Drug Interactions of Protease Inhibitors and Psychiatric Medications

Taken from an article by Dan H. Karasic and James W. Dilley

Antiretroviral drugs -- especially protease inhibitors -- may interact with medications used to treat mood and anxiety disorders. Protease inhibitors have varying degrees of inhibition of the cytochromes P450 enzymes for liver oxidate metabolism. In particular, ritonavir (Norvir) is a powerful inhibitor of various P450 isoenzymes, particularly 2D6 and 3A4, that metabolize antidepressants, benzodiazepines and nueroleptics. Patients receiving TCAs should have their dosage cut by one half to two thirds initially, with blood levels checked to establish a safe and effective dose. Bupropion is contraindicated with ritonavir.

The SSRIs have a very wide therapeutic window, without the danger of overdose existing with tricyclics; however, the SSRI dose should also initially be cut by one half to two thirds, then increased again as needed for therapeutic response.

Benzodiazepines that do not interact with ritonavir include lorazepam (Ativan), temazepam (Restoril), and oxazepam (Serax). It is recommended that patients receiving other benzodiazepines, such as diazepam (Valium), or clonazepam (Klonopin) for anxiety, be switched to lorazepam prior to starting ritonavir. Patients receiving other benzodizepines, such as triazolam (Halcion) and flurazepam (Dalmane), or zolpidem (Ambien) for insomnia, should be switched to temazepam.

Neuroleptic doses should be decreased prior to starting ritonavir, and the patient closely monitored. Pimozide (orap) is contraindicated. Among mood stabilizers, carbamazepine levels are increased by ritonavir but valporic acid and lithium levels are not. The protease inhibitors indinavir, saquinavir, and nelfinavir have much less effect on psychotropic drug levels, but may inhibit cytochrome P450 3A4. The nonnucleotide reverse transcriptase inhibitors efavirenz and delavirdine also can inhibit CYP 3A4. Therefore, triazolam and pimozide should be avoided with these medications.

SSRIs and nefazodone may also increase protease inhibitor blood levels, particularly through cytochrome P450 3A4 inhibition; the clinical significance of this interaction is not known. Internists, psychiatrists, and others prescribing for persons with HIV must be aware of all medications that the patient is taking to attempt to minimize harmful interactions. The primary medical provider can facilitate this coordination by encouraging the patient to carry a list of all current medications to share with the psychiatrist and other physicians.