Pointers on Depression Care in People With HIV: An 'Opportunity for Movement'

An Interview With Brian W. Pence, Ph.D.

Brian W. Pence, Ph.D.
Brian W. Pence, Ph.D., associate professor, Department of Epidemiology, University of North Carolina-Chapel Hill
Dr. Pence has become a leading researcher on mental health and behavioral issues in people with HIV infection. His recent work includes the randomized SLAM DUNC trial assessing the impact of measurement-based antidepressant therapy and a study of psychiatric comorbidity and consequences in HIV-positive people with depression. With Kathryn Whetten, Dr. Pence coauthored the second edition of You're the First One I've Told: The Faces of HIV in the Deep South (Rutgers University Press, 2013), integrating qualitative findings from the first edition with quantitative findings on more than 600 HIV-positive people in the US Coping With HIV/AIDS in the Southeast (CHASE) longitudinal cohort. He holds an M.P.H. in epidemiology from Columbia University and a Ph.D. in epidemiology from the University of North Carolina-Chapel Hill.
The Center for AIDS Information & Advocacy

Keys to Screening for and Diagnosing Depression

Should clinicians screen everyone with HIV for depression?

I think they should. We have good data that depression is prevalent in the HIV population -- up to 30% of patients in care may have a depression diagnosis.1 It is often chronic but can also arise as a result of new circumstances. The US Preventive Services Task Force recommends routine depression screening for patients in primary care, and those recommendations have continued to expand to other populations, including geriatric populations and women during the perinatal period.2 Given the prevalence of depression in people with HIV infection and the negative clinical consequences observed with depression, it's a highpriority condition to identify and treat.

Should a clinician screen an HIV patient at the first evaluation? And how regularly should screening be repeated as care continues?

Clinical practices will differ. To identify depression in our SLAM DUNC trial,3 we worked with our partnering clinics to start with one-time screening of all patients. Then we rescreened patients every 6 months at their regular clinical appointments. Certainly we know that a new HIV diagnosis and entry into care are very vulnerable periods for patients and a real opportunity to link patients into additional service and try to set them up for success in the long term. So early screening makes a lot of sense. Updated semiannual or annual screening in my opinion is quite important to try to catch new-onset depression and to try to link patients into services that can help them. [The European AIDS Clinical Society also recommends initial screening of all HIV patients and regular rescreening thereafter.4]

How should clinicians screen for depression and then go on to establish that someone with depressive symptoms has major depressive disorder?

There are a number of good, low-burden, selfreport screening tools out there. In our studies we used the Patient Health Questionnaire-9 (PHQ-9), which is a 9-item patient self-report that has been widely used and validated5. It's an easy thing to integrate into standard intake paperwork when patients register. Some clinics already have PDAs [personal digital assistants] that allow patients to enter certain information on intake. So there's a pretty low-burden way to screen.

Of course the screens aren't diagnostic, but they're a good first cut at picking up the patients who need to be assessed further. In our studies we trained social workers, nurses, and other personnel in the clinic to confirm that diagnosis. Clinicians can also confirm the diagnosis themselves, relying on a standardized assessment (Table 1) as well as on clinical judgment.

Table 1. DSM-IV Diagnostic Criteria for Depression5

For major depressive disorders, at least five of the following symptoms must be present most of the day, nearly every day, for at least 2 weeks. At least one of the first two bolded symptoms must be present.

  1. Depressed mood
  2. Markedly diminished interest in usual activities
  3. Significant increase/loss in appetite/weight
  4. Insomnia/hypersomnia
  5. Psychomotor agitation/retardation
  6. Fatigue or loss of energy
  7. Feelings of worthlessness or guilt
  8. Difficulty with thinking, concentrating, or making decisions
  9. Recurrent thoughts of death or suicide

Deciding How to Start Therapy

When a patient needs treatment for depression, how should the clinician decide whether to recommend psychotherapy or antidepressant therapy or both?

It's really a personal decision between the provider and the patient. The evidence base is that psychotherapy and antidepressant treatment are comparably effective, but they don't always work for the same people. Some patients respond really well to antidepressants and some don't; some respond really well to psychotherapy and some don't.

Partly it's a matter of patient preference for medication versus therapy. At the same time, providers and patients have to weigh the pros and cons of each. Antidepressants have a faster onset of action than psychotherapy, but after a few months they have about the same efficacy. For treatment-resistant depression or chronic depression, a combination of antidepressant medication plus psychotherapy may be the most helpful for patients.

Is a selective serotonin reuptake inhibitor (SSRI) always the first choice for antidepressant therapy?

SSRIs have been the workhorse for quite a while, and a lot of them are generic now, which is a big plus. Also, SSRIs have a pretty low side-effect burden and tend not to interact with antiretrovirals. Those are all good things.

For all of these medications, there are tradeoffs. If a patient really does not want sexual side effects, then an SSRI may not be the first choice. If a patient is really concerned about sleep or weight gain, that might drive a particular choice. SSRIs have been the first choice for a long time and for good reason. But some newer agents work better for some patients and may provide a preferable side-effect profile.

What are those other agents?

Bupropion is one, mirtazapine is another. Also venlafaxine, desvenlafaxine, and duloxetine. The last three are SNRIs -- serotonin and norepinephrine reuptake inhibitors. Those are five agents that provide alternatives to the SSRI class. [See pages 33-37 of reference 5.]

How do standard therapies for depression compare in efficacy in people with versus without HIV?

They work just fine in people with HIV. Several meta-analyses that specifically address that question demonstrate that standard interpersonal counseling -- psychotherapy -- is effective, with effect sizes comparable to what you see in general primary care.6,7 Similarly, meta-analyses of antidepressant trials show effect sizes comparable to what you would expect to see in general clinical care.6,8 And there have been several trials of collaborative care models for depression integrated into routine HIV care that have shown positive impacts on depression.3,9-11

"To me that's the main difference between HIV patients with depression and a typical primary care patient population: People with HIV often have additional psychiatric diagnoses that can complicate the response to treatment."

We have to remember, though, that HIV patients may present not only with depression, but also with cooccurring posttraumatic stress disorder, panic disorder, substance abuse, or alcohol dependence.12 In those individuals antidepressant therapy or psychotherapy may be helpful but may not be enough to address those other comorbidities. To me that's the main difference between HIV patients with depression and a typical primary care patient population: People with HIV often have additional psychiatric diagnoses that can complicate the response to treatment. Advice on referrals and management algorithms

When is referral to a specialist appropriate for depression diagnosis or treatment?

There's been a big push in medical training toward training nonpsychiatrists to manage antidepressant treatment in nonpsychiatric care settings. We know that primary care doctors can do a great job prescribing and managing first- or second-line antidepressants, and HIV providers can do that as well. We demonstrated that in our trial,3 and other trials have relied on the HIV provider as that first prescriber. There are good tools providers can use [see references 5 and 9].

But there are situations when more specialized treatment is helpful. As I said, patients with co-occurring psychiatric conditions have a more complicated picture and can be harder to treat. If posttraumatic stress disorder or substance abuse is part of the picture, for example, more specialized resources may be helpful. Clinics usually have protocols in place if there are acute safety or suicidality concerns, and such concerns can certainly be one indication for referral. If the depressive illness is really bipolar disorder or a psychotic illness with depressive features, those can be more complicated conditions and may be out of the comfort zone of many HIV providers.

SLAM DUNC3,9 and other trials10,11 in HIV populations used response-driven algorithms interpreted by nonphysicians to guide depression management. Can these algorithms be adapted to clinical practice?

The algorithm we used in SLAM DUNC3 was heavily based on what was used in the original STAR*D depression trial in primary care 10 years ago.13 It's an adaptation of a standard chronic disease management approach to managing depression, and that algorithm was designed for use in primary care. The Depression Management Tool Kit, a great resource from the MacArthur Foundation, details the same approach using the PHQ-9 [see page 20 of reference 5] and offers primary care clinicians other practical guides to depression screening, diagnosis, and treatment.5 The University of Washington also has a toolkit for collaborative care for depression that presents many of these same elements.14 We have also published our adaptation of the approach for HIV care so others can use it.9

In SLAM DUNC we specifically looked carefully at interactions between antiretrovirals and antidepressants, but there really weren't many interactions to be very concerned about. So the principles present in the toolkits available are just as applicable to HIV clinical care.

"One of the big gaps in primary care and other nonpsychiatric management of depression is that an antidepressant may be started, but it may be many months before there's any sort of assessment of whether it's helping."

The really key aspect of these algorithms is the emphasis on measuring depressive symptom severity regularly -- in particular about 4 weeks after any new prescription or dose adjustment -- to see if the treatment is working. If the patient is still depressed, the treatment plan probably needs to be adjusted. One of the big gaps in primary care and other nonpsychiatric management of depression is that an antidepressant may be started, but it may be many months before there's any sort of assessment of whether it's helping. Several scales, like the PHQ-9 for example, are well validated as tools that can measure depressive severity and guide treatment adjustment decisions.

What other issues should HIV clinicians be aware of in caring for people with depression?

I think there are great lessons to be learned from the experience of primary care over the last 10 to 15 years in expanding depression identification and treatment. That primary care model could be very helpful in structuring depression management in the HIV clinic.

We know depression is highly prevalent in people with HIV infection; we know that it can be identified reliably; and we know that much of it can be managed well in the HIV clinical home with the algorithms we discussed. At the same time we know that many HIV-positive patients don't have access to good mental health care elsewhere. Even though we really wish they could all be treated by a psychiatrist or a specialty mental health clinic, that's simply not the reality for many of these patients. There's a real opportunity within HIV clinical care to greatly improve quality of life for a substantial proportion of patients and at the same time try to head off some of the disengagement from care, poor adherence, disease progression, and poor clinical outcomes -- all consequences that have been linked to depression. I think there's opportunity for movement in improving primary HIV care of depression.


  1. Asch SM, Kilbourne AM, Gifford AL, et al. Underdiagnosis of depression in HIV: who are we missing? J Gen Intern Med. 2003;18:450-460.
  2. US Preventive Services Task Force. Final recommendation statement: Depression in adults: Screening. 2016.
  3. Pence BW, Gaynes BN, Adams JL, et al. The effect of antidepressant treatment on HIV and depression outcomes: results from a randomized trial. AIDS. 2015;29:1975-1986.
  4. EACS European AIDS Clinical Society. Guidelines. Version 8.0. October 2015.
  5. The MacArthur Foundation Initiative on Depression & Primary Care. Depression management tool kit. 2009.
  6. Sherr L, Clucas C, Harding R, Sibley E, Catalan J. HIV and depression -- a systematic review of interventions. Psychol Health Med. 2011;16:493-527.
  7. Himelhoch S, Medoff DR, Oyeniyi G. Efficacy of group psychotherapy to reduce depressive symptoms among HIV-infected individuals: a systematic review and meta-analysis. AIDS Patient Care STD. 2007;21:732-739.
  8. Himelhoch S, Medoff DR. Efficacy of antidepressant medication among HIV-positive individuals with depression: a systematic review and meta-analysis. AIDS Patient Care STD. 2005;19:813-822.
  9. Adams JL, Gaynes BN, McGuinness T, Modi R, Willig J, Pence BW. Treating depression within the HIV 'medical home': a guided algorithm for antidepressant management by HIV clinicians. AIDS Patient Care STD. 2012;26:647-654.
  10. Pyne JM, Fortney JC, Curran GM, et al. Effectiveness of collaborative care for depression in human immunodeficiency virus clinics. Arch Intern Med. 2011;171:23-31.
  11. Brown LK, Kennard BD, Emslie GJ, et al. Effective treatment of depressive disorders in medical clinics for adolescents and young adults living with HIV: a controlled trial. J Acquir Immune Defic Syndr. 2016;71:38-46.
  12. Gaynes BN, O'Donnell J, Nelson E, et al. Psychiatric comorbidity in depressed HIV-infected individuals: common and clinically consequential. Gen Hosp Psychiatry. 2015;37:277-282.
  13. Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163:28-40.
  14. University of Washington. AIMS Center. Collaborative care.