What is a good medication to add to Vyvanse (lisdexamfetamine) for treating depression?

Medications to Add to Vyvanse (Lisdexamfetamine) for Depression

Bupropion (Wellbutrin) is the best medication to add to Vyvanse for treating depression due to its activating properties, complementary mechanism of action, and low risk of drug interactions with stimulants. 1

First-Line Options for Augmenting Vyvanse

Bupropion (Wellbutrin)

• Initial dosage: 37.5 mg every morning, then increase by 37.5 mg every 3 days

• Maximum dosage: 150 mg twice daily

• Benefits:

  • Activating properties that complement Vyvanse
  • Possible rapid improvement in energy levels
  • Different mechanism of action (norepinephrine-dopamine reuptake inhibitor)
  • Minimal risk of serotonergic interactions with stimulants 2

• Cautions:

  • Should not be used in patients with seizure disorders
  • To minimize insomnia risk, give second dose before 3 PM 2

Mirtazapine (Remeron)

• Initial dosage: 7.5 mg at bedtime
• Maximum dosage: 30 mg at bedtime
• Benefits:
  • Potent and well-tolerated
  • Promotes sleep, appetite, and weight gain
  • Can counterbalance potential appetite suppression from Vyvanse 2
  • Minimal drug interactions through CYP450 system 1

Second-Line Options

Sertraline (Zoloft)

• Initial dosage: 25-50 mg daily
• Maximum dosage: 200 mg daily
• Benefits:
  • Well-tolerated SSRI
  • Compared with other SSRIs, has less effect on metabolism of other medications 2, 3
  • Moderate CYP2D6 inhibitor, but less likely to interact with stimulants than other SSRIs 3

Citalopram (Celexa)

• Initial dosage: 10 mg daily
• Maximum dosage: 40 mg daily (20 mg maximum in elderly due to QT prolongation risk)
• Benefits:
  • Well-tolerated
  • Appears to have little effect on major CYP isoforms, reducing drug interaction risk 3
  • Some patients may experience nausea and sleep disturbances 2

Medications to Avoid with Vyvanse

Fluoxetine (Prozac) and Paroxetine (Paxil)

• These SSRIs are potent CYP2D6 inhibitors that may increase Vyvanse levels 3
• Fluoxetine's metabolite (norfluoxetine) has a long half-life, causing inhibitory effects to persist for weeks after discontinuation 3
• Higher rates of adverse effects, especially in older adults 1

Fluvoxamine (Luvox)

• Potent inhibitor of multiple CYP enzymes (CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4)
• Highest risk of drug interactions among SSRIs 3

Evidence on Lisdexamfetamine for Depression

Despite the question focusing on adding medication to Vyvanse for depression, it's worth noting that:

• Recent research shows lisdexamfetamine (Vyvanse) itself has not demonstrated superiority over placebo as an antidepressant augmentation strategy in major depressive disorder 4, 5
• A meta-analysis found only a small effect in improving depressive symptoms that approached trend-level significance 5

Monitoring and Follow-up

• Regular monitoring using standardized measures (e.g., PHQ-9) every 2-4 weeks
• Allow adequate trial duration (6-8 weeks) before determining efficacy
• Monitor for activation of mania/hypomania, particularly in patients with bipolar disorder
• Watch for potential drug interactions and side effects 1

Treatment-Resistant Depression Considerations

If initial augmentation fails, consider:

• SNRIs (venlafaxine, duloxetine)
• Atypical antipsychotics
• Electroconvulsive therapy for severe cases not responding to multiple medication trials 1, 6

Remember that approximately 38% of patients do not achieve treatment response during 6-12 weeks of treatment with second-generation antidepressants, and 54% do not achieve remission 1. Multiple medication trials may be necessary.