What are the potential drug-drug interactions between propranolol, quetiapine, fluoxetine, modafinil, bupropion, guanfacine, lamotrigine, Adderall (amphetamine/dextroamphetamine), vortioxetine, and aripiprazole?

Significant Drug-Drug Interactions Between Multiple Psychiatric Medications

The combination of propranolol, quetiapine, fluoxetine, modafinil, bupropion, guanfacine, lamotrigine, Adderall, vortioxetine, and aripiprazole presents multiple clinically significant drug interactions that could lead to serious adverse effects including serotonin syndrome, cardiac complications, and altered drug levels requiring dose adjustments.

Key Interaction Pathways

CYP450 Enzyme Interactions

• Fluoxetine: Potent inhibitor of CYP2D6 and CYP3A4

  • Increases levels of aripiprazole, risperidone, and quetiapine 1
  • Increases propranolol levels by inhibiting CYP2D6 2
  • May increase lamotrigine concentrations 3

• Bupropion: Strong CYP2D6 inhibitor

  • Increases levels of aripiprazole and risperidone 4
  • Can increase propranolol concentrations 2
  • Combined with fluoxetine increases risk of serotonin syndrome 5

• Modafinil: CYP inducer

  • May decrease levels of aripiprazole, quetiapine, and other antipsychotics 1
  • Listed as a contraindicated interaction with oral contraceptives 1
  • Can reduce effectiveness of propranolol through enzyme induction 2

Serotonergic Interactions

• Risk of Serotonin Syndrome with multiple serotonergic agents:
  • Fluoxetine + bupropion + vortioxetine creates high risk 6, 5
  • Adderall (amphetamine) increases serotonin release, adding to this risk
  • Symptoms include confusion, agitation, hyperthermia, tremor, and autonomic instability

Cardiovascular Interactions

• Propranolol interactions:
  • With quetiapine: May enhance hypotensive effects and increase risk of bradycardia 2
  • With Adderall: Opposing effects (beta-blocker vs. sympathomimetic) may reduce effectiveness of both medications
  • With aripiprazole: Increased risk of QTc prolongation 4

Specific Critical Interactions

1. Fluoxetine + Bupropion + Vortioxetine:

   • Triple serotonergic combination creates high risk of serotonin syndrome 6, 5
   • Monitor for confusion, agitation, tremor, hyperthermia, and autonomic instability

2. Propranolol + Quetiapine:

   • Increased risk of hypotension and bradycardia
   • Propranolol can inhibit metabolism of quetiapine via CYP2D6 inhibition 2

3. Modafinil + Multiple Medications:

   • Reduces levels of quetiapine, aripiprazole, and potentially other medications through enzyme induction 1
   • May decrease effectiveness of propranolol 2

4. Fluoxetine + Aripiprazole:

   • Fluoxetine inhibits metabolism of aripiprazole, potentially doubling its levels
   • Aripiprazole dose may need to be reduced by 50% 4

5. Lamotrigine + Multiple Medications:

   • Lamotrigine levels may be affected by other medications
   • May increase clozapine levels (similar mechanism might affect quetiapine) 3

6. Adderall + Antipsychotics:

   • Opposing mechanisms (dopamine agonist vs. antagonist)
   • May reduce effectiveness of antipsychotics or increase side effects

Monitoring Recommendations

1. Baseline Assessment:

   • ECG for QTc interval (especially with quetiapine, aripiprazole, and propranolol combination)
   • Blood pressure and heart rate
   • Complete metabolic panel including liver function tests

2. Ongoing Monitoring:

   • Blood pressure and heart rate at each visit (weekly initially)
   • Signs of serotonin syndrome (confusion, agitation, tremor, hyperthermia)
   • Therapeutic drug monitoring for medications with narrow therapeutic windows
   • QTc interval monitoring, especially with multiple QTc-prolonging agents

Dose Adjustment Considerations

• Aripiprazole: Consider 50% dose reduction when combined with fluoxetine or bupropion 4
• Quetiapine: May need dose reduction with fluoxetine; may need dose increase with modafinil
• Lamotrigine: Monitor levels closely with this complex regimen
• Propranolol: May need dose adjustment when combined with CYP inhibitors like fluoxetine 2

Alternative Strategies

• Consider replacing fluoxetine with a less interactive SSRI such as escitalopram
• If possible, reduce the total number of medications to minimize interaction risk
• Consider therapeutic drug monitoring for medications with narrow therapeutic windows

This complex medication regimen requires careful monitoring and potential dose adjustments to minimize risks of serious adverse effects while maintaining therapeutic efficacy.