While these are only a few questions that may arise with new treatments, these thoughts may evoke a myriad of feelings including helplessness, loss of control, rejection, hopelessness, isolation, withdrawal, anger, sadness and fear. These feelings may become what is known as depression or in clinical terms, a major depressive episode. With changes in treatment, many people experience these feelings with the multiple losses of control that occur in the context of HIV infection. One might assume that HIV-infected individuals would "naturally" become depressed upon learning of their infection or upon the realization that they are unable to tolerate a protease inhibitor. Studies have investigated this, and although there have been no large-scale epidemiological studies, as with many chronic illnesses, this is not the case. Depression in HIV infection is similar to depression in other chronic illness such as heart disease or diabetes.
|Table 1: Symptoms of a Major Depression|
Adapted from the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), 4th edition. Washington, DC: American Psychiatric Press 1994:327.
Depression has a significant effect on quality of life, progression of disability and ability to receive good medical care. With the development of HAART, which has the potential to manage HIV infection and prolong life, treatment of depression is even more important, since untreated depression could both compromise medication adherence leading to viral resistance and also potentiate the disabling effects of the illness.
It was initially suggested that HIV itself causes depression, that HIV-associated neurocognitive changes (now referred to as HIV-Associated Cognitive Impairment) may be a cause of depression or that HIV associated medications may cause mood changes. There are a few case reports that address these issues, but there is very little evidence to support any of these hypotheses. Depression has a biological and neuro-chemical basis in the context of an individual's social functioning. From the opposite standpoint, many reports have investigated whether depression leads to HIV illness progression with a decline in the CD4 count and increase in the viral load. While viral load studies haven't been reported for large populations, these reports all seem to indicate that depression is not associated with progression of illness. Other lymphocyte markers such as natural killer cells or CD16 cells may be more associated with stress, depression and coping, but these need to be further studied. Recent reports suggest such associations.
|Table 2: Risk Factors for Major Depression in HIV-Positive or At-Risk Populations|
Many depressive symptoms are difficult to assess in individuals with chronic illness. Chronic illness may generate symptoms that look like depression and depression can mimic symptoms of a medical illness. Identification of physical symptoms (associated with medical illness) or psychological symptoms (anxiety or loss of interest in activities when bed-ridden, housebound, or unable to participate in social and recreational activities) is important. In the early stages of HIV infection, these symptoms rarely coexist with true depression, however, as HIV infection progresses, physical symptoms attributable to HIV itself are difficult to separate from the symptoms of a depressive disorder. In these cases, it is important to rule out a physical illness first. Then, your healthcare provider should review the symptoms present and consider the most prominent ones. When other causes have been ruled out, depressed mood is most often the prominent symptom.
|Table 3: Medical Symptoms Mimic Depression|
If you have any clusters of medical symptoms that include but are not limited to the following you may want to talk with your primary care provider about depression
All forms of therapy involve supportive elements that play a role in the success of the therapy, but supportive and insight-oriented therapy define support as paramount. Not only is the supportive relationship between therapist and patient a vehicle for exchange of information between patient and therapist, but the relationship itself is of therapeutic benefit in a variety of ways.
IPT has been studied in outpatient HIV-positive individuals with MDD. For these people, IPT helped them relate changes in mood to changes in their environment or in role changes. The therapist engages the client in their emotional life issues, conceptualizing difficulties within one of four interpersonal problem areas: grief, role dispute, role transition, or interpersonal deficits. The therapist then uses specific strategies to deal with the problem areas, focusing on the here and now, on what the patient wants to achieve, and on what options exist to achieve it.
In contrast, CBT is based on the philosophy that depressed people distort reality in a particularly negative way. CBT involves setting goals, defining target symptoms, problem solving, and investigating relationships between thoughts and emotions and their underlying assumptions. In the context of CBT, self-defeating behaviors and interpersonal and coping skills are often addressed. For example, a CBT therapist would challenge a HIV-positive client's view that their life is hopeless. The goal is to help the client believe that people have the capacity to construct a positive sense of the future. The CBT therapist would engage the client in an effort to identify hypotheses that would support or reject their beliefs.
Group therapy has been used extensively with HIV-positive individuals in a variety of contexts and is highly efficient. Sessions provide psychoeducation, confrontation regarding misperceptions about the illness, and shared experiences, all of which help to improve patients' mood and quality of life.
The goal of counseling should be to help individuals to function as well as they can. Therapists should try to adapt the psychotherapy method they are most comfortable with the special needs of the person living with HIV. People living with HIV are not significantly different from other clients. The therapist should provide an objective but empathic environment where the individual can freely express their emotions. Therapy should attempt to engage clients in assessment and mobilization of their resources, including those provided by family, friends, and community. Psychoeducation should be provided about HIV, its course, treatment and effects.
|Table 4: Treatment Options|
MDD in patients with HIV infection has been effectively treated in open trials with almost all antidepressant medications. Of these, only three (imipramine, fluoxetine and paroxetine) have been investigated in randomized placebo-controlled trials. Imipramine demonstrated an effective antidepressant response that was similar to that seen in medically healthy depressed patients. The efficacy of fluoxetine appears similar to that of desipramine, sertraline and paroxetine. When compared to tricyclic antidepressant, fluoxetine, paroxetine, sertraline, and citalopram (known as "SSRIs") are more tolerable and have fewer side effects, which may lead to an increased overall effectiveness.
Testosterone replacement has been shown to improve depressive symptoms in individuals with low testosterone levels, especially for those with decreased libido or sexual dysfunction. Before testosterone is administered, a patient's testosterone levels should be checked.
Additionally, stimulants have been shown to improve mood, energy and alertness and have been shown to be effective in medically ill populations. Several open trials that used stimulants have suggested that people benefit from them with a decrease in depressive symptoms and an improvement in cognitive deficits. It is important to note that stimulants have side effects that include insomnia, agitation, weight loss and paranoid ideation, plus tolerance may develop after initial benefit. There have yet to be significant randomized, placebo-controlled trials that more thoroughly evaluate stimulants against other antidepressants with respect to tolerability and overall efficacy.
Side effects and tolerability are important aspects to treatment in the HIV-positive person. People may have many concerns about medications including loss of control, the ability to distinguish symptoms that may indicate physical illness, increase or change in weight, sedation, and sexual dysfunction. All of these side effects can affect how a person tolerates a medication. The provider initiating antidepressant treatment should consider the individual's HIV-related symptoms when selecting an antidepressant. Tricyclic antidepressants (TCAs) may be more sedating and therefore may be helpful for insomnia. On the other hand, the anticholinergic side effects (the side effects due to blocking a branch of the nervous system) may actually be helpful for managing chronic diarrhea, concurrent neuropathy or neuropathic pain. SSRI antidepressants are not usually sedating and can cause nausea, exacerbate chronic diarrhea or have sexual side effects, but may alleviate chronic constipation. Stimulants may increase cognitive processing, but can cause agitation and weight loss.
The newer antidepressants including citalopram, venlafaxine, nefazodone, and mirtazapine have all been investigated in open (non randomized, non blinded) trials. They have different side-effect profiles from the TCA's and SSRIs and may be especially helpful in people who cannot tolerate these other classes of antidepressants. Venlafaxine has properties of both TCAs and SSRIs, but side effects are avoided at low doses. Nefazodone has no reported sexual side effects and although it is known to cause dry mouth, and dizziness upon initiation of therapy, these symptoms are often easily tolerated and resolve. Mirtazapine may be useful in patients who are experiencing insomnia and need to gain weight. These newer antidepressants, as with both the TCAs and SSRIs, all need to be evaluated in the context of the individual's current HIV-related symptoms and how they are affecting their quality of life.
In general, SSRIs and the newer antidepressant medications have several advantages over TCAs for patients with HIV illness. These drugs are likely to be better tolerated with fewer side effects leading to a lower incidence of side-effect related dropout and increased compliance with treatment and as a result are likely to be more effective in treating depression. They are not sedating and do not have the anticholinergic side effects seen with TCAs. Therapeutic dosing is easier, as well, often allowing management by the primary care provider.
Clients should be educated about the length of time it takes for antidepressant response (often 3 to 4 weeks) and about common side effects they might experience with a particular antidepressant and how this may affect their HIV illness. And finally, it is especially important for individuals to reinforce compliance by arranging contact with their health care provider within a brief time after initiation of therapy in order to evaluate side effects, treatment effect, and expectations.
|Table 5: Types/Classes of Antidepressant Medications|
Tricyclics: Amitriptyline, Nortriptyline Desipramine, Imipramine
Second Generation: Venlafaxine, Mirtazapine, Bupropion, Nefazodone
SSRI's: Paroxetine, Sertraline, Fluoxetine, Fluvoxamine, Citalopram, Escitalopram
MAOI's: Parnate, Nardil
Stimulants: Methylphenidate, Dextroamphetamine
|Approach to Pharmacotherapy With Antidepressants in HIV Infection|
Andrew Elliott, M.D., M.P.H. works with the Madison Clinic at Harborview Medical Center University of Washington, Department of Psychiatry and Behavioral Sciences.