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Treatment of bipolar depression: making sensible decisions.
CNS Spectr. 2014 Dec; 19 Suppl 1:4-11; quiz 1-3, 12.CS

Abstract

A major challenge in the treatment of major depressive episodes associated with bipolar disorder is differentiating this illness from major depressive episodes associated with major depressive disorder. Mistaking the former for the latter will lead to incorrect treatment and poor outcomes. None of the classic antidepressants, serotonin specific reuptake inhibitors, or serotonin-norepinephrine reuptake inhibitors have ever received regulatory approval as monotherapies for the treatment of bipolar depression. At present, there are only 3 approved medication treatments for bipolar depression: olanzapine/fluoxetine combination, quetiapine (immediate or extended release), and lurasidone (monotherapy or adjunctive to lithium or valproate). All 3 have similar efficacy profiles, but they differ in terms of tolerability. Number needed to treat (NNT) and number needed to harm (NNH) can be used to quantify these similarities and differences. The NNTs for response and remission for each of these interventions vs placebo range from 4 to 7, and 5 to 7, respectively, with overlap in terms of their 95% confidence intervals. NNH values less than 10 (vs placebo) were observed for the spontaneously reported adverse events of weight gain and diarrhea for olanzapine/fluoxetine combination (7 and 9, respectively) and somnolence and dry mouth for quetiapine (3 and 4, respectively). There were no NNH values less than 10 (vs placebo) observed with lurasidone treatment. NNH values vs placebo for weight gain of at least 7% from baseline were 6, 16, 58, and 36, for olanzapine/fluoxetine combination, quetiapine, lurasidone monotherapy, and lurasidone combined with lithium or valproate, respectively. Individualizing treatment decisions will require consideration of the different potential adverse events that are more likely to occur with each medication. The metric of the likelihood to be helped or harmed (LHH) is the ratio of NNH to NNT and can illustrate the tradeoffs inherent in selecting medications. A more favorable LHH was noted for treatment with lurasidone. However, OFC and quetiapine monotherapy may still have utility in high urgency situations, particularly in persons who have demonstrated good outcomes with these interventions in the past, and where a pressing clinical need for efficacy mitigates their potential tolerability shortcomings. In terms of maintenance therapy, adjunctive quetiapine is the only agent where the NNT vs lithium or valproate alone is less than 10 for both the prevention of mania and the prevention of depression.

Authors+Show Affiliations

Department of Psychiatry and Behavioral Sciences,New York Medical College,Valhalla,New York,USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

25407667

Citation

Citrome, Leslie. "Treatment of Bipolar Depression: Making Sensible Decisions." CNS Spectrums, vol. 19 Suppl 1, 2014, pp. 4-11; quiz 1-3, 12.
Citrome L. Treatment of bipolar depression: making sensible decisions. CNS Spectr. 2014;19 Suppl 1:4-11; quiz 1-3, 12.
Citrome, L. (2014). Treatment of bipolar depression: making sensible decisions. CNS Spectrums, 19 Suppl 1, 4-11; quiz 1-3, 12. https://doi.org/10.1017/S109285291400056X
Citrome L. Treatment of Bipolar Depression: Making Sensible Decisions. CNS Spectr. 2014;19 Suppl 1:4-11; quiz 1-3, 12. PubMed PMID: 25407667.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Treatment of bipolar depression: making sensible decisions. A1 - Citrome,Leslie, Y1 - 2014/11/19/ PY - 2014/11/20/entrez PY - 2014/11/20/pubmed PY - 2015/2/27/medline KW - Antidepressants KW - bipolar depression KW - bipolar disorder KW - likelihood to be helped or harmed KW - lithium KW - lurasidone KW - major depressive disorder KW - number need to treat KW - number needed to harm KW - olanzapine/fluoxetine combination KW - quetiapine KW - valproate SP - 4-11; quiz 1-3, 12 JF - CNS spectrums JO - CNS Spectr VL - 19 Suppl 1 N2 - A major challenge in the treatment of major depressive episodes associated with bipolar disorder is differentiating this illness from major depressive episodes associated with major depressive disorder. Mistaking the former for the latter will lead to incorrect treatment and poor outcomes. None of the classic antidepressants, serotonin specific reuptake inhibitors, or serotonin-norepinephrine reuptake inhibitors have ever received regulatory approval as monotherapies for the treatment of bipolar depression. At present, there are only 3 approved medication treatments for bipolar depression: olanzapine/fluoxetine combination, quetiapine (immediate or extended release), and lurasidone (monotherapy or adjunctive to lithium or valproate). All 3 have similar efficacy profiles, but they differ in terms of tolerability. Number needed to treat (NNT) and number needed to harm (NNH) can be used to quantify these similarities and differences. The NNTs for response and remission for each of these interventions vs placebo range from 4 to 7, and 5 to 7, respectively, with overlap in terms of their 95% confidence intervals. NNH values less than 10 (vs placebo) were observed for the spontaneously reported adverse events of weight gain and diarrhea for olanzapine/fluoxetine combination (7 and 9, respectively) and somnolence and dry mouth for quetiapine (3 and 4, respectively). There were no NNH values less than 10 (vs placebo) observed with lurasidone treatment. NNH values vs placebo for weight gain of at least 7% from baseline were 6, 16, 58, and 36, for olanzapine/fluoxetine combination, quetiapine, lurasidone monotherapy, and lurasidone combined with lithium or valproate, respectively. Individualizing treatment decisions will require consideration of the different potential adverse events that are more likely to occur with each medication. The metric of the likelihood to be helped or harmed (LHH) is the ratio of NNH to NNT and can illustrate the tradeoffs inherent in selecting medications. A more favorable LHH was noted for treatment with lurasidone. However, OFC and quetiapine monotherapy may still have utility in high urgency situations, particularly in persons who have demonstrated good outcomes with these interventions in the past, and where a pressing clinical need for efficacy mitigates their potential tolerability shortcomings. In terms of maintenance therapy, adjunctive quetiapine is the only agent where the NNT vs lithium or valproate alone is less than 10 for both the prevention of mania and the prevention of depression. SN - 1092-8529 UR - https://www.unboundmedicine.com/medline/citation/25407667/Treatment_of_bipolar_depression:_making_sensible_decisions_ L2 - https://www.cambridge.org/core/product/identifier/S109285291400056X/type/journal_article DB - PRIME DP - Unbound Medicine ER -