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Randomized Controlled Trial
. 2011 Jun;26(6):573-83.
doi: 10.1002/gps.2565.

Do treatment effects vary among differing baseline depression criteria in depression in Alzheimer's disease study ± 2 (DIADS-2)?

Lea T Drye  1 , Barbara K Martin, Constantine E Frangakis, Curtis L Meinert, Jacobo E Mintzer, Cynthia A Munro, Anton P Porsteinsson, Peter V Rabins, Paul B Rosenberg, Lon S Schneider, Daniel Weintraub, Constantine G Lyketsos; DIADS-2 Research Group
Collaborators, Affiliations
Randomized Controlled Trial

Do treatment effects vary among differing baseline depression criteria in depression in Alzheimer's disease study ± 2 (DIADS-2)?

Lea T Drye et al. Int J Geriatr Psychiatry. 2011 Jun.

Abstract

Objective: To determine if the effect of sertraline in the depression in Alzheimer's disease study - 2 (DIADS-2) differed in subgroups of patients defined by baseline depression criteria.

Methods: DIADS-2 was a randomized, parallel, placebo-controlled, multicenter trial designed to evaluate the efficacy and safety of sertraline (target dose of 100 mg/day) for the treatment of depression in patients with Alzheimer's disease. DIADS-2 enrolled 131 patients who met criteria for the depression of Alzheimer's disease (dAD). Analyses reported here examined if the effect of sertraline differed in various subgroups, including those meeting criteria for major depressive episode (MaD), minor depressive episode (MiD), and Alzheimer's-associated affective disorder (AAAD) at baseline.

Results: At baseline, 52 of 131 participants (39.7%) met criteria for MaD, 54 (41.2%) for MiD, and 90 (68.7%) for AAAD. For the primary outcome of modified Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (mADCS-CGIC) scores at 12 weeks of follow-up, the odds of being at or better than a given mADCS-CGIC category did not significantly differ between the two treatment groups for those patients with MaD at baseline (OR(sertraline) = 0.66 [95% CI: 0.24, 1.82], p = 0.42); tests for interactions between treatment group and baseline depression diagnostic subgroup were not significant for MaD versus MiD versus neither (χ(2) = 1.05 (2df), p = 0.59) or AAAD versus no AAAD (χ(2) = 0.06 (1df), p = 0.81).

Conclusions: There was no evidence that sertraline treatment was more efficacious in those patients meeting baseline criteria for MaD compared to MiD or to neither.

Trial registration: ClinicalTrials.gov NCT00086138.

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Conflict of interest statement

Conflict of interest

  1. These disclosures refer to the period between 7/1/02 and 10/31/08, and include any anticipated conflicts through 12/31/09, according to the DIADS-2 Conflict of Interest Policy (available upon request from the study PI).

  2. Barbara Martin is involved in another trial for which Pfizer donated a different drug.

  3. Paul Rosenberg has served as a consultant for Forest regarding the drug memantine, and has received research funds from Pfizer and Merck in amounts greater than $10,000.

  4. Jacobo Mintzer has received research support from Abbot to study donepezil and divalproex sodium, from AstraZeneca to study quetiapine, from BMS to study aripiprazole, from Eli Lilly to study olanzapine, from Forest to study both citalopram and memantine, from Janssen to study galantamine and risperidone, and from Pfizer to study donepezil and memantine; Dr. Mintzer also has been a consultant, paid directly or indirectly, for AstraZeneca, BMS, Eli Lilly, Janssen, Pfizer, Forest, and Aventis. He also has been an unpaid consultant for Targacept and has participated in Speaker’s Bureaus for Janssen, Forest, and Pfizer.

  5. Daniel Weintraub has received research support from Boehringer Ingelheim; Dr. Weintraub also has been a paid consultant for Acadia Pharmaceuticals, Novartis Pharmaceuticals, Boehringer Ingelheim, Osmotica Pharmaceutical, BrainCells Inc., EMD Serono, and Sanofi Aventis, and has participated on a Speaker’s Bureau for Pfizer.

  6. Anton Porsteinsson is involved in research sponsored by Pfizer to study donepezil and PF04494700, Eli Lilly to study atomoxetine, a gamma-secretase inhibitor and a beta amyloid antibody, Wyeth to study a beta amyloid antibody, GSK to study a PPAR inhibitor and Forest to study memantine and neramexane; Dr. Porsteinsson has been a paid consultant and participated on a Speaker’s Bureau for Pfizer and Forest.

  7. Lon S. Schneider is involved in research sponsored by Pfizer, the manufacturer of sertraline and other drugs used to treat mood disorders; Dr. Schneider has been a paid consultant for Abbott, AstraZeneca, Eli Lilly, Forest, GlaxoSmithKline, Johnson and Johnson, Lundbeck, Merck, and Wyeth, manufacturers of antidepressants or drugs used to treat mood disorders.

  8. Constantine Frangakis has no conflict of interests.

  9. Lea Drye has no conflict of interests.

  10. Peter Rabins has participated on Speaker’s Bureaus for Wyeth, Eli Lilly, and Pfizer.

  11. Cynthia Munro has no conflict of interests.

  12. Curtis Meinert is involved in another trial for which Pfizer donated a different drug; Dr. Meinert owns shares of GSK stock.

  13. Constantine Lyketsos was involved in another trial for which Pfizer donated a different drug; he also was involved in research sponsored by Forest to study escitalopram and citalopram and Pfizer to study sertraline and donepezil; Dr. Lyketsos served as a consultant for Organon, Eisai, GSK, Lilly, Wyeth, and Pfizer.

Figures

Figure 1
Figure 1
Venn diagram showing overlap of depression criteria at baseline
Figure 2
Figure 2
Treatment effect estimates (sertraline vs. placebo) for mADCS-CGIC in subgroups of patients meeting depression criteria at baseline (Odds ratio* [OR] and 95% CI) *OR is the odds ratios (calculated using proportional odds logistic regression) of being at or better than a given mADCS-CGIC category for sertraline vs. placebo.
Figure 3
Figure 3
Treatment effect estimates (sertraline vs. placebo) for CSDD in subgroups of patients meeting depression criteria at baseline (difference and 95% CI in median CSDD*) *Confidence intervals for medians calculated using bootstrapping.
Figure 4
Figure 4
Treatment effect estimates (sertraline vs. placebo) for remission* in subgroups of patients meeting depression criteria at baseline (Odds ratio** [OR] and 95% CI) * Remission of depression was defined as mADCS-CGIC score ≤2 and CSDD score ≤6. **OR was calculated using logistic regression.
See this image and copyright information in PMC

References

    1. Lyketsos CG, Lopez O, Jones B, Fitzpatrick AL, Breitner J, DeKosky S. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA. 2002;288(12):1475–1483. - PubMed
    1. Steinberg M, Shao H, Zandi P, Lyketsos CG, Welsh-Bohmer KA, Norton MC, Breitner JC, Steffens DC, Tschanz JT. Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study. Int J Geriatr Psychiatry. 2008;23(2):170–177. - PMC - PubMed
    1. Lee HB, Lyketsos CG. Depression in Alzheimer’s disease: heterogeneity and related issues. Biol Psychiatry. 2003;54(3):353–362. - PubMed
    1. Rosenberg PB, Onyike CU, Katz IR, Porsteinsson AP, Mintzer JE, Schneider LS, Rabins PV, Meinert CL, Martin BK, Lyketsos CG. Clinical application of operationalized criteria for ‘Depression of Alzheimer’s Disease’. Int J Geriatr Psychiatry. 2005;20(2):119–127. - PubMed
    1. Olin JT, Katz IR, Meyers BS, Schneider LS, Lebowitz BD. Provisional diagnostic criteria for depression of Alzheimer disease: rationale and background. Am J Geriatr Psychiatry. 2002;10 (2):129–141. - PubMed

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