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The Ubiquity of Depression

What are the newest directions for research into this challenging diagnosis?

The June 18, 2003, edition of the Journal of the American Medical Association is devoted to the subject of depression and provides a snapshot of the current state of research into this challenging diagnosis.

Two key papers highlight the public health significance of depressive disorders. One article reports the results from the National Comorbidity Survey Replication, the first new survey about depression in 10 years.¹ Results of face-to-face household interviews conducted by nonclinicians throughout the U.S. showed that among the 9090 participants (age, >18), the lifetime prevalence of major depression meeting DSM-IV criteria was 16.2%; the 12-month prevalence was 6.6%. Patients with severe depression in the past 12 months were more likely to be divorced, unemployed, or poor. Although 97% of patients with depression within the previous year reported role impairment, only 57% received any treatment, and fewer than a third of these were treated by mental-health specialists.

The other article with public health implications presents an economic analysis of the impact of depression on productivity.² In this study, 692 workers with depressive symptoms and 435 workers without depression, all of whom had participated in a productivity survey, underwent additional assessments for depression and somatic symptoms. Health-related loss of productive time in the depressed workers averaged 5.6 hours per week, compared with 1.5 hours per week in the nondepressed workers; the authors estimate that this decreased productivity among depressed workers represents an additional loss of US$32 million per year.

The issue also contains 2 reports of very large treatment studies. In one, investigators present data from a collaborative study of factors that enhanced recovery from coronary artery disease among 2481 patients with myocardial infarction and with depression or low perceived social support.³ The patients were randomized to 6 months of cognitive-behavioral therapy or usual care; antidepressants were also provided to CBT recipients who had severe depression (as measured on standardized rating scales) or who did not respond to CBT. Follow-up averaged 29 months. Depression treatment showed significant effects on depression and social isolation but had little effect on subsequent cardiac events.

In the other report, researchers conducted a randomized, controlled trial to investigate the efficacy of 16 weeks of group interpersonal therapy in 224 depressed participants living in 30 rural villages in Uganda.⁴ After the intervention, significantly fewer intervention recipients had depression than did controls who had received no treatment (6.5% vs. 54.7%). This study is unique, demonstrating that an evidence-based depression treatment that uses newly trained therapists and a group format can be slightly modified and then successfully disseminated to a rural population in the developing world.

PET scanning continues to provide new information about the effects of depression on the brain. In a randomized, crossover study, 18 patients with remitted depression, all of whom were taking norepinephrine reuptake inhibitors, underwent PET scans after receiving placebo or -methylparatyrosine, which depletes brain norepinephrine and dopamine.⁵ The researchers found that after -methylparatyrosine treatment, depressive symptoms returned in 11 of the 18 patients. Recipients of -methylparatyrosine who developed depressive symptoms also showed decreased metabolism in the same brain areas (orbitofrontal and dorsolateral prefrontal cortex) thought to be crucially involved in the medical treatment of depressive illness.

Developments in depression-study design also are examined in this issue. Keller⁶ discusses varying definitions of treatment outcome in depression. He emphasizes the importance of focusing on full remission of symptoms as the most relevant outcome and argues that measuring remission by symptomatic and psychosocial improvement is the best we can do until researchers identify suitable physiologic measures. Insel and Charney have written a provocative article on strategies and priorities for future studies on depression.⁷ They emphasize the importance of identifying vulnerability genes for depression, elucidating the neural basis for mood dysregulation, clarifying developmental risk factors, and discovering new treatments while expanding the provision of established treatments to patients who still do not receive them.

Comment: This issue of JAMA contains other articles and commentaries pertinent to depression. The real importance of the issue, however, is as a sign of the increasing recognition of the importance of depression in medical practice in general and in the treatment of medical conditions. The improved appreciation of the neurobiologic risk factors and substrates for depression will further solidify depression's place as a bona fide medical disorder that has potent public health consequences and is as deserving of medical attention as are other medical disorders.

— Gary Tucker, MD

Published in Journal Watch Psychiatry August 21, 2003

Citation(s):

1.Kessler RC et al. The epidemiology of major depressive disorder: Results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003 Jun 18; 289:3095-105.

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2.Stewart WF et al. Cost of lost productive work time among US workers with depression. JAMA 2003 Jun 18; 289:3135-44.

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3.Writing Committee for the ENRICHD Investigators. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: The Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial. JAMA 2003 Jun 18; 289:3106-16.

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4.Bolton P et al. Group interpersonal psychotherapy for depression in rural Uganda: A randomized controlled trial. JAMA 2003 Jun 18; 289:3117-24.

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5.Bremner JD et al. Regional brain metabolic correlates of -methylparatyrosine-induced depressive symptoms: Implications for the neural circuitry of depression. JAMA 2003 Jun 18; 289:3125-34.

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6.Keller MB. Past, present, and future directions for defining optimal treatment outcome in depression: Remission and beyond. JAMA 2003 Jun 18; 289:3152-60.

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7.Insel TR and Charney DS. Research on major depression: Strategies and priorities. JAMA 2003 Jun 18; 289:3167-8.

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