A 52-year-old man undergoes follow-up for persistent major depressive disorder. He is currently being treated with venlafaxine (Effexor); he previously took fluoxetine (Prozac) titrated to the maximum dosage before it was tapered off owing to minimal response and sexual side effects. He also takes aripiprazole (Abilify) and receives psychotherapy. He reports no improvement in his symptoms, which do not include mania or hypomania. He has not had suicidal ideation. He has no other medical conditions and takes no other medications.
On exam, vital signs are normal. He appears sad with a blunted affect. PHQ-9 (Patient Health Questionnaire-9) for depression screening & severity monitoring is 17 which is consistent with moderately severe depression, which is slightly worse from his previous score.
Which of the following is the most appropriate treatment?
- A) Add intranasal esketamine (Spravato)
- B) Add valproic acid
- C) Add lithium
- D) Discontinue aripiprazole and initiate risperidone
- E) Discontinue venlafaxine and initiate paroxetine (Paxil)
A) Add intranasal esketamine (Spravato)
Patients who have severe major depression that is unresponsive to combination oral therapy with a second-generation antidepressant and an atypical antipsychotic agent as well as psychotherapy, are candidates for intranasal esketamine.
Esketamine must be administered intranasally in a physician's office under direct supervision, and physicians must be enrolled in an FDA-mandated Risk Evaluation and Mitigation Strategies (REMS) program.
Lithium and valproic acid are indicated for the treatment of bipolar 1 disorder and not an approved therapy for major depressive disorder.
Risperidone, is an antipsychotic agent, but is not indicated for the treatment of major depressive disorder. However, the addition of other atypical antipsychotic medications to SGAs is an appropriate strategy for treatment failure. Approved regimens include olanzapine plus fluoxetine, and aripiprazole or quetiapine plus any SGA
This patient's symptoms have already failed to respond to treatment with one SSRI at maximum doses. In addition, the sexual side effects he experienced can occur with all SSRIs and are likely to recur with paroxetine.
Key Learning Point
Intranasal esketamine can be added for treatment-resistant major depressive disorder. Unlike most other antidepressant therapies, esketamine has an almost immediate effect on depression symptoms. In August 2020, it was approved by the FDA with the added indication for the short-term treatment of suicidal thoughts.
Dr. Raj Dasgupta
Dr. Raj Dasgupta