Treatment Augmentation for Depression in a Patient on Citalopram 40mg, Bupropion SR 150mg, and Lisdexamfetamine 40mg
The most evidence-based approach is to augment citalopram with sustained-release bupropion at a higher dose (up to 400mg daily) rather than adding a new agent, as this patient is currently on a subtherapeutic bupropion dose of only 150mg. 1
Optimize Current Medications First
Before adding new agents, the existing regimen should be optimized:
Increase bupropion SR to 300-400mg daily 1. The STAR*D trial demonstrated that bupropion SR augmentation at doses up to 400mg/day produced remission rates of 39% and response rates of 31.8% when added to citalopram in patients who failed initial SSRI monotherapy 1. The current 150mg dose is below the therapeutic range used in augmentation studies.
Citalopram is already at maximum dose 2. The FDA-approved maximum is 40mg daily due to QT prolongation risk 2. This dose has demonstrated robust antidepressant effects in moderate-to-severe depression 3.
Lisdexamfetamine 40mg is appropriate for addressing residual symptoms like low energy or cognitive dysfunction, though this is an off-label use.
Second-Step Treatment Options if Optimization Fails
If increasing bupropion to 300-400mg daily does not achieve remission after 6-8 weeks 4, consider these evidence-based strategies:
Switch Strategies
- Switch to a different antidepressant such as venlafaxine extended-release, duloxetine, escitalopram, or sertraline 4. The STAR*D trial found that approximately 25% of patients achieved remission after switching, with no significant differences between switch options 4.
Augmentation Strategies
Aripiprazole augmentation (2-15mg daily) has demonstrated efficacy superior to bupropion augmentation in one trial (55.4% vs 34.0% remission, p=0.031) 4, though this study had high risk of bias.
Mirtazapine augmentation (15-45mg at bedtime) showed equivalent efficacy to switching strategies in trials involving over 1200 participants 4. Mirtazapine is particularly useful if insomnia, poor appetite, or weight loss are prominent symptoms 4.
Lithium augmentation (targeting blood levels of 0.2-0.6 mEq/L, typically 150-300mg daily in adults) can be considered 4, though evidence is limited in this specific context.
Important Safety Considerations
Monitor for serotonin syndrome given the combination of citalopram (SSRI), bupropion (weak serotonin effects), and lisdexamfetamine (stimulant with serotonergic properties) 2. Symptoms include mental status changes, autonomic hyperactivity, and neuromuscular abnormalities 4.
Cardiovascular monitoring is essential:
- Citalopram can prolong QT interval at 40mg daily 2
- Lisdexamfetamine can increase heart rate and blood pressure
- Bupropion at higher doses may increase blood pressure
- Obtain baseline and periodic ECGs, especially if adding other QT-prolonging agents 2
Assess for treatment-resistant depression criteria: This patient has failed adequate trials of two mechanistically different antidepressants (SSRI and NDRI) at therapeutic doses. If augmentation strategies fail, consider referral for specialized interventions or re-evaluation of the diagnosis 4.
Monitoring Timeline
- Reassess within 1-2 weeks after any medication change to monitor for adverse effects, particularly suicidality, agitation, or anxiety 4
- Evaluate therapeutic response at 6-8 weeks using standardized rating scales 4
- If no adequate response by 6-8 weeks, modify the treatment strategy rather than continuing ineffective therapy 4
What NOT to Add
Avoid adding another SSRI or combining with MAOIs due to serotonin syndrome risk 2. Tricyclic antidepressants would add anticholinergic burden and cardiac risk without clear benefit in this context 4. Buspirone augmentation is less effective than bupropion augmentation (30.1% vs 29.7% remission) and has higher discontinuation rates due to side effects (20.6% vs 12.5%) 1.