Approach to Medication Reduction in a Stable Patient on Triple Therapy
Do Not Discontinue Medications When Feeling Well
The patient should continue all three medications (buspirone, bupropion 300mg, and fluoxetine) because feeling well indicates the current regimen is working, not that medications are no longer needed. 1, 2 Depression requires several months or longer of antidepressant treatment beyond achieving initial response, and premature discontinuation significantly increases relapse risk. 2
Evidence Against Medication Reduction in Stable Patients
Maintenance treatment is essential - The FDA label for bupropion explicitly states that acute episodes of depression require several months or longer of treatment beyond the initial response, and it is unknown whether a lower maintenance dose would be as effective as the dose that provided initial response. 2
Relapse risk with discontinuation - When patients who responded to combination therapy (mirtazapine plus another antidepressant) had one agent discontinued in a double-blind fashion, approximately 40% relapsed, demonstrating that both medications were contributing to the therapeutic effect. 3
Combination therapy superiority - Studies show that combination antidepressant therapy from treatment initiation produces remission rates of 46-58% compared to only 25% with monotherapy, suggesting that multiple mechanisms are needed for optimal response. 3
Critical Monitoring Parameters
Reassess periodically - The FDA recommends periodic reassessment of the need for maintenance treatment and appropriate dosing, but this should be done by the prescribing physician, not initiated by the patient. 2
Watch for early warning signs - If reduction is attempted against medical advice, monitor closely for agitation, irritability, unusual behavioral changes, worsening mood, or emergence of suicidal thoughts, especially in the first 1-2 months after any medication change. 4
Adequate trial before judging failure - Any medication change requires 6-8 weeks at an adequate dose before determining treatment response. 1
If Discontinuation is Absolutely Necessary
If the patient insists on reducing medications despite counseling, taper bupropion first because it can be discontinued more safely than the other agents, though this is not the recommended approach. 2
Taper bupropion from 300mg to 150mg daily for at least 1-2 weeks before complete discontinuation to minimize withdrawal symptoms and allow monitoring for depression recurrence. 2
Never abruptly discontinue fluoxetine - The FDA black box warning emphasizes that abrupt discontinuation can be associated with severe symptoms, and medication should be tapered as rapidly as feasible while recognizing discontinuation risks. 4
Buspirone can be continued as it has anxiolytic properties and may help manage any anxiety that emerges during antidepressant adjustment. 5
Common Pitfall to Avoid
The most dangerous mistake is assuming that feeling well means medications are no longer needed. This is analogous to stopping blood pressure medication because blood pressure is controlled - the medication is working, which is why the patient feels well. Discontinuing effective treatment will likely result in symptom recurrence within weeks to months. 2, 4