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Who will benefit from antidepressants in the acute treatment of bipolar depression? A reanalysis of the STEP-BD study by Sachs et al. 2007, using Q-learning.

Wu F, Laber EB, Lipkovich IA, Severus E - Int J Bipolar Disord (2015)

Bottom Line: There is substantial uncertainty regarding the efficacy of antidepressants in the treatment of bipolar disorders.Using data from the acute depression randomized care (RAD) pathway of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we estimate an optimal dynamic treatment regime via Q-learning.The estimated optimal treatment regime presents some evidence that patients in the RAD pathway of STEP-BD who experienced a (hypo)manic episode before the depressive episode may do better to forgo adding an antidepressant to a mandatory mood stabilizer.

View Article: PubMed Central - PubMed

Affiliation: Department of Statistics, North Carolina State University, 2311 Stinson Drive, Raleigh, 27695 USA.

ABSTRACT

Background: There is substantial uncertainty regarding the efficacy of antidepressants in the treatment of bipolar disorders.

Methods: Traditional randomized controlled trials and statistical methods are not designed to discover if, when, and to whom an intervention should be applied; thus, other methodological approaches are needed that allow for the practice of personalized, evidence-based medicine with patients with bipolar depression.

Results: Dynamic treatment regimes operationalize clinical decision-making as a sequence of decision rules, one per stage of clinical intervention, that map patient information to a recommended treatment. Using data from the acute depression randomized care (RAD) pathway of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we estimate an optimal dynamic treatment regime via Q-learning.

Conclusions: The estimated optimal treatment regime presents some evidence that patients in the RAD pathway of STEP-BD who experienced a (hypo)manic episode before the depressive episode may do better to forgo adding an antidepressant to a mandatory mood stabilizer.

No MeSH data available.


Related in: MedlinePlus

Estimated optimal first-stage decision rule. Note that subjects with (hypo)manic episodes immediately preceding the current major depressive episode are recommended to receive placebo.
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Fig5: Estimated optimal first-stage decision rule. Note that subjects with (hypo)manic episodes immediately preceding the current major depressive episode are recommended to receive placebo.

Mentions: The first-stage Q-function has the form , where: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} $${\small{ \begin{aligned} h_{10} &= (1,\text{AGE}, \text{SUMM0}, \text{SUMD0}, \text{PRONSET1}, \text{PRONSET2})^{\intercal};\\ h_{11} &= (1, \text{SUMM0}, \text{PRONSET1}, \text{PRONSET2})^{\intercal}; \\ h_{12} &= (1, \text{SUMM0}, \text{PRONSET1}, \text{PRONSET2})^{\intercal}; \end{aligned}}} $$ \end{document}h10=(1,AGE,SUMM0,SUMD0,PRONSET1,PRONSET2)⊺;h11=(1,SUMM0,PRONSET1,PRONSET2)⊺;h12=(1,SUMM0,PRONSET1,PRONSET2)⊺;a11=1 if a1=Bupriopion otherwise a11=0; a12=1 if a1=Paroxetine otherwise a12=0; PRONSET1=1 if PRONSET=remission otherwise PRONSET1=0; and PRONSET2=1 if PRONSET=manic or hypomanic otherwise PRONSET2=0. The estimated coefficients and 90% bootstrap intervals (corrected for non-regularity as suggested by (Chakraborty et al. 2013)) are listed in Table 3. Figure 5 shows the first-stage optimal decision rule implied by the estimated Q-function. An interesting feature of the first-stage decision rule is that subjects with a (hypo)manic episode immediately preceding the current major depressive episode are recommended to receive placebo. This supports the hypothesis that subjects with (hypo)manic episodes immediately preceding a major depressive episode might not benefit from an adjuvant antidepressant. Figure 5 also shows that among the subjects experiencing remission or mixed/cycling before the current major depressive episodes, Bupropion is recommended to older patients and Paroxetine is recommended to younger patients.Figure 5


Who will benefit from antidepressants in the acute treatment of bipolar depression? A reanalysis of the STEP-BD study by Sachs et al. 2007, using Q-learning.

Wu F, Laber EB, Lipkovich IA, Severus E - Int J Bipolar Disord (2015)

Estimated optimal first-stage decision rule. Note that subjects with (hypo)manic episodes immediately preceding the current major depressive episode are recommended to receive placebo.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383759&req=5

Fig5: Estimated optimal first-stage decision rule. Note that subjects with (hypo)manic episodes immediately preceding the current major depressive episode are recommended to receive placebo.
Mentions: The first-stage Q-function has the form , where: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} $${\small{ \begin{aligned} h_{10} &= (1,\text{AGE}, \text{SUMM0}, \text{SUMD0}, \text{PRONSET1}, \text{PRONSET2})^{\intercal};\\ h_{11} &= (1, \text{SUMM0}, \text{PRONSET1}, \text{PRONSET2})^{\intercal}; \\ h_{12} &= (1, \text{SUMM0}, \text{PRONSET1}, \text{PRONSET2})^{\intercal}; \end{aligned}}} $$ \end{document}h10=(1,AGE,SUMM0,SUMD0,PRONSET1,PRONSET2)⊺;h11=(1,SUMM0,PRONSET1,PRONSET2)⊺;h12=(1,SUMM0,PRONSET1,PRONSET2)⊺;a11=1 if a1=Bupriopion otherwise a11=0; a12=1 if a1=Paroxetine otherwise a12=0; PRONSET1=1 if PRONSET=remission otherwise PRONSET1=0; and PRONSET2=1 if PRONSET=manic or hypomanic otherwise PRONSET2=0. The estimated coefficients and 90% bootstrap intervals (corrected for non-regularity as suggested by (Chakraborty et al. 2013)) are listed in Table 3. Figure 5 shows the first-stage optimal decision rule implied by the estimated Q-function. An interesting feature of the first-stage decision rule is that subjects with a (hypo)manic episode immediately preceding the current major depressive episode are recommended to receive placebo. This supports the hypothesis that subjects with (hypo)manic episodes immediately preceding a major depressive episode might not benefit from an adjuvant antidepressant. Figure 5 also shows that among the subjects experiencing remission or mixed/cycling before the current major depressive episodes, Bupropion is recommended to older patients and Paroxetine is recommended to younger patients.Figure 5

Bottom Line: There is substantial uncertainty regarding the efficacy of antidepressants in the treatment of bipolar disorders.Using data from the acute depression randomized care (RAD) pathway of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we estimate an optimal dynamic treatment regime via Q-learning.The estimated optimal treatment regime presents some evidence that patients in the RAD pathway of STEP-BD who experienced a (hypo)manic episode before the depressive episode may do better to forgo adding an antidepressant to a mandatory mood stabilizer.

View Article: PubMed Central - PubMed

Affiliation: Department of Statistics, North Carolina State University, 2311 Stinson Drive, Raleigh, 27695 USA.

ABSTRACT

Background: There is substantial uncertainty regarding the efficacy of antidepressants in the treatment of bipolar disorders.

Methods: Traditional randomized controlled trials and statistical methods are not designed to discover if, when, and to whom an intervention should be applied; thus, other methodological approaches are needed that allow for the practice of personalized, evidence-based medicine with patients with bipolar depression.

Results: Dynamic treatment regimes operationalize clinical decision-making as a sequence of decision rules, one per stage of clinical intervention, that map patient information to a recommended treatment. Using data from the acute depression randomized care (RAD) pathway of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we estimate an optimal dynamic treatment regime via Q-learning.

Conclusions: The estimated optimal treatment regime presents some evidence that patients in the RAD pathway of STEP-BD who experienced a (hypo)manic episode before the depressive episode may do better to forgo adding an antidepressant to a mandatory mood stabilizer.

No MeSH data available.


Related in: MedlinePlus