Some individuals with depression may try multiple adequate treatments (sufficient dosage for sufficient duration) without significant improvement. These individuals are considered to have treatment-resistant depression (also called treatment-refractory depression). It is particularly important for these patients to work closely with their psychiatrist to find the appropriate medication regimen. Often medication may be supplemented with psychotherapy. For some patients, supplementation of an antidepressant with triiodothyronine (T3), a thyroid hormone, leads to mood improvement. Patients with treatment resistant depression tend to show more severe circadian dysregulation than patients in whom depression is more easily treated. For this reason circadian interventions, such as light therapy, may play a role in treatment. In some instances therapies such as transcranial magnetic stimulation (TMS) or electroconvulsive therapy (ECT) may be considered.
From 2001 to 2006 the NIMH funded the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study. The goal of the study was to determine the effectiveness of different treatments for people with major depression who did not respond to initial treatment with an antidepressant. Over 4,000 participants enrolled over a period of six years, which makes this the largest and longest study ever conducted to evaluate depression treatment. More information about the study and its outcomes can be found on the NIMH site's STAR*D Study page.
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