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Pharmacological approaches to the challenge of treatment-resistant depression.

ABSTRACT: Although monoaminergic antidepressants revolutionized the treatment of Major Depressive Disorder (MDD) over a half-century ago, approximately one third of depressed patients experience treatment-resistant depression (TRD). Such patients account for a disproportionately large burden of disease, as evidenced by increased disability, cost, human suffering, and suicide. This review addresses the definition, causes, evaluation, and treatment of unipolar TRD, as well as the major treatment strategies, including optimization, augmentation, combination, and switch therapies. Evidence for these options, as outlined in this review, is mainly focused on large-scale trials or meta-analyses. Finally, we briefly review emerging targets for antidepressant drug discovery and the novel effects of rapidly acting antidepressants, with a focus on ketamine.

SUBMITTER: Ionescu DF

PROVIDER: S-EPMC4518696 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Pharmacological approaches to the challenge of treatment-resistant depression.

Ionescu Dawn F DF Rosenbaum Jerrold F JF Alpert Jonathan E JE

Dialogues in clinical neuroscience 20150601 2

Although monoaminergic antidepressants revolutionized the treatment of Major Depressive Disorder (MDD) over a half-century ago, approximately one third of depressed patients experience treatment-resistant depression (TRD). Such patients account for a disproportionately large burden of disease, as evidenced by increased disability, cost, human suffering, and suicide. This review addresses the definition, causes, evaluation, and treatment of unipolar TRD, as well as the major treatment strategies, ...[more]

PMID: 26246787

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Project description:BackgroundPeripartum depression is a leading cause of disease burden for women and yet there is little evidence as to how often peripartum depression does not respond to treatment and becomes treatment resistant depression. We sought to determine the incidence of treatment resistant depression (TRD) in women with peripartum depression.MethodsPopulation based retrospective cohort study using a large US claims database. Peripartum depression was defined as having a depression diagnosis during pregnancy or up to 6 months after the end of pregnancy. We included women with prevalent or incident depression. The outcome was the development of TRD within 1 year after the diagnosis of peripartum depression. TRD was defined as having 3 distinct antidepressants or 1 antidepressant and 1 antipsychotic in 1 year. Women with peripartum depression may not be exposed to pharmacological treatments early in pregnancy, therefore we created two groups: 1. women with peripartum depression, and 2. women with peripartum depression diagnosed 3 months before a live birth delivery or within 6 months after that delivery.ResultsThere were 3,207,684 pregnant women, of whom 2.5% had peripartum depression. Of these women half had incident depression during pregnancy. Five percent of women with peripartum depression developed TRD within 1 year of the depression diagnosis. The risk of developing TRD was 50% higher in women with prevalent depression than in women with incident peripartum depression (P < 0.0001). Results were similar in women with peripartum depression diagnosed later in their pregnancy. Women who went on to develop TRD had more substance use disorders, anxiety, insomnia and painful conditions.ConclusionsTRD occurs in approximately 5% of women with peripartum depression. The risk of TRD is higher in pregnant women with a history of depression. Women who went on to develop TRD had more psychiatric comorbidities and painful conditions than women who did not.

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Pharmacological approaches to the challenge of treatment-resistant depression.

Publications

Pharmacological approaches to the challenge of treatment-resistant depression.

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