Емдеуге төзімді депрессия: себептері мен емдеу жолдары

Treatment resistant depression (TRD) is a term used in psychiatry to describe people with major depressive disorder (MDD) who do not respond adequately to a course of appropriate antidepressant medication within a certain time. Definitions of treatment resistant depression vary, and they do not include a resistance to psychotherapy. Inadequate response has most commonly been defined as less than 50% reduction in depressive symptoms following treatment with at least one antidepressant medication, although definitions vary widely. Some other factors that may contribute to inadequate treatment are: a history of repeated or severe adverse childhood experiences, early discontinuation of treatment, insufficient dosage of medication, patient noncompliance, misdiagnosis, cognitive impairment, low income and other socio economic variables, and concurrent medical conditions, including comorbid psychiatric disorders. In treatment resistant depression adding further treatments such as psychotherapy, lithium, or aripiprazole is weakly supported as of 2019.

Comorbid psychiatric disorders commonly go undetected in the treatment of depression. If left untreated, the symptoms of these disorders can interfere with both evaluation and treatment. Anxiety disorders are one of the most common disorder types associated with treatment resistant depression. The two disorders commonly co exist, and have some similar symptoms. Some studies have shown that patients with both MDD and panic disorder are the most likely to be nonresponsive to treatment. Substance abuse may also be a predictor of treatment resistant depression. It may cause depressed patients to be noncompliant in their treatment, and the effects of certain substances can worsen the effects of depression. Other psychiatric disorders that may predict treatment resistant depression include attention deficit hyperactivity disorder, personality disorders, obsessive compulsive disorder, and eating disorders.

Some people who are diagnosed with treatment resistant depression may have an underlying undiagnosed health condition that is causing or contributing to their depression. Endocrine disorders like hypothyroidism, Cushing's disease, and Addison's disease are among the most commonly identified as contributing to depression. Others include diabetes, coronary artery disease, cancer, HIV, and Parkinson's disease. Another factor is that medications used to treat comorbid medical disorders may lessen the effectiveness of antidepressants or cause depression symptoms.

Increasing the dosage of an antidepressant is a common strategy to treat depression that does not respond after adequate treatment duration. Practitioners who use this strategy will usually increase the dose until the person reports intolerable side effects, symptoms are eliminated, or the dose is increased to the limit of what is considered safe.

Studies have shown a wide variability in the effectiveness of switching antidepressants, with anywhere from 25 to 70% of people responding to a different antidepressant. There is support for the effectiveness of switching people to a different SSRI; 50% of people that were non responsive after taking one SSRI were responsive after taking a second type. Switching people with treatment resistant depression to a different class of antidepressants may also be effective. People who are non responsive after taking an SSRI may respond to moclobemide or tricyclic antidepressants, bupropion or an MAOI.

Medications that have been shown to be effective in people with treatment resistant depression include lithium, liothyronine, benzodiazepines, atypical antipsychotics, and stimulants. Adding lithium may be effective for people taking some types of antidepressants; it does not appear to be effective in patients taking SSRIs. Liothyronine (synthetic T3) is a type of thyroid hormone and has been associated with improvement in mood and depression symptoms. Benzodiazepines may improve treatment resistant depression by decreasing the adverse side effects caused by some antidepressants and therefore increasing patient compliance. Since the entry of olanzapine into psychopharmacology, many psychiatrists have been adding low dose olanzapine to antidepressants and other atypical antipsychotics such as aripiprazole and quetiapine. Eli Lilly, the company that sells both olanzapine and fluoxetine individually, has also released a combination formulation which contains olanzapine and fluoxetine in a single capsule. Some low to moderate quality evidence points to success in the short term (8–12 weeks) using mianserin (or antipsychotics cariprazine, olanzapine, quetiapine or ziprasidone) to augment antidepressant medications. These have shown promise in treating refractory depression but come with serious side effects. Stimulants such as amphetamines and methylphenidate have also been tested with positive results but have potential for abuse. However, stimulants have been shown to be effective for the unyielding depressed combined lacking addictive personality traits or heart problems. Ketamine has been tested as a rapid acting antidepressant for treatment resistant depression in bipolar disorder, and major depressive disorder. Spravato, a nasal spray form of esketamine, was approved by the FDA in 2019 for use in treatment resistant depression when combined with an oral antidepressant.

A 2016 placebo randomized controlled trial evaluated the rapid antidepressant effects of the psychedelic ayahuasca in treatment resistant depression with positive outcome.

Electroconvulsive therapy is generally only considered as a treatment option in severe cases of treatment resistant depression. It is used when medication has repeatedly failed to improve symptoms, and usually when the patient's symptoms are so severe that they have been hospitalized. Electroconvulsive therapy has been found to reduce thoughts of suicide and relieve depressive symptoms. It is associated with an increase in glial cell line derived neurotrophic factor.

rTMS (repetitive transcranial magnetic stimulation) is gradually becoming recognised as a valuable therapeutic option in treatment resistant depression. A number of randomised placebo controlled trials have compared real versus sham rTMS. These trials have consistently demonstrated the efficacy of this treatment against major depression. There have also been a number of meta analyses of RCTs confirming the efficacy of rTMS in treatment resistant major depression, as well as naturalistic studies showing its effectiveness in "real world" clinical settings.

dTMS (deep transcranial magnetic stimulation) is a continuation of the same idea as rTMS, but with the hope that deeper stimulation of subcortical areas of the brain leads to increased effect.

Vagus nerve stimulation has also been used for treatment resistant depression.

Deep brain stimulation has been used in a small number of clinical trials to treat people with severe treatment resistant depression.

Magnetic seizure therapy is currently being investigated for treating refractory depression.

Transcranial direct current stimulation is a form of neuromodulation that uses constant, low direct current delivered via electrodes on the head.

There is sparse evidence on the effectiveness of psychotherapy in cases of treatment resistant depression. However, a review of the literature suggests that it may be an effective treatment option. Psychotherapy may be effective in people with treatment resistant depression because it can help relieve stress that may contribute to depressive symptoms. A Cochrane systematic review has shown that psychological therapies (including cognitive behavioural therapy, dialectal behavioural therapy, interpersonal therapy and intensive short term dynamic psychotherapy) added to usual care (with antidepressants) can be beneficial for depressive symptoms and for response and remission rates over the short term (up to six months) for patients with treatment resistant depression. Medium‐ (7–12 months) and long‐term (longer than 12 months) effects seem similarly beneficial. Psychological therapies added to usual care (antidepressants) seem as acceptable as usual care alone.

Treatment resistant depression is associated with more instances of relapse than depression that is responsive to treatment. One study showed that as many as 80% of people with treatment resistant depression who needed more than one course of treatment relapsed within a year. Treatment resistant depression has also been associated with lower long term quality of life. Another study saw just 8 of 124 patients in remission after two years of standard depression treatment.