| Research on Treatments for Depression | |
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Medication
Studies on the mechanisms of action of antidepressant medication comprise an important area of NIMH depression research. Existing antidepressant drugs are known to influence the functioning of certain neurotransmitters in the brain, primarily serotonin and norepinephrine, known as monoamines. Older medications – tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) – affect the activity of both of these neurotransmitters simultaneously.Their disadvantage is that they can be difficult to tolerate due to side effects or, in the case of MAOIs, dietary restrictions.
Newer medications, such as the selective serotonin reuptake inhibitors (SSRIs), have fewer side effects than the older drugs, making it easier for patients to adhere to treatment. Both generations of medications are effective in relieving depression, although some people will respond to one type of drug, but not another.
Antidepressant medications take several weeks to be clinically effective even though they begin to alter brain chemistry with the very first dose. Research now indicates that antidepressant effects result from slow-onset adaptive changes within the brain cells, or neurons.
Further, it appears that activation of chemical messenger pathways within neurons, and changes in the way that genes in brain cells are expressed, are the critical events underlying long-term adaptations in neuronal function relevant to antidepressant drug action.
A current challenge is to understand the mechanisms that mediate, within cells, the long-term changes in neuronal function produced by antidepressants and other psychotropic drugs and to understand how these mechanisms are altered in the presence of illness.
Knowing how and where in the brain antidepressants work can aid the development of more targeted and potent medications that may help reduce the time between first dose and clinical response. Further, clarifying the mechanisms of action can reveal how different drugs produce side effects and can guide the design of new, more tolerable, treatments.
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.
NIMH Depression Index
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