People with HIV maintain physical health by adhering to complicated medication regimens, eating well, exercising, and visiting a primary care provider regularly. While you may take good mental health for granted, the many stresses that accompany HIV infection, in addition to substance abuse or other medications, can contribute to the development of psychiatric conditions. It is important to address these conditions and treat them appropriately as they develop so that they won't get in the way of maintaining your physical health.

At the recent Community Forum, Drs. Philip Bialer and Ron Wenchel discussed treatments for psychiatric conditions and some of the possible drug interactions between these treatments and HIV medications. This summary will introduce common psychiatric conditions and treatments, and then examine the drug interactions presented at the Forum.

A Primer in Psychiatric Conditions

Common Conditions

Cognitive Impairment and Dementia - People with advanced HIV sometimes experience cognitive impairment, a condition marked by difficulty with processes related to knowing, thinking, learning, and judging. Cognitive impairment can result in poor concentration and decreased motor skills. Tests that evaluate memory, problem solving skills, and information processing are used to diagnose cognitive impairment. Dementia is a general loss of intellectual abilities, including memory, judgment, and abstract thinking skills, usually accompanied by changes in personality.

Manic Syndrome - Mental and physical hyperactivity, accompanied by disorganized behavior and elevated or irritated mood, characterizes manic syndrome. Causes of mania include the high steroid doses used to treat PCP, amphetamine/cocaine use, and bipolar disorder.

Depression - Although estimates on the prevalence of depression in people with HIV vary, depressive disorder is a common diagnosis for this population. Symptoms of depression (a mental state of depressed mood) can include changes in sleep, changes in appetite and weight, loss of interest or pleasure in daily activities, agitation, feelings of worthlessness or guilt, poor concentration, and suicidal thoughts/thoughts of death. Causes of depression can be external, like the multiple stresses of living with HIV, or can be manifestations of drug or alcohol abuse or central nervous system disease. Ceasing alcohol and drug use can improve depression, as can treatment with various anti-depressants.

Anxiety - Among the causes of anxiety are uncertainty regarding various aspects of life, such as financial insecurity or the social losses associated with HIV. Individuals with good coping skills are less likely to experience anxiety than those who are unable to cope with stress. Other causes of anxiety include alcohol and nicotine use, cocaine use, and medications such as steroids and decongestants. Persistent anxiety and panic attacks should be treated.

Treatment Recommendations

Listed below are some of the psychotropic medications used to treat the psychiatric conditions described in the previous section.

Discuss all treatment options with your care provider to learn full side effects and dosing information.

Condition	Treatment Options
Delirium	Neuroleptics Haloperidol (Haldol) Chlorpromazine (Thorazine) Risperidone (Risperdal) Perphenazine (Trilaphon) Molindone (Moban) Olanzapine (Zyprexa)
	Benzodiazapenes Lorazepan (Ativan) Clonazepam (Klonopin) Diazepam (Valium) Midazolam (Versed) Triazolam (Halcion)
	Non-pharmaceutical interventions Place a calendar and clock in patient's room and keep the room well-lit.
Cognitive Impairment and Dementia
	Psychostimulants Methylphenidate (Methylin, Ritalin)
	Neuroleptics
Manic Syndrome
	Anticonvulsants Divalproex sodium (Depakote) Carbamazepine (Epital, Carbatrol) Lamotrigine (Lamictal) Gabapentin (Neurontin)
	Neuroleptics
	Benzodiazapenes
Depression
	Selective Serotonin Uptake Inhibitors (SSRIs) Fluoxetine (Prozac) Sertraline (Zoloft) Paroxetine (Paxil) Fluvoxamine (Luvox)
	TCAs Desipramine (Norpramin) Nortriptyline (Pamelor)
	Other Antidepressants Bupropion (Wellbutrin) Nefazodone (Serzone) Mirtazapine (Remeron) Venlafaxine (Effexor)
	Non-pharmaceutical interventions Interpersonal psychotherapy; Structured group therapy emphasizing active-behavioral coping skills; Relaxation techniques and problem-solving skills development
Anxiety
	Benzodiazapenes
	Anxiolytics Buspirone (Buspar)
	SSRIs
	Non-pharmaceutical interventions: Psychotherapy; Relaxation techniques; Structured group therapy

Drug Interactions

Most of the drugs listed above can be used safely in combination with treatments for HIV. Some special considerations are required for their use with protease inhibitors, however. Protease inhibitors inhibit an enzyme system that processes medications in the liver. This enzyme system, called P450, contains 25 to 30 enzymes, including two enzymes called 2D6 and 3A4. 2D6 and 3A4 metabolize psychotropic medications (including antidepressants, benzodiazepines, and neuroleptics). Ritonavir (Norvir) is a powerful inhibitor of 2D6 and 3A4. When 3A4 is inhibited, psychotropic medications cannot be processed properly, producing high blood levels and intensifying the side effects of the medications.

Package inserts for protease inhibitors include long lists of contraindicated psychotropic medications (psychotropic medications that should not be taken with the protease inhibitor). Dr. Wenchel noted that many of the recommendations are not based clinical experience or clinical trials, but are instead based on the assumption that there are negative interactions because of enzyme mechanisms. In Dr. Wenchel's experience, with careful monitoring of psychotropic drug side effects and blood levels, it is safe to use most psychotropic medications with HIV medications. Lower dosing may be necessary, and certain medications (Serzone, Zanax, Valium, Versed, and Wellbutrin) should not be taken with Norvir.

Dr. Bialer explained that Nucleoside Reverse Transcriptase Inhibitors (NRTIs - drugs like AZT and 3TC) are not metabolized by P450 enzymes, and will not influence psychotropic drug levels. Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs), however, may interact. Delavirdine (Rescriptor) inhibits 3A4, and has the same effect on psychotropic medications as the protease inhibitors. Efavirenz (Sustiva), on the other hand, induces 3A4, increasing the rate at which psychotropic drugs are metabolized. This will result in psychotropic medication levels below the threshold at which they are effective. On the flip side, Prozac and Zoloft can inhibit 3A4, resulting in higher antiretroviral drug levels, and barbituates and phenytoin sodium (Dilantin), an antiepileptic drug, can induce 3A4, causing faster processing of antiretroviral drugs, resulting in blood drug levels that are lower than the most effective levels.

For successful treatment of psychiatric conditions and HIV, Dr. Bailer recommends starting with a low dose of any of the medications listed above, monitoring for side effects, and facilitating communication between a patient's primary care provider and his or her psychiatrist.

Questions and Answers

Q: Are there any psychotropic medicines that can be used without regularly scheduled doses for mild depression?

A: An SSRI like Prozac must be taken on a regular dosing schedule in order to reach an adequate concentration in the blood. Ritalin, dosed as needed, has a fairly immediate stimulant effect, and is effective in patients with low energy, but Ritalin will not treat other symptoms of depression, such as isolation, low mood or lack of pleasure in routine activities. The irregular use of Ritalin could contribute to the development of Ritalin dependency, and its mechanism is not fully understood, so people with HIV who are taking Ritalin should be monitored closely.

Q: Please comment on the effectiveness of St. John's Wort in treating depression.

A: St. John's Wort should only be used for mild depression; it is not effective in the treatment of moderate to severe depression. St. John's Wort may induce induce 3A4, causing faster processing of antiretroviral drugs, resulting in sub-optimal blood drug levels.