Question

Which of the following would be your next step?

Increase the mirtazapine (Remeron) to the full FDA dose of 45 mg/d

Increase the alprazolam (Xanax) to a higher, more effective dose to treat her agitation

Change to a more effective hypnotic agent to better treat her insomnia

Review her current medications further to see if any are CYP450 2D6 or 2C19 substrates that are likely to be poorly metabolized and induce immense side effects

Continue to motivationally suggest she consider psychotherapy as a side-effect-free treatment

Attending physician’s mental notes: initial evaluation (continued)

This patient seems to be undertreated due to

• – Clear medical reasons (CYP450 2D6 and 2C19 deficiencies)

• – Phobic reactions given her initial experience with interferon and her antidepressants

• – Good doses/duration of antidepressant treatment have not been utilized

• – Much rapport/trust building and very slow titrations will likely be needed to treat her effectively

All prescribing will need to be cross-checked for CYP450 2D6 and 2C19 interactions as she is vulnerable to toxicity and side effects if agents are metabolized through these isoenzyme systems

It is possible that her liver is more affected by her hepatitis C than we suspect, causing her to process medications even more poorly. Could she be a candidate for sofosbuvir (Sovaldi) as an alternate to interferon treatment?

She seems very guilt-ridden and ruminative about her decline. Will need to continue to investigate if this is delusional

She does meet criteria for MDD

It is unclear if her anxiety is truly comorbid or if her MDD is fostering the anxiety symptoms

If psychosis and comorbid anxiety become more evident, then her prognosis worsens further

Further investigation

Is there anything else you would especially like to know about this patient?

What about details concerning her CYP450 deficiencies? How poor of a metabolizer is she?

Cytochrome CYP450 genotype revealed that she is a poor to intermediate 2D6 metabolizer, and an intermediate 2C19 metabolizer

Therefore, drugs that are metabolized and broken down by these enzymes will not be processed efficiently hepatically, causing increased plasma drug levels and likely greater side effects

In patients like this, each prescribed drug should have its metabolic pathways evaluated before prescribing

Drugs known to interact could be used, but dosing must be adjusted to lower doses to avoid toxicity and side effects

Her current medications may have some interactions

• – Zolpidem (Ambien) is largely metabolized through 3A4 enzymes and should not present any interaction as she has no genetic enzyme deficiencies for this isoenzyme

• – Alprazolam (Xanax) is metabolized by the 3A4 enzyme system as well

• – Mirtazapine (Remeron) 15 mg/d is metabolized, as noted earlier, through 3A4 and 2C19. She should have minimal problems as her mild to moderately deficient 2C19 enzyme system can be adequately supported, again by 3A4 enzymes for which she has no deficiency

What about details regarding her liver functioning in face of her untreated hepatitis C?

This patient has AST and ALT hepatic enzyme levels that fluctuate between 200 U/L and 300 U/L, which are considered three to four times greater than normal values

She is considered to be stable by her gastroenterology physicians, but her liver is at risk for ongoing damage as a result of her hepatitis