Download Article PDF/SlidesDr. Ferrando began his September 2005 PRN lecture by explaining that depression is the most common psychiatric disorder for which HIV-infected patients receive treatment. “A number of epidemiological studies have been conducted,” he said. “However, the rates of depression vary greatly. This has a lot to do with variations in the studies themselves. The studies have been conducted in different settings and involved different risk groups.” Some studies assessed depression using screening instruments in clinic settings. While screenings are efficient, they tend to overestimate prevalence rates. Others involved highly structured psychiatric clinical diagnostic interviews in research cohorts. Regardless of the settings and methods of assessment, Dr. Ferrando explained, rates of depression and other psychiatric disorders are elevated in HIV-positive patients.
Dr. Eric Bing and his colleagues at the Charles R. Drew University of Medicine and Science in Los Angeles analyzed data from the HIV Cost and Services Utilization Study (HCSUS) to examine mental health and substance use in a large, nationally representative probability sample of adults receiving care for HIV in the United States (Bing, 2001). Study participants were administered a brief instrument that screened for mental health disorders and drug use during the previous 12 months.
Nearly half of the sample screened positive for a psychiatric disorder in the past 12 months, including 36% for major depression; 26.5% for dysthymia, a chronic yet less severe form of depression; 15.8% for generalized anxiety disorder; and 10.5% for history of panic attacks. Nearly 40% reported using an illicit drug other than marijuana, and more than 12% screened positive for drug dependence.
The proportion of people screening positive for mental health and substance abuse disorders in the HCSUS sample is considerably higher than that obtained from general population samples. For example, the proportion of people screening positive for major depression in HCSUS is nearly five times greater than the proportion found in the National Household Survey on Drug Abuse (NHSDA).
In another study, conducted at Weill Cornell Medical Center, Dr. Judith Rabkin and her colleagues, including Dr. Ferrando, assessed the prevalence of major psychiatric disorders in HIV-positive gay and bisexual men with AIDS-defining conditions (Rabkin, 1997). Secondary goals were to identify correlates of distress and psychopathology, and to determine whether there is a gradient of distress associated with progressive HIV illness.
The study enrolled 112 men with AIDS-defining conditions; 61 HIV+ men without AIDS, and 84 HIV-negative gay men were assessed. Measures included the Structured Clinical Interview for DSM-IV (SCID), Hamilton Rating Scale for Depression (HAM-D), and other dimensional measures of distress and outlook, as well as laboratory markers of HIV stage, including viral load assays.
Rates of major depression, consistent with other findings using structured diagnostic interviews, were in the 5% to 10% range. Mean scores on dimensional measures of distress and outlook were within the "not depressed" range and did not increase despite increasing HIV illness severity. However, rates of dysthymia were elevated among men with CD4+ counts less than 500 cells/mm3, and the cumulative rates of any current axis I depressive disorder for three of the four study groups were in the range of 15% to 20%. The strongest correlates of dimensional measures of distress were current HIV symptoms and social support, and to a lesser extent, a lifetime history of major depression and current use of antidepressants and/or anxiolytics.
As for injection drug users receiving methadone maintenance treatment, Dr. Ferrando highlighted data published by Dr. Steven Batki and his colleagues at the State University of New York Upstate Medical University (Batki, 1996). Dr. Batki’s group found 80% to be receiving psychiatric intervention, including 42% for depression, 19% for cognitive disorders, 17% for insomnia disorders, 8% for anxiety disorders, 8% for psychotic disorders, and 2% for bipolar disorders. More than 70% of these patients were actively abusing illicit non-opioid drugs while in MMT, including cocaine (60%), alcohol (36%), benzodiazepines (23%), and amphetamines (11%).
As for axis I disorders among medically hospitalized patients with HIV and AIDS, Dr. Ferrando and his colleagues found that 31% had major depression, 19% had delirium and/or dementia, 19% had current substance abuse disorders, 16% had bipolar spectrum disorders, and 13% had anxiety disorders (Ferrando, 1998).
There have also been studies looking at rates of depression over time, whether it’s as HIV disease progresses or improves in response to antiretroviral therapy.
A study conducted by Dr. Constantine Lyketsos and his colleagues at Johns Hopkins University sought to determine whether rates of depressive symptoms change from early- to late-stage HIV infection and to determine the predictors of depressive symptoms as AIDS develops. The data for this study were from 911 HIV-positive men enrolled in the Multicenter AIDS Cohort Study. None of the patients had symptomatic disease upon enrolling in the MACS; all developed AIDS while participating in the study. The outcome measures—overall depressive symptoms, nonsomatic depressive symptoms, syndromal depression, and severe depression—were assessed over the five years before and the two years after AIDS diagnosis from responses on the Center for Epidemiologic Studies Depression Scale (CES-D Scale).
Depressive symptoms were stable over time from month 60 to month 18 before AIDS developed. However, beginning 12 to 18 months before the AIDS diagnosis, there was a significant rise in all measures of depression, which reached a plateau within six months before AIDS developed. At this plateau, there was a 45% increase in mean CES-D Scale scores above baseline. An elevated CES-D Scale score in the earlier stages of infection, a self-report of AIDS-related symptoms (e.g., lymphadenopathy), concurrent unemployment, cigarette smoking, and limited social supports were consistent predictors of higher rates of depression as AIDS developed.
Dr. Ferrando also reviewed data evaluating the impact of depression on morbidity and mortality in the setting of HIV (Ickoviks, 2001). These data, involving HIV-positive women participating in the HIV Epidemiologic Research Study (HERS), are particularly noteworthy given the fact that women with HIV may have higher rates of depression than their male counterparts.
A total of 765 HIV-positive women aged 16 to 55 years were included in the analysis. The main outcome measures were HIV-related mortality and CD4+ cell count slope decline over a maximum of seven years, compared among women with limited or no depressive symptoms, intermittent depressive symptoms, or chronic depressive symptoms, as measured using the self-report CES-D Scale.
In multivariate analyses controlling for clinical, treatment, and other factors, women with chronic depressive symptoms were two times more likely to die than women with limited or no depressive symptoms. Among women with CD4+ counts of less than 200 cells/mm3, HIV-related mortality rates were 54% for those with chronic depressive symptoms and 48% for those with intermittent depressive symptoms, compared with 21% for those with limited or no depressive symptoms. Chronic depressive symptoms were also associated with significantly greater declines in CD4+ cell counts after controlling for other variables in the model, especially among women with baseline CD4+ counts of less than 500 cells/mm3 and baseline viral loads greater than 10,000 copies/mL.
The relationship between psychiatric problems and the return to physical health using combination antiretroviral therapy has also been explored. One report published in 2000 by Dr. Rabkin and her colleagues was based on five semiannual assessments of medical, psychosocial, and psychiatric parameters in a group of gay and bisexual men with symptomatic HIV/AIDS who enrolled in a Cornell-based longitudinal study in mid-1995 (Rabkin, 2000). “The intention of this cohort at the time was to follow medically symptomatic patients as they approached death to look at end-of-life issues,” Dr. Ferrando explained. “Of course, this isn’t what ended up happening, given that protease inhibitors and triple-combination therapy became mainstay therapies by the end of 1995. In turn, we ended up looking at psychosocial and psychiatric parameters associated with restoration of health rather than diminution of health over time.”
Dr. Rabkin’s group observed a statistically significant but clinically modest reduction in measures of depression and hopelessness in the sample as a whole. Overall, the decline in distress was significantly correlated with increasing CD4+ cell count, declining HIV symptoms, and improved social support. As seen in previous studies, physical symptoms were more strongly correlated to psychological distress than were laboratory findings.
| Diagnosis of Depression | Top of page |
Given the high rates of depression in HIV, screening for depression and other mental health and substance abuse issues is a vital component of the clinical management of HIV-infected individuals.
There are both affective and somatic symptoms to be aware of. Affective symptoms include depressed mood, loss of interest, feelings of guilt and/or worthlessness, and suicidal ideation. Somatic symptoms include appetite and/or weight loss, sleep disturbances, psychomotor agitation or retardation, and fatigue. “Of course,” Dr. Ferrando said, “the diagnosis of depression in HIV-infected patients may be confounded by somatic symptoms common to depression and HIV illness itself.”
A diagnosis of Major Depressive Disorder (MDD) requires the presence of five or more symptoms, including depressed mood and/or loss of interest, for two weeks or more (see Table 1)
| Table 1. Diagnosis of Depression in HIV Infection | ||
| Cognitive/Affective | Somatic | |
| I. | Depressed mood | Appetite/weight loss |
| II. | Loss of interest | Sleep disturbance |
| III. | Guilt, worthlessness | Psychomotor agitation/retardation |
| IV. | Suicidal ideation | Fatigue |
| V. | Loss of concentration | |
A diagnosis of depression requires five or more symptoms, including depressed mood and/or loss of interest, for two weeks or more to meet the diagnositc criteria for Major Depressive Disorder. |
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| Source: Stephen J. Ferrando, MD | ||
As evident in the epidemiological studies discussed above, there are several validated instruments for screening to identify depressive symptoms (see Table 2). The Beck Depression Inventory (BDI) and clinician-administered Hamilton Rating Scale for Depression (HAM-D) are frequently used in studies. "The BDI is a self-report," Dr. Ferrando said. "It has been used for many years. The HAM-D is really the gold standard in psychopharmacological research, but does require administration by a trained clinician." There is also CES-D, used mostly in epidemiological studies, which measures generalized distress rather than being specific for depressive symptoms.
| Table 2. Screening Instruments for Patients with Depression | ||
| Screening Instrument | Administration | Notes |
| Beck Depression Inventory (BDI) | Self-report | Cognitive and somatic subscales; widely used clinically. |
| Hamilton Rating Scale for Depression (HAM-D) | Clinician | Affective and vegetative symptom subscales; primarily used in depression treatment research. |
| Center for Epidemiological Studies--Depression (HAM-D) | Self-report | Cognitive and somatic subscales; cut-scores for clinically relevant symptoms; primarily used in epidemiological research. |
| Patient Health Questionnaire-9 (PHQ-9) Depression Module | Self-report | Extensively validated in primary-care settings; keyed to depression diagnostic criteria; other modules screen for somatic symptoms, anxiety disorders, and substance abuse. |
| Hospital Anxiety and Depression Scale (HADS) | Self-report | Screens depression and anxiety; designed for use in medical settings; excludes somatic symptoms. |
| Source: Stephen J. Ferrando, MD | ||
For primary care clinicians, Dr. Ferrando recommends the Patient Health Questionnaire-9 (PHQ-9) Depression Module, which can provide a provisional psychiatric diagnosis. “This screening instrument was designed for use in primary care settings,” he explained. “The idea was to take the DSM and make it user friendly. The advantage of this questionnaire is that is has all of the nine symptom criteria for major depression and has a scoring algorithm. It has been extensively validated in primary-care settings. Basically, a score of ten or more is considered to be clinically significant. And, of course, you always want to query your patients about suicide. Suicidal ideation is highly correlated with depression. The questionnaire takes two to three minutes to look over and it takes very little time for patients to fill out.”
When it comes to depression, the differential diagnosis is very broad in HIV. HIV infection of the central nervous system—manifested as minor cognitve motor disorder (MCMD) or HIV-associated dementia (HAD)—is an important consideration, along with CNS opportunistic illnesses and cancers. “Substance intoxication and withdrawal can also mimic symptoms of depression,” Dr. Ferrando said. Neuropsychiatric side effects of other medications—including efavirenz, interferon, and steroids—should also be considered. “We also have endocrine abnormalities,” Dr. Ferrando said. “The association between testosterone deficiency—hypogonadism—and depression is well established, especially in HIV-positive men. “
One important issue in diagnosing depression is to screen for bipolar disorder. The reason is that antidepressant medications, when given as monotherapy to such patients, can cause mood cycling or precipitate mania (antidepressants should usually be accompanied by lithium or an anticonvulsant in such patients). Patients with bipolar disorder have histories of episodes of mania or hypomania (periods of euphoric or irritable mood, that may include increased energy, decreased sleep, grandiose thinking, increased talkativeness and gregariousness, change in personality, impaired judgment, and paranoia and psychosis in the most extreme form). A simple clinical screen is to ask patients: Have they ever been told they had bipolar illness? Do they have a family history of bipolar illness? Have there been any episodes in the past of sustained elevated mood or energy or uncharacteristic behavior?
| References | Top of page |
