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A "cocktail" of three antiviral drugs is turning out to be a lifeline for some people with AIDS, but it requires that they adhere to a complex, long-term, and unpleasant regimen that often causes severe side effects. As a result, physicians have been frustrated by the difficulty of convincing patients to stick to this complicated ritual, even when patients know that straying from it will give the virus the opening it needs to begin replicating.
When the HIV-infected individual also suffers from a mental illness or substance abuse disorder, the obstacles to adherence become enormous.
Psychiatrists can, however, take several steps to increase the likelihood that their patients will comply with the three-drug regimen, including not viewing adherence as solely the patient's responsibility, said Dan H. Karasic, M.D., at the APA annual meeting in June. It is also critical that psychiatrists become familiar with the array of HIV medications, their potential interactions with psychiatric medications, and which ones must be taken with meals and which on an empty stomach.
Karasic, a psychiatrist at San Francisco General Hospital and an assistant clinical professor at the University of California, San Francisco medical school, cautioned, for example, against prescribing triazolam and pimozide when an HIV-infected patient is taking protease inhibitors. When using ritonavir, one of the frequently prescribed protease inhibitors, both SSRI and tricyclic antidepressant doses should be cut initially by one-half to three-quarters compared with traditional starting doses and then increased gradually as needed, he pointed out.
He also urged psychiatrists to avoid prescribing buspirone and to use a great deal of caution when giving a patient nefazodone or trazodone.
In addition, because of possible drug interactions with the protease inhibitors, he has stopped prescribing most of the benzodiazepines. Among those he does find effective with this patient population are lorazepam and oxazepam for anxiety and temazepam for insomnia.
Carbamazepine can cause interactional side effects as well, so Karasic recommended using lithium, divalproex sodium, gabapentin, or lamotrogine instead when an HIV-infected patient needs a mood stabilizer.
Nonadherence to protease inhibitor regimens-patients often have to take 15 pills a day-is linked to several psychological factors, particularly alcohol use and depressed mood, he pointed out. Other correlates are high levels of perceived stress, pessimism about their HIV-related health status, young age, and working outside the home. One recent survey found that 43 percent of people taking the three-drug combination fail to adhere strictly to the regimen.
Strictly adhering to drug regimens forces patients to "make major lifestyle adaptations," said Charles T. Robinson, M.D., director of the mental health and substance abuse service at the University of Maryland's HIV/AIDS clinic in Baltimore. Several of the pills must be taken with meals, others without. Some must be taken alone, others in combination. The time of day the drugs are taken is also critical to their efficacy.
Patients who have experienced some type of trauma earlier in their lives are at particularly high risk of failing to adapt to a three-drug regimen, Robinson said, just as they were more apt to engage in behaviors, such as having multiple sex partners and using intravenous drugs, that put them at greater risk of HIV infection in the first place.
Educating physicians and other care-givers about what many of these patients have been through before they contracted AIDS could alert them to factors that, if dealt with therapeutically, could encourage medication compliance in their patients, Robinson emphasized. Because of the possibility that a patient may blame his or her parents for one or more developmental traumas, however, he also warned clinicians to "beware of the easy answer of encouraging patients to reengage with their family."
Psychiatrist George Harrison, M.D., noted as well that some patients with mental disorders let their medication regimens lapse because they can cope with only a limited number of tasks.
Harrison, who directs the AIDS Health Project at the University of California, San Francisco, described for the annual meeting audience some common scenarios seen in HIV-infected people with mental disorders that should alert clinicians to the possibility that a crisis is imminent and could interfere with a patient's medication adherence.
Deterioration of the patient's physical health can, for instance, trigger an emotional crisis, especially for those who learn they have "progressed beyond the point of effective treatment," Harrison said. Statements indicating that a patient views his or her illness progression as a step "closer to a welcome death" is also a signal for heightened vigilance. Ironically, dramatic improvements can have the same effect. Remember that these people are "being asked to make complex medical decisions at a time when they are not future oriented," he added.
Other signs to which psychiatrists and other caregivers should be alert are a patient's failure to show up for medical appointments and evidence that a patient is "collecting providers" and then relying on those clinicians to make decisions for the patient, Harrison stated.
Karasic suggested several elements of a strategy psychiatrists can use to increase the likelihood of patients' adherence to these complicated regimens. Stabilize any psychiatric illness or substance abuse problem before the patient begins antiretroviral therapy, he advised. Also, "encourage active behavioral coping" so that the patient senses that he or she has control over his or her own health care.
Particularly critical for psychiatrists, Karasic added, is regular communication with the patient's internist and familiarity with social work, home nursing, and substance abuse resources in the patient's community.