Dr. Cook: There are many options available to convert a partial response to a more complete improvement. In the STAR*D study, augmentation was achieved by adding agents—including lithium and thyroid hormone and other psychotropics, such as bupropion and buspirone, and even the addition of cognitive behavioral therapy (CBT).3
Some atypical antipsychotic medications, such as aripiprazole, have received [US] FDA approval for use as an augmentation agent. Unfortunately, there is a dearth of
Narrator: In the few head-to-head studies that have compared different options, their efficacy has been generally comparable; therefore, it is reasonable to consider different sequences of the available drugs.4 For example, the remission rates were comparable in an
Dr. Cook: So, selection is probably best made on an individual patient basis, balancing the benefits and side effects of each option to the context of a particular patient's symptom profile, their comorbid conditions, and the potential for
Narrator: Drug-drug interactions between antidepressants and adjunctive medications such as second-generation antipsychotics, benzodiazepines, lithium, or triiodothyronine are generally not problematic. But combining an MAOI with another antidepressant—an SSRI, for example—can cause complications, including the serotonin syndrome or a hypertensive crisis.7
As examples of some other factors to consider, patients with a history of extrapyramidal side effects may wish to avoid aripiprazole, and overweight patients may wish to avoid quetiapine, risperidone, and olanzapine. Lithium is contraindicated in those with renal or thyroid disease, and the same generally goes for thyroid hormone in patients with compromised cardiovascular function. As another consideration—
Patients who are treated with an add-on drug and do not respond within six to twelve weeks of reaching the target dose—or do not tolerate the combination—should advance to treatment with a second medication combination.