In this podcast, we will review strategies for the evaluation and management of HIV-associated mood and cognitive changes and we’ll list potential drug interactions between psychiatric and antiretroviral medications.
Published On: 1/16/2023
Duration: 15 minutes, 31 seconds
Referenced Article: “Management of Depression and Neurocognitive Impairment in Patients With HIV,” The Carlat Hospital Psychiatry Report, Jan/Feb/March 2023
Dr. Hendrick: Human immunodeficiency virus (HIV) is a retrovirus that causes not only progressive immunologic disease but also neurologic disease. With the advent of effective highly active antiretroviral therapy (HAART), HIV has become a chronic, treatable illness. However, many patients experience mood and cognitive changes, especially if their HIV is poorly controlled. In this podcast, we will review approaches for the evaluation and management of depression and neurocognitive impairment in patients with HIV.
Welcome to The Carlat Psychiatry Podcast
This is a special episode from The Carlat Hospital Psychiatry Report.
I’m Dr. Victoria Hendrick, the Editor-in-Chief of The Carlat Hospital Psychiatry Report, and a clinical professor at the David Geffen School of Medicine at UCLA. I’m also the director of inpatient psychiatry at Olive View -- UCLA Medical Center.
Prabhjot Gill: And I’m Prabhjot Gill. I graduated from UC Santa Cruz with a BS degree in neuroscience and I am currently applying to PsyD programs. I work as a content coordinator at Carlat Publishing where I write CME questions and podcast scripts. I will be joining Dr. Hendrick on this podcast today.
Dr. Hendrick, how does the risk of depression compare between individuals with HIV or AIDS and the general population?
Dr. Hendrick: Individuals with HIV or AIDS have more than double the risk for depression compared to the general population, occurring in roughly 30% of patients. This high rate appears due in part to distress from the HIV diagnosis, loss of loved ones to HIV, stigma associated with the virus, side effects from highly active antiretroviral therapy, and direct effects of the virus on the brain.
Prabhjot Gill: Since many depressive-related symptoms, like fatigue and poor concentration, can be caused by HIV medication side effects or HIV-related complications, such as HIV-associated neurocognitive disorders, how can clinicians determine whether a patient’s depressive symptoms are attributed to an underlying depressive disorder?
Dr. Hendrick: If a patient’s HIV infection is well controlled and their viral load is undetectable, we treat depressive symptoms as primary depression. In patients with more advanced infections or poor compliance with treatment, lethargy and cognitive impairment may be secondary to the HIV infection rather than depression. Screening for anhedonia, hopelessness, and suicidality can help in reaching the right diagnosis.
I want to emphasize that HIV-infected patients are at high risk for suicide, particularly in the days immediately after their HIV diagnosis. Suicide risk correlates most strongly with the development of depression, but several other factors contribute to this risk, including substance use, personality disorders, and disease progression. The use of certain antiretroviral drugs also increases the risk of depression and suicidality. It’s important to perform suicide screenings for all patients with HIV, ideally with validated screening instruments such as the Columbia-Suicide Severity Rating Scale (C-SSRS).
Prabhjot Gill: When evaluating patients with HIV, what should providers focus on? And what types of tests do you recommend ordering?
Dr. Hendrick: Clinicians should focus on the identification of psychosocial stressors, medication changes, substance use, and the progression of the patient’s HIV infection. Tests such as hepatic and thyroid function tests, HIV viral loads, CD4 counts, tests of gonadal function including testosterone and dehydroepiandrosterone, and hematological function tests involving hemoglobin, hematocrit, and serum erythropoietin are helpful.
Prabhjot Gill: What can each of these tests specifically tell us about a patient with HIV?
Dr. Hendrick: So, most psychiatric medications are metabolized by the liver, and HIV infection is often comorbid with hepatitis C and other liver infections, thus a liver function panel can alert us to any hepatic dysfunction. Hypothyroidism is a potential cause of depressive symptoms and should be screened for in this population. CD4 counts and viral loads help assess for compliance with highly active antiretroviral therapy and are a marker for disease progression. Hypogonadism and low testosterone levels are common in HIV-infected men and may produce lethargy and low libido. Testosterone replacement can be considered in severe cases. Lastly, since anemia can be a source of fatigue, hemoglobin and hematocrit levels help in the workup of low energy in patients with HIV.
Prabhjot Gill: What types of depression screenings do you recommend?
Dr. Hendrick: Some clinicians use screening scales like the Beck Depression Inventory (BDI), but HIV-associated somatic symptoms (eg, fatigue, loss of appetite) might inflate the scales’ scores, potentially causing patients to seem more depressed than they are. The Hospital Anxiety and Depression Scale (HADS) is a validated instrument for detecting depression and anxiety in hospital and outpatient clinics and was found in one study to not be confounded by the presence of HIV symptomatology. So, it may represent a more reliable and valid screening method for depression and anxiety in HIV patients.
Prabhjot Gill: So we talked about assessment, but what about treatment? What does research show to be the most effective therapies for the treatment of depression and anxiety in patients with HIV?
Dr. Hendrick: Psychotherapy and selective serotonin reuptake inhibitors (SSRIs) are first-line therapies for the treatment of depression and anxiety in patients with HIV. Tricyclic antidepressants, which slow gastrointestinal motility and promote weight gain, may be particularly good options for patients with diarrhea and wasting. However, tricyclics are highly anticholinergic and can produce or exacerbate cognitive impairment. Mirtazapine is another option as it stimulates appetite without producing anticholinergic side effects. Bupropion is helpful in cases where fatigue and impaired concentration are primary symptoms, but its dose-dependent seizure risk complicates treatment in patients with neurologic complications from HIV such as cerebral toxoplasmosis. Clinicians can use psychostimulants, including modafinil, methylphenidate, and dextroamphetamine, as adjunctive treatments for fatigue and apathy when these are refractory to other treatment options.
Hypotension is a frequent complication of advanced HIV disease, so providers should minimize the use of medications that lower blood pressure like prazosin and clonidine. Electroconvulsive therapy (ECT) for HIV-infected patients is not ideal due to its risk of cognitive dysfunction, including anterograde and retrograde memory loss. When I prescribe antidepressants to patients on HAART, I try to be mindful of drug interactions. If you refer to the winter 2023 issue of the CHPR, you’ll see a table listing “Drug Interactions Associated With HAART.”
I urge patients to join support groups, as group psychotherapy not only improves depressive symptoms but also enhances social supports, coping skills, and the delivery of HIV education. A form of cognitive behavioral therapy—CBT for adherence and depression (CBT-AD)—also improves depressive symptoms while enhancing adherence with highly active antiretroviral therapy treatment.
Prabhjot Gill: When working with patients with HIV, you will likely encounter some degree of cognitive impairment. HIV-associated neurocognitive disorder, also known as “HAND,” encompasses a spectrum of cognitive and functional impairments with three main symptom severity categories. One such category is asymptomatic neurocognitive impairment, which pertains to mild cognitive impairment without functional impairment. Then there’s mild neurocognitive disorder which describes cases of mild to moderate cognitive impairment with some functional impairment. Lastly, HIV-associated dementia corresponds to cases of severe cognitive impairment with substantial functional disruption.
So, how common is HIV-associated neurocognitive disorder, and how can clinicians detect it?
Dr. Hendrick: Thankfully, the availability of highly active antiretroviral therapy has decreased the incidence of HIV-associated dementia to about 5%, but the prevalence of mild neurocognitive disorder is largely unchanged, affecting about 45% of infected patients. This may be due to patients’ longer life spans and continued viral replication in the central nervous system even when serum levels show undetectable viral loads.
In terms of detecting cases of mild or moderate neurocognitive impairment, cognitive screening scales may not be sensitive enough to pick up cognitive deficits. If you suspect mild or moderate cognitive impairment, then it might be warranted to seek formal neuropsychological testing to identify specific areas of dysfunction.
Prabhjot Gill: What about HIV-associated dementia?
Dr. Hendrick: HIV-associated dementia is a diagnosis of exclusion and thus requires a full workup for other potential causes of psychomotor slowing (eg, Parkinson’s disease). It produces prominent symptoms such as decreased psychomotor speed, poor attention, poor concentration, and impaired memory, learning, and executive function. For screening, some clinicians like to use the Trail-Making Test as a sensitive and easy-to-use screening tool. Another viable instrument is the International HIV rDementia Scale which is a more comprehensive assessment of memory and psychomotor functioning but it does take longer to administer.
Prabhjot Gill: Can any lab tests or imaging be performed to assess for HIV-associated dementia?
Dr. Hendrick: Neuroimaging often shows cerebral atrophy, enlarged ventricles, and T2-hyperintensities in white matter tracts, and an EEG is likely to show mild background slowing—although I don’t normally obtain an EEG unless I suspect seizures. A cerebrospinal fluid analysis will only show nonspecific findings. There’s little reason to obtain a cerebrospinal fluid analysis in most cases, but if a patient’s symptoms have progressed rapidly or their CD4 count drops below 100, cerebrospinal fluid analysis can help rule out other HIV-related diseases, such as cryptococcal meningitis and toxoplasmosis.
Prabhjot Gill: And, what are the available treatment options for HIV-associated dementia and HIV-associated neurocognitive disorder?
Dr. Hendrick: The optimal treatment for HIV-associated dementia and HIV-associated neurocognitive disorder is to control viral replication with highly active antiretroviral therapy, as good management of the HIV infection correlates with improved cognitive function. Currently, there are no medications approved for the treatment of HIV-associated dementia and/or HIV-associated neurocognitive disorder, but medications for comorbid psychiatric symptoms, like agitation, can be helpful.
Prabhjot Gill: Earlier you mentioned that medications for HIV can induce neuropsychiatric symptoms. Can you touch on how you would manage a patient with HIV receiving highly active antiretroviral therapy who is presenting for new-onset neuropsychiatric symptoms?
Dr. Hendrick: If a patient with HIV demonstrates new-onset cognitive changes or psychiatric symptoms, I look for recent changes to their treatment regimen. Several medications for HIV produce neuropsychiatric disturbances, so I encourage our infectious disease colleagues to take these side effects into account when choosing highly active antiretroviral therapy medications. This is especially important for patients with a history of preexisting psychiatric disorders or with active, poorly controlled psychiatric symptoms. Of the available highly active antiretroviral therapies, Raltegravir appears to produce a lower risk of neuropsychiatric side effects compared to other options.
Prabhjot Gill: Patients with HIV/AIDS are at high risk of depression and suicide, especially in the days following the HIV diagnosis.
Dr. Hendrick: Many patients with HIV also struggle with cognitive impairment from HIV-associated neurocognitive disorder, and about 5% develop HIV-associated dementia. Psychotherapy and antidepressants help treat patients’ moods, and highly active antiretroviral therapy diminishes the risk of cognitive impairment. Watch for drug interactions and neuropsychiatric side effects from antiretroviral medications.
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Prabhjot Gill: And don’t forget, you can now earn CME credits for listening to our podcasts. Just click the link in the description to access the CME post-test for this episode.
As always, thanks for listening and have a great day!