Can reducing bupropion (Wellbutrin) to 75mg SR, combining it with modafinil (Provigil) 100mg, and switching from quetiapine (Seroquel) to clozapine or other atypical antipsychotics alleviate extreme side effects and erectile dysfunction (ED) caused by multiple sedatives?

Managing Medication Side Effects and Sexual Dysfunction

Reducing bupropion to 75mg SR and adding modafinil 100mg may help manage side effects while potentially improving erectile dysfunction from sedatives, but switching from quetiapine to clozapine is not recommended as first-line due to clozapine's serious side effect profile.

Bupropion Dose Reduction

• Reducing bupropion from 150mg to 75mg SR is a reasonable approach for managing side effects such as extreme thirst, sweating, palpitations, constipation, and insomnia 1
• The American Academy of Child and Adolescent Psychiatry guidelines acknowledge that dose reduction is an appropriate strategy for managing stimulant-related side effects 1
• Lower doses of bupropion (75mg SR daily) may still provide some therapeutic benefit while minimizing adverse effects 2
• Bupropion-induced side effects can be dose-dependent, with symptoms improving when dosage is reduced 3

Modafinil Addition for ED

• Adding modafinil 100mg to a lower dose of bupropion may help counteract sedation-induced erectile dysfunction
• Modafinil acts on different neurotransmitter systems than bupropion and may provide complementary effects
• There is limited direct evidence on modafinil for antipsychotic-induced sexual dysfunction, but it may help with the sedative effects that contribute to ED
• Bupropion itself has a lower risk of sexual dysfunction compared to SSRIs and may help counteract ED from other medications 4

Antipsychotic Considerations

• Switching from quetiapine to clozapine is not recommended as a first-line strategy for managing erectile dysfunction 1
• Clozapine requires careful monitoring due to serious potential side effects including agranulocytosis, and should be reserved for treatment-resistant cases 1
• Consider these alternative options instead:
  1. Aripiprazole has a more favorable sexual side effect profile and lower prolactin elevation 5
  2. Olanzapine or quetiapine at optimized doses may have fewer sexual side effects than other antipsychotics 5
  3. Dose reduction of current antipsychotic if clinically appropriate

Management Algorithm

1. First step: Reduce bupropion to 75mg SR daily to manage autonomic side effects (thirst, sweating, palpitations)

   • Monitor for 2-4 weeks for symptom improvement
   • If depression worsens, consider alternative antidepressants with lower side effect profiles

2. Second step: Add modafinil 100mg in the morning

   • May help counteract sedation from other medications
   • May indirectly improve erectile function by reducing overall sedation
   • Monitor for potential stimulant-related side effects (insomnia, anxiety)

3. Third step: If erectile dysfunction persists, consider:

   • Sildenafil as needed for erectile dysfunction (strongest evidence base) 6
   • Switching to an antipsychotic with lower sexual side effect profile (aripiprazole, olanzapine) 5
   • Dose reduction of sedating medications if clinically appropriate

Important Cautions

• Combining stimulant medications (bupropion and modafinil) requires careful monitoring for additive side effects such as increased blood pressure, heart rate, and insomnia 1
• Start with lower doses of both medications and titrate slowly while monitoring for side effects
• Avoid abrupt discontinuation of any psychotropic medication; taper gradually to prevent withdrawal symptoms
• Clozapine should only be considered after multiple failed trials of other antipsychotics due to its serious side effect profile 1

Monitoring Recommendations

• Follow up within 2 weeks of medication changes to assess for improvement in side effects and sexual function
• Monitor vital signs, particularly blood pressure and heart rate, when combining stimulant medications
• Assess for any worsening of psychiatric symptoms with medication changes
• Regular evaluation of both therapeutic benefits and side effects to optimize medication regimen

Remember that erectile dysfunction from multiple sedatives may improve with overall reduction in sedative burden rather than specific medication additions.