Adult patients with treatment-resistant, mild to moderate unipolar major depression

SSRI: selective serotonin reuptake inhibitor, PHQ-9: Patient Health Questionnaire – Nine Item.

* Mild to moderate unipolar major depression is indicated by a score <20 points on the PHQ-9. Response is defined as reduction of baseline symptoms ≥50%; implicit in response is that the patient tolerates the treatment option. Patients not achieving response are often referred to clinicians who specialize in treatment-resistant depression. The duration of an adequate treatment trial is generally 6 to 12 weeks. However, for patients who show little improvement (eg, reduction of baseline symptoms <25%) after four to six weeks, it is reasonable to administer next-step treatment. If patients progress to severe depression, different treatments are indicated. Refer to UpToDate topic for treatment-resistant depression.

¶ Refer to UpToDate topic on maintenance treatment of unipolar major depression.

Δ Refer to UpToDate topic on treatment-resistant depression for choosing between augmentation and switching.

◊ If a second drug is added, the dose is initially titrated up to the minimum therapeutic dose, and if response is insufficient, the dose is further titrated up within the therapeutic range.

§ From this point on, it is reasonable to add transcranial magnetic stimulation.

¥ Second-generation antipsychotics in general order of preference: aripiprazole, risperidone, quetiapine, and brexpiprazole.

‡ Certain antidepressant combinations should be avoided; as an example, a monoamine oxidase inhibitor plus an SSRI can cause the serotonin syndrome or a hypertensive crisis. Refer to Lexicomp drug interactions tool included in UpToDate.