Mood Disorders
Pedro Ruiz
Mood disorders are very common; depression constitutes the second most frequently observed illness worldwide. In the United States, depression is observed in about 5.8% of the general population.1 Among chronically ill persons, the rate of depression is 9.5%. Among patients who suffer from human immunodeficiency virus (HIV) infection or acquired immuno- deficiency syndrome (AIDS), the rate of depression is 20% to 35%.2 Additionally, suicide ideation tends to be present among two thirds of patients who are depressed and the rate of suicide among depressed patients is 10% to 15%. Among patients who have HIV disease or AIDS, however, the suicide rate goes up to 36%.2
In a recent meta-analysis conducted on the relationship between HIV infection and risk for depressive disorders, it was found that the frequency of major depressive disorder was nearly two times higher among HIV-positive subjects than among HIV-negative comparison subjects.3 Among women, the rate of major depressive disorder was found to be four times higher (19.4%) in HIV-seropositive women than in HIV-seronegative (4.8%) women.4 HIV-infected women were also found to have higher mean depressive symptom scores on the 17-item Hamilton Depression Scale relative to comparison subjects who were HIV-negative.4 Major depression is one of the most commonly observed psychiatric conditions among persons living with HIV disease or AIDS.
Given the fact that stigma, prejudice, and discrimination are still very high regarding individuals with HIV disease or AIDS, the evaluation and treatment of these patients tend to be delayed because of their fear of discrimination, in its many, varied forms. Additionally, today patients with HIV disease or AIDS live longer because of new treatment discoveries and better understanding of the mechanisms and factors related to this illness; thus the rate of depression has increased in this population. Fortunately, however, treatment approaches for depressive disorders in this population have also improved, as well as become more effective. This chapter presents a clinical review of diagnosis and treatment approaches on the clinical management of mood disorders among patients with HIV disease or AIDS.
Diagnosis and Symptoms Manifestations
The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)1 diagnostic category of depression is fully applicable to patients with HIV disease or AIDS. With respect to differential diagnosis, however, we must be cognizant of certain psychiatric illnesses that tend
to be common in patients with HIV disease or AIDS. Among them are post-traumatic stress disorder (PTSD), primary sleep disorders, mood disorders due to a general medical condition, cognitive disorders, and dementia.1 For example, among patients with HIV-associated dementia (HAD), symptoms of apathy, social withdrawal, psychomotor slowing, and memory problems may mimic a depressive disorder.5
to be common in patients with HIV disease or AIDS. Among them are post-traumatic stress disorder (PTSD), primary sleep disorders, mood disorders due to a general medical condition, cognitive disorders, and dementia.1 For example, among patients with HIV-associated dementia (HAD), symptoms of apathy, social withdrawal, psychomotor slowing, and memory problems may mimic a depressive disorder.5
Other than HAD, opportunistic infection illnesses and malignancies may masquerade as depression. The most common are toxoplasmosis, cryptoccocal meningitis, cytomegalovirus (CMV) encephalitis, progressive multifocal leukoencephalopathy (PML), and central nervous system (CNS) lymphoma.5 Neurotoxic effects of medications that could lead to mood disorders include steroids (mania or depression), interferon (neurasthenia, fatigue syndrome and depression), interlukin-2 (depression), zidovudine (mania or depression), vinblastine (depression); and efavirenz (depression).2,5 Other medical conditions associated with mood disorders present in patients with HIV disease or AIDS are malnutrition, vitamin deficiencies (specifically B6 and B12), hypogonadism, Addison’s disease, anemia, and hepatic encephalopathy.2,5
Risk Factors
Patients with HIV disease or AIDS at highest risk for depression are those with a personal or family history of mood disorders, alcoholism, substance use, suicide attempts, or anxiety disorders or current use of alcohol or drugs, exposure to chronic stress, inadequate social support, passive coping style, nondisclosure of HIV status, presence of multiple losses, female gender, advanced illness, or treatment failure or success.6,7 Among patients with HIV disease, the rate of depression increases 18 months before the diagnosis of AIDS.
Treatment Modalities
Antidepressants
As general principles when using antidepressants medications for the treatment of depression among patients with HIV disease or AIDS, clinicians should do the following:
Educate the patient about depression and the use of antidepressants.
Start with lower doses of antidepressants and titrate up slowly.
Use the simplest drug regimens possible.
Be cognizant of the side effect profile of the antidepressant being used.
Avoid as much as possible the use of antidepressants with high anticholinergic properties.
Avoid, if possible, the use of high doses of antidepressants, and monitor carefully the treatment when using high dosages.
Monitor potential drug–drug interactions
Be aware that untreated or undertreated major depression may lead to increased utilization of health care services, increased likelihood of unprotected sexual activity, prolonged hospitalization in medical-surgical settings, and poor adherence to both antidepressant and antiretroviral therapy.
Untreated or undertreated depression also leads to a decrease in the patients’ quality of life.
Untreated and undertreated depression will lead to an increase in the number of suicide attempts and completed suicide.
When entertaining psychopharmacologic interventions for the treatment of depression among patients with HIV disease or AIDS, possible unwanted CNS effects of psychotropic
agents must be considered.2,5 Clinicians should also be aware of the potential for drug–drug interactions between antidepressants and antiviral and primary medical therapies used to treat HIV infection and AIDS.2,5,8 For example, antidepressant absorption from the gastrointestinal tract may be altered by antiviral agents; alterations in protein binding may influence free drug levels of both medication regimens; activation of the cytochrome P (CYP) 450 isoenzyme system may alter drug levels via induction or inhibitory mechanisms; and the potential use or abuse of addictive substances may also interact with these kinetic and dynamic factors and exert deleterious effects in both the medical and mood-related therapies.
agents must be considered.2,5 Clinicians should also be aware of the potential for drug–drug interactions between antidepressants and antiviral and primary medical therapies used to treat HIV infection and AIDS.2,5,8 For example, antidepressant absorption from the gastrointestinal tract may be altered by antiviral agents; alterations in protein binding may influence free drug levels of both medication regimens; activation of the cytochrome P (CYP) 450 isoenzyme system may alter drug levels via induction or inhibitory mechanisms; and the potential use or abuse of addictive substances may also interact with these kinetic and dynamic factors and exert deleterious effects in both the medical and mood-related therapies.
Among the antidepressant drugs used to treat depression in patients with HIV disease or AIDS, the selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed.2 Although SSRIs are all equivalent in the treatment of depression, their different pharmacologic profiles should be carefully considered in the selection of a specific agent for use in patients receiving antiretroviral therapy. Of all the SSRIs, escitalopram and sertraline are the least likely to cause adverse events in patients receiving antiretroviral therapies inclusive of the protease inhibitors. For a full discussion of potential drug–drug interactions between antidepressants and medical therapies, see Chapter 16.
Bupropion can be helpful in withdrawn and anergic patients. Some suggest that it should be avoided in persons with advanced HIV disease, AIDS, or dementia because of its potential for seizures and inducing abnormal involuntary movements.2 Nefazodone and fluvoxamine are highly protein bound and are inhibitory of the CYP450 3A4 isoenzyme system. Adding them to an established antiviral regimen will likely increase the serum levels of the antivirals and toxicity. Mirtazapine has a low affinity for the CYP450 isoenzyme system, is sedating, and produces weight gain. It is most helpful in the treatment of patients with poor appetite, weight loss, and significant anxiety and insomnia.2,8
All the tricyclic antidepressants have proven efficacy in the treatment of depression in the context of HIV disease and AIDS. Nortriptyline, desipramine, doxepin, imipramine, and amitriptyline have been reported useful. However, their anticholinergic burden, 1 affinity, and interaction with the CYP450 2D6 isoenzyme system greatly increase the risk of significant treatment-related side effects, including cardiac toxicity, undesirable CNS anticholinergic side effects, sedation, and orthostatic hypotension.2,8 If at all possible, they should be avoided in treating depression in patients with HIV disease or AIDS.
Psychostimulants
The use of psychostimulants might be indicated in the treatment of depression in patients with HIV disease or AIDS.9,10 For example, methylphenidate and dextroamphetamine are often useful adjuvants in treatment of depression among medically ill patients, including those with HIV disease or AIDS.10 Methylphenidate and d-amphetamine have been shown to produce an 85% to 95% positive response in mood symptoms. Psychostimulants can serve to enhance cognition in patients with HIV or AIDS CNS involvement.10 This effect is independent of their mood-altering effects. Psychostimulants are also helpful in patients who suffer from significant disease-related fatigue.
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