Treatment-resistant depression 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 psychological therapies. 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 factors that 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. Cases of treatment-resistant depression may also be referred to by which medications people with treatment-resistant depression are resistant to (e.g.: SSRI-resistant). 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.

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