Treatment-resistant depression
| Treatment-resistant depression | |
|---|---|
| Other names | Treatment-refractory depression |
Depressive mood, anhedonia, low energy | |
| Complications | Self-harm, suicide |
Treatment-resistant depression (TRD) is a term used in
Risk factors
Comorbid psychiatric disorders
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,[5] personality disorders, obsessive compulsive disorder, and eating disorders.[6]
Comorbid medical 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.[6]
Features of depression
People with depression who also
Treatment
There are three basic categories of drug treatment that can be used when a medication course is found to be ineffective. One option is to switch the patient to a different
Medication
Antidepressants
Dose increase
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.[9]
Switching antidepressants
Studies have shown a wide variability in the effectiveness of switching
Some off label antidepressants are low dose ketamine and highly serotonergic catecholamines (including very controlled use of MDMA in the treatment of PTSD and crippling depression/anxiety).[citation needed] For lethargic syndromes, dysthymia, or caffeine-resistant amotivation, a dopaminergic stimulant such as methylphenidate, or even dextroamphetamine or methamphetamine can be helpful.[citation needed]
Primarily dopaminergic or norepinephrine releasing stimulants, in low doses, have been used especially in the past, or in conjunction with a multidisciplinary therapy approach, although more targeted and "mild" agents, including modafinil and atomoxetine are considered first line[by whom?] for both childhood and adult lethargy and inattention disorders, due to their virtually nonexistent abuse potential (limited to one or two cases per 10 000), and higher selectivity, safety, and thus slightly broader therapeutic index. When depression is related or co-morbid to an inattention disorder, often ADHD, then both can be carefully managed with the same first line stimulant medication, typically both methylphenidate and lisdexamfetamine.[11]
Other medications
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.[12]
Since the entry of
Ketamine has been tested as a rapid-acting antidepressant[18] for treatment-resistant depression in bipolar disorder, and major depressive disorder.[19] 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.[20][21]
Research
A 2016 placebo randomized controlled trial evaluated the rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression with positive outcome.[22][23]
Physical psychiatric treatments
Electroconvulsive therapy
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.[24] It is associated with an increase in glial cell line derived neurotrophic factor.[25]
rTMS
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[26] confirming the efficacy of rTMS in treatment-resistant major depression, as well as naturalistic studies showing its effectiveness in "real world" clinical settings.[27][28]
dTMS
dTMS (
Vagus Nerve Stimulation
Vagus nerve stimulation has also been used for treatment-resistant depression.[30]
Deep Brain Stimulation
Deep brain stimulation has been used in a small number of clinical trials to treat people with severe treatment-resistant depression.[31]
Magnetic seizure therapy
Magnetic seizure therapy is currently being investigated for treating refractory depression.
Transcranial direct-current stimulation
Transcranial direct-current stimulation is a form of neuromodulation that uses constant, low direct current delivered via electrodes on the head.
Psychotherapy
There is sparse evidence on the effectiveness of psychotherapy in cases of treatment-resistant depression.[7] However, a review of the literature suggests that it may be an effective treatment option.[32] Psychotherapy may be effective in people with treatment-resistant depression because it can help relieve stress that may contribute to depressive symptoms.[33]
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.[34]
Outcomes
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.[35][clarification needed]
Another study saw just 8 of 124 patients in remission after two years of standard depression treatment.[36]
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