Disturbances of mood occur frequently in the context of HIV
infection. Treatment studies are quite varied with regard to variables
such as severity of mood disorder, methodology to categorize or
diagnose mood disorders, outcome measures, and stage of HIV illness.
a) Acute treatment of depressive disorderssomatic
Many studies, including randomized controlled trials, open-label
trials, case series, and case reports, support the efficacy
and safety of many antidepressants in the acute treatment
of depressive disorders, including major depression, in a wide range
of HIV-infected populations at all disease stages.
Wagner and colleagues (286) reported on a series of 6-week
studies that used random assignment and placebo control to examine
the efficacy of standard and alternative antidepressants for major depression
in HIV-infected patients. The agents used at standard doses were
fluoxetine, sertraline, imipramine, dextroamphetamine, and testosterone.
Response rates to the different agents ranged from 70% to
93% and were significantly higher than placebo.
Similar findings were reported in a randomized, placebo-controlled
clinical trial conducted by Elliot and colleagues (287) in 75 HIV
patients (45% with AIDS) who had major depression. Both imipramine-
and paroxetine-treated groups improved significantly compared to
placebo at weeks 6, 8, and 12. The dropout rate due to side effects
was higher for those receiving imipramine (48%) than it
was for placebo (24%) or paroxetine (20%).
One randomized, placebo-controlled clinical trial (N=120)
found that fluoxetine was an efficacious antidepressant agent among
depressed HIV patients; the response rate for fluoxetine was 74% versus
47% for placebo (289). The same study reported significant
differences between ethnic groups in terms of antidepressant efficacy;
the response rates were 84% for white, 67% for
Latino, and 50% for black subjects (414). Despite the effectiveness
of fluoxetine in treating depression, because both placebo response
and attrition were high, the researchers suggested that the addition
of another medication in patients with serious medical illness who
require multiple concomitant medications may be a significant barrier
to the treatment of depression.
In a double-blind, placebo-controlled trial that compared
desipramine to fluoxetine in 14 women with advanced HIV
disease, both agents were linked to symptom improvement; however,
for most of the women significant depressive symptoms remained after
the 6-week trial (294). These findings are consistent with those
of an open-label fluoxetine trial that compared HIV-positive and
HIV-negative depressed men, which found that improvement in the
HIV-positive cohort was significantly delayed beyond the
8-week trial compared to the HIV-negative patients (415).
The randomized trials are supported by uncontrolled studies
of depression in HIV populations and confirm the effectiveness of
fluvoxamine (295) and fluoxetine (293, 416, 417) in HIV-infected asymptomatic patients
and of paroxetine, sertraline, and fluoxetine in symptomatic HIV
patients (285, 418). In an open trial in which HIV-positive depressed
women were given either fluoxetine or sertraline, both drugs were
found to be effective treatments (419). Another open-label study
found nefazodone effective in the treatment of depressed
HIV-positive patients (288). One open-label trial of 32 patients
with advanced HIV disease found venlafaxine effective among depressed
patients who also had minor cognitive motor disorder (420).
The use of psychostimulants for treatment of major depression
in HIV-infected outpatients has been supported in smaller studies,
including five case reports, one open-label trial, and one placebo-drug-placebo
clinical trial (321, 322, 421, 422). These studies suggest that
methylphenidate, up to 35 mg/day, or dextroamphetamine,
up to 10 mg/day, can improve major depression.
An open trial of testosterone replacement for hypogonadal
men found that of 34 study participants with major depressive disorder,
79% had significant improvement in mood (126). There is
a case report of a patient with HIV infection and comorbid major
depressive disorder whose depression resolved with treatment with
the antiretroviral agent zidovudine (423). For patients with severe
major depression who are delusional or have failed medication treatment,
ECT has been found to be safe and effective (424).
b) Acute treatment of depressive disorderspsychotherapy
Several studies of psychotherapeutic treatment of depression
in HIV patients have been conducted. In a randomized, controlled
trial, Targ and colleagues (425) compared structured group therapy
plus fluoxetine to structured group therapy with placebo in 20 asymptomatic
homosexual men with major depression or adjustment disorder and
Hamilton Depression Rating Scale scores 16.
Both groups showed significant improvements in depression after
6 weeks of treatment, but there were no differences between treatment
groups (425). In contrast, another randomized, placebo-controlled
clinical trial that compared the efficacy and safety of fluoxetine
plus group psychotherapy versus group psychotherapy alone in 47
depressed HIV-positive men for 7 weeks found that fluoxetine
in addition to group therapy was more efficacious than group psychotherapy
alone. Differences were particularly apparent for patients
whose initial depressive episodes were rated as severe
(Hamilton depression score 24)
Markowitz and colleagues (426) conducted a randomized, placebo-controlled
clinical trial that compared 16-week interventions with interpersonal
psychotherapy, cognitive behavior therapy, supportive psychotherapy,
and supportive psychotherapy plus imipramine in 101 HIV
patients with depressive symptoms (Hamilton depression score 15).
Patients randomly assigned to interpersonal psychotherapy and supportive
psychotherapy plus imipramine had significantly greater symptom
improvement than those receiving supportive psychotherapy alone
or cognitive behavior therapy.
In an earlier study (427), the Markowitz group demonstrated
the benefits of interpersonal psychotherapy in HIV-positive, asymptomatic
outpatients in an open study of men and women with DSM-III-R major
depression or dysthymia. Twenty (87%) out of 23 patients
achieved a full remission after 6 weeks by clinical assessment;
mean Hamilton depression scores at baseline and follow-up were 25
and 6.8, respectively. Levine et al. (428) reported that four outpatients
with major depression remained euthymic for 9 months with
structured group psychotherapy after acute remission was achieved
with fluoxetine, 20–40 mg/day.
Other studies such as two retrospective chart reviews (284, 429) and a prospective effectiveness study (430) support the findings
from controlled and uncontrolled treatment studies of major depression
that treatment with a number of different antidepressant agents
is effective and generally tolerated in HIV patients.
c) Treatment of other types of depression
Other studies have investigated the efficacy of treatment
for other types of depression in HIV patients. These studies generally
use screening instruments (e.g., the Center for Epidemiologic Studies
Depression Scale [CES-D Scale]) rather than structured
interviews or clinical evaluations to diagnose specific depressive
disorders. All involved ambulatory patients who had no significant clinical
manifestations of HIV disease. In a study of patients with depression
(CES-D Scale score >16) but with unknown psychiatric diagnoses,
investigators compared cognitive behavior therapy and brief supportive
group therapy to a waiting list control condition. Outpatients
(N=68) were randomly assigned to an 8-week intervention
of cognitive behavior therapy, support group, or a control group.
While both types of psychotherapy were superior to the control condition,
neither led to significant reductions on the CES-D Scale into the
nondepressed range (431).
Eller (432) conducted a randomized, placebo-controlled clinical
trial of alternative therapies for depression and assigned 81 male
and female outpatients with HIV infection to guided imagery, relaxation
therapy, or usual care. The sample had a mean CES-D Scale score
of 19. There were no significant declines in CES-D Scale scores
during treatment in any of the three groups.
d) Treatment of mania/bipolar disorder
One chart review (433) and one case report (434) have addressed
the treatment of manic syndromes in HIV-infected patients. The chart
review study identified seven male outpatients with mania who did
not improve with lithium or neuroleptic treatment due
to toxicity. Three patients had been treated with valproic acid
(750–1750 mg/day), two with clonazepam (2 mg/day),
one with phenytoin, and one with carbamazepine. All seven patients
experienced remission of their manic syndrome with the agent used
(433). The case report described the effectiveness of valproic acid
in the treatment of acute mania in a patient with AIDS complicated
by dementia (434). There are no published studies of maintenance
treatments for mania or bipolar disorders in HIV-infected populations.