Effectiveness of adjunctive antidepressant treatment for bipolar depression

Gary S. Sachs, Andrew A. Nierenberg, Joseph R. Calabrese, Lauren B. Marangell, Stephen R. Wisniewski, Laszlo Gyulai, Edward S. Friedman, Charles L. Bowden, Mark D. Fossey, Michael J. Ostacher, Terence A. Ketter, Jayendra Patel, Peter Hauser, Daniel Rapport, James M. Martinez, Michael H. Allen, David J. Miklowitz, Michael W. Otto, Ellen B. Dennehy, Michael E. Thase

Research output: Contribution to journalArticle

671 Citations (Scopus)

Abstract

BACKGROUND: Episodes of depression are the most frequent cause of disability among patients with bipolar disorder. The effectiveness and safety of standard antidepressant agents for depressive episodes associated with bipolar disorder (bipolar depression) have not been well studied. Our study was designed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania. METHODS: In this double-blind, placebo-controlled study, we randomly assigned subjects with bipolar depression to receive up to 26 weeks of treatment with a mood stabilizer plus adjunctive antidepressant therapy or a mood stabilizer plus a matching placebo, under conditions generalizable to routine clinical care. A standardized clinical monitoring form adapted from the mood-disorder modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, was used at all follow-up visits. The primary outcome was the percentage of subjects in each treatment group meeting the criterion for a durable recovery (8 consecutive weeks of euthymia). Secondary effectiveness outcomes and rates of treatment-emergent affective switch (a switch to mania or hypomania early in the course of treatment) were also examined. RESULTS: Forty-two of the 179 subjects (23.5%) receiving a mood stabilizer plus adjunctive antidepressant therapy had a durable recovery, as did 51 of the 187 subjects (27.3%) receiving a mood stabilizer plus a matching placebo (P = 0.40). Modest nonsignificant trends favoring the group receiving a mood stabilizer plus placebo were observed across the secondary outcomes. Rates of treatment-emergent affective switch were similar in the two groups. COCLUSIONS: The use of adjunctive, standard antidepressant medication, as compared with the use of mood stabilizers, was not associated with increased efficacy or with increased risk of treatment-emergent affective switch. Longer-term outcome studies are needed to fully assess the benefits and risks of antidepressant therapy for bipolar disorder.

Original languageEnglish (US)
Pages (from-to)1711-1722
Number of pages12
JournalNew England Journal of Medicine
Volume356
Issue number17
DOIs
StatePublished - Apr 26 2007

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Bipolar Disorder
Antidepressive Agents
Placebos
Therapeutics
Group Processes
Mood Disorders
Diagnostic and Statistical Manual of Mental Disorders
Outcome Assessment (Health Care)
Interviews
Depression
Safety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Sachs, G. S., Nierenberg, A. A., Calabrese, J. R., Marangell, L. B., Wisniewski, S. R., Gyulai, L., ... Thase, M. E. (2007). Effectiveness of adjunctive antidepressant treatment for bipolar depression. New England Journal of Medicine, 356(17), 1711-1722. https://doi.org/10.1056/NEJMoa064135

Effectiveness of adjunctive antidepressant treatment for bipolar depression. / Sachs, Gary S.; Nierenberg, Andrew A.; Calabrese, Joseph R.; Marangell, Lauren B.; Wisniewski, Stephen R.; Gyulai, Laszlo; Friedman, Edward S.; Bowden, Charles L.; Fossey, Mark D.; Ostacher, Michael J.; Ketter, Terence A.; Patel, Jayendra; Hauser, Peter; Rapport, Daniel; Martinez, James M.; Allen, Michael H.; Miklowitz, David J.; Otto, Michael W.; Dennehy, Ellen B.; Thase, Michael E.

In: New England Journal of Medicine, Vol. 356, No. 17, 26.04.2007, p. 1711-1722.

Research output: Contribution to journalArticle

Sachs, GS, Nierenberg, AA, Calabrese, JR, Marangell, LB, Wisniewski, SR, Gyulai, L, Friedman, ES, Bowden, CL, Fossey, MD, Ostacher, MJ, Ketter, TA, Patel, J, Hauser, P, Rapport, D, Martinez, JM, Allen, MH, Miklowitz, DJ, Otto, MW, Dennehy, EB & Thase, ME 2007, 'Effectiveness of adjunctive antidepressant treatment for bipolar depression', New England Journal of Medicine, vol. 356, no. 17, pp. 1711-1722. https://doi.org/10.1056/NEJMoa064135
Sachs GS, Nierenberg AA, Calabrese JR, Marangell LB, Wisniewski SR, Gyulai L et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. New England Journal of Medicine. 2007 Apr 26;356(17):1711-1722. https://doi.org/10.1056/NEJMoa064135
Sachs, Gary S. ; Nierenberg, Andrew A. ; Calabrese, Joseph R. ; Marangell, Lauren B. ; Wisniewski, Stephen R. ; Gyulai, Laszlo ; Friedman, Edward S. ; Bowden, Charles L. ; Fossey, Mark D. ; Ostacher, Michael J. ; Ketter, Terence A. ; Patel, Jayendra ; Hauser, Peter ; Rapport, Daniel ; Martinez, James M. ; Allen, Michael H. ; Miklowitz, David J. ; Otto, Michael W. ; Dennehy, Ellen B. ; Thase, Michael E. / Effectiveness of adjunctive antidepressant treatment for bipolar depression. In: New England Journal of Medicine. 2007 ; Vol. 356, No. 17. pp. 1711-1722.
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T1 - Effectiveness of adjunctive antidepressant treatment for bipolar depression

AU - Sachs, Gary S.

AU - Nierenberg, Andrew A.

AU - Calabrese, Joseph R.

AU - Marangell, Lauren B.

AU - Wisniewski, Stephen R.

AU - Gyulai, Laszlo

AU - Friedman, Edward S.

AU - Bowden, Charles L.

AU - Fossey, Mark D.

AU - Ostacher, Michael J.

AU - Ketter, Terence A.

AU - Patel, Jayendra

AU - Hauser, Peter

AU - Rapport, Daniel

AU - Martinez, James M.

AU - Allen, Michael H.

AU - Miklowitz, David J.

AU - Otto, Michael W.

AU - Dennehy, Ellen B.

AU - Thase, Michael E.

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N2 - BACKGROUND: Episodes of depression are the most frequent cause of disability among patients with bipolar disorder. The effectiveness and safety of standard antidepressant agents for depressive episodes associated with bipolar disorder (bipolar depression) have not been well studied. Our study was designed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania. METHODS: In this double-blind, placebo-controlled study, we randomly assigned subjects with bipolar depression to receive up to 26 weeks of treatment with a mood stabilizer plus adjunctive antidepressant therapy or a mood stabilizer plus a matching placebo, under conditions generalizable to routine clinical care. A standardized clinical monitoring form adapted from the mood-disorder modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, was used at all follow-up visits. The primary outcome was the percentage of subjects in each treatment group meeting the criterion for a durable recovery (8 consecutive weeks of euthymia). Secondary effectiveness outcomes and rates of treatment-emergent affective switch (a switch to mania or hypomania early in the course of treatment) were also examined. RESULTS: Forty-two of the 179 subjects (23.5%) receiving a mood stabilizer plus adjunctive antidepressant therapy had a durable recovery, as did 51 of the 187 subjects (27.3%) receiving a mood stabilizer plus a matching placebo (P = 0.40). Modest nonsignificant trends favoring the group receiving a mood stabilizer plus placebo were observed across the secondary outcomes. Rates of treatment-emergent affective switch were similar in the two groups. COCLUSIONS: The use of adjunctive, standard antidepressant medication, as compared with the use of mood stabilizers, was not associated with increased efficacy or with increased risk of treatment-emergent affective switch. Longer-term outcome studies are needed to fully assess the benefits and risks of antidepressant therapy for bipolar disorder.

AB - BACKGROUND: Episodes of depression are the most frequent cause of disability among patients with bipolar disorder. The effectiveness and safety of standard antidepressant agents for depressive episodes associated with bipolar disorder (bipolar depression) have not been well studied. Our study was designed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania. METHODS: In this double-blind, placebo-controlled study, we randomly assigned subjects with bipolar depression to receive up to 26 weeks of treatment with a mood stabilizer plus adjunctive antidepressant therapy or a mood stabilizer plus a matching placebo, under conditions generalizable to routine clinical care. A standardized clinical monitoring form adapted from the mood-disorder modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, was used at all follow-up visits. The primary outcome was the percentage of subjects in each treatment group meeting the criterion for a durable recovery (8 consecutive weeks of euthymia). Secondary effectiveness outcomes and rates of treatment-emergent affective switch (a switch to mania or hypomania early in the course of treatment) were also examined. RESULTS: Forty-two of the 179 subjects (23.5%) receiving a mood stabilizer plus adjunctive antidepressant therapy had a durable recovery, as did 51 of the 187 subjects (27.3%) receiving a mood stabilizer plus a matching placebo (P = 0.40). Modest nonsignificant trends favoring the group receiving a mood stabilizer plus placebo were observed across the secondary outcomes. Rates of treatment-emergent affective switch were similar in the two groups. COCLUSIONS: The use of adjunctive, standard antidepressant medication, as compared with the use of mood stabilizers, was not associated with increased efficacy or with increased risk of treatment-emergent affective switch. Longer-term outcome studies are needed to fully assess the benefits and risks of antidepressant therapy for bipolar disorder.

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