HIV-related psychopharmacological interventions for people with preexisting schizophrenia follow similar guidelines for patients with new-onset psychosis associated with HIV infection. In advanced HIV infection, traditional neuroleptic agents have been found to produce modest but significant reductions in psychotic symptoms but have been eschewed for newer, atypical antipsychotics for the primary reason that such patients are very sensitive to extrapyramidal side effects due to viral involvement of the basal ganglia (American Psychiatric Association 2000; Fernandez and Levy 1993; Sewell et al. 1994). With progression of HIV, people with preexisting psychiatric conditions may thus develop new or increased side effects on medications that they were previously able to tolerate (Horwath 1996).
A large number of medications are prescribed to people with HIV infection, including antibacterial, antifungal, antineoplastic, antiretroviral, and other antiviral agents (Horwath 1996), particularly in later stages of HIV disease, when numerous present or potential complications require active treatment or prophylaxis. Any attempt to diagnose drug-induced neuropsychiatric syndromes requires an appreciation of both the therapeutic use and potential side effects of these medications. Some of these are described in the Practice Guideline for the Treatment of Patients With HIV/AIDS of the American Psychiatric Association (2000; access at www.psych.org), but new antiretroviral agents are being developed at a rapid pace, and existing medications to treat HIV-related infections and neoplasms are too numerous to describe fully. Neuropsychiatric side effects of antiretrovirals have been reported most commonly with efavirenz (Sustiva) and occasionally with nevirapine (Viramune). There are many in vitro predictions of drug-drug interactions (which can be found in handheld databases, those available through hospital pharmacies, and those online at a variety of Web sites), but experienced prescribers generally find they can use the full range of psychotropic medications if they start with low doses and slowly increase the medication. Overlapping toxicities between different medications must also be taken into consideration. It is important to be aware that advanced HIV infection is associated with greater sensitivity to both the therapeutic effects and side effects of psychotropic medications, which is another reason why it is best to start with the lowest possible doses and increase medications slowly. Drug levels, if available, should be monitored closely, especially when patients are on complex medication regimens. Recreational drugs also can affect medication levels; for dually diagnosed patients on methadone, doses of methadone often need to be adjusted, usually upward but occasionally downward depending on the antiretroviral regimen (i.e., delavirdine, nevirapine).
Most psychiatric medications are metabolized by the liver and therefore may require more careful monitoring in those chronically infected with hepatitis C. In particular, for those who manifest clinical or laboratory signs of liver failure, medication metabolism can be dangerously reduced to the point where patients may accumulate toxic levels of drugs they normally can take.
In general, it is relatively safe to use most of the psychiatric medications both with HIV and HCV treatments. In the presence of HCV illness, periodic liver function tests are the standard of care. Because some psychotropics may elevate liver enzymes (e.g., valproic acid, carbamazepine, nefazodone), it is important to check these at baseline, early after initiation of therapy (2-4 weeks), and every 2-3 months thereafter. Nevertheless, data from a large retrospective study in Seattle, Washington, found that among 94 HCV seropositive patients treated with valproic acid, 81.9% showed minimal or no evidence of serum transaminase elevations (Barnes et al. 2001). Yet combined toxicities are important to consider, particularly during treatment with medications that can have an impact on bone marrow activity (e.g., clozapine, carbamazepine, zidovudine, interferon, rib-avirin) or may cause other additive side effects. Initiating interferon treatment should involve follow-up by a psychiatrist, both to evaluate the patient with schizophrenia as a candidate for long-term interferon on the basis of compliance with psychiatric therapy, and to monitor for psychiatric symptom exacerbation.
Psychiatric patients, like medical patients, often are nonadherent to their medication regimen, which they may perceive as one of the few aspects of their lives they can control. It is important to time the beginning of an antiretroviral regimen with a commitment to the treatment and to help patients see that following an HIV or HCV medication regimen can be part of gaining control. Working with a patient to promote adherence to psychotropic medications will be the best predictor of whether the patient can follow an HIV/HCV medication regimen. The clinician and infectious disease specialist must communicate about the patient's need for and readiness to begin antiretrovirals, select in concert with the patient regimens that avoid drug-drug interactions, keep the number and doses of pills the patient has to take to the minimum necessary, and coordinate his or her treatment plans.
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