We searched PubMed from June, 2005, to June, 2010, for the terms “depression”, “antidepressants”, and “depression treatment”. Although the search was updated in December 2010, publications were mainly selected from the past 5 years. Other bibliographies of selected articles were reviewed to obtain additional relevant references, especially for neurobiology, genetics, and neuroimaging in depression. We excluded non-English publications.
SeminarMajor depressive disorder: new clinical, neurobiological, and treatment perspectives
Section snippets
Epidemiology, comorbidity, and diagnosis
Worldwide, depression is a seriously disabling public health problem of very high prevalence.1 Major depressive disorder has a 12-month prevalence of 6·6% and a lifetime prevalence of 16·2%, is twice as common in women as in men, and causes considerable impairment. Age-of-onset distributions suggest that depression is prevalent for the entire lifespan.2 The disorder not only produces decrements in health that are equivalent to those of other chronic diseases (eg, angina, arthritis, asthma, and
Genetic studies
Genetic, molecular, and neuroimaging studies continue to contribute to advances in our understanding of the neurobiological basis of major depressive disorder. However, the extent to which findings from neurobiological studies can help improve the clinical and functional outcome of individuals with the disorder is still uncertain. Thus, in the past 5 years, neurobiological research of depression has become two-tiered to: (1) understand the pathophysiology of the illness; and (2) identify the
Depression-specific psychotherapies
Pharmacotherapy and manual-driven depression-specific psychotherapy are both effective treatments for unipolar depression, either as monotherapies, or in combination.97, 98 Although similar results are reported for depression-specific psychotherapy in primary-care samples, fewer published works are available in this area than in psychiatric samples.99, 100 These studies suggest that interpersonal psychotherapy alone, or in combination with pharmacotherapy, is effective for the acute treatment
Treatment of psychotic depression
Patients with psychotic depression (presence of delusions or hallucinations) are often difficult to treat and need several interventions. Although new pharmacological strategies are being tested, electroconvulsive therapy is important as a frequently used and effective treatment. Antipsychotics and antidepressants are being used more often to treat psychotic depression. In two studies,123, 124 the combination of an antidepressant with an antipsychotic showed greater efficacy than did the
Drug development
In the past 5 years, several strategies have been developed to improve depression outcomes, including the use of new compounds and several older drugs. An example is a report showing the benefit of ademetionine (S-adenosyl methionine [SAMe]) augmentation in major depressive disorder.125, 126 One strategy focuses on the use of N-methyl-D-aspartate glutamate-receptor antagonists providing the promise of rapid antidepressant action,127 including clinically significant effects from one dose that
Suicide risk with SSRIs
The safety of SSRIs has been debated because of their potential association with suicidal ideation and behaviour as noted from studies of adolescents with depression.134 Some work suggests that adults treated with antidepressant drugs, including SSRIs, are no more likely to attempt or complete suicide than those not treated with an antidepressant.134, 135 However, other research suggests a reduced risk of suicide attempt in adults after start of SSRI treatment, particularly with sertraline,135
Conclusions
Increased data for imaging and genetics in major depressive disorder, and other neurobiological data, provide potential biomarkers for the assessment of treatment outcomes. If a description of precise subgroups based on such data were to emerge, short-term and long-term benefits of treatment might be improved. Although new reports about treatment response in multisite studies have emerged in the past 5 years, treatment advances are somewhat lagging because of an inability to undertake adequate
Search strategy and selection criteria
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