Harvard Mental Health Letter

Cytochrome P450 enzymes and psychiatric drugs

How a patient's genetic profile and other medications can alter drug response.

The American Journal of Psychiatry published an article describing the hypothetical case of a woman who sought treatment for depression while taking tamoxifen, a drug often prescribed to reduce the likelihood of breast cancer recurrence. The case was intended to illustrate the impact that the liver's cytochrome P450 enzymes can have on psychiatric drug choice, especially when patients are taking multiple medications.

Tamoxifen is broken down in the liver by several cytochrome P450 enzymes that also metabolize psychiatric drugs. In the case above, prescribing fluoxetine (Prozac) or paroxetine (Paxil) could affect blood levels of both tamoxifen and the antidepressant. Fluoxetine and paroxetine are metabolized by one of the cytochrome P450 enzymes that helps break down tamoxifen. They also compete with other drugs for use of this pathway (see table, below).

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