What are the potential interactions between lorazepam, quetiapine (Seroquel), bupropion (Wellbutrin), and suvorexant (Belsomra)?

Potential Interactions Between Lorazepam, Quetiapine, Bupropion, and Suvorexant

The combination of lorazepam, quetiapine, bupropion, and suvorexant carries significant risk of CNS depression, potential serotonin syndrome, and additive sedative effects that could lead to serious adverse outcomes including respiratory depression.

CNS Depression and Sedation Risks

Lorazepam and quetiapine both cause significant CNS depression, and their combination presents a serious risk:

• Lorazepam (benzodiazepine) causes sedation, dizziness, and increased risk of falls 1
• Quetiapine (atypical antipsychotic) is sedating and may cause drowsiness, dizziness, and orthostatic hypotension 1
• Suvorexant (Belsomra) is a sleep medication that adds another layer of sedation
• The combination of benzodiazepines with antipsychotics can lead to oversedation and respiratory depression 1

Specific High-Risk Interaction:

• Combining benzodiazepines with high-dose antipsychotics has been associated with fatalities 1
• Elderly or frail patients and those with COPD are at particularly high risk and require lower doses of these medications 1

Serotonergic Effects and Risks

Bupropion combined with quetiapine presents risk for serotonergic effects:

• Bupropion inhibits norepinephrine and dopamine reuptake with some effects on serotonergic activity 2
• Quetiapine has some serotonergic properties
• This combination may increase risk of serotonin syndrome, characterized by:
  • Mental status changes (confusion, agitation, anxiety)
  • Neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity)
  • Autonomic hyperactivity (hypertension, tachycardia, arrhythmias, diaphoresis) 1

A case report has documented serotonin syndrome in a patient taking bupropion, trazodone, and quetiapine 3, highlighting this risk.

Pharmacokinetic Interactions

These medications have complex metabolic pathways that can interact:

• Bupropion is a strong inhibitor of CYP2D6 2, which may:

  • Increase blood levels of quetiapine, which is partially metabolized by this enzyme
  • Potentially increase the risk of side effects from quetiapine

• Quetiapine is metabolized primarily through CYP3A4 4, and drug interactions affecting this pathway could alter its levels

Specific Monitoring Recommendations

When these medications must be used together:

1. Start with lower doses of each medication, particularly:

   • Lower doses of lorazepam (0.25-0.5 mg) if co-administered with quetiapine 1
   • Reduced quetiapine doses in elderly patients or those with hepatic impairment 1

2. Monitor for:

   • Excessive sedation and respiratory depression
   • Signs of serotonin syndrome (especially within first 24-48 hours after combining medications) 1
   • Orthostatic hypotension (particularly with quetiapine)
   • Cognitive impairment and increased fall risk

3. Consider staggering administration times to minimize peak concentration overlaps

Alternative Approaches

If clinically appropriate, consider:

• Using only one sedating agent rather than multiple (lorazepam, quetiapine, and suvorexant all cause sedation)
• Exploring non-pharmacological approaches for insomnia
• For anxiety/depression, considering alternatives to bupropion if serotonergic medications are needed

Specific Cautions

• Avoid this combination in patients with:

  • Severe pulmonary insufficiency
  • Severe liver disease
  • History of substance abuse (increased risk with benzodiazepines)
  • Sleep apnea (risk of respiratory depression)

• Use extreme caution in elderly patients, who are more sensitive to CNS depressant effects and at higher risk for falls and cognitive impairment

This medication combination requires careful monitoring and consideration of whether the benefits outweigh the substantial risks of additive CNS depression and potential serotonergic effects.