How Much Do You Know About Pharmacotherapy for Treatment-Resistant Depression?

Pharmacotherapy for Treatment-Resistant Depression

• Treatment-refractory unipolar major depression can be treated with antidepressant monotherapy or in combination with another drug.
• The choice of drug begins with those that have not been previously used for the current depressive episode.
• The efficacy of different antidepressants is generally comparable, and drug selection is based on safety and adverse effects.
• Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are the first-line antidepressants.
• Second-generation antipsychotics have the best balance of efficacy and tolerability among augmentation agents, followed by lithium and a second antidepressant from a different class.
• Intravenous ketamine and intranasal esketamine can also be useful for treatment-refractory depression.
• The combination of a tricyclic antidepressant and a monoamine oxidase inhibitor (MAOI) is a treatment of last resort due to potential life-threatening drug interactions.
• The MAOI is added after a failed trial of tricyclic monotherapy, and the dose for each drug is comparable to the dose used for monotherapy.
• Clinicians generally avoid complex medication regimens due to the lack of data supporting their utility and cumulative side effects.
• Lack of response to numerous standard treatments may lead to prescribing multiple concomitant medications (≥4 psychotropic drugs).
• Second-generation antipsychotics have the best balance of efficacy and tolerability among augmentation agents, particularly in combination with first-line antidepressants such as SSRIs and SNRIs.
• The role of ketamine and esketamine in treating major depression, as well as their administration, efficacy, and adverse effects, are discussed separately.