then both can be carefully managed with the same first line stimulant medication, typically both methylphenidate and lisdexamfetamine. Other medications Medications that have been shown to be effective in people with treatment-resistant depression include lithium, triiodothyronine, 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. Triiodothyroxine (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. Research A 2016 placebo randomized controlled trial evaluated the rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression with positive outcome. 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. It is associated with an increase in glial cell line derived neurotrophic factor. 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