CDRS-R </li></ul></ul><ul><ul><li>Greatest improvement in depressive symptoms based on the CDRS-R occurred in the group treated with combination fluoxetine and CBT </li></ul></ul><ul><ul><li>Combination of fluoxetine and CBT yielded statistically significant improvement in depressive symptoms compared with placebo </li></ul></ul><ul><ul><li>Improvement with fluoxetine alone and CBT alone was not statistically different from placebo. </li></ul></ul>
  51. 52. Choice of Therapy: Research and Recommendations <ul><li>Adolescents : TADS Preliminary Data </li></ul><ul><ul><li>Based on CGI-I results: </li></ul></ul><ul><ul><ul><li>fluoxetine alone was effective </li></ul></ul></ul><ul><ul><ul><li>but not as effective as the combination of fluoxetine and CBT. </li></ul></ul></ul><ul><ul><ul><li>At the end of treatment, a greater proportion of those treated with combination therapy reported a much improved or very much improved mood on the CGI-I </li></ul></ul></ul><ul><ul><ul><ul><li>71 : 61 % for combination : fluoxetine monotherapy </li></ul></ul></ul></ul><ul><ul><ul><ul><li>71 : 43 % combination : CBT monotherapy </li></ul></ul></ul></ul><ul><ul><ul><ul><li>35 % improvement for placebo. </li></ul></ul></ul></ul>
  52. 53. Choice of Therapy: Research and Recommendations <ul><li>Adolescents : TADS Preliminary Data </li></ul><ul><ul><li>CGI-I results continued: </li></ul></ul><ul><ul><ul><li>Both the combined treatment group and fluoxetine monotherapy yielded statistically significant reports of improvement compared with placebo </li></ul></ul></ul><ul><ul><ul><li>Treatment with CBT alone was not statistically different from placebo. </li></ul></ul></ul>
  53. 54. Choice of Therapy: Research and Recommendations <ul><li>Adolescents : TADS Preliminary Data </li></ul><ul><ul><li>The combination of fluoxetine and CBT appeared to be protective against harm-related adverse events (nonsuicidal self-harm, worsening of suicidal ideation without self-harm, suicide attempt, aggressive or violent ideation or action against another person or property) </li></ul></ul>
  54. 55. Choice of Therapy: Research and Recommendations <ul><li>Adolescents : </li></ul><ul><ul><li>Severe, Moderate, & Mild Depression: </li></ul></ul><ul><ul><ul><li>Combination Psychopharmacologic Therapy in short term </li></ul></ul></ul><ul><ul><ul><ul><li>Supported by TADS study preliminary data </li></ul></ul></ul></ul><ul><ul><ul><li>Family needs to be involved </li></ul></ul></ul><ul><ul><ul><li>Education separate from or included in Psychotherapy </li></ul></ul></ul>
  55. 56. Choice of Therapy: Research and Recommendations <ul><li>Adolescents : </li></ul><ul><ul><li>Psychotherapy: </li></ul></ul><ul><ul><ul><li>CBT </li></ul></ul></ul><ul><ul><ul><li>Interpersonal therapy for adolescents (IPT-A) </li></ul></ul></ul><ul><ul><ul><ul><li>Adapted from adult IPT described earlier </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Adds consideration for developmental stages and tasks </li></ul></ul></ul></ul>
  56. 57. Choice of Therapy: Research and Recommendations <ul><li>Adolescents : Pharmacotherapy </li></ul><ul><ul><li>TCAs : studies in children and adolescents have failed to show that TCAs are more effective than placebo </li></ul></ul>
  57. 58. <ul><li>Adolescents : Pharmacotherapy </li></ul><ul><ul><li>SSRIs : </li></ul></ul><ul><ul><ul><li>Fluoxetine has been shown to be efficacious improving depressive symptoms in more than one study (but not all) </li></ul></ul></ul><ul><ul><ul><li>The other SSRIs have inconsistent or negative efficacy </li></ul></ul></ul>Choice of Therapy: Research and Recommendations
  58. 59. Choice of Therapy: Research and Recommendations <ul><li>Adolescents : Pharmacotherapy </li></ul><ul><ul><li>SSRIs continued : </li></ul></ul><ul><ul><ul><li>In the studies showing a beneficial effect of SSRI, the difference in the response rate between the SSRI and placebo ranged from 26 percent (for fluoxetine) to 10 percent (for sertraline) </li></ul></ul></ul><ul><ul><ul><li>The placebo response rate across available studies ranges from 33 to 59 percent </li></ul></ul></ul>
  59. 60. Choice of Therapy: Research and Recommendations <ul><li>Adolescents : Pharmacotherapy </li></ul><ul><ul><li>SSRIs continued : </li></ul></ul><ul><ul><ul><li>Adverse are similar to those shown for adults with one addition </li></ul></ul></ul><ul><ul><ul><li>Studies suggest that compared with placebo, the use of antidepressant medications in some children and adolescents may result in a small increase in the risk of suicidal thoughts and behavior, but do not increase the risk of completed suicide. </li></ul></ul></ul>
  60. 61. Choice of Therapy: Research and Recommendations <ul><li>Adolescents : </li></ul><ul><ul><li>As with adults MAOIs and the newly developed antidepressants are reserved for 2 nd or 3 rd line use </li></ul></ul><ul><ul><li>Adjunctive Therapy is similar to that in adults </li></ul></ul><ul><ul><li>As is Follow-up and Treatment Duration </li></ul></ul>