1. EBM seminar: Treatment of severe depression in an elderly patient Brian Mickey Gregory Dalack March 23, 2006

2. Brief case history 77 year old man with recurrent unipolar depression. Currently in episode, BDI and HAM-D in severe range. Mild psychotic ideation. History of excellent response to ECT, but his comorbidities make this less favorable now. 77 year old man with recurrent unipolar depression. Currently in episode, BDI and HAM-D in severe range. Mild psychotic ideation. History of excellent response to ECT, but his comorbidities make this less favorable now.

3. Initial clinical question What would be the best treatment for this patient’s depression? What would be the best treatment for this patient’s depression?

4. An answerable clinical question For elderly patients with recurrent, moderate-to-severe, major depression... For elderly patients with recurrent, moderate-to-severe, major depression......does one class of antidepressant medication or ECT......does one class of antidepressant medication or ECT......when compared to other classes of antidepressant......when compared to other classes of antidepressant......result in better improvement of depressive symptoms?...result in better improvement of depressive symptoms? patient patient intervention intervention comparison comparison outcome outcome

5. Literature search goal: to (quickly) find evidence at the level of meta- analysis or systematic review goal: to (quickly) find evidence at the level of meta- analysis or systematic review UM Medsearch (OVID) UM Medsearch (OVID) difficulties difficulties choosing a database, using limits choosing a database, using limits choosing search terms, sensitivity vs specificity choosing search terms, sensitivity vs specificity strategies strategies limit to “EBM review” limit to “EBM review” limit to English limit to English restrict to “elderly” or “geriatric” restrict to “elderly” or “geriatric” results results “antidepressant” → 88 hits “antidepressant” → 88 hits “electroconvulsive therapy” → 5 hits “electroconvulsive therapy” → 5 hits

6. Selected results Antidepressant treatment Antidepressant treatment Mottram et al. Antidepressants for depressed elderly. The Cochrane Database of Systematic Reviews 2006, Issue 1. Mottram et al. Antidepressants for depressed elderly. The Cochrane Database of Systematic Reviews 2006, Issue 1. Wijkstra et al. Pharmacological treatment for psychotic depression. The Cochrane Database of Systematic Reviews 2005, Issue 4. Wijkstra et al. Pharmacological treatment for psychotic depression. The Cochrane Database of Systematic Reviews 2005, Issue 4. Electroconvulsive therapy Electroconvulsive therapy van der Wurff et al. Electroconvulsive therapy for the depressed elderly. The Cochrane Database of Systematic Reviews 2003, Issue 2. van der Wurff et al. Electroconvulsive therapy for the depressed elderly. The Cochrane Database of Systematic Reviews 2003, Issue 2. van der Wurff et al. The efficacy and safety of ECT in depressed older adults, a literature review. Int J Geriatr Psychiatry 2003; 18: 894–904. van der Wurff et al. The efficacy and safety of ECT in depressed older adults, a literature review. Int J Geriatr Psychiatry 2003; 18: 894–904.

7. Cochrane review: Antidepressants for depressed elderly Objectives: Objectives: examine efficacy, withdrawal rate, and side effect profiles of antidepressant classes among elderly patients examine efficacy, withdrawal rate, and side effect profiles of antidepressant classes among elderly patients Methods: Methods: meta-analysis of all randomized controlled trials of at least two antidepressants meta-analysis of all randomized controlled trials of at least two antidepressants five classes: TCA, TCA-related, SSRI, MAOI, atypical five classes: TCA, TCA-related, SSRI, MAOI, atypical Results: Results: 29 trials (several thousand patients) were identified 29 trials (several thousand patients) were identified no differences in efficacy were found no differences in efficacy were found due to small samples, type II error is likely due to small samples, type II error is likely SSRIs were better tolerated than TCAs and TCA-related agents SSRIs were better tolerated than TCAs and TCA-related agents Limitations: Limitations: heterogeneity of depressive disorders and severity heterogeneity of depressive disorders and severity

8. Cochrane review: Pharmacological treatment for psychotic depression Objectives: Objectives: examine effectiveness of antidepressant vs antipsychotic vs combination therapy for psychotic depression examine effectiveness of antidepressant vs antipsychotic vs combination therapy for psychotic depression Methods: Methods: meta-analysis of randomized controlled trials of psychotic depression meta-analysis of randomized controlled trials of psychotic depression Results: Results: 10 trials (548 patients) were identified 10 trials (548 patients) were identified both antidepressant alone and antidepressant + antipsychotic were superior to antipsychotic alone both antidepressant alone and antidepressant + antipsychotic were superior to antipsychotic alone antidepressant + antipsychotic was no more effective than antidepressant alone (N.B. Post-script- at the seminar, this was viewed as a controversial conclusion and will be the focus of another EBM seminar at a later date- stay tuned) antidepressant + antipsychotic was no more effective than antidepressant alone (N.B. Post-script- at the seminar, this was viewed as a controversial conclusion and will be the focus of another EBM seminar at a later date- stay tuned) 2 trials compared TCA to non-TCA (fluvoxamine, mirtazapine): TCA more effective 2 trials compared TCA to non-TCA (fluvoxamine, mirtazapine): TCA more effective Limitations: Limitations: no data available for elderly subgroup no data available for elderly subgroup

9. Cochrane review: Electroconvulsive therapy for the depressed elderly Objectives: Objectives: assess the efficacy and safety of ECT in depressed elderly people assess the efficacy and safety of ECT in depressed elderly people Methods: Methods: meta-analysis of randomized controlled trials of ECT vs simulated ECT or antidepressants meta-analysis of randomized controlled trials of ECT vs simulated ECT or antidepressants Results: Results: 3 trials (roughly 60 patients) were identified 3 trials (roughly 60 patients) were identified the objectives of this review could not be addressed due to methodological shortcomings the objectives of this review could not be addressed due to methodological shortcomings Limitations: Limitations: restriction to RCTs results in no clinically useful conclusions! restriction to RCTs results in no clinically useful conclusions!

10. IJGP review: The efficacy and safety of ECT in depressed older adults Objectives: Objectives: assess the efficacy and safety of ECT in depressed elderly people assess the efficacy and safety of ECT in depressed elderly people Methods: Methods: review of randomized and non-randomized studies of ECT vs simulated ECT or antidepressants review of randomized and non-randomized studies of ECT vs simulated ECT or antidepressants Results: Results: 121 studies (roughly 1400 patients) were identified 121 studies (roughly 1400 patients) were identified ECT was found to be effective and generally safe in the acute treatment of late-life depression ECT was found to be effective and generally safe in the acute treatment of late-life depression Limitations: Limitations: questions that could not be answered include relative efficacy compared to antidepressants, long-term efficacy, morbidity and mortality, and efficacy in patient subgroups questions that could not be answered include relative efficacy compared to antidepressants, long-term efficacy, morbidity and mortality, and efficacy in patient subgroups

11. Results from an alternative search strategy Amore. The pharmacological treatment of depression in the elderly. Minerva Psichiatrica. Vol. 46(4)(pp 261-272), 2005. Amore. The pharmacological treatment of depression in the elderly. Minerva Psichiatrica. Vol. 46(4)(pp 261-272), 2005. Karp and Reynolds. Pharmacotherapy of depression in the elderly: Achieving and maintaining optimal outcomes. Primary Psychiatry. Vol. 11(5)(pp 37-46), 2004. Karp and Reynolds. Pharmacotherapy of depression in the elderly: Achieving and maintaining optimal outcomes. Primary Psychiatry. Vol. 11(5)(pp 37-46), 2004. Rudorfer and Potter. Metabolism of tricyclic antidepressants. Cellular & Molecular Neurobiology. Vol. 19(3)(pp 373-409), 1999. Rudorfer and Potter. Metabolism of tricyclic antidepressants. Cellular & Molecular Neurobiology. Vol. 19(3)(pp 373-409), 1999. Lane et al. The SSRIs: Advantages, disadvantages and differences. Journal of Psychopharmacology. Vol. 9(2 SUPPL.)(pp 163-178), 1995. Lane et al. The SSRIs: Advantages, disadvantages and differences. Journal of Psychopharmacology. Vol. 9(2 SUPPL.)(pp 163-178), 1995. Cipriani et al. Fluoxetine versus other types of pharmacotherapy for depression. Cochrane Database of Systematic Reviews. 1, 2006. Cipriani et al. Fluoxetine versus other types of pharmacotherapy for depression. Cochrane Database of Systematic Reviews. 1, 2006. Flint. Pharmacologic treatment of depression in late life. CMAJ: Canadian Medical Association Journal. Vol. 157(8)(pp 1061-1067), 1997. Flint. Pharmacologic treatment of depression in late life. CMAJ: Canadian Medical Association Journal. Vol. 157(8)(pp 1061-1067), 1997.