Elsevier

The Lancet

Volume 379, Issue 9820, 17–23 March 2012, Pages 1045-1055
The Lancet

Seminar
Major depressive disorder: new clinical, neurobiological, and treatment perspectives

https://doi.org/10.1016/S0140-6736(11)60602-8Get rights and content

Summary

In this Seminar we discuss developments from the past 5 years in the diagnosis, neurobiology, and treatment of major depressive disorder. For diagnosis, psychiatric and medical comorbidity have been emphasised as important factors in improving the appropriate assessment and management of depression. Advances in neurobiology have also increased, and we aim to indicate genetic, molecular, and neuroimaging studies that are relevant for assessment and treatment selection of this disorder. Further studies of depression-specific psychotherapies, the continued application of antidepressants, the development of new treatment compounds, and the status of new somatic treatments are also discussed. We address two treatment-related issues: suicide risk with selective serotonin reuptake inhibitors, and the safety of antidepressants in pregnancy. Although clear advances have been made, no fully satisfactory treatments for major depression are available.

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

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.

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