Depression, Treatment Resistant
- Major depressive disorder (MDD) that has failed to respond to ≥2 adequate trials of antidepressant therapy in ≥2 different classes is considered to be “treatment resistant.”
- Individual antidepressants must be given for 6 weeks at standard doses before being considered a failure.
- Depression affects >16 million people in the United States and >350 million people worldwide.
- The average adult has a 16% lifetime risk of MDD, with majority experiencing onset before the age of 30 years.
- Approximately 1/3 of patients with MDD will develop treatment-resistant depression.
Etiology and Pathophysiology
- Unclear; low levels of neurotransmitters (serotonin, norepinephrine, dopamine, and γ-aminobutyric acid [GABA]) have been indicated.
- Serotonin has been linked to irritability, hostility, and suicidal ideation.
- Norepinephrine has been linked to low energy.
- Dopamine may play a role in low motivation and depression with psychotic features.
- GABA can help with feelings of anxiety, stress, and fear.
- Environmental stressors, such as abuse and neglect, may affect both the function and levels of neurotransmitters.
- Inflammation and oxidative stress in the brain can contribute to treatment-resistant depression.
A genetic abnormality in the serotonin transporter gene (5-HTTLPR) may increase risk for treatment-resistant depression.
- Severity of disease
- Mislabeling bipolar patients as depressed
- Comorbid medical disease (including chronic pain)
- Comorbid personality disorder
- Comorbid anxiety disorder
- Comorbid substance use disorder
- Genetic familial predisposition to poor response to antidepressants
- Medication adherence in combination with psychotherapy
- Maintenance electroconvulsive therapy (ECT) may prevent relapse.
Commonly Associated Conditions
- Bipolar disorder
- Substance use disorders
- Anxiety disorders
- Eating disorders
- Somatic symptom disorders
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