Two Adequate Trials and Still a PHQ-9 of 19: Choosing Between Switching and Augmenting for a 52-Year-Old With Treatment-Resistant Depression, Guided by VAST-D and STAR*D
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University of Phoenix
PMH/504: Psychiatric Management Of Adult And Geriatric Patients
Week 2 Assignment
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[Date]
The patient is a composite written for a model paper.
Ms. T., a 52-year-old accountant, has had major depression for 14 months. She took sertraline, titrated to 200 mg for 10 weeks, with partial response, then venlafaxine extended-release to 225 mg for 10 weeks, again with partial response. Her PHQ-9 is 19. She takes her medications daily, confirmed by pharmacy fills. She asks, "Is there anything else?" This paper describes the next step.
Confirming Treatment Resistance
Before labeling depression treatment-resistant, pseudoresistance must be excluded. Both trials used adequate doses for adequate durations. Adherence is confirmed. I reassess the diagnosis: she has no history of hypomania on structured questioning, no psychotic features and no substance use disorder. Thyroid function, B12 and a sleep evaluation are normal. Her depression meets a common definition of treatment resistance: inadequate response to two adequate antidepressant trials.
What STAR*D Showed
The STAR*D study found that remission rates decline with each successive treatment step, from about 37% at step one to about 31% at step two and about 13% at steps three and four, with higher relapse rates among those needing more steps (Rush et al., 2006). At the second step, Trivedi et al. (2006) compared augmentation of citalopram with bupropion or buspirone and found similar remission rates, about 30%, with bupropion producing greater symptom reduction and fewer dropouts due to side effects.
What VAST-D Showed
Mohamed et al. (2017) randomly assigned 1,522 veterans with depression unresponsive to at least one antidepressant to switch to bupropion, augment with bupropion or augment with aripiprazole. Remission at 12 weeks was 22.3% with switching, 26.9% with bupropion augmentation and 28.9% with aripiprazole augmentation; aripiprazole augmentation exceeded switching in remission, while other comparisons did not differ significantly. Aripiprazole caused more akathisia and weight gain, while bupropion caused more anxiety.
The best option in the trial helped fewer than a third of people reach remission; the decision is about modest gains and specific side effects.
Choosing for Ms. T.
Ms. T. has had partial responses, which favors augmentation over switching, since augmentation preserves gains. She is anxious, which makes bupropion less attractive. Her BMI is 24, and she is willing to monitor weight. After discussion, she chooses aripiprazole augmentation added to venlafaxine, starting at 2 mg daily and increasing to 5 mg after two weeks if tolerated.
Why Not Switch Again
Switching to a third antidepressant would discard the partial benefit she has gained. STAR*D showed that each additional step yields lower remission (Rush et al., 2006), so preserving gains through augmentation is reasonable when response is partial. Switching makes more sense when the current drug produces no benefit or intolerable side effects.
Why Not Bupropion Augmentation
Bupropion augmentation performed similarly to aripiprazole in VAST-D and to buspirone in STAR*D, and it avoids weight gain and akathisia (Mohamed et al., 2017; Trivedi et al., 2006). For Ms. T., whose anxiety is prominent, bupropion's tendency to cause anxiety tipped the choice, but it remains a good alternative if aripiprazole is not tolerated.
Explaining Modest Benefits
Ms. T. hoped for a cure. I explain honestly that each step helps some people, not all, and that combining medication with therapy and other approaches raises the chances. Realistic hope supports adherence better than promises.
Measuring Response
Response is defined as a 50% reduction in PHQ-9 score, and remission as a score under 5. Tracking every two weeks will show within six to eight weeks whether augmentation is working.
Checking for Missed Causes Again
Before augmenting, I ask once more about alcohol, sleep apnea, chronic pain and life stressors that can maintain depression. She reveals caring for her mother with dementia on weekends, a heavy burden. A referral to caregiver support is added, since stress may be perpetuating her illness.
Other Evidence-Based Options
For treatment-resistant depression, lithium augmentation has long evidence, esketamine nasal spray is approved for adults with treatment-resistant depression and electroconvulsive therapy has the highest remission rates for severe cases. Transcranial magnetic stimulation offers a nonmedication option. I describe these so Ms. T. knows that if this step fails, others remain.
Monitoring
Akathisia, an inner restlessness, is the most common reason people stop aripiprazole; I explain it, ask about it at each visit and will lower the dose or stop if it occurs. Baseline and follow-up weight, waist, fasting glucose and lipids track metabolic effects. PHQ-9 is measured every two weeks.
If This Does Not Work
If aripiprazole augmentation does not produce meaningful improvement in six to eight weeks, options include lithium augmentation, esketamine, electroconvulsive therapy for severe cases and transcranial magnetic stimulation. Psychotherapy should be added or intensified at any step.
Psychotherapy
Ms. T. has not had structured psychotherapy. I refer her for cognitive behavioral therapy, which can improve outcomes when combined with medication in treatment-resistant depression.
Measuring Side Effects
At each visit, I ask specifically about restlessness, weight, sleep and sexual side effects, using a short checklist, because patients often do not volunteer side effects unless asked.
Documentation
The note records the doses and durations of both prior trials, adherence confirmation, the diagnostic reassessment and the rationale for aripiprazole augmentation, which future prescribers will need if further steps are required.
Follow-Up
Visits every two weeks for the first two months, then monthly once response is clear.
Why Veterans' Data Apply
VAST-D enrolled mostly male veterans, and Ms. T. is a woman in civilian life. The trial's general finding, modest benefit from augmentation over switching, is consistent with STAR*D, which enrolled a broader population, supporting its application to her (Trivedi et al., 2006).
Her Goals
Ms. T. wants to return to full days at work without exhaustion. We track her energy and work hours alongside the PHQ-9, since meaningful recovery includes function, not only symptom scores.
If Akathisia Appears
If restlessness develops, options include reducing the dose, adding propranolol at a low dose or stopping aripiprazole and trying bupropion augmentation instead. Explaining these options in advance makes her more likely to report the symptom rather than stop on her own.
Coordination With Her Therapist
With her consent, I share the medication plan with her therapist so that therapy sessions can reinforce behavioral goals and notice side effects or worsening mood between medication visits.
Safety
She denies suicidal thoughts, but treatment-resistant depression carries elevated risk, so I review warning signs and a crisis plan at each visit.
Documentation of the Choice
Her reasons, avoiding anxiety and preserving partial gains, are written in the note beside the evidence and the alternatives she declined, with the date of review.
Conclusion
After confirming true treatment resistance, I compared switching with augmentation using VAST-D and STAR*D. Aripiprazole augmentation offered a modest remission advantage over switching, with akathisia and weight gain as its main risks, and it preserves Ms. T.'s partial response. Close monitoring and psychotherapy accompany the change, with a clear plan if it fails.
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., Rao, S. D., Pilkinton, P. D., Wilcox, J. A., . . . Little, J. T. (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
Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Nierenberg, A. A., Stewart, J. W., Warden, D., Niederehe, G., Thase, M. E., Lavori, P. W., Lebowitz, B. D., McGrath, P. J., Rosenbaum, J. F., Sackeim, H. A., Kupfer, D. J., Luther, J., & Fava, M. (2006). Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report. American Journal of Psychiatry, 163(11), 1905-1917. https://doi.org/10.1176/ajp.2006.163.11.1905
Trivedi, M. H., Fava, M., Wisniewski, S. R., Thase, M. E., Quitkin, F., Warden, D., Ritz, L., Nierenberg, A. A., Lebowitz, B. D., Biggs, M. M., Luther, J. F., Shores-Wilson, K., & Rush, A. J. (2006). Medication augmentation after the failure of SSRIs for depression. New England Journal of Medicine, 354(12), 1243-1252. https://doi.org/10.1056/NEJMoa052964
How this PMH 504 Week 2 example is structured
The PMH/504 Week 2 work usually addresses treatment-resistant depression. This paper first confirms that the resistance is real, then compares strategies with trial data and chooses one, stating the tradeoffs openly. Students search this week as PMH 504 Week 2, PMH504 Wk 2 or PMH/504 Wk 2; all three are the same assignment.
PMH/504 Week 2 questions, answered
What does PMH/504 Week 2 usually ask for?
Many sections ask students to manage treatment-resistant depression, including confirming resistance, comparing next-step strategies and monitoring.
What is pseudoresistance?
Apparent treatment resistance due to inadequate dose or duration, poor adherence, misdiagnosis such as unrecognized bipolar disorder, or unaddressed substance use or medical illness.
Does augmentation work better than switching?
In the VAST-D trial, augmentation with aripiprazole produced a modestly higher remission rate than switching to bupropion, though absolute remission rates were low across strategies.
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