Pharmacotherapy for Treatment-Refractory Unipolar Major Depression

What is the general order of preference in choosing an antidepressant?

What is the general order of preference in selecting augmentation agents?

Which augmentation agent has the best balance of efficacy and tolerability?

What are some other augmentation agents that can be useful for treatment-refractory depression?

Why is combining tricyclics and MAOIs a treatment of last resort?

What should be done before adding an MAOI to a tricyclic monotherapy?

Is there evidence supporting the use of a tricyclic plus an MAOI?

Why are complex medication regimens with ≥4 psychotropic drugs generally avoided?

What is discussed separately in the text regarding the role of ketamine and esketamine in treating major depression?

Where can additional information about choosing adjunctive pharmacotherapy be found?

Pharmacotherapy for Treatment-Refactory Unipolar Major Depression

Patients with treatment-refractory unipolar major depression often receive an antidepressant augmented with another drug, but antidepressant monotherapy is a reasonable alternative.
The efficacy of different antidepressants is generally comparable across and within classes, and the drug choice is based on factors such as safety and adverse effects.
The general order of preference in choosing an antidepressant is SSRI, SNRI, atypical antidepressant, serotonin modulator, tricyclic antidepressant, and MAOI.
For selecting augmentation agents, the general order of preference is second-generation antipsychotic, lithium, second antidepressant from a different class, and thyroid hormone.
Second-generation antipsychotics have the best balance of efficacy and tolerability among these options, particularly in combination with first-line antidepressants such as SSRIs and SNRIs.
Other augmentation agents that can be useful for treatment-refractory depression are intravenous ketamine and intranasal esketamine.
The combination of a tricyclic antidepressant and an MAOI is a treatment of last resort due to potential life-threatening drug-drug interactions.
Combining tricyclics and MAOIs requires a thorough discussion of risks and benefits, as well as careful monitoring, and the MAOI is added after a failed trial of tricyclic monotherapy.
Low-quality evidence supporting the use of a tricyclic plus an MAOI includes a retrospective study of 62 cases.
Complex medication regimens with ≥4 psychotropic drugs are generally avoided because there is no data supporting their utility, and patients may feel worse due to the cumulative side effects.
The role of ketamine and esketamine in treating major depression, as well as their administration, efficacy, and adverse effects, are discussed separately.
Additional information about choosing adjunctive pharmacotherapy, including the efficacy and tolerability of different options, is discussed separately in the context of treatment-resistant depression.

Take this quiz to test your knowledge about pharmacotherapy for treatment-refractory unipolar major depression. Learn about the different antidepressants and augmentation agents that can be used, their order of preference, and potential drug interactions. Explore the efficacy and tolerability of various options and gain a deeper understanding of the complex medication regimens involved in treating major depression. Test your understanding of this important topic and enhance your knowledge of the latest treatment options for depression.