Adult patients with unipolar major depression of mild to moderate severity that does not respond to initial monotherapy with a selective serotonin reuptake inhibitor (SSRI)

SSRI: selective serotonin reuptake inhibitor; SNRI: serotonin-norepinephrine reuptake inhibitor.
* Mild to moderate unipolar major depression is indicated by a score of <20 points on the Patient Health Questionnaire – Nine Item (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 trial for each treatment option below is generally 6 to 12 weeks. However, for patients who show little improvement (eg, reduction of baseline symptoms <25%) after 4 to 6 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 information on how to choose between switching and augmentation.
◊ 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.
§ Minimal response is often defined as reduction of baseline symptoms <25%, and partial response as reduction of baseline symptoms 25 to 49%.
¥ At any point in this pathway, it is reasonable to switch to transcranial magnetic stimulation.
‡ Refer to UpToDate topic on treatment-resistant depression for information on choosing an antipsychotic.
† Certain antidepressant combinations should be avoided; as an example, a monoamine oxidase inhibitor plus an SSRI, a serotonin modulator, or a tricyclic can cause the serotonin syndrome or a hypertensive crisis. Refer to Lexicomp drug interaction tool included in UpToDate.
** Refer to UpToDate topic on highly resistant (refractory) depression.