INTRODUCTION

HIV infection is spread through intimate contact, which involves specific behaviors that place patients at risk. Since the late 1980s, prevention programs have focused on education for populations at risk for HIV, and those who are unable to change behaviors despite education often suffer from vulnerabilities, like major psychiatric illness, impulsivity, or cognitive limitations. Those same vulnerabilities often prove to be major obstacles to effective treatment. It takes organization, support, and education to participate in the antiretroviral treatment necessary to suppress this disease. Being able to guide each patient to his or her highest level of functioning goes a long way toward promoting disease suppression. For that reason, HIV care providers need familiarity with the psychiatric problems commonly present in those with HIV and AIDS. This chapter will present descriptions and practical management approaches to the psychiatric problems frequently encountered in the care of HIV patients.

THE ROLE OF PSYCHIATRIC ILLNESS IN HIV TRANSMISSION

Prior to the mid-1980s, the public was relatively unaware of the risk factors related to both contracting and transmitting HIV. As education improved, individuals learned to protect themselves by avoiding the risky behaviors well understood to transmit the virus.^1,² Historically, risk reducing measures have included screening donors and donated blood products, abstinence from sex or safe sexual practices, and using clean needles for injection drugs. Due to these public health efforts, much of the developed world understands the transmission routes and risk factors of HIV and AIDS. Despite this, vulnerable populations of people continue to engage in activities that place them at risk for contracting and transmitting HIV.

Individuals with severe mental illness (such as recurrent major depression, bipolar affective disorder, and schizophrenia) and substance abuse problems (also a psychiatric problem) make up a large part of this vulnerable population. Between 3% and 23% of adults with severe mental illness are HIV positive, compared to 0.6% of the population in the United States.³ Those with severe mental illness are at risk for contracting HIV through high-risk sexual and drug use behavior. A 1996 epidemiologic study of 2864 patients receiving medical care for HIV found a 1-year prevalence of ∼50% for psychiatric illness, with only 27.2% using a psychotropic medication.⁴ In the outpatient HIV clinic at Johns Hopkins Hospital (Moore Clinic), just over half of the patients who seek medical care have a major psychiatric disorder other than substance abuse (75% have a substance abuse disorder).^5,⁶

Patients with HIV/AIDS and mental illness often lack the capacity to adhere to complicated medication regimens.^7,⁸ Additionally, we now know that HIV infection carries its own psychiatric sequelae, such as AIDS mania and dementia, compounding the disease manifestations and containment efforts in certain patients. In effect, AIDS has become a psychiatric epidemic, in which those individuals at greatest risk of exposure to and spread of the virus are mentally ill patients who are unable to incorporate preventive, educational, or medical measures into their lives. Treatment of co-morbid psychiatric illness can improve patient care and therapeutic outcomes, effectively fighting the spread of the AIDS epidemic.

PSYCHIATRIC FORMULATION

A thorough psychiatric formulation, like its counterpart in any medical field, allows the physician to develop a comprehensive treatment plan that addresses all the problems of the patients, therefore increasing the chances of treatment success. Psychiatric diagnosis is limited by the lack of chemical, genetic, and radiological tests assisting in the placement of presenting signs and symptoms under a diagnostic label that guides evidence-based treatment. This situation makes a comprehensive formulation guiding overall treatment vital. One method of organizing the complicated clinical details which the patients present has been described.⁹ It is a formulation that involves looking at the details of a comprehensive history, mental state exam, and physical exam so as to develop a formula that encompasses four different vantages, or perspectives. Those perspectives are (1) the disease, (2) the dimension, (3) the behavior, and (4) the life story.

The Disease

The disease perspective assumes that some psychiatric disorders represent the results of specific deficits in brain function, such as a lesion. This perspective categorizes patients into distinct groups, based upon the presence of defining characteristics of an illness. Disease reasoning implies the presence of a lesion or pathophysiologic etiology to explain the presenting signs and symptoms that are common across patient populations. There are a few psychiatric diseases despite the lack of identified lesions (this is an area of controversy). The idiopathic forms of schizophrenia, recurrent major depression, and bipolar disorder are likely to be related to specific disease states of focal brain function. Some of these conditions can be modeled using lesions in the brains of animals, but the models remain incomplete. Panic-like anxiety may fall in this category also. The recognition of disease states in psychiatry, guides research and empirical treatment of conditions that have a major impact on the well-being and self-care of patients.

The Dimension

The dimensional perspective takes into account individual variations in psychological determinants, such as extraversion or intelligence. Dimensional characteristics of humans include height, weight, and skin color. It is the same for personality characteristics and intelligence. Recognizing that your patient may, in fact, be mildly mentally retarded by asking questions about schooling, special education, and prior testing may go a long way toward helping clinicians craft a productive treatment plan. It goes the same for recognizing patient personality types such as introverted and extraverted, stable and unstable, and how these features of a person affect the care plan. It is clear that these features are related to risky behaviors and the ability to adapt to the constraints of HIV infection.

The Behavior

This perspective presumes that some patients have disorders based on specific goal-directed behaviors that interfere with other types of functioning. This approach assumes that certain behaviors are conditioned, that is, that they are entrained by rewards and consequences until they become automatic. Addictions to drugs and alcohol, eating disorders and other behaviors are the result of appetite-based drives and cravings. Many patients are in the HIV clinic as a direct result of something they did while trying to accomplish an altogether different goal. The drive for these behaviors seems overwhelming to patients, who feel that they ‘cannot help it’ when they use drugs, eat too much, or compulsively starve themselves, or go out to look for anonymous sexual partners of a particular sort. The behaviors are ‘shaped’ by a complex set of internal and external rewards and consequences that ultimately result in specific behavioral actions. Changing behavior is one of the most difficult and critical aspects to improving the life of patients.

The Life Story

The events of a person’s life have a profound impact on the way diseases, personalities, and behaviors are expressed. One must evaluate psychiatric disorders within the context of the life that they occur in and appreciating that story and understanding its interplay with the patient’s personality, motivated behaviors, and illnesses, allows you the opportunity to help them change course. This is the part of psychiatry that understands that a person who was molested as a child may have trust issues as an adult, or that someone who grew up in an oppressive environment may have difficulty with figures of authority. The psychological makeup of a person develops in large part from their experience.

PSYCHIATRIC TREATMENT

The treatment plan for each patient must be informed by the following:

1. the diagnosis and available treatments;

2. the availability of treatment for a particular patient;

3. the patient’s ability to engage in and tolerate the treatment and its side effects; and

4. the interactions the psychiatric treatment may have with other treatments (for instance, will the antidepressant interact with a protease inhibitor).

Unfocused, symptomatic treatment is less desirable than diagnostically driven treatment. For instance, providing anxiety-relieving benzodiazepines (like alprazolam) to treat a patient’s anxiety is far less productive than diagnosing a panic disorder (if it is present), educating the patient about it, and treating with an antidepressant (like sertraline). Understanding the patient and diagnosis creates the opportunity to evaluate the benefit of treatment compared with the side effects of the treatment. The process of illness education and discussion of risks and benefits of treatment is critical when developing a therapeutic alliance with the patient. The therapeutic alliance serves the purpose of bringing patients back to the clinic and promoting their adherence to the medications and other treatments prescribed.^10,¹¹

In many psychiatric conditions, available evidence supports a number of treatment options (like cognitive behavioral therapy, medication, or a combination of the two). There is no evidence that one antidepressant is more effective than others at treating major depression in HIV-positive patients. Therefore, clinicians have the option to initiate treatment with any approved antidepressant. Similarly, data often show similar success rates for medication and behavioral therapy-based treatment options. In panic disorder, the literature suggests that cognitive behavioral treatments, including exposure/desensitization therapy, and medications have similar efficacy.¹²^–¹⁴ Combination treatment with cognitive behavioral therapy and medication may have even greater success.¹⁵ The availability of treatments may have a large impact on what is chosen for your patient. For instance, is cognitive behavioral therapy available for a patient with a depression or anxiety disorder and does his insurance cover it? Can he or she engage in therapy or make use of it? Does the treating clinician have time to provide the labor-intensive therapy? These questions realistically guide the psychiatric treatment.

MEDICATION INTERACTIONS

Patients living with HIV and AIDS routinely have complicated medical regimens, involving multiple antiretroviral and antimicrobial drugs. As a result, rational treatment of psychiatric disorders in these patients requires careful consideration of potential drug interactions. Like patients with other chronic medical conditions, HIV-positive patients may have delayed absorption, metabolism, and excretion of medications, as well as diminished renal and hepatic clearance. These differences can complicate treatment decisions and worsen medication interactions.

Decisions regarding medications require some understanding of the cytochrome P450 metabolism of both antiretrovirals and psychiatric medications. All antiretrovirals beside the nucleoside reverse transcriptase inhibitors (NRTIs) and fusion inhibitor, enfuvirtide, are metabolized by the CYP system. HIV protease inhibitors (PIs), such as lopinavir and ritonavir, typically inhibit the CYP 3A4 and 2D6 isoenzymes. Non-nucleoside reverse transcriptase inhibitors (NNRTIs), including nevirapine and efavirenz, generally induce these same systems.¹⁶^–²⁰ Fortunately, in spite of these theoretical drug interactions, there are few clinically significant adverse reactions, likely because most medications utilize multiple metabolic pathways. At the same time, real increases in plasma concentrations may have little or no clinical impact as a result of the wide therapeutic indices of many medications. Many documented interactions involve ritonavir, which appears to be one of the most powerful inhibitors of the CYP 3A and 2D6 isoenzymes. The clinical relevance of most potential interactions remains largely unknown, necessitating the need for close observation of patients with co-administration of these drug classes.^21,²² While this is an area that needs additional research, we are hopeful that the improved mental health and medication adherence that can result from the use of psychotropics outweighs the potential impact on antiretroviral blood levels.²³

MAJOR PSYCHIATRIC SYNDROMES AND THEIR TREATMENT

Demoralization and Major Depression

Depression is the most common psychiatric complaint in the HIV clinic. Depression is a symptom, but is often treated in the literature as a diagnostic category. The complaint of depression should generate a differential diagnosis that includes many psychiatric conditions, including subcortical dementia and delirium, but we will focus on major depression (endogenous depression or melancholia) and demoralization. Major depression and demoralization commonly occur in patients infected with HIV. Both conditions present with low mood. Major depression and its associated changes in mood, self-attitude, and vital sense, represents a form of organic brain dysfunction in the domain of affect, fitting best into the disease category. On the other hand, demoralization is a low mood that can be understood as a response to stresses and life events. Unlike major depression, demoralization is a ubiquitous human experience. People get sad, have sleep and appetite disturbances, and may even contemplate suicide when loved ones die or serious stresses (such as a physically debilitating medical illness) occur.

Major depression is a risk factor for acquiring HIV. Epidemiologic data show a correlation between risky behaviors in HIV-negative individuals and higher scores on screening tools for psychological distress.³⁰ Another study revealed a sevenfold increase in the lifetime prevalence of mood disorders among nonsubstance-abusing patients who presented for HIV testing when compared to the general population.³¹ Furthermore, researchers have clearly identified major depression as a risk factor for unsafe behaviors, such as substance abuse, that may lead to HIV infection.³²^–³⁴

The literature has shown marked decreases in antiretroviral compliance among HIV-infected patients suffering from major depression compared to infected individuals who are free from mental illness.^35,³⁶ Treatment of co-morbid depression appears to improve adherence to antiretroviral regimens³⁷ and therapeutic outcomes.³⁸ Unfortunately, data show that over half of HIV-positive patients reporting a major depressive disorder do not receive antidepressant therapy.³⁹ In one clinic study, early recognition and treatment of major depression with both pharmacotherapy and psychotherapy helped 85% of patients and restored half of them to baseline.⁴⁰

Treatment of Major Depression

Antidepressant drugs are targeted to treat the underlying chemical imbalance in the brain that is associated with major depression (see Fig. 63-1). Patients with HIV/AIDS are prescribed antidepressants more often than any other class of psychotropics.⁴¹ Antidepressants include selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and other atypical drugs (bupropion, venlafaxine, duloxetine, mirtazipine, and trazodone). The development of SSRIs brought to market a class of antidepressants that were relatively easy to use, had limited side effects, and were safer in overdose. Though not more effective than tricyclics or MAOIs, the newer antidepressants offered primary care (and specialist) physicians the opportunity to treat the depressions seen so often in their clinics. To date, studies have shown no antidepressant more effective than others in treating depression among HIV-positive patients as a group. For that reason, much of the discussion here is generally related to the treatment of depression in all patients. In general, side effect profiles can guide the selection of an antidepressant agent because of their similar efficacies as a whole. For example, the side effects of TCAs can be capitalized on to treat an HIV-positive patient who is underweight, has diarrhea, and sleeping problems. Table 63-1 ⁴² provides a list of antidepressants, dose ranges, and clinically important side effects and benefits (aside from antidepressant effects).

Figure 63-1 Algorithm for pharmacologic treatment of depression.

Table 63-1 Clinically Useful Information About Commonly Prescribed Antidepressants

General Considerations

Successful antidepressant treatment requires consistent patient adherence and titration to an adequate therapeutic dose. We cannot overemphasize the importance of close follow-up with patients suffering from depression. It is not appropriate to diagnose a depression (with its inherent risk of suicide), start a medication (that may be initially agitating and cause other side effects prior to any benefit) and have the patient follow-up in 3 to 4 weeks. Close follow-up (initially weekly) gives the opportunity to provide support, stability, and close observation of any side effects that might warrant action. In order to minimize side effects, clinicians should start therapy at low doses and slowly increase to full doses or therapeutic serum levels (available for some of the tricyclic antidepressants). If a patient experiences any intolerable side effects, he may have already stopped the medicine (this is important to ask). If changing medications due to side effects, drugs in the same class still have the potential to offer improved response and decreased adverse reactions.⁴³ At the same time, patients experiencing relief of depressive symptoms and annoying but tolerable side effects such as insomnia, constipation, or sexual dysfunction should be encouraged and receive adjunctive treatments (e.g., trazodone for insomnia or increased water and fiber intake for constipation). A full trial of an antidepressant is 6 to 8 weeks at a standard therapeutic dose.⁴⁴^–⁴⁶ After this time, patients experiencing minimal or partial relief of symptoms should be considered for higher doses, a different medicine, or an augmenting agent. Lithium addition is the augmenting strategy best supported by evidence. Other promising augmenting agents include triiodothyronine, pindolol, and DHEA.⁴⁷

Selective Serotonin Reuptake Inhibitors

As a group, SSRIs have broad clinical indications, including major depression (fluoxetine, sertraline, paroxetine, citalopram, escitalopram), bulimia (fluoxetine), panic disorder (fluoxetine, sertraline, paroxetine), obsessive compulsive disorder (fluoxetine, fluvoxamine, sertraline, paroxetine), generalized anxiety disorder (paroxetine, escitalopram), post-traumatic stress disorder (sertraline, paroxetine), social phobia (sertraline, paroxetine), and premenstrual dysphoric disorder (fluoxetine, sertraline, paroxetine). Common side effects include anxiety, restlessness (akathisia), nausea, diarrhea (increased gastric motility), insomnia, and sexual dysfunction (including decreased arousal or erections, delayed ejaculation, and anorgasmia). Randomized clinical trials have noted fluoxetine most effective of the SSRIs in treating major depression in HIV-positive patients. However, paroxetine, sertraline, and citalopram have also demonstrated clinical efficacy.⁴⁸

A small number of studies have examined the combination of SSRIs and antiretrovirals for drug interactions. Fluoxetine has been shown to increase concentrations of ritonavir with co-administration.⁴⁹ At the same time, researchers examining a series of five cases of serotonin syndrome concluded that co-administered ritonavir increased levels of fluoxetine through inhibition of CYP 2D6.⁵⁰ Although no evidence exists addressing interactions between other SSRIs and antiretrovirals, adverse reactions are possible with all combinations through the potential for CYP450 inhibition, necessitating careful observation of all HIV-positive patients taking SSRIs.^51,⁵² However, SSRIs differ in their pharmacokinetics and potential inhibitory effect on CYP450, possibly making certain drugs, such as citalopram and escitalopram, better choices in patients taking numerous medications.⁵³