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HIV and Mood Disorders

Summer 2006

Everyone feels sad or discouraged sometimes. Emotions such as grief and unhappiness are a normal part of life, especially when a person is experiencing high levels of stress or dealing with major losses and life readjustments. Events occur in most lives that are upsetting or stressful, but one may be unhappy without necessarily being clinically depressed. The distinction between "ordinary unhappiness" and clinical depressive disorders depends on the duration and severity of the low mood and the occurrence of related problems, such as loss of interest in most or all activities, changes in appetite/weight or sleep, low energy, persistent thoughts about death, guilty feelings, and other symptoms. The extent to which a depressed mood interferes with work, relationships, and recreation is also considered in distinguishing between sadness and clinical depression. In this article, the term "depression" refers to clinical disorders, not everyday sadness.

Depression is a common disorder, affecting people of all ages, races and walks of life. Psychiatrists distinguish between major depression, which has many symptoms occurring together; minor depression, characterized by low mood and/or loss of interest but fewer associated symptoms; and dysthymia, which refers to a more chronic and often milder depression that is present on most days for at least two years without a period of well-being of at least two months. Rates of depression in the general population have been studied worldwide for many years. A reasonable estimate of those who have experienced major depression in the past year is about 4 or 5%, and about 2% for dysthymia (Narrow, 2002; Waraich, 2004). (Minor depression was not evaluated in these population studies.)

Among people with HIV/AIDS, depression is the most common psychiatric disorder (not including substance use disorders), but most HIV-positive people are not depressed most of the time. While rates of depression vary depending on how depression is defined and how it is measured, the consensus is that rates of major depression are elevated in the context of HIV/AIDS, with estimates using diagnostic criteria ranging from 5% to 20%, depending on the measures used and the groups being studied (Evans et al. 2005). These estimates usually do not include "minor" depression, which has fewer symptoms but still manifests as persistent sadness with diminished ability to experience pleasure and satisfaction.

Some evidence suggests that HIV-positive women have higher rates of major depression and dysthymia than men with HIV, as do those with current substance use disorders. However, women in general and non-HIV drug users also have elevated rates of depression, so HIV/AIDS may not be the major cause of this increased incidence. Much higher rates have been reported when self-report symptom scales or diagnostic screens are used to identify depression, but as a rule these measures are not intended by themselves to establish a diagnosis.

On the other hand, several factors may complicate the diagnosis of depression in a person who is HIV positive, because of the overlap between symptoms of depression (like insomnia and loss of appetite), and symptoms of HIV itself or medication side effects. A good diagnostician needs to be familiar with both the standard criteria for depression and the clinical presentation of HIV and the possible adverse effects of medications.

When trying to sort out the relationship of HIV and depression, the age when depression is first experienced needs to be considered. In our psychiatric research program, in which we have seen over 1,200 HIV-positive adults in the past 15 years, 60-80% reported that their first episode of depression occurred long before they discovered their HIV status. For example, among gay men, adolescence and the process of coming out may be the period when depression is first experienced. Other factors that put people at risk for depression independent of HIV status are a family history of depression (perhaps reflecting a genetic predisposition) and abuse of alcohol or recreational drugs.

Depression is generally one of psychiatry's success stories: Many antidepressant medications and several kinds of time-limited psychotherapy such as cognitive behavioral therapy have been shown to be effective. For milder depression, support groups often can be helpful, but for major depression, antidepressant medication with or without psychotherapy is the standard of care. Research has shown that HIV-positive depressed patients respond as well and as often to such treatments as do people without HIV/AIDS.

Untreated depression is costly. Quality of life is diminished, relationships with family and friends may be impaired, and work may be disrupted. For HIV-positive people, there are additional costs: Depression repeatedly has been associated with poorer adherence to medical care. People who are depressed are less likely to take their HIV medications or keep medical appointments regularly than those who are not, and are more likely to neglect nutrition and pay less attention to their overall health, so that HIV disease progression may be a consequence. It may be difficult to tell one's doctor or care provider about feeling depressed, but it is important to do so or to seek evaluation and treatment elsewhere. (If someone does not know where treatment is available in New York City, there is a citywide service for referrals that can be reached at 1-800-LIFENET.)

Bipolar Disorder

This condition includes episodes of both depression and mania, and is sometimes called manic-depressive disorder. Mania is characterized by periods of abnormally elevated or irritable mood, greatly decreased need for sleep, racing thoughts, distractibility, and uncharacteristic risk-taking behavior. Such periods of abnormal mood must last at least one week (or less if hospitalization is required), to meet the diagnostic definition. The diagnosis needs to be made when the person is not high on recreational drugs, since drug use can confuse the diagnostic picture. Bipolar disorder appears to have a fairly strong genetic component and occurs in about 1% of the general population. It often first appears in the early 20s but may start in adolescence. Bipolar II disorder (hypomania) is a milder form with episodes of shorter duration.

Bipolar disorder most often precedes HIV infection in people with both conditions. Sometimes, however, "secondary" mania may develop because of HIV brain involvement in advanced AIDS, often associated with significant cognitive impairment (Ferrando & Wapenyi, 2002). Fortunately, secondary mania is far less common since the advent of antiretroviral therapy. In other cases, new-onset mania may be precipitated by medications such as corticosteroids (e.g., prednisone), which may be prescribed for various medical conditions including asthma. Corticosteroid-induced mania may be managed by lowering the dose or tapering off if that is medically feasible, or by prescribing a mood stabilizer.

Depression and Fatigue

Fatigue is more common than depression among people with HIV; estimates of prevalence cluster around 40%. Fatigue is usually defined as a lack of energy, tiredness, lethargy, inability to feel rested that is not due to insomnia, and low stamina. In contrast to depression, the person with fatigue is interested in doing things and can list activities he or she wants to engage in, but lacks the energy to do them. The substantial overlap between fatigue and depression is to some extent circular by definition, in that fatigue is one of the nine criteria for the diagnosis of major or minor depression, and fatigue is also associated with problems such as poor concentration, which is another criterion for diagnosing major depression. There may be a reverse causal direction as well. When fatigue restricts activities and pleasant events, limits social interactions, interferes with work, and leads to long days alone, depressed mood is a likely consequence.

Fatigue may be due to a variety of medical conditions, such as anemia, low thyroid hormone or low testosterone, or it may be related to HIV medications. When depression is not the obvious cause, fatigue may be treated with testosterone supplementation for men, or stimulant medications such as Ritalin (methylphenidate) or Dexedrine (dextroamphetamine), although the latter are seldom appropriate for those with a history of drug addiction. One promising but as yet unproven medication is Provigil (modafinil), which appears not to cause euphoria or to have addictive potential. Our group is currently studying its effectiveness in a short-term clinical trial for the treatment of fatigue in HIV-positive adults.

Depression and Hepatitis C

It is estimated that about 300,000 HIV-positive patients in the United States, or about 30% of people with HIV, are co-infected with hepatitis C (HCV). Among patients with chronic HCV infection, fatigue is the most common initial symptom (Crone et al, 2004). Although depression also has been reported, this may be secondary to intravenous drug use, which is the most common source of HCV infection and which is often associated with depression (Hauser, 2004). In one study, however, symptoms not severe enough to qualify for a diagnosis of depression have been observed in up to 70% of co-infected patients (Hooshyar, 2004).

Depressive symptoms and disorders are a common side effect of the standard treatment for HCV, alpha interferon and ribavirin. It is estimated that 60% of co-infected patients experience some treatment-induced neuropsychiatric symptoms, and about 30% experience clinical depression as reported in recent clinical trials (e.g. Laguno et al, 2004; Torriani et al, 2004). Most patients with HCV treatment-induced depression respond well to antidepressants, allowing them to complete treatment which otherwise may be prematurely discontinued (Hauser, 2002).

Hepatologists may be reluctant to begin HCV treatment in patients who are already depressed or who have other psychiatric disorders, and this contributes to undertreatment of HCV. Rather than declining to treat depressed patients, psychiatric consultation and antidepressant treatment are recommended and then, after depressive symptoms have lessened (usually after several weeks), HCV treatment can be started.

Depression and Substance Use: Crystal Meth

Although the immediate effect of crystal methamphetamine (MA) is euphoria and heightened energy, depression follows swiftly after the drug effects wear off. In fact, depression is both a precursor and a consequence of chronic MA use. A history of depression is more common among gay and bisexual men than heterosexual men, among people with HIV/AIDS than HIV-negative people, and also among MA abusers, most of whom in New York City are gay men with or without HIV infection, than nonusers.

Depression is particularly prevalent during acute withdrawal, but has been found in high rates even 2-5 years after drug treatment despite significant reductions in MA abuse (Rawson et al, 2002). In a prospective study of 162 gay male MA abusers who participated in a 16-week treatment study, 29% reported at least moderate depressive symptoms at study entry, with significant decreases in symptoms within the first week and through the end of treatment among both HIV-positive and HIV-negative participants, associated with cessation of MA use (Peck et al, 2005).

Acute withdrawal, which occurs within 24 hours after the last use, may resemble a major depressive disorder with loss of interest, depressed mood, fatigue, and suicidal thoughts. Other serious psychiatric effects of prolonged MA use include paranoia, auditory, visual or tactile hallucinations, irritability, and aggressiveness. Cognitive problems, including impaired concentration and memory, are common and may last for months (Jones, 2005). HIV-positive men with hepatitis C who abuse MA have particularly high rates of cognitive impairment.

Overall, use of methamphetamine, past or current, is a significant risk factor for depression; while drug treatment may alleviate depressive symptoms, more focused treatment may be needed.

What Next?

In order to treat depression, it first needs to be identified. With some exceptions, doctors don't ask, and patients don't tell. In HIV settings, both doctors and patients are busy with lab results, prescription renewals, and discussion of medical status, which are their essential tasks. Providers could, however, greatly facilitate discussion of depressed mood and related problems like substance use by asking directly about mood. A simple question such as, "Have you been feeling depressed lately?" can open a conversation, and indicate that the topic is acceptable to address. If appropriate, such a discussion can lead to referral for care if the provider does not feel comfortable prescribing antidepressant medication. Depression screening is recommended at all initial treatment visits, and at least annually thereafter or at any visit if the doctor notices a change in the patient's mood and appearance.

The majority of depressed patients in the United States are treated by their primary providers, not psychiatrists, and increasing numbers of HIV providers prescribe marketed antidepressants to patients with uncomplicated depression. Referral to a psychiatrist is indicated for patients with bipolar disorder or additional psychiatric conditions, including anxiety or psychotic disorders. Psychiatric referral is always needed for patients with severe depression, and for those who express active suicidal thoughts and plans. In addition, if the patient has not responded to one or two antidepressants of adequate length (8 or more weeks) and dose levels, and the patient is actually taking the antidepressant as prescribed, a psychiatric referral may be needed. Once an effective medication regimen has been established and the patient has responded, the primary provider can take over medication prescription in many cases.

Fortunately, increasing numbers of New York City HIV clinics have psychiatrists on site several days a week or full time, which greatly facilitates both treatment access and collaboration between primary provider and psychiatrist. In this respect, clinic patients have an advantage over those who see their HIV physicians in private offices. In addition, Medicaid covers all antidepressant medications, while an increasing number of private insurance companies do not.

Future research concerning depression treatment in HIV/AIDS would best be conducted on-site in HIV clinics, rather than in academic medical centers that may select for more motivated patients who take the time and trouble to travel to participate in studies. In addition, time-limited forms of psychotherapies, whether individual or group, that can be conducted in clinic settings also warrant study, since antidepressant medication may not always be needed or acceptable to some patients.

Finally, it is not only the responsibility of the care provider to ask about problems with depression. People with HIV and their friends and family should recognize that persistent low, sad, or "blue" mood, accompanied by other signs of depression such as loss of appetite, insomnia, guilty feelings, or recurrent thoughts of death, are signals to seek professional evaluation and treatment. Since care providers do not see their patients in everyday situations and surroundings, friends and family can often be the first to spot changes in mood, and can play a vital role in alerting both provider and patient that there may be a problem.

Judith Rabkin is a clinical psychology researcher at Columbia University.

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This article was provided by AIDS Community Research Initiative of America. It is a part of the publication ACRIA Update. Visit ACRIA's website to find out more about their activities, publications and services.