Among patients with HIV infection, clinical depression is the most frequently observed psychiatric disorder, affecting between 4 percent and 14 percent of gay men and non-drug-using women, with higher rates among both infected and uninfected injection drug users. But while these rates demonstrate a connection between HIV disease and depression, it is not a direct one: despite the intuition that HIV disease might bring on depression, the evidence suggests that there is rarely a cause-and-effect relationship between the two. The majority of HIV-infected people with current depressive disorders have a history of depression that antedates HIV infection, and depression is not correlated with disease stage, T-helper cell count, or HIV-related medication use.
By reviewing the data on HIV disease and depression, this article seeks to dispel the belief that the two are inextricably linked. In doing so, it clarifies when and among whom HIV-related depression is likely to arise. In these cases, both psychotherapy and aggressive antidepressant treatment can be extremely effective.
Epidemiology: Scope of the Problem
Early descriptive reports of psychiatric morbidity among those with HIV infection, which relied primarily on self-report rating scales and samples seen in medical settings, described exceptionally high rates of symptomatic depression and anxiety. More recent studies of community samples and research volunteers, using either symptom checklists or structured diagnostic instruments and trained professional interviewers, have found rates among seropositive gay men to be approximately equal to their seronegative counterparts. When researchers compare rates for HIV-infected populations to general population rates, some investigators have found higher rates of depression, while others have not. Nevertheless, it has become increasingly clear that clinical depression is not the norm and therefore should not be expected among people with HIV disease.
At the same time, while transient mood states are not routinely recorded in epidemiologic studies, it is important to recognize that the majority of HIV-infected people are likely to experience periods of sadness and distress from time to timeþparticularly in relation to the illness or the death of friends. This is to be expected and is common. Therefore, the absence of a current depressive episode does not necessarily signify a total absence of distress.
Follow-up studies of HIV-infected men and women suggest that rates of depression do not increase over time. For example, a Chicago study of 436 subjects using self-rating scales to assess depressive symptoms found stable scores over a period of six bi-annual evaluations.1 A Cornell University study of 328 seropositive and seronegative, gay and heterosexual men and women found a decline in depressive symptom severity over time on both clinician and self-rated scales.2 There was no difference between infected and uninfected subjects on any occasion. A Columbia University study similarly failed to observe increased rates of depressive disorders among either seropositive or seronegative gay men followed over four years or among injection drug users surveyed at three semi-annual visits.3
Cross-sectional studies comparing symptomatic and asymptomatic men and women have resulted in inconsistent findings regarding rates of psychopathology. More recent reports have not found different rates of depression in samples at different stages of HIV illness The cumulative evidence does not support the notion that depression increases as HIV disease progresses.
Diagnosis of Depression
Diagnosis may be complicated by the fact that both depression and HIV disease result in similar somatic or physical symptoms. Fatigue, lethargy, low libido, low appetite, and weight loss may be manifestations of either HIV-related illnesses or depressive disorder. In contrast, cognitive and affective symptomsþsuch as feeling sad, losing interest in formerly enjoyable activities, guilt, and irritabilityþare components of mood alone. In evaluating "interest," for example, practitioners must distinguish between loss of physical energy and loss of interest per se. Clients might say that they have to push themselves to do things, or that they have stopped engaging in formerly pleasurable activities, but this may be due to either depression, fatigue, or loss of physical functioning. For clarification, a therapist might ask, "If you had the energy, are there things youþd like to do today?
Similarly, if reduced appetite and weight loss occur in the presence of medical problemsþsuch as oral lesions, which make eating difficult, gastrointestinal disease, or antibiotics known to cause anorexia or nauseaþthese indicators would not be considered depressive symptoms if they were not also initiated, maintained, or exacerbated by depressed mood. Typically, clients can assist clinicians in making these distinctions. For example, ask the client, "If it were not for the lesions in your mouth, or the antibiotic you are taking, would you feel like eating?" With experience, the diagnosis of depression even in the context of severe medical illness can be done with greater confidence.
Risk Factors for Depression in HIV Illness
What factors related to HIV disease are likely to be associated with depression? Researchers have looked at a variety of factors including being gay, taking HIV-related medications, being immune-suppressed, and being HIV-infected. None of these studies support the conclusion that HIV disease and depression are inherently associated with one another. Studies of current and past psychopathology in community samples of gay men have revealed surprisingly high lifetime rates of depressive disorders, despite low rates of current depression. Investigators at both Cornell and Columbia reported lifetime prevalence of depression in the range of 30 percent to 35 percent for gay men compared to 5 percent for the general population. Given the recurrent nature of depression, these findings suggest increased vulnerability to future episodes of depression in this group.
There appears to be no systematic published research regarding the effects on mood of any HIV-related medication or on the interactions between these medications and antidepressant drugs. Some published case reports suggest that zidovudine (ZDV; AZT) may be mood-enhancing or mania-inducing, although occasionally clients report that ZDV causes depression. It is of course difficult to separate out the symbolism of initiating antiviral treatment from the chemical effects of the compound, or the effects of multiple HIV-related medications prescribed prophylactically or acutely as illness progresses. Overall, in view of the widespread use of these medications, especially ZDV, and the absence of documentation otherwise, the case reports may represent idiosyncratic rather than common mood effects.
It has been suggested but not demonstrated that HIV itself causes mood changes and that HIV-associated dementia induces depression. However, there is little evidence to support either of these hypotheses. A study of HIV-infected men did not find depressed mood to be associated with early subtle cognitive changes.4 Apathy, rather than sadness, appears to be the predominant affect in HIV-associated dementia.
Finally, published studies on the relationship between depression and HIV-related immune compromise continue to offer inconsistent results. Some investigators have reported an association between depression and the decline in T-helper cell count. In contrast, a longitudinal study of 113 seropositive gay men found no relationship between syndromal depression, psychiatric distress, or psychosocial stressors and immune status or HIV illness stage.3 Greater distress was not associated with greater immunosuppression or more advanced illness stage, either concurrently or over time. Other studies also support this conclusion.5,6
Overall, the weight of the evidence does not support "a measurable or substantial effect" of psychosocial factors such as depression or stress "on [enumerative measures of] the immune system in relation to physical disorders such as AIDS" using the endpoints of medical outcome and death.7 With the advent of more direct measures of viral load such as polymerase chain reaction (PCR) and branch DNA, further study may be worthwhile.
Treatment of depression in the general population is one of psychiatry's success stories, and there is no evidence that it should be different for people with HIV disease. While limited, published research on antidepressant treatment for seropositive clients together with extensive clinical experience suggests that HIV-infected depressed patients respond as their uninfected counterparts to both antidepressant medications and brief, focused psychotherapies.8 Tricyclic antidepressants, serotonin re-uptake inhibitors, and psychostimulants have all been shown to be effective in this population. Preliminary evidence suggests that testosterone replacement therapy may also have positive mood effects. In a study of men with advanced immunosuppression and clinical symptoms of hypogonadism (low testosterone levels), 69 percent of those who complained of depressed mood showed clear-cut mood improvement after eight weeks of treatment.9
Psychotherapy is also an effective approach to depression, particularly in terms of adjusting to a seropositive statusþa process that requires integrating new information into an existing identity. This process necessarily includes questioning assumptions about life, redefining priorities, establishing new goals, and acquiring new skills. It is an effort that takes time and can also evoke a sequence of grief, loss, and rage in the patient. During this process, people living with HIV disease typically experience a wide range of emotional reactions to the actual, as well as the anticipated, events in their lives. They may feel hopeful, calm, and connected one day, and pessimistic, fearful, and alienated on another. Psychotherapy can validate this wide range of feelings as normal and can provide a safe environment in which clients can express emotion, allowing them to "ride the roller coaster" without "falling apart."
There are specific times in the course of HIV disease during which clients are particularly vulnerable to acute distress: the confirmation of HIV infection, the initial onset of physical symptoms, a sudden decline in T-helper cell count, the first opportunistic infection. While time-limited psychotherapy and antidepressant medication are effective in responding to this distress, they do not assure sustained well-being. Given the unpredictable nature of HIV progression, it is prudent for therapists to encourage clients to maintain contact and return to treatment during difficult times.
To treat HIV-related depression effectively, therapists need to be flexible in terms of availability during illness episodes, willingness to make home or hospital visits, and the scope of their attention during late stage illness when partners, close friends, or family members may also be at the bedside. They must also be prepared to talk about progressive physical decline, approaching death, and the circumstances of dying.
Clinicians have remarked upon the surprisingly gratifying nature of working with HIV-infected patients. As the awareness of a foreshortened life may be associated with grief and depression, it may also help patients to focus on what is important, and to motivate efforts to accomplish goals and reach clarity about concerns that really matter. Even if we cannot prolong life, we can help make life worth living.
It is understandable that therapists might assume that people faced with disability, pain, and a threat to life might become depressed. But the presumption that all or even most people with HIV disease suffer from clinical depression is wrong and does a disservice to clients. The data show that depression is neither more common among people with HIV infection nor likely to increase as HIV disease progresses.
While HIV-infected individuals may experience distress during the course of disease, depression is not "normal" for them. This is important for two reasons. It implies that people with HIV disease are more psychologically resilient than we may assume, and it suggests that when clinical depression does arise in a client, therapists should not dismiss it as usual and understandable but should instead treat it aggressively.
Joseph JG, Caumartin SM, Tal M, et al. Psychological functioning in a cohort of gay men at risk for AIDS: A three-year descriptive study. Journal of Nervous and Mental Disease. 1990; 178(10): 607-615.
Perry S, Fishman B, Jacobsberg L, et al. Relationships over one year between lymphocyte subsets and psychosocial variables among adults with infection by HIV. Archives of General Psychiatry. 1992; 49(5): 396-401.
Rabkin JG, Williams JBW, Remien RH, et al. Depression, distress, lymphocyte subsets and HIV symptoms on two occasions in HIV-positive homosexual men. Archives of General Psychiatry. 1991; 48(2): 111-119.
4. Stern Y, Marder K, Bell K, et al. Multidisciplinary baseline assessment of homosexual men with and without HIV infection: III. Neurologic and neuropsychologic findings. Archives of General Psychiatry. 1991; 48(2): 131-138.
Evans D, Lesserman J, Perkins D. Stress-related reduction of natural killer cells in HIV. Presentation from the VII International Conference on AIDS, Florence, Italy, June 1991.
Kessler RC, Foster C, Joseph J, et al. Stressful life events and symptom onset in HIV infection. American Journal of Psychiatry. 1991; 148(6): 733-738.
Stein M, Miller AH, Trestman RL. Depression, the immune system and health and illness: Findings in search of meaning. Archives of General Psychiatry. 1991; 48(2): 171-177.
Markowitz JC, Rabkin JG, Perry SW. Treating depression in HIV+ patients. AIDS. 1994; 8(4): 403-412.
Rabkin JG, Rabkin R, Wagner G. Testosterone replacement therapy in HIV illness. General Hospital Psychiatry. 1995; 17(1):37-42.
Judith G. Rabkin. PhD is Professor of Clinical Psychology in Psychiatry at the College of Physicians and Surgeons, Columbia University, and a Research Scientist at New York State Psychiatric Institute. She is co-author, with Dr. Remien, of Good Doctors/Good Patients: Partners in HIV Treatment (NCM Publishers, Inc., 1994).
Robert H. Remien, PhD is Assistant Professor of Clinical Psychology in Psychiatry at the College of Physicians and Surgeons, Columbia University, and a Research Scientist at New York State Psychiatric Institute.
1995 UC Regents: All rights reserved. Reproduced with permission. Rights to further reproduction must be requested by writing. FOCUS, UCSF AIDS Health Project, Box 0884, San Francisco, CA 94143-0884, 415/476-6430. Subscription information: Twelve issues of FOCUS are $36 for U.S. residents, ($48 foreign), $90 for U.S. institutions, ($110 foreign), and $24 for those with limited incomes. Make checks payable to "UC Regents." Address subscription requests and correspondence to: FOCUS, UCSF AIDS Health Project, Box 0884, San Francisco, CA 94143-0884. Back issues are $3 each: for a list, write to the above address or call: 415/476-6430.