From the Guidelines
For continued crying and depression despite Effexor 187.5 mg and Abilify 5 mg daily, I would recommend adding bupropion XL 150 mg daily, which could be increased to 300 mg daily after 1-2 weeks if well-tolerated, as this provides a different mechanism of action through dopamine and norepinephrine effects, which can be particularly helpful for energy, motivation, and anhedonia symptoms, as supported by the most recent and highest quality study 1.
Rationale for Recommendation
The patient's current medication regimen includes Effexor, a serotonin-norepinephrine reuptake inhibitor (SNRI), and Abilify, an atypical antipsychotic with dopamine system modulation properties. Despite this combination, the patient continues to experience depressive symptoms, indicating a need for an adjustment in the treatment plan.
Consideration of Options
- Increasing the Effexor to 225 mg daily, the maximum FDA-approved dose, could potentially maximize serotonin and norepinephrine reuptake inhibition, but this may not address other symptom domains effectively.
- Increasing the Abilify to 10 mg daily could enhance dopamine system modulation, but the evidence for its efficacy in treating depression, especially as an adjunct, is less clear compared to other options.
- Adding bupropion XL, as recommended, offers a distinct mechanism of action that can complement the existing regimen by targeting dopamine and norepinephrine pathways, which are crucial for addressing symptoms of energy, motivation, and anhedonia.
Evidence Support
The recommendation to add bupropion XL is supported by the systematic review and network meta-analysis for a clinical guideline by the American College of Physicians 1, which found that various switch and augmentation strategies, including the addition of bupropion, rendered similar symptom relief in patients with major depressive disorder. This study, being the most recent and of high quality, provides the best evidence for guiding the next step in treatment.
Clinical Considerations
Any medication adjustment should be made with caution, monitoring closely for potential side effects such as increased anxiety, insomnia, or akathisia. Additionally, ensuring the patient receives appropriate psychotherapy, particularly cognitive behavioral therapy, is crucial as combination treatment typically yields better outcomes than medication alone. The patient's response to the medication change should be evaluated regularly to determine the effectiveness of the new treatment strategy.
From the FDA Drug Label
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.
The patient is experiencing continued crying and depression despite being on Effexor (venlafaxine) 187.5 mg and Abilify 5 mg daily.
- Medication adjustment is needed as the current regimen is not effective.
- Discontinuing or changing the current medication regimen should be considered.
- The decision to adjust the medication should be made with caution and under close monitoring of the patient's symptoms.
- It is also important to monitor the patient for emergent suicidality or symptoms that might be precursors to worsening depression or suicidality 2.
From the Research
Medication Adjustment Options
Given the patient's continued crying and depression despite Effexor 187.5 mg and Abilify 5 mg daily, several medication adjustment options can be considered:
- Changing the antidepressant medication: According to 3, when initial antidepressant medication is not effective, second-line medication treatment includes changing antidepressant medication, which has an approximately equal likelihood of success based on a network meta-analysis.
- Adding a second antidepressant: 3 also suggests that adding a second antidepressant is a viable option for patients who do not respond to initial treatment.
- Augmenting with a nonantidepressant medication: 3 mentions that augmenting with a nonantidepressant medication is another option for patients who do not respond to initial treatment.
- Combining a classic monoamine oxidase inhibitor with a tricyclic antidepressant: Although considered contra-indicated due to the risk of serotonin syndrome, 4 suggests that this combination may be effective for some patients with therapy-resistant depression, provided that it is monitored carefully and TCAs with marked serotonergic affinity are avoided.
Considerations for Medication Adjustment
When considering medication adjustments, the following factors should be taken into account:
- Severity of depression: 5 notes that in severe depression, only prescription antidepressants and electroconvulsive therapy are known to improve symptoms.
- Patient history: 6 highlights the importance of considering the patient's history of depressive episodes and their current treatment regimen when making decisions about medication adjustments.
- Potential risks and benefits: 4 emphasizes the need to carefully weigh the potential risks and benefits of combining different medications, particularly when it comes to the risk of serotonin syndrome.
Monitoring and Follow-up
Regardless of the medication adjustment chosen, close monitoring and follow-up are crucial to ensure the patient's safety and effectiveness of treatment:
- Regular assessments: 3 stresses the importance of regular assessments to monitor the patient's response to treatment and adjust the medication regimen as needed.
- Collaborative care: 3 also highlights the benefits of collaborative care programs, which include systematic follow-up and outcome assessment, in improving treatment effectiveness.