Treatment Adjustment for Worsening Depression, Anxiety, and Sleep Disturbances
Increase Wellbutrin XL from 150mg to 300mg daily as the first-line intervention for Amanda's worsening depressive symptoms. 1
Rationale for Wellbutrin Dose Optimization
The FDA-approved dosing for bupropion XL indicates that after 4 days at 150mg, the dose may be increased to the target dose of 300mg once daily in the morning for major depressive disorder 1. Amanda is currently on a subtherapeutic dose, and increasing to 300mg daily represents standard dosing rather than augmentation 1.
- Bupropion demonstrates efficacy for depression with comorbid anxiety without the sexual dysfunction and weight gain associated with SSRIs 2, 3
- The medication maintains good daytime energy (which Amanda reports as beneficial) while addressing depressive symptoms 2, 3
- Bupropion should be dosed before 3 p.m. to minimize insomnia risk 2
Addressing the Sleep Disturbance
Prioritize behavioral sleep hygiene restoration before adding pharmacotherapy for insomnia. Amanda acknowledges not following her nighttime routine, and external factors are disrupting sleep 2.
If sleep does not improve with behavioral interventions after optimizing Wellbutrin:
- Consider adding mirtazapine 7.5-15mg at bedtime, which promotes sleep, has rapid onset, and provides additional antidepressant effects 2
- Alternatively, trazodone showed improvement in sleep scores over other antidepressants in patients with depression and insomnia 2
- Avoid nefazodone due to hepatotoxicity concerns despite its efficacy for anxiety and sleep 2
Managing Anxiety Symptoms
The increased Wellbutrin dose should address anxiety symptoms associated with depression 2. Evidence shows that bupropion has similar efficacy to SSRIs for treating anxiety in the context of major depressive disorder 2.
- Second-generation antidepressants show no significant differences in efficacy for treating anxiety accompanying depression 2
- If anxiety persists after 4-6 weeks at 300mg Wellbutrin, consider adding an SSRI (sertraline or escitalopram) rather than switching, as combination therapy improves outcomes in patients with inadequate response to monotherapy 3
- Venlafaxine may be superior to some SSRIs for anxiety with depression, but represents a switch rather than augmentation 2
Monitoring the Vyvanse
Continue Vyvanse 30mg but reassess timing and weekend dosing patterns given the reported hyperfocus on weekends 1.
- Stimulants can exacerbate anxiety and insomnia, though Amanda reports Vyvanse is "very helping" for focus 1
- The "masking" sensation may improve with better depression control rather than requiring Vyvanse adjustment
- Monitor for drug interactions: bupropion inhibits CYP2D6, though lisdexamfetamine metabolism is not primarily through this pathway 1
Implementation Timeline
Week 1-4:
- Increase Wellbutrin XL to 300mg daily, taken in the morning 1
- Reinforce sleep hygiene practices (consistent bedtime routine, limiting evening stimulation)
- Continue Vyvanse 30mg daily
Week 4-6 Assessment:
- Evaluate depressive symptoms (PHQ-9), anxiety (GAD-7), and sleep quality
- If depression/anxiety persist: consider adding mirtazapine 7.5-15mg at bedtime for dual benefit on mood and sleep 2
- If only sleep remains problematic: add trazodone 25-50mg at bedtime 2
Week 8-12:
- If inadequate response to optimized Wellbutrin, consider adding low-dose SSRI (sertraline 25-50mg or escitalopram 5-10mg) 3
- Combination therapy of bupropion with SSRIs has demonstrated improved outcomes in treatment-resistant cases 3
Critical Safety Considerations
Monitor for serotonin syndrome if combining bupropion with SSRIs, though bupropion's primary mechanism is dopamine-norepinephrine reuptake inhibition 4. Bupropion inhibits CYP2D6, which can increase SSRI levels 1, 4.