Depression Research at NIMH - Diagnosis and Treatment of Depression

Written by NIMH

As one route toward learning about the distinct biological processes that go awry in different forms of depression, NIMH researchers are investigating the differential effectiveness of various antidepressant medications in people with particular subtypes of depression. For example, this research has revealed that people with atypical depression, a subtype characterized by reactivity of mood (mood brightens in response to positive events) and at least two other symptoms (weight gain or increased appetite, oversleeping, intense fatigue, or rejection sensitivity), respond better to treatment with MAOIs, and perhaps with SSRIs than with TCAs.

Many patients and clinicians find that combinations of different drugs work most effectively for treating depression, either by enhancing the therapeutic action or reducing side effects. Although combination strategies are used often in clinical practice, there is little research evidence available to guide psychiatrists in prescribing appropriate combination treatment. NIMH is in the process of revitalizing and expanding its program of clinical research, and combination therapy will be but one of numerous treatment interventions to be explored and developed.

Untreated depression often has an accelerating course, in which episodes become more frequent and severe over time. Researchers are now considering whether early intervention with medications and maintenance treatment during well periods will prevent recurrence of episodes. To date, there is no evidence of any adverse effects of long-term antidepressant use.

Psychotherapy

Like the process of learning, which involves the formation of new connections between nerve cells in the brain, psychotherapy works by changing the way the brain functions. NIMH research has shown that certain types of psychotherapy, particularly cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT), can help relieve depression. CBT helps patients change the negative styles of thinking and behaving often associated with depression. IPT focuses on working through disturbed personal relationships that may contribute to depression.

Research on children and adolescents with depression supports CBT as a useful initial treatment, but antidepressant medication is indicated for those with severe, recurrent, or psychotic depression. Studies of adults have shown that while psychotherapy alone is rarely sufficient to treat moderate to severe depression, it may provide additional relief in combination with antidepressant medication. In one recent NIMH-funded study, older adults with recurrent major depression who received IPT in combination with an antidepressant medication during a three-year period were much less likely to experience a recurrence of illness than those who received medication only or therapy only. For mild depression, however, a recent analysis of multiple studies indicated that combination treatment is not significantly more effective than CBT or IPT alone.

Preliminary evidence from an ongoing NIMH-supported study indicates that IPT may hold promise in the treatment of dysthymia.

Electroconvulsive Therapy (ECT)

Electroconvulsive therapy (ECT) remains one of the most effective yet most stigmatized treatments for depression. Eighty to ninety percent of people with severe depression improve dramatically with ECT. ECT involves producing a seizure in the brain of a patient under general anesthesia by applying electrical stimulation to the brain through electrodes placed on the scalp. Repeated treatments are necessary to achieve the most complete antidepressant response. Memory loss and other cognitive problems are common, yet typically short-lived side effects of ECT. Although some people report lasting difficulties, modern advances in ECT technique have greatly reduced the side effects of this treatment compared to earlier decades. NIMH research on ECT has found that the dose of electricity applied and the placement of electrodes (unilateral or bilateral) can influence the degree of depression relief and the severity of side effects.

A current research question is how best to maintain the benefits of ECT over time. Although ECT can be very effective for relieving acute depression, there is a high rate of relapse when the treatments are discontinued. NIMH is currently sponsoring two multicenter studies on ECT follow-up treatment strategies. One study is comparing different medication treatments, and the other study is comparing maintenance medication to maintenance ECT. Results from these studies will help guide and improve follow-up treatment plans for patients who respond well to ECT.

Genetics Research

Research on the genetics of depression and other mental illnesses is a priority of NIMH and constitutes a critical component of the Institute's multi-level research effort. Researchers are increasingly certain that genes play an important role in vulnerability to depression and other severe mental disorders.

In recent years, the search for a single, defective gene responsible for each mental illness has given way to the understanding that multiple gene variants, acting together with yet unknown environmental risk factors or developmental events, account for the expression of psychiatric disorders. Identification of these genes, each of which contributes only a small effect, has proven extremely difficult.

However, new technologies, which continue to be developed and refined, are beginning to allow researchers to associate genetic variations with disease. In the next decade, two large-scale projects that involve identifying and sequencing all human genes and gene variants will be completed and are expected to yield valuable insights into the causes of mental disorders and the development of better treatments. In addition, NIMH is currently soliciting researchers to contribute to the development of a large-scale database of genetic information that will facilitate efforts to identify susceptibility genes for depression and other mental disorders.