 | | Background | | Major depression is a cause of significant morbidity among people with HIV disease.
Management of this condition may be complicated by its multifactorial etiology. A
diagnosis of HIV may not only cause psychological crisis, but may also complicate
underlying psychological or psychiatric problems (eg, preexisting depression, anxiety,
or substance abuse). In addition, direct viral infection of the central nervous system
(CNS) can cause several neuropsychiatric syndromes. Finally, both constitutional disease
and medications can impair neurologic function and mood. The clinician's task is 4-fold:  | Maintain a high index of suspicion for depression and screen frequently for mood
disorders. | | | Elicit any history of psychiatric diagnoses or treatment. | | | Rule out organic causes of mood or functional alterations. | | | Refer for appropriate psychiatric evaluation and psychosocial support, including
substance abuse counselors and domestic violence service providers. | |
Patients with untreated depression experience substantial morbidity and may become
self-destructive or suicidal. They are also at continuing risk for unsafe behaviors
that may lead to HIV transmission. Major depression in persons with comorbid medical illness, including HIV infection,
has been associated with numerous adverse events, such as the following: | Decreased survival | | | Impaired quality of life | | | Decreased treatment adherence | | | Longer hospital stays | | | Increased risk behaviors | | | Suicide | |
Although depression occurs independently of physical symptoms, recent research has
concluded that it is associated with higher mortality rates in HIV-infected individuals.
Stress and depressive symptoms, especially when they occur jointly, are associated with
diminished immune defenses in HIV-infected individuals. | |
| SOAP (Subjective, Objective, Assessment, Plan) | | | Subjective | | The patient may complain of the following: | Appetite changes with weight changes (increase or decrease) | | | Decreased ability to concentrate | | | Depressed mood, sadness, hopelessness | | | Diminished interest or pleasure in activities | | | Fatigue or loss of energy | | | Feelings of worthlessness or guilt | | | Insomnia or hypersomnia | | | Psychomotor agitation or retardation | | | Recurrent thoughts of death or suicide | |
| History | | Inquire about the symptoms listed above, and about associated symptoms. If 5 of these
symptoms occur on most days for at least 2 weeks, a clinically significant major
affective disorder is present and requires intervention. Depressed mood or
diminished interest or pleasure must be 1 of the 5 symptoms present. Take a careful history of the timing of symptoms, their relationship to life events
(eg, HIV testing, loss of a friend) and any other physical changes noted along with
the mood changes. Elicit personal and family histories of depression or suicidal
behavior. Probe for suicidal thoughts, plans, and materials to execute the plans.
Inquire about hallucinations, paranoia, and other symptoms. Take a thorough history
of medication use and substance abuse. | |
| |
| Assessment | | | Partial Differential Diagnosis | | Rule out nonpsychiatric causes of symptoms, which may include the following: | Vitamin B12, folate (B6), zinc, or vitamin A deficiency | | | Hypothyroidism or hyperthyroidism | | | Endocrine disorders such as Addison disease or hypotestosteronism (hypogonadism) | | | HIV dementia or minor cognitive motor disorder | | | HIV encephalopathy | | | Neurosyphilis | | | Opportunistic illnesses affecting CNS (eg, toxoplasmosis, cryptococcal disease,
CNS cytomegalovirus, progressive multifocal leukoencephalopathy) | | | Medication adverse effects (eg, from steroids, efavirenz, isoniazid,
interferon-alfa) | | | Substance-induced mood disorder (intoxication or withdrawal) | |
| |
| Partial Psychiatric Differential Diagnosis | | | Adjustment disorder (eg, acute reaction to a life crisis, such as HIV diagnosis,
bereavement, job loss) | | | Anxiety disorders | | | Bereavement | | | Dysthymia (depressed mood of long duration with less intensive symptoms) | | | Psychotic depression | |
| |
| |
| Plan | | | Treatment | | Make sure that the patient has been referred to available community organizations for
support. Refer immediately for psychiatric evaluation or treatment if the patient is: | Suicidal (see chapter Suicidal Ideation)
| | | Displaying psychotic symptoms | | | Debilitated or functionally impaired by severe symptoms | | | Not responding to treatment | |
| Pharmacotherapy | | When selecting antidepressant medications, consider their side effect profiles as
a means to treat other symptoms. For example, activating medications can be
taken in the morning if the patient complains of low energy; medications that
increase appetite may be useful for patients with wasting syndrome; sedating
medications may be taken at bedtime if the patient complains of sleep problems. Monitor patients closely after starting antidepressant medications. Some patients
may be at risk of worsening depression, including suicidality, after initiation
of therapy. Because of the potent inhibition of the microsomal cytochrome P450 isoenzymes by
protease inhibitors (especially ritonavir), antidepressants used concomitantly
with protease inhibitors should be started at low dosages and titrated
cautiously to prevent antidepressant adverse effects and toxicity. Interactions
between selective serotonin reuptake inhibitors (SSRIs) and HIV medications are
fairly common. For patients who are starting antiretroviral medications
(particularly protease inhibitors) and are on a stable antidepressant regimen,
an empiric dosage reduction of antidepressant therapy should be considered,
especially if the antidepressant dosage is at the high end of the range or the
patient is having adverse effects of the antidepressant before starting
antiretroviral therapy. Consultation with an HIV expert, psychiatrist, and
clinical pharmacist can assist in developing an effective antidepressant and HIV
therapy combination. A therapeutic trial consists of treatment for 4-6 weeks at a therapeutic dosage.
Medications should be continued for 6-9 months beyond the resolution of symptoms
to reduce the risk of recurrence. After this time, treatment may be gradually
tapered if the patient wishes, with careful monitoring for recurrence of
symptoms. The risk of recurrence is higher if the first depressive episode is
inadequately treated or if the patient has had multiple depressive episodes. Table 1 lists the available antidepressant medications (SSRIs and
serotonin/norepinephrine reuptake inhibitors [SNRIs]), including therapeutic
dosages and possible positive and negative effects. Table 1. SSRI and SNRI Antidepressant Medications and Possible Positive and Negative Effects| Medication: Usual Dosage | Possible Positive Effects | Possible Negative Effects |
|---|
|
* When discontinuing paroxetine therapy, carefully titrate the
dosage reduction to avoid serious adverse effects associated with abrupt
discontinuation. Such effects include confusion, agitation, irritability,
sensory disturbances, and insomnia.
** Note: Monitor blood pressure at
higher dosages of venlafaxine. | |
Fluoxetine (Prozac): 10-40 mg once daily |
Rarely sedating, often energizing, no cardiovascular
adverse effects, no anticholinergic effects, nonfatal in overdose |
Insomnia, agitation, nausea, headache, sexual
dysfunction in men and women, long half-life | |
Paroxetine* (Paxil): 10-40 mg once daily |
May be sedating (for patients experiencing sedation
with paroxetine, dose at bedtime; can be useful with
depression-associated insomnia) |
Insomnia, agitation (for patients experiencing these
effects, administer dose in mornings), nausea, headache, sexual
dysfunction in men and women | |
Sertraline (Zoloft): 50-100 mg once daily |
May have lower incidence of significant drug-drug
interactions compared with fluoxetine and paroxetine; nevertheless,
start with lower dosages when this medication is used with protease
inhibitors |
Insomnia, agitation, nausea, headache, sexual
dysfunction in men and women, long half-life | |
Venlafaxine XR** (Effexor XR): 75-375 mg once daily |
May have lower risk of significant drug-drug
interactions compared with SSRIs |
Nausea, headache, nervousness, sexual dysfunction | |
Citalopram (Celexa): 10-60 mg once daily or
escitalopram (Lexapro): 10-20 mg once daily |
May have lower risk of significant drug-drug
interactions than other SSRIs |
Mild nausea, possible sedation | | |
| |
| Other Agents | | Newer antidepressants such as mirtazapine may be particularly useful in patients who
have significant insomnia and in those who have experienced sexual dysfunction with
other antidepressant agents such as SSRIs. | Mirtazapine (Remeron) should be administered at bedtime because of its
sedating effects. Sedation is commonly noted with the starting dosage of 15 mg
once daily, but may be lessened by increasing the dosage to 30 mg at bedtime.
Individuals may also experience an increase in appetite, weight gain, and dry
mouth. Mirtazapine has minimal drug-drug interactions. The therapeutic dosage
range is 15-45 mg once daily. Consider starting with 15 mg at bedtime for 7
days, then increasing to 30 mg if sedation is problematic. | | | Bupropion (Wellbutrin) sustained-release (SR) or extended-release (XL)
formulation may be used in individuals with depression who experience sexual
dysfunction with other antidepressant agents. Bupropion SR or XL dosing should
not exceed 400 mg per day (the SR formulation should be administered twice daily
in divided doses) because of an increased risk of seizures at higher bupropion
dosages, particularly in individuals who have other risk factors for seizures.
For patients taking protease inhibitors, caution should be used as the dosage
approaches 300-400 mg per day because of possible increases in levels of
bupropion. Bupropion may have an activating effect, which some patients may
experience as agitation, insomnia, or both, and also may have an appetite
suppressant effect. | | | Nefazodone (Serzone) may cause liver toxicity and generally is not recommended
as an antidepressant for patients with HIV/AIDS because of the high rates of
preexisting liver abnormalities in HIV-infected patients. This medication has
recently received a black box warning regarding severe liver toxicity from the
U.S. Food and Drug Administration. If the patient has ever had liver toxicity
from the drug, restarting is contraindicated. | | | Tricyclic antidepressants may be effective, but in general have a higher risk
of adverse effects than SSRIs and are dangerous if overdosed. | | | Treatment may involve antidepressant combinations, including psychostimulants. | | | Patients with prominent insomnia may benefit from the addition of trazodone
25-50 mg, given 1-2 hours before bedtime. | | | St. John's wort is an herbal antidepressant that is contraindicated
for use with protease inhibitors and nonnucleoside reverse transcriptase
inhibitors. St. John's wort can significantly decrease serum
concentrations of these HIV medications. | |
| |
| |
| |
| Patient Education | | |
| Providers should explain to patients that illness (physical or emotional) is not a
character flaw or a moral or spiritual weakness. It is an expected aspect of HIV
infection. Sadness is a normal part of life, but major depression is always abnormal
and often can be alleviated with medication, therapy, or both. | | | Antidepressants typically are given for a long time, usually for a year or longer,
to help patients with the chemical imbalances associated with depression. | | | When starting an antidepressant medication, patients should expect that it will
take 2-4 weeks for them to notice any improvement. Their symptoms should continue to
decrease over the following weeks. If they do not have much improvement in symptoms,
their providers may choose to adjust the dosage of the medication or to change
medications. Patients must continue taking their medications so that the symptoms of
depression do not return. | | | Some patients develop problems with sexual function while they are taking
antidepressants. They should report any problems to their prescribers. | | | Patients should note the major symptoms of depression and be aware of what factors
led them to seek treatment. They will need to monitor themselves for recurrences and
get help if the symptoms come back. Providers should explain to patients that if
they notice changes in their sleep, appetite, mood, activity level, or
concentration, or if they notice fatigue, isolation, sadness or helplessness, it is
time to get help. | |
|
|
| |
| References | | | The appearance of external hyperlinks does not constitute endorsement by the Department of Veterans Affairs of the linked Web sites, or the information, products or services contained therein. | | |
| American Psychiatric Association. Diagnostic and Statistical Manual of Mental
Disorders. Washington: American Psychiatric Association; 1994. |  | | Ickovics JR, Hamburger ME, Vlahov D, et al. Mortality, CD4 cell count decline, and depressive symptoms among HIV-seropositive women: longitudinal analysis from the HIV Epidemiology Research Study. JAMA. 2001 Mar 21;285(11):1466-74. | | | Leserman J, Petitto JM, Perkins DO, et al. Severe stress, depressive symptoms, and changes in lymphocyte subsets in human immunodeficiency virus-infected men. A 2-year follow-up study. Arch Gen Psychiatry. 1997 Mar;54(3):279-85. | | | Mayne TJ, Vittinghoff E, Chesney MA, et al. Depressive affect and survival among gay and bisexual men infected with HIV. Arch Intern Med. 1996 Oct 28;156(19):2233-8. | | | Motivala SJ, Hurwitz BE, Llabre MM, et al. Psychological distress is associated with decreased memory helper T-cell and B-cell counts in pre-AIDS HIV seropositive men and women but only in those with low viral load. Psychosom Med. 2003 Jul-Aug;65(4):627-35. | | | Schatzberg AF, Nemeroff CB, eds. Textbook of Psychopharmacology. Washington:
American Psychiatric Press Inc.; 1998:257-263, 1017. | | | Stober DR, Schwartz JAJ, McDaniel JS, et al. Depression and HIV disease:
prevalence, correlates and treatment. Psychiatric Annals 1997:27(5):372-377.
| |
| |
| | | |
