Copyright © 2006 Elsevier Ltd All rights reserved.
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The burden of severe depression: A review of diagnostic challenges and treatment alternatives
Received 21 September 2005;
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Abstract
Among the factors making recognition of severe depression problematic for clinicians are the heterogeneous nature of the condition, lack of standardized definitions, and concomitant comorbidities that confound differential diagnosis of symptoms. The spectrum of severity in depressive disorders is extraordinarily broad, and severity assessment is comprised of several metrics including symptom intensity, diagnostic subtypes, suicidality risk, and hospitalization status. The overall diagnosis is achieved through consideration of symptom types and severities together with the degree of functional impairment as assessed by the psychiatric interview. It is likely that no single fundamental neurobiological defect underlies severe depression. The chronicity and heterogeneity of this disorder lead to frequent clinic visits and a longer course of treatment; therefore, successful approaches may require an arsenal of treatments with numerous mechanisms of action. The categories of drugs used to treat severe depression are detailed herein, as are several non-pharmacologic options including a number of experimental treatments. Pharmacotherapies include tricyclic antidepressants, selective serotonin reuptake inhibitors, atypical antidepressants such as serotonin-norepinephrine reuptake inhibitors and monoamine oxidase inhibitors, and combination and augmentation therapies. Drugs within each class are not equivalent, and efficacy may vary with symptom severity. Patient adherence makes tolerability another critical consideration in antidepressant choice. The role of non-pharmacological treatments such as electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation, and deep brain stimulation remain active avenues of investigation. Improved knowledge and treatment approaches for severe depression are necessary to facilitate remission, the ideal treatment goal.
Keywords: Tricyclic antidepressant; Selective serotonin reuptake inhibitor; Serotonin norepinephrine reuptake inhibitor; Electroconvulsive therapy; Vagus nerve stimulation; Transcranial magnetic stimulation; Severe depression
Article Outline
- 1. Introduction
- Financial Disclosure
- 2. Severe depression diagnosis and definitions
- 3. Treatment of severe depression
- 3.1. Selective serotonin reuptake inhibitors
- 3.2. Comparisons of SSRIs with TCAs
- 3.3. Comparisons between SSRIs
- 3.4. Summary
- 4. Newer generation antidepressants
- 4.1. Serotonin-norepinephrine reuptake inhibitors and norepinephrine-serotonin reuptake inhibitors (NSRIs)
- 4.1.1. Venlafaxine
- 4.1.2. Milnacipran
- 4.1.3. Duloxetine
- 4.2. Summary
- 4.3. Other novel pharmacotherapies
- 4.3.1. Mirtazapine
- 4.3.2. Bupropion
- 4.3.3. Nefazodone
- 4.3.4. Trazodone
- 4.3.5. Moclobemide
- 4.4. Summary
- 5. Non-pharmacologic treatments
- 5.1. Electroconvulsive therapy
- 5.2. Transcranial magnetic stimulation
- 5.3. Vagus nerve stimulation
- 5.4. Deep brain stimulation
- 5.5. Summary
- 6. Combination and augmentation therapy
- 6.1. Antidepressants
- 6.2. Lithium
- 6.3. Triiodothyronine
- 6.4. Buspirone
- 6.5. Atypical antipsychotics
- 6.6. Dopamine agonists
- 6.7. Summary
- 7. Discussion
- Disclosure statement
- Acknowledgements
- References






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