Clinical value of early partial symptomatic improvement in the prediction of response and remission during short-term treatment trials in 3369 subjects with bipolar I or II depression

JOURNAL OF AFFECTIVE DISORDERS

卷:130

Article

Kemp, David E.¹  Ganocy, Stephen J.¹  Brecher, Martin²  Carlson, Berit X.³  Edwards, Suzanne⁴  Eudicone, James M.³  Evoniuk, Gary⁴  Jansen, Wim⁵  Leon, Andrew C.⁶  Minkwitz, Margaret⁷  Pikalov, Andrei⁸  Stassen, Hans H.⁹  Szegedi, Armin¹⁰  Tohen, Mauricio¹¹  Van Willigenburg, Arjen P. P.¹²  Calabrese, Joseph R.¹ 

[1] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA

[2] SK Life Sci, Fair Lawn, NJ USA

[3] Bristol Myers Squibb Co, Plainsboro, NJ USA

[4] GlaxoSmithKline, Res Triangle Pk, NC USA

[5] Schering Plough Corp, Boxmeer, Netherlands

[6] Weill Cornell Med Coll, New York, NY USA

[7] AstraZeneca Wilmington, Wilmington, DE USA

[8] Dainippon Sumitomo Pharma Amer Inc, Ft Lee, NJ USA

[9] Psychiat Univ Hosp Zurich, Zurich, Switzerland

[10] Merck Res Labs, Summit, NJ USA

[11] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA

[12] Complete Healthcare Commun Europe, Amsterdam, Netherlands

关键词: Bipolar disorder;    Early improvement;    Bipolar depression;    Onset of action;    Operating characteristics;    Aripiprazole;    Lamotrigine;    Olanzapine-fluoxetine combination;    Quetiapine;   

DOI  :  10.1016/j.jad.2010.10.026

来源: Elsevier

【 摘 要 】

Objective: To evaluate the clinical value of early partial symptomatic improvement in predicting the probability of response during the short-term treatment of bipolar depression. Methods: Blinded data from 10 multicenter, randomized, double-blind, placebo-controlled trials in bipolar I or II depression were used to determine if early improvement (>= 20% reduction in depression symptom severity after 14 days of treatment) predicted later short-term response or remission. Sensitivity, specificity, efficiency, and positive and negative predictive values (PPV, NPV) were calculated using an intent to treat analysis of individual and pooled study data. Results: 1913 patients were randomized to active compounds (aripiprazole, lamotrigine, olanzapine/olanzapine-fluoxetine, and quetiapine), and 1456 to placebo. In the pooled positive studies, early improvement predicted response and remission with high sensitivity (86% and 88%, respectively), but rates of false positives were high (53% and 59%, respectively). Pooled negative predictive values for response/remission (i.e. confidence in knowing the drug will not result in response or remission) were 74% and 82%, respectively, with low rates of false negatives (14% and 12%, respectively). Conclusion: Early improvement in an individual patient does not appear to be a reliable predictor of eventual response or remission due to an unacceptably high false positive rate. However, the absence of early improvement appears to be a highly reliable predictor of eventual non-response, suggesting that clinicians can have confidence in knowing when a drug is not going to work during short-term treatment. Patients who fail to demonstrate early improvement within the first two weeks of treatment may benefit from a change in therapy. (C) 2010 Elsevier B.V. All rights reserved.

【 授权许可】

Free