NUR 7642 Module 4 Treatment-Resistant Depression Case: VAST-D Augmentation, Esketamine and TMS Example

Two Antidepressants Later: Confirming Treatment Resistance and Choosing the Next Step for a 47-Year-Old Chemistry Teacher

Student Name

M.S. in Nursing, Psychiatric Mental Health Nurse Practitioner, Thomas Edison State University

NUR-7642: Advanced Assessment, Differential Diagnosis, and Management of Psychiatric Disorders: Adult Population, Part B

Mentor Name

Month Day, Year

Two Antidepressants Later: Confirming Treatment Resistance and Choosing the Next Step for a 47-Year-Old Chemistry Teacher

Still Not Herself

Elena, an invented patient, is 47 and has taught chemistry at a public high school in Montclair for twenty years. Her current depression began fourteen months ago, after her mother's death and a hard divorce in the same year. She has low mood most days, no pleasure in the garden she loved, poor sleep, low energy and trouble grading papers. Some nights she has thought her teenagers might manage better without her, but no plan and no past attempts.

Her primary care clinician started sertraline, raised it to 150 mg and kept it there for ten weeks with partial benefit. She was then switched to venlafaxine, raised to 225 mg and held for twelve weeks. Her PHQ-9 went from 21 to 15. She has been in weekly therapy for six months. Her thyroid tests, vitamin B12 and blood count are normal. She drinks a glass of wine a few nights a week. Her sister has bipolar disorder.

She has kept working, which she says has saved her, but she now spends her evenings in bed and her weekends asleep. Her two teenagers have noticed and have started cooking dinner. Her principal has asked if she is all right. She is frightened that she will never feel like herself again and asks whether something is wrong with her brain that medicine cannot reach. The paper takes that fear seriously and answers it with what the evidence offers next.

Is It Truly Treatment Resistant?

Before calling depression treatment resistant, the paper checks four things. First, adequacy: both drugs reached usual therapeutic doses for at least eight weeks, and her pharmacy records show she filled them on time. Second, diagnosis: her sister's bipolar disorder raises the question of a bipolar depression, but Elena has never had a hypomanic period, confirmed by her best friend of thirty years. Third, contributors: alcohol is modest, and her thyroid is normal. Fourth, therapy: she is in an evidence-based therapy. With two adequate failed trials in this episode, she meets the common definition.

Switch or Augment?

Mohamed et al. (2017) randomly assigned 1,522 veterans with major depression that had not responded to at least one adequate antidepressant trial at 35 medical centers to switch to bupropion, add bupropion or add aripiprazole for 12 weeks. Remission occurred in 22.3 percent of the switch group, 26.9 percent of the bupropion augmentation group and 28.9 percent of the aripiprazole augmentation group. Only the aripiprazole augmentation exceeded switching for remission, and its response rate was also higher than either bupropion option. Aripiprazole brought more weight gain, restlessness and sleepiness, while bupropion brought more anxiety.

For Elena, venlafaxine has given partial benefit, so augmentation keeps that gain. Aripiprazole is added at 2 mg and raised to 5 mg after two weeks. Restlessness is explained so she can report it early, and her weight, glucose and lipids are checked at baseline and twelve weeks. Her mood is tracked with the PHQ-9 every two weeks.

Augmentation also has a cost the paper names. Aripiprazole is an antipsychotic, and although the dose used for depression is low, it can cause restlessness, weight gain and, rarely, movement problems over time. Elena is told this plainly, and a movement scale is recorded at baseline. She asks whether taking an antipsychotic means she is psychotic, and the paper records the answer: the drug is used here for its effect on mood at a dose far below the doses used for psychosis.

If Augmentation Fails

Popova et al. (2019) tested esketamine nasal spray, given twice weekly in a clinic with a newly started oral antidepressant, against the new antidepressant with a placebo spray in 227 adults with depression that had not responded to at least two antidepressants. At 28 days, depression scores had fallen four points more on the Montgomery-Asberg scale with esketamine, with improvement seen earlier as well. Dissociation, nausea, vertigo, altered taste and dizziness were more common with esketamine. Because of dissociation and sedation, each dose is given under observation for two hours, and patients cannot drive that day.

O'Reardon et al. (2007) randomly assigned 301 medication-free patients with major depression that had not responded to past treatment to active or sham transcranial magnetic stimulation over the left dorsolateral prefrontal cortex, five days a week for four to six weeks. Active stimulation was superior on several depression scales at weeks 4 and 6, remission rates were roughly twice as high at week 6, and only 4.5 percent dropped out for side effects, mostly scalp discomfort.

Elena, who teaches all day, prefers to try aripiprazole first. If she has not responded by eight weeks, TMS could be arranged with early morning sessions before school, and esketamine would need afternoons off twice a week for the first month.

Therapy and Safety

Her therapy shifts to behavioral activation, rebuilding the garden one bed at a time, and to grief work for her mother. Her passive thoughts of death are checked at each visit, and a safety plan names her sister, her pastor and the crisis line. Because her sister has bipolar disorder, Elena is told the signs of hypomania to watch for on any new treatment.

Conclusion

Elena has treatment-resistant depression, confirmed by two adequate trials, a careful look for bipolar disorder and normal laboratory tests. Aripiprazole augmentation, chosen from the VAST-D trial, keeps her partial gain from venlafaxine and offers the best remission rate among the options studied. Esketamine and TMS are ready as next steps, chosen by evidence and by what her teaching schedule allows. Behavioral activation, grief work, safety planning and PHQ-9 tracking continue throughout.

References

Mohamed, S., Johnson, G. R., Chen, P., Hicks, P. B., Davis, L. L., Yoon, J., Gleason, T. C., Vertrees, J. E., Weingart, K., Tal, I., Scrymgeour, A., Lawrence, D. D., Planeta, B., Thase, M. E., Huang, G. D., & Zisook, S. (2017). Effect of antidepressant switching vs augmentation on remission among patients with major depressive disorder unresponsive to antidepressant treatment: The VAST-D randomized clinical trial. JAMA, 318(2), 132-145. https://doi.org/10.1001/jama.2017.8036

O'Reardon, J. P., Solvason, H. B., Janicak, P. G., Sampson, S., Isenberg, K. E., Nahas, Z., McDonald, W. M., Avery, D., Fitzgerald, P. B., Loo, C., Demitrack, M. A., George, M. S., & Sackeim, H. A. (2007). Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: A multisite randomized controlled trial. Biological Psychiatry, 62(11), 1208-1216. https://doi.org/10.1016/j.biopsych.2007.01.018

Popova, V., Daly, E. J., Trivedi, M., Cooper, K., Lane, R., Lim, P., Mazzucco, C., Hough, D., Thase, M. E., Shelton, R. C., Molero, P., Vieta, E., Bajbouj, M., Manji, H., Drevets, W. C., & Singh, J. B. (2019). Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: A randomized double-blind active-controlled study. American Journal of Psychiatry, 176(6), 428-438. https://doi.org/10.1176/appi.ajp.2019.19020172