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HIV Treatment Series
II - Part four of four
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sponsored in part by
an unrestricted grant from
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| Coping
with Depression
by Ross Slotten, MD
Depression is the most common psychiatric
disorder in the United States. According to the National Institute
of Mental Health, 10% of American adults, or nineteen million
people over the age of eighteen, suffers from some sort of
depression every year and a third of the adult population
will experience a major depressive episode in their lifetimes.
The  incidence
of depression in individuals living with HIV is twice as high.
This is not surprising, since depression occurs at higher
rates in all groups of people with chronic illnesses. The
economic costs of depression in terms of lost time at work
and medical care are considerable; but the greatest effects
are on health. In patients with HIV disease, severity of depression
correlates with rapidity of decline in CD4 counts, suggesting
that a failure to treat depression may accelerate HIV disease
progression and impact survival. Thus, depression can be as
serious as certain co-infections, like hepatitis B and C.
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Despite clear-cut criteria
for diagnosing depression, depression is not always easy
to diagnose or manage.
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Although there has been considerable progress
in our understanding of the brain, the ultimate cause of depression
is unknown. Even the role of certain neurotransmitters like
serotonin is still unclear, despite intense marketing by the
pharmaceutical industry. The hallmark of depression is an
alteration in mood, but there are physical symptoms as well.
Psychiatrists have identified ten symptoms of depression,
which include the following:
- persistent sad, anxious or empty moods;
- feelings of hopelessness or
pessimism;
- feelings of guilt, worthlessness
or helplessness;
- loss of interest in pleasurable
activities like sex or hobbies;
- decreased energy, fatigue or feeling
“slowed down;”
- difficulty concentrating, remembering
or making decisions;
- sleep disturbances (insomnia,
frequent awakenings or oversleeping)
- appetite and/or unintentional
weight changes;
- thoughts of death or suicide
or suicide attempts; and
- restlessness and irritability.
If five or more of these symptoms are
present every day for at least two weeks, then a person is
suffering from a major depressive episode. If the depressed
moods and two or more of the above symptoms persist for at
least two years, then the person is diagnosed with a dysthymic
disorder (an antiquated term derived from the Greek, meaning
diseased mind—in this case, representing mild, chronic
depression). If in addition to one or more major depressive
episodes, the person experiences wild mood swings in the opposite
direction—that is, inflated self-esteem, grandiosity,
pressured speech and so-called “flight of ideas,”
and abnormally high energy—then he or she is said to
be bipolar.
Diagnosis
Complicating the diagnosis of any mood
disorder is substance abuse, which not only can mask underlying
mental illness but can also mimic one mood disorder or another.
Crystal methamphetamine, for example, elevates a person’s
moods to the height of mania, until the person crashes and
appears profoundly depressed. Chronic use can lead to depletion
of serotonin, which may result in permanent depression unresponsive
to antidepressant medications. Crystal methamphetamine attracts
depressed individuals because it  creates
a temporary sense of well-being and high energy, counterbalancing
the low self-esteem and other debilitating somatic and cognitive
symptoms of depression. After ingestion, this drug can also
produce intense anxiety and palpitations or chest pain; patients
frequently request antianxiety medications like Xanax or Valium
to calm their nerves. Frequent requests for such medication
should raise suspicions of substance abuse. In some studies,
nearly three quarters of HIV-infected individuals who abuse
drugs and alcohol suffers from some sort of psychiatric disorder,
including depression.
Despite clear-cut criteria for diagnosing
depression, depression is not always easy to diagnose or manage.
Patients present with headaches, fatigue and weight loss,
just as people do with other illnesses. If depression is suggested
as a cause, they may insist that something else is wrong.
In HIV-positive patients, the diagnosis of depression is especially
tricky because they may indeed have serious underlying disease.
But unless a person has end-stage AIDS or is on the downward
slope of uncontrolled HIV infection, most HIV-positive people
are relatively healthy—the various nonspecific symptoms
that they are suffering from may be due not to a deadly opportunistic
infection but to depression. Yet ruling out other causes may
be greeted with resistance or skepticism. It is ironic that,
because of the stigma attached to mental illness in our country,
people would rather be told that they have some dreaded disease
than depression.
The public still does not equate psychiatric
disorders with organic disease—diseases of the mind seem
less legitimate than pneumonia or lymphoma. A blood test,
CT scan, MRI or an X ray will not diagnose depression; it
remains a clinical diagnosis, after other diseases have been
ruled out. And treatment is no easier. The prevailing belief
is that depression can be solved by a change in attitude,
finding a new job, moving to a new city, or ending a relationship—all
of which may happen without improvement in symptoms before
the true problem is addressed. In the meantime, the patient
is lonely, unhappy and living in strange surroundings without
adequate emotional support. Moreover, the notion of psychotherapy
or antidepressants repels most people, even though depression
is a treatable condition, unlike the dreaded disease the patient
thinks he or she has.
As mentioned, other diseases should be
ruled out before diagnosing depression. First and foremost
is advancing HIV infection. Patients with declining CD4 counts
and rising viral loads may exhibit a few of the characteristics
of depression, such as fatigue and weight loss. If the patient
has never been treated for his or her HIV infection, or the
patient with resistant disease has remaining treatment options,
then highly active antiretroviral therapy (HAART) should improve
symptoms in a few weeks. AIDS-dementia, now rare, may also
present as a depression-like illness. In more subtle cases,
neuropsychiatric testing—a battery of written and oral
testing by a specially trained psychologist—must be conducted
in order to distinguish between organic brain diseases like
HIV encephalopathy and a mood disorder. Unlike depression,
dementia progresses over time, with profound impairment of
mental processes, radical personality changes, and eventual
alterations in levels of consciousness before death.
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The management of depression
in HIV infection is usually multidisciplinary… The
primary health care provider rarely has the time or expertise
to provide the full scope of services to the depressed person.
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Two other medical conditions should be
considered before treating depression: hypogonadism and hypo-
or hyperthyroidism. Hypogonadism, or abnormally low testosterone
levels, may cause fatigue, weight loss and depressed moods.
For reasons that are unclear, impairment of testosterone production
is common in HIV-infected men. Testosterone deficiency is
defined as a total serum testosterone < 300 ng/dL or a
serum free testosterone < 5-7 pcg/mL. Replacement of testosterone
by injection, topical patches or gel restores a sense of well
being. Both low (hypo) and high (hyper) thyroid levels can
affect mood, which improves when the thyroid problem is treated.
Finally, a number of anti-HIV medications
have so-called neuropsychiatric side effects. The most infamous
in the category of antiretroviral agents is efavirenz (Sustiva
in the U.S. and Stocrin in some other countries), which can
cause an
array of symptoms, from vivid dreams to mood-altering states
mimicking depression. AZT (Retrovir) and abacavir (Ziagen)
can produce extreme fatigue, loss of energy, and depression.
Cause and effect are usually obvious, occurring within days
or weeks of initiation of therapy. When the patient finds
these side effects intolerable, stopping the medication resolves
the problem; persistence suggests another reason for alterations
in mood. Many other agents used to treat a variety of non-HIV
related problems can also depress mood or induce somatic complaints,
but the list is too long to enumerate in this article.
The management of depression in HIV infection
is usually multidisciplinary, involving psychologists, social
workers and psychiatrists. The primary health care provider
rarely has the time or expertise to provide the full scope
of services to the depressed person. When substance abuse
is a problem, access to a good treatment program with sensitivity
to issues unique to HIV like sexuality is essential. In addition
to restoring emotional health, major goals of psychotherapy
are the prevention of the transmission of HIV to uninfected
individuals or reinfection with a resistant strain of HIV,
and adherence to the HIV-treatment regimen.
Most of the DHHS recommendations are common
sense. Implementation of these recommendations, however, can
be a challenge. The clinician must overcome a number of barriers
to ensure proper therapy—social, psychological and medical.
Some of these barriers have nothing to do with the patient
but everything to do with our health care system, which is
fragmentary and driven by third-party payers. Yet until the
creation of a comprehensive health care system in this country—whether
in the form of a single-payer, government-managed system,
or one resembling the mix of government and private payers
cobbled together by the Clinton administration—certain
barriers, such as access to affordable health care for the
working poor, will be impossible to overcome.
First, the patient must be convinced that
he or she is depressed, which, as already noted, is not always
easy. Second, the patient must agree to see a psychotherapist,
at least for an evaluation. For those who lack or have insufficient
mental health benefits, access to less expensive or free mental
health care varies from community to community. In communities
offering such services, quality is not always consistent.
Psychotherapy may span weeks or years, which is a significant
time commitment; out-of-pocket expenses can be considerable,
even for those having the most extensive insurance coverage.
Gay patients often prefer to see a gay therapist, which HMOs
and other managed health care plans may not be able to guarantee,
though insurers have become increasingly sensitive to sexual
orientation in recent years. In some parts of the developing
world, psychotherapists do not exist; patients who emigrate
from those countries may not be amenable to psychotherapy
because they do not accept the Freudian or post-Freudian model
of the mind. Thus, there may be cultural barriers that prevent
patients from obtaining psychotherapy. Third, the primary
care physician or psychiatrist may recommend prescription
medication that patients are reluctant to take. Patients often
resent the addition of yet another medication to an already
burdensome regimen, or they may fear antidepressants, which
they equate with mind-altering substances like LSD. They may
also worry about side effects, especially the impact on sexual
function.
Treatment
The pharmacological treatment of people
with HIV and depression has been studied extensively, though
not every drug available has been examined. The oldest class
of antidepressants, the tricyclics (amitryptilline, imipramine,
desipramine and nortryptilline), were the first drugs subjected
to a scientific evaluation. Approximately three-quarters of
patients given imipramine, for example, responded favorably
as compared to 30% on placebo. However, almost a third of
the patients stopped imipramine because of side effects, which
include constipation, dry mouth, drowsiness, headaches, cognitive
problems and sexual dysfunction. This is unfortunate, because
tricyclics are inexpensive. Today, their role is limited mainly
to the treatment of pain from peripheral neuropathy, which
improves with a dose lower than that for depression. More
expensive medications, like fluoxetine (Prozac), sertraline
(Zoloft), paroxetine (Paxil), citalopram  (Celexa)
and a derivative of citalopram, Lexipro, which belong to the
SSRI class (selective serotonin uptake inhibitors), have produced
response rates as high as 90% in some studies. Side effects
are relatively few, though sexual dysfunction, which is the
most common complaint, occurs at rates higher than the pharmaceutical
companies like to admit. Rarely are erections a problem; most
aggravating is time to ejaculation. In this setting, Viagra,
Levitra and Cialis are of no use, since these agents help
only those men who have difficulty obtaining or maintaining
an erection and do nothing to speed up ejaculation. Venlafaxine
(Effexor), nefazodone (Serzone), buproprion (Wellbutrin) and
mirtazapine (Remeron)—the non SSRI antidepressants—seem
to cause less sexual dysfunction. In fact, bupropion is sometimes
added to an SSRI-containing regimen to improve sexual function.
Few studies with these agents have been conducted in HIV infected
patients—which does not mean they are not effective in
this population. Moreover, there may be a significant interaction
between these non-SSRI agents and antiretroviral regimens
containing Norvir (ritonavir). These drugs should therefore
be used with caution in patients on Norvir boosted PIs or
Kaletra.
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Clinicians, patients,
their families and significant others should suspect depression
when there is no other explanation for depressed mood, fatigue,
or other vague somatic complaints that impair social functioning.
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Psychostimulants, like methylphenidate
(Ritalin), can also help patients who are suffering from depressed
mood, fatigue and cognitive impairment. Their onset of action
is more rapid than that of the tricyclics, SSRIs, and other
antidepressants, which may take four to six weeks before maximal
benefit is observed. Ritalin works in a matter of hours; but
its abuse potential is high and tolerance to its effects typical.
Annoying side effects include overstimulation and insomnia;
and for those who are concerned about maintaining weight or
lipodystrophy, amphetamines suppress appetite. This class
of drugs works best in patients with end-stage disease or
in those whom the clinician suspects adult attention deficit
disorder, a syndrome whose symptoms are difficult to distinguish
from chronic anxiety disorder as well as depression. Finally,
St. John’s wort should be mentioned. Although shown to
be effective for mild depression, St. John’s wort negatively
interacts with indinavir (Crixivan), making regimens containing
indinavir less effective. Its interactions with other protease
inhibitors are unknown. St. John’s wort should not be
used in patients taking HIV medications until further studies
support its safety and efficacy.
In conclusion, depression is a common,
treatable problem in people with HIV infection. It may be
due to a condition long preceding HIV infection or to substance
abuse; or it may arise in the course of infection, either
as a result of HIV medications, illnesses, or the overwhelming
emotional response to HIV itself. If not treated or recognized,
it can profoundly affect quality of life and life expectancy.
Clinicians, patients, their families and significant others
should suspect depression when there is no other explanation
for depressed mood, fatigue, or other vague somatic complaints
that impair social functioning. Psychotherapy and the appropriate
use of antidepressant medications can restore such individuals
to normal emotional health, which, by curtailing self-destructive
behavior and improving adherence to antiretroviral regimens,
will help ensure a long, productive life.
Ross A. Slotten, M.D., M.P.H. is a family
physician in Chicago with a large HIV/AIDS practice.
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Management of Psychiatric Ilnesses in
HIV/AIDS
The U.S. Department of Health and Human
Services (DHHS) has published guidelines for the management
of psychiatric illnesses in HIV/AIDS patients. Management
includes the establishment and maintenance of a therapeutic
alliance, or trust, between patient and health care provider;
collaboration and coordination of care with other mental health
and medical providers; diagnosis and treatment of all associated
psychiatric disorders as well as substance abuse disorders;
facilitation of adherence to overall treatment plan; risk
reduction strategies to minimize the spread of HIV; maximization
of psychological and social functioning; harm-reduction counseling
to substance abusers to minimize unsafe sexual behavior during
drug intoxication and promote adherence to HAART therapy;
assessment and support of the role of religion or spirituality;
ensuring access to housing and financial assistance; preparation
for issues of disability, death and dying; and the education
of significant others or family regarding sources of care
and support.
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