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Treatment-resistant depression is a term mental health professionals use to describe cases of major depression that don’t improve even after doctors use multiple treatment methods. More than 30 percent of all people diagnosed with major depression develop this form of the disorder. Current evidence indicates that many of the people who fail to respond to multiple treatments may not actually have straightforward cases of depression. Instead, they may have another form of mental illness called bipolar disorder or a form of depression that includes symptoms of psychosis.

Treatment-Resistant Depression Basics

Standard treatment for major depression typically involves antidepressant medications and/or some form of psychotherapy. Types of antidepressants in wide use include SSRIs (selective serotonin reuptake inhibitors) and SSNRIs (selective serotonin and norepinephrine reuptake inhibitors). Doctors also sometimes use classes of medication called tricyclic antidepressants and MAOIs (monoamine oxidase inhibitors), both of which have a higher chance of producing unwanted side effects than SSRIs or SSNRIs. Forms of psychotherapy used in major depression treatment include interpersonal therapy (IPT), cognitive behavior therapy (CBT), psychodynamic therapy, and group or family therapy. Some depressed people may only receive antidepressant treatment, while others with mild or moderate symptoms may only receive psychotherapy. In many cases, the combined use of medication and psychotherapy produces the best overall results.

Only roughly 33 percent of all people with major depression gain adequate relief from their symptoms after taking just one type of antidepressant medication, Harvard Health Publications reports. In many cases, people who fail to respond well to initial treatment do much better when they switch to a second medication or receive a combination of multiple medications. However, some people don’t improve after their doctors modify their treatment.

There is no single standard definition for treatment-resistant depression, according to the results of a study review published in 2006 in the Journal of Clinical Psychiatry. Instead, doctors use one of several available guidelines or checklists on how to proceed after initial depression treatments fail. In addition to switching to other medication options, common steps that occur before a treatment-resistant case is declared include adjusting the dose of a medication currently in use, determining whether herbal or over-the-counter substances are interfering with the effectiveness of an antidepressant medication, identifying physical ailments that may contribute to depression symptoms, and determining whether a patient has a genetic trait that can reduce the effectiveness of antidepressants.

Effects of Other Mental Health Problems

Some people initially diagnosed with major depression actually have bipolar disorder, a condition that can produce periods of mild to severe depression, as well as periods of mild to severe mania. While people with bipolar disorder may receive antidepressant medications as part of their treatment, the overall course of treatment for the disorder differs significantly from the course of treatment used for major depression. Many mental health experts believe that misdiagnosis of bipolar disorder accounts for many or most cases of treatment-resistant depression. However, a review of over 4,000 cases of treatment-resistant depression, published in 2011 in the American Medical Association’s Archives of General Psychiatry, contradicts this viewpoint. The authors of the review concluded that the presence of a psychotic or psychosis-like mental state plays a primary role in treatment resistance, not bipolar disorder.

Treatment Options

Doctors have several different options for addressing the effects of treatment-resistant depression. One of these options, called electroconvulsive therapy (ECT) involves the controlled use of electricity to trigger a purposeful brain seizure and alter the way nerves inside the brain communicate with each other; ECT can help even in cases where severe depression symptoms are present. Another option for treatment, called transcranial magnetic stimulation, involves the controlled use of a magnetic field to produce roughly the same types of brain changes triggered by electroconvulsive therapy. A third option for treatment-resistant depression, called vagus nerve stimulation, involves the use of electricity to stimulate one of two paired nerves that pass from the brain through either side of the neck; it also produces brain changes like those associated with ECT.

People with treatment-resistant depression can also take additional steps to improve their treatment outcomes, the Mayo Clinic reports. Examples of these steps include getting adequate sleep, participating consistently in some form of exercise, avoiding the use of alcohol and/or recreational drugs, taking steps to manage the effects of daily or unusual stress, and following antidepressant dosing instructions as closely as possible.

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