Should thyroxine be increased to 18.75 mg, fenofibrate decreased to 67 mg, and ezetimibe 5 mg added, and would adding modafinil 100 mg help with low libido, erectile dysfunction, and daytime sleepiness in a patient on multiple sedatives?

Management of Daytime Sleepiness, Erectile Dysfunction, and Medication Adjustments

Based on the patient's complex medication regimen and symptoms, adding modafinil 100mg in the morning is recommended to address daytime sleepiness and potentially improve sexual function, while thyroxine should be increased to 18.75mg due to the rising TSH level. 1

Medication Adjustments for Daytime Sleepiness and Sexual Function

Modafinil Addition

• Adding modafinil 100mg in the morning is appropriate for this 44-year-old male experiencing daytime sleepiness and sexual dysfunction while on multiple sedating medications 2, 1
• Modafinil is specifically recommended for counteracting medication-induced sedation and can help improve daytime alertness 2
• Recent evidence suggests modafinil may also help improve antidepressant-induced sexual dysfunction 3, 4
• Common side effects to monitor include headache, nausea, nervousness, and anxiety 5
• Morning-only dosing is critical to avoid interference with sleep 2

Thyroid Medication Adjustment

• Increasing thyroxine from 12.5mg to 18.75mg is warranted given the TSH increase from 2.11 to 3.85, which may be contributing to fatigue and sexual dysfunction
• Monitor TSH levels after 6-8 weeks of dose adjustment

Sedative Medication Management

• Discontinuing doxepin 6mg as planned is appropriate as it's contributing to sedation with minimal benefit 1
• Increasing mirtazapine from 7.5mg to 11.25mg as planned may help with insomnia but could potentially worsen daytime sedation and sexual dysfunction
• Gradually tapering clonazepam to 0.5mg as mentioned in the question is appropriate to reduce sedation while maintaining sleep benefits

Lipid Management Approach

• Decreasing fenofibrate from 160mg to 67mg is reasonable given the excellent response (triglycerides decreased from 225 to 116mg/dL)
• Adding ezetimibe 5mg is appropriate to maintain lipid control while reducing fenofibrate dose 6
• This combination approach can effectively maintain improvements in LDL, HDL, and triglycerides with lower fenofibrate dosing 6

Implementation and Monitoring Plan

1. Week 1:

   • Start modafinil 100mg in the morning
   • Increase thyroxine to 18.75mg daily
   • Decrease fenofibrate to 67mg and add ezetimibe 5mg
   • Discontinue doxepin 6mg
   • Increase mirtazapine to 11.25mg as planned

2. Week 2-4:

   • Assess for improvements in daytime alertness and sexual function
   • Monitor for modafinil side effects (headache, anxiety, insomnia)
   • Begin gradual clonazepam taper to 0.5mg

3. Week 6-8:

   • Check TSH, lipid panel, and liver function tests
   • Consider increasing modafinil to 200mg if daytime sleepiness persists without side effects 2, 1

Cautions and Considerations

• Modafinil has been associated with rare cases of hypersexuality at higher doses (>400mg), so dosing should not exceed 200mg daily 7
• Monitor for potential drug interactions between modafinil and other medications, particularly through cytochrome P450 pathways 5
• Be aware that excessive stimulation from modafinil could potentially worsen insomnia if taken too late in the day 2
• While rare, modafinil can cause serious skin reactions including Stevens-Johnson Syndrome 5

This management approach addresses the patient's complex symptoms while making targeted medication adjustments to improve quality of life and minimize polypharmacy risks.