HIV/AIDS Bureau - HIV Primary Care Guide 2004

Why is it important to address mental health disorders in persons living with HIV?

HIV infection increases the risk of developing psychiatric disorders, including depression, mania, psychosis, and substance abuse (Treisman, 1999). For patients with preexisting mental illness, a diagnosis of HIV can significantly impact their ability to cope with HIV disease, adhere to treatment regimens, and take advantage of support networks and care systems, and can result in deterioration in their quality of life. Individuals with previous histories of mood, cognitive, or anxiety disorders may exhibit a reemergence or exacerbation of symptoms. As persons with HIV/AIDS live longer and the focus of care shifts from acute to chronic, the long-term psychological impact of HIV disease becomes more apparent.

It is essential for primary care providers to be aware of the need for a comprehensive evaluation of psychiatric symptoms in persons with HIV disease. Many psychiatric symptoms can indicate an underlying opportunistic disease or other condition (see Table 14-1).

What are the most common mistakes made in mental health management of HIV-infected patients?

Primary care providers commonly 1) under-diagnose depression, 2) under-dose antidepressant medications, 3) neglect substance use management and treatment, 4) stigmatize patients with psychiatric disorders, and 5) assume that psychotherapy implies a lengthy and detailed conversation.

Table 14-1. HIV-Related Conditions That Can Present
With Psychiatric Symptoms
Type of Problem	Condition
Opportunistic brain infections	Toxoplasmosis, cryptococcal meningitis, cytomegalovirus infection, tuberculosis, progressive multifocal leukoencephalopathy, neurosyphilis
Opportunistic malignancies	Lymphoma, Kaposi sarcoma
Metabolic complications	Fever, anemia, blood infections, hypoxia, hypotestosteronism
Drug toxicity	Corticosteroids, alpha-interferon, efavirenz (EFV)
Substance abuse complications	Recreational drugs (cocaine, alcohol, methamphetamine, hallucinogens, nitrate inhalant, opiates). Prescribed drugs (benzodiazepines, opiates, psychostimulants)

Providers should obtain psychiatric consultation in 1) major depression refractory to medication trials, 2) bipolar disorder, 3) schizophrenia, and 4) suicidal or homicidal thoughts.

Delirium, which is a state of global derangement of cerebral function, occurs more frequently in medically ill, brain injured, or metabolically unstable patients. The clinical presentation and the differential diagnosis in HIV patients are the same as in HIV noninfected individuals, with the additional possibility that delirium is HIV-related. Presentation may vary in the presence of psychomotor agitation or retardation. Emotional changes are common and often unpredictable, and hallucinations and delusions are frequently seen. Electroencephalography may show diffuse slowing of the background alpha rhythm, which resolves as confusion clears. The syndrome has an acute or sub-acute onset and remits fairly rapidly once the underlying cause is treated.

Non-pharmacologic treatments include identification and removal of the underlying cause, reorientation of the patient (calendars, clocks, view of outside world, and active engagement with staff members), and pharmacologic management of behavior or psychosis. Low doses of high-potency antipsychotic agents such as haloperidol are often useful. Newer, atypical antipsychotics are currently being used with some success, but those with more anticholinergic activity may worsen the condition. Benzodiazepines should be used cautiously, as they may contribute to delirium in some patients, except in cases of alcohol or benzodiazepine withdrawal deliria. Physical restraint should be used as little as possible as it often worsens delirium.

MCMD is a less severe neurocognitive disorder of earlier HIV infection, and the symptoms are often overlooked because they may be very subtle. Cognitive and motor slowing are most prominent and are often discovered as a result of a minor complaint, such as taking longer to read a novel, dysfunction when performing fine motor tasks, or an increased tendency to stumble. Diagnosis is made by the finding of 2 or more of the following symptoms for more than a month: impaired attention and concentration, mental slowing, impaired memory, slowed movements, lack of coordination, and changes in personality (irritability or emotional lability). Some patients continue to have minor problems, while others progress to frank dementia. Antiretroviral therapy (ART) may be of some benefit in slowing progression, but this conclusion is confounded by a lack of understanding of factors that lead some patients to progress while others remain static.

HIV-associated dementia presents with the typical triad of symptoms seen in other subcortical dementias-memory and psychomotor speed impairments, depressive symptoms, and movement disorders. Initially, patients may notice slight problems with reading, comprehension, memory, and mathematical skills. Patients later develop global dementia, with marked impairments in naming, language, and praxis. Clouding of consciousness is absent, and there is no evidence of another cause. Motor symptoms are often subtle in early stages, including occasional stumbling while walking or running, slowing of fine repetitive movements, and slight tremor. There may be impaired saccadic eye movements, dysdiadochokinesia, and hyperreflexia. Apathy is also a common early symptom, often causing noticeable withdrawal from social activity. A frank depressive syndrome also commonly develops, typically with irritable mood and anhedonia instead of sadness and crying spells. Sleep disturbances are quite common, as is weight loss. Psychosis may develop in a significant number of patients and generally presents with paranoid beliefs, although hallucinations may exist. In 5%-8% of patients, a syndrome known as AIDS mania develops in addition to the HIV-associated dementia. In later stages, there may be frontal release signs and rather severe motor symptoms, including marked difficulty in smooth limb movements, especially in the lower extremities.

HIV dementia is typically seen in late stages of illness, usually in patients who have had a CD4 count nadir of <200 cells/mm³. Certain risk factors have been associated with eventual development of HIV dementia, namely, higher HIV RNA viral load, lower education level, older age, anemia, illicit drug use, and female sex. Prognosis is rather poor, with a rapidly progressive nature, usually ending in death within 2 years.

Standard of care is to ensure an optimal ART regimen and treat associated symptoms aggressively. Depression can be treated with standard antidepressants, and in some cases methylphenidate or other stimulants may be useful in the treatment of apathy. Safety assessments should be performed as with any other case of dementing illness.

Psychosis, including schizophrenia, contributes to behaviors that may lead to HIV infection, including higher rates of injection drug use, unprotected sex, multiple sex partners, trading sex for money or other goods, and sex while intoxicated (Cournos et al, 1994). Providers who see patients with psychosis should be sensitive to the risk of acquiring HIV and should screen patients carefully for risk behaviors.

Accumulating evidence suggests that HIV infection may be directly linked to the onset of psychosis. Psychosis can be a manifestation of delirium, affective disorders, or schizophrenia, but can it occur in the absence of these conditions. Estimates of the prevalence of new-onset psychosis in patients with HIV range from 0.5%-15%, which is higher than in the general population (Kendler et al, 1996; Sewell et al, 1994). New-onset psychosis may also be a manifestation of HIV-associated encephalopathy. History of substance abuse also is more common among patients with psychosis.

The principles of treatment for HIV-infected patients with schizophrenia follow the same basic principles as for any other patient with schizophrenia, namely, control of symptoms with medications and psychosocial support and rehabilitation. Quite often, patients require long-term treatment and require various antipsychotic medications to control the delusions, hallucinations, and overall level of disorganization.

Personality disorders represent extremes of normal personality characteristics and are disabling conditions. Clinical observation suggests that patients with personality disorders who are highly extroverted and highly neurotic are most prone to engage in HIV risk behavior. These individuals are preoccupied by and act upon their feelings, and their actions tend to be unpredictable and inconsistent. Past experience and future consequences have little salience in decisionmaking for individuals who are ruled by feeling; the present is paramount. Their overarching goal is to achieve immediate pleasure or removal of pain, regardless of circumstances. Patients are more fixed upon the reward of sex and remarkably inattentive to the STDs they may acquire. In addition, substance abuse is more likely a comorbidity with these patients. Injection drug use is markedly more common because the experience is much more intense and pleasurable. Thus, patients with personality disorders are at risk for HIV infection, and if they are already HIV-positive they are at risk for transmitting HIV to others. Management of patients with personality disorders includes encouraging a focus on thoughts rather than feelings, use of a behavioral contract, emphasis on constructive rewards, use of relapse prevention strategies, and coordination with additional health and psychosocial care providers.

Adjustment disorders are common emotional responses to HIV and often account for the "hopeful highs" and "helpless lows" experienced by some patients. These reactions are typically situational and transient, but reflect significant distress in the patient. Adjustment issues vary according to a variety of factors in addition to stage of illness, risk factors, socieoeconomic status, level of education, characteristics of support networks, and comorbid psychiatric disorders. Adjustment reactions are most likely to occur at the time of significant medical events, especially during transition points in the illness. These conditions typically are accompanied by less severe depression and/or anxiety than are classic mood disorders. Treatment is usually non-pharmacologic and includes promotion of a structured environment, reassurance, engagement of the patient in the treatment process, close monitoring for progression of symptoms, and supportive counseling and psychotherapy.

Bipolar disorder, also known as manic-depressive illness, is a condition in which patients classically alternate between extended episodes of depression and briefer periods of hypomania or mania with increased mood, increased energy, increased confidence, and grandiose ideas. Manic episodes are associated with increased rates of substance abuse and impulsive behavior, and there has been speculation that bipolar disorder may be a risk factor for HIV infection. AIDS-related mania appears to be specifically associated with late-stage HIV infection and is associated with cognitive impairment and a lack of previous episodes or family history. The history will usually reveal progressive cognitive decline prior to the onset of mania. Irritable mood is more typical than euphoria, and prominent psychomotor slowing may replace the expected hyperactivity of mania, complicating the diagnosis. The presentation is usually quite severe in its course. AIDS mania appears to be more characteristically chronic, has few spontaneous remissions, and readily relapses with cessation of treatment (Lyketsos et al, 1997).

The treatment of mania in early-stage HIV infection is responsive to mood stabilizing medications, particularly lithium, valproic acid, and carbamazepine. Antipsychotic agents, particularly atypical agents, are often utilized in the acute phase as well. These medications decrease manic symptoms and may prevent recurrence. Treatment strategies may be somewhat different in advanced HIV disease. AIDS mania may respond to treatment with antipsychotics alone. In general, patients are often exquisitely sensitive to dosage changes that might otherwise seem trivial. Few data exist for the newer anticonvulsants such as gabapentin and lamotrigine, and these medications should be used sparingly. The major problem with lithium in AIDS patients has been rapid fluctuations in blood level, even when on previously stable doses. Lithium intoxication is not uncommon in this setting. Valproic acid has been successfully used when titrating to usual therapeutic serum levels of 50-100 ng/dL. Hepatotoxicity may significantly limit treatment, particularly in the setting of chronic viral hepatitis or severe hepatic Mycobacterium avium complex infiltration. Hematopoietic abnormalities may also occur, requiring close monitoring of white blood cell and platelet levels. Carbamazepine may be effective but is poorly tolerated because of sedation and potential for bone marrow suppression in combination with antiviral medications and viral burden. Patients with late-stage HIV are also significantly affected by toxic side effects of antipsychotic medications, and a much lower dosage may be required than in other settings.

Several lines of evidence suggest that HIV is a causal factor in depression, and that depression is a causal factor in HIV-related morbidity (Ciesla and Roberts, 2001). Differentiating appropriate sadness from pathologic depression may be difficult in the person infected with HIV. Psychomotor retardation and apathy of AIDS dementia complex may be confused with depression, but will often improve in patients who are on combination antiretroviral treatment. Organic mood disorders may also have symptoms similar to major depression and are responsive to antidepressant medication.

**Table 14-2. Risk Factors for Depression**
History of prior mood disorder History of substance abuse or active substance use Prior suicide attempt History of anxiety disorder Family history of depression or suicide Inadequate social support Nondisclosure of HIV status Multiple losses Advancing illness Treatment failure

Depression is underrecognized, underdiagnosed, and undertreated (see Table 14-2). At the same time, it is important for providers to consider alternative diagnostic possibilities for depressive symptomatology (see Table 14-3).

Table 14-3. Differential Diagnosis of
Major Depression
Nonpathologic states of grief and mourning Dysthymia Delirium Dementia Demoralization Substance intoxication Substance withdrawal CNS injury or infection Acute medical illness

Pharmacotherapy is the mainstay of treatment for major depression (see Table 14-4). No single antidepressant has been found to be superior in treating HIV-infected patients as a group. Patient adherence to regimens is critical, and those who take adequate doses of antidepressants have the best chance of improving. A general rule is to start with low doses of any medication, titrating up to a full dose slowly, in order to minimize early side effects that may act as obstacles to adherence.

The first week of treatment usually determines whether a patient will be able to tolerate the medication at all. Following this period, the dosage should be increased slowly to either a typical therapeutic dose or serum level, when appropriate. Patients should be encouraged to wait as long as possible for the therapeutic effect, which may take at least 6 weeks to achieve. Close monitoring for side effects should be done at every visit, and the side effects treated whenever possible. For example, insomnia because of selective serotonin reuptake inhibitor (SSRI) use may respond well to low doses of trazodone. Constipation from tricyclic antidepressants is often relieved by increasing water and fiber intake. Sexual side effects from SSRIs are common and may be treated with sildenafil in some, or by drug holidays, switching to bupropion, and addition of buspirone, cyproheptadine, or ginkgo biloba.

For patients showing only partial response to antidepressant medications after an adequate trial period, several other agents are often useful for augmentation strategies. The best studied is lithium, yet its side-effect profile often prevents use in the HIV setting. Olanzapine, risperidone, and pindolol have also been reported to be effective augmenting agents, as well as addition of a second antidepressant, other mood stabilizers, trazodone, methylphenidate, benzodiazepines, sleep deprivation, and phototherapy.

If no benefit is gained from the primary antidepressant, even after augmentation, a new primary agent should be chosen and similarly titrated slowly, and augmented if necessary. There is evidence to suggest that a response may be seen from 1 drug where none was seen from another in the same class.

Psychotherapy is an integral part of the treatment of major depression. Treatment with medication plus psychotherapy has been shown to be more effective for patients than either modality alone. Patients often require education about the disease nature of their depression, encouragement, and therapeutic optimism that the treatments will work. Medical providers who keep the concept of psychotherapy in mind will structure their interactions with patients to slowly empower and enable the patients to take control of their lives, thus relying on their providers less and less.

Anxiety disorder, which can include generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder, is a common response to the stressors of HIV infection at any stage. True anxiety disorders tend to be less prevalent than depressive disorders, particularly at later stages of HIV infection. Anxiety is often a component of major depression, and further history should be ascertained for patients presenting with symptoms of panic or anxiety. Anxiety may also be due to substance use, and neurologic and physical impairment.

Physicians must aggressively screen for major depression in patients presenting with anxiety symptoms, because both conditions often coexist. In particular, anxiety is a frequent symptom of major depression. Antidepressant medications are very effective in most cases.

In particularly debilitating cases, however, anxiolytic medications can be used for time-limited intervention and in low doses. Exclusion of patients with comorbid substance abuse is essential prior to initiation of anxiolytic medication, because of the abuse liability. Medications with a short half-life should be very cautiously used, as dependence may easily develop over a short period of usage. Particular attention should be given to the issues of hepatic function and choice of anxiolytic. Lorazepam, oxazepam, and temazepam avoid hepatic glucuronide conjugation by means of an alternate metabolic pathway and should be chosen as first-line medications for patients with HIV-associated liver dysfunction, as in patients with viral hepatitis.

What are nonpharmacologic treatments for HIV-infected patients with anxiety?

Specific advantages to utilizing nonpharmacologic intervention for anxiety include a decrease in pill burden, decrease in CNS sedation and cognitive impairment, lack of drug-drug interaction, and avoiding polypharmacy. Some interventions are 1) muscle relaxation, 2) meditation techniques, 3) psychotherapy, 4) exercise, 5) biofeedback, 6) behavioral techniques, 7) guided imagery, and 8) cognitive therapy.

Lyketsos CG, Hanson A, Fishman M, McHugh PR, Treisman GJ. "Screening for psychiatric morbidity in a medical outpatient clinic for HIV infection: the need for a psychiatric presence." Int J Psychiatr Med. 1994;24:103-113.

Angelino AF, Treisman GJ. "Management of psychiatric disorders in patients infected with human immunodeficiency virus." Clin Infect Dis. 2001;33:847-856.

Treisman G, Fishman M, Schwartz J, Hutton H, Lyketsos C. "Mood disorders in HIV infection." Depress Anxiety. 1998;7:178-187.

Ickovics JR, Hamburger ME, Vlahov D, et al. "Mortality, CD4 cell count decline, and depressive symptoms among HIV-seropositive women: Longitudinal analysis from the HIV Epidemiology Research Study." JAMA. 2001;285:1466-1474.

Lyketsos CG, Hoover DR, Guccione M, et al. "Changes in depressive symptoms as AIDS develops." Am J Psychiatry. 1996;153:1430-1437.

Sher KJ, Trull TJ. "Substance use disorder and personality disorder." Current Psychiatry Reports. 2002;4:25-29.

Ciesla JA, Roberts JE. "Meta-analysis of the relationship between HIV infection and risk for depressive disorders." Am J Psychiatry. 2001;158:725-730.

Cournos F, Guido JR, Coomaraswamy S, Meyer-Bahlburg H, Sugden R, Horwath E. "Sexual activity and risk of HIV infection among patients with schizophrenia." Am J Psychiatry. 1994;151:228-232.

Kendler KS, Gallagher TJ, Abelson JM, Kessler RC. "Lifetime prevalence, demographic risk factors, and diagnostic vulnerability of nonaffective psychosis as assessed in a US community sample." The National Comorbidity Survey. Arch Gen Psychiatry. 1996; 53:1022-1031.

Lyketsos CG, Schwartz J, Fishman M, Treisman G. "AIDS mania." J Neuropsychiatry Clin Neurosci. 1997;9:277-279.

Sewell DD, Jeste DV, Atkinson JH, et al. "HIV-associated psychosis: a study of 20 cases." San Diego HIV Neurobehavioral Research Center Group. Am J Psychiatry. 1994;151:237-242.

Treisman GJ. "AIDS education for psychiatrists." Primary Psychiatry. 1999;6:71-73.