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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

RAD design. At the beginning (stage 1), there are 365 patients in total. Eighty-five patients take Bupropion, 93 patients take Paroxetine, and 187 patients take placebo. After 6 weeks, 104 patients’ information are lost. Only 78 patients are tracked with non-response at the end of stage 1. At stage 2, patients with non-response are assigned to secondary treatment intervention. Patients taking Bupropion or Paroxetine at stage 1 will increase current doses. But patients taking placebo at stage 1 will be assigned Bupropion or Paroxetine.
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Fig2: RAD design. At the beginning (stage 1), there are 365 patients in total. Eighty-five patients take Bupropion, 93 patients take Paroxetine, and 187 patients take placebo. After 6 weeks, 104 patients’ information are lost. Only 78 patients are tracked with non-response at the end of stage 1. At stage 2, patients with non-response are assigned to secondary treatment intervention. Patients taking Bupropion or Paroxetine at stage 1 will increase current doses. But patients taking placebo at stage 1 will be assigned Bupropion or Paroxetine.

Mentions: During the study, patients need to visit their doctors every week to fill in the CMF (Sachs et al. 2002). Patients were allowed to switch to SCP (opt out) at any time by their preference or doctor’s opinion. Patients who had severe adverse effects or met criteria for hypomania or mania discontinued the antidepressant or placebo and received open treatment while remaining in STEP-BD. Since after 6 weeks, only one patient with non-response on the antidepressant was assigned to add another antidepressant, we ignored this one observation and supposed patients with non-response to antidepressant after 6 weeks were only assigned to increase the dose of their current antidepressant. Figure 2 shows a schematic for the RAD protocol. Response for a given subject was defined as at least 50% improvement over their initial SUMD (scale scores for depression) and not meeting the DSM-IV criteria for hypomania or mania. Scores on the continuous symptom subscale for depression (SUMD) range from 0 to 22, with higher scores indicating more severe symptoms. Both SUMD and SUMM (symptom subscale for mood elevation, SUMM scores range from 0 to 16) are part of the modified clinical monitoring form for mood disorders (Sachs et al. 2002). Because subjects in RAD are potentially randomized multiple times with randomizations occurring at crucial points of the disease process, RAD is an example of a Sequential Multiple Assignment Randomized Trial (SMART) (Lavori and Dawson 2004; Murphy 2003). Data collected in SMARTs can be used to efficiently estimate and evaluate DTRs. In the next section, we formalize the notion of an optimal DTR and introduce a regression-based approach called Q-learning for estimating an optimal DTR from a SMART.Figure 2


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)

RAD design. At the beginning (stage 1), there are 365 patients in total. Eighty-five patients take Bupropion, 93 patients take Paroxetine, and 187 patients take placebo. After 6 weeks, 104 patients’ information are lost. Only 78 patients are tracked with non-response at the end of stage 1. At stage 2, patients with non-response are assigned to secondary treatment intervention. Patients taking Bupropion or Paroxetine at stage 1 will increase current doses. But patients taking placebo at stage 1 will be assigned Bupropion or Paroxetine.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: RAD design. At the beginning (stage 1), there are 365 patients in total. Eighty-five patients take Bupropion, 93 patients take Paroxetine, and 187 patients take placebo. After 6 weeks, 104 patients’ information are lost. Only 78 patients are tracked with non-response at the end of stage 1. At stage 2, patients with non-response are assigned to secondary treatment intervention. Patients taking Bupropion or Paroxetine at stage 1 will increase current doses. But patients taking placebo at stage 1 will be assigned Bupropion or Paroxetine.
Mentions: During the study, patients need to visit their doctors every week to fill in the CMF (Sachs et al. 2002). Patients were allowed to switch to SCP (opt out) at any time by their preference or doctor’s opinion. Patients who had severe adverse effects or met criteria for hypomania or mania discontinued the antidepressant or placebo and received open treatment while remaining in STEP-BD. Since after 6 weeks, only one patient with non-response on the antidepressant was assigned to add another antidepressant, we ignored this one observation and supposed patients with non-response to antidepressant after 6 weeks were only assigned to increase the dose of their current antidepressant. Figure 2 shows a schematic for the RAD protocol. Response for a given subject was defined as at least 50% improvement over their initial SUMD (scale scores for depression) and not meeting the DSM-IV criteria for hypomania or mania. Scores on the continuous symptom subscale for depression (SUMD) range from 0 to 22, with higher scores indicating more severe symptoms. Both SUMD and SUMM (symptom subscale for mood elevation, SUMM scores range from 0 to 16) are part of the modified clinical monitoring form for mood disorders (Sachs et al. 2002). Because subjects in RAD are potentially randomized multiple times with randomizations occurring at crucial points of the disease process, RAD is an example of a Sequential Multiple Assignment Randomized Trial (SMART) (Lavori and Dawson 2004; Murphy 2003). Data collected in SMARTs can be used to efficiently estimate and evaluate DTRs. In the next section, we formalize the notion of an optimal DTR and introduce a regression-based approach called Q-learning for estimating an optimal DTR from a SMART.Figure 2

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