One of the problems with the medicines that are given to persons with AIDS is that very little is written or really understood about the side effects in our very vulnerable population. Since the HIV virus has a special affinity for brain and neural tissue, it has an impact on mood in and of itself. Additionally some persons with the illness may have had depression or other mood disorders prior to getting infected and thus can be doubly vulnerable. Add to that the other multimorbid medical illnesses and the stigma of AIDS and you have a volatile combination that is readily ignited by a drug that navigates through the blood brain barrier.
By developing a study to assess these issues and doing a survey of experts and with the APA, a study of patients and the full national psychiatric organization, we can establish a data base.
Below is the listserv discussion about the neuropsychiatric side effects of efavirenz. This discussion led to the formation of a task force at the 2010 SIG meeting to research the issue and to include the topics in our 2011 symposium.
Robert Daroff
Tue, 9 Nov 2010 13:46:17 -0800
Subject: Efavirenz and h/o depression?
Hello, OAP members,
I’m finding mixed reports on the association of a h/o depressive disorder with the likelihood of experiencing significant neuropsychiatric side effects on efavirenz.
I’m wondering if there is any consensus in this group regarding the practice I have seen of ID docs avoiding efavirenz altogether in patients with a h/o depressive disorder?
Thanks!
-Rob
Adriana Carvalhal
Tue, 9 Nov 2010 18:07:31 -0500
Subject: Re: Efavirenz and h/o depression?
Hi Robert
I had several patients that either got more depressed after start on EFZ or developed it after a while. It’s not clear when this start and here in Canada we are trying to identify risk factors in out patients and avoid EFZ as first line treatment. When psychiatric assessment is available, we offer it and perhaps if the best choice in terms of ARVs still EFZ, the patient would start on it and will receive a close FU. As you know a lot of ID prefer the EFZ (mostly Atripla) due the high chances for adherence. The rational for this is the same we use in patients that will receive HCV treatment and the risks of IFN to precipitate or trigger depression. Using the knowledge and experience we did accumulate over the years with mono and co-infected HCV patients, we are using the same approach.
What is your experience in this cases?
Cheers,
Adriana
Stephen Stern
Tue, 9 Nov 2010 17:20:59 -0600
Subject: RE: Efavirenz and h/o depression?
I have not noticed much of an increased incidence of depression in patients treated with efavirenz. I did have a patient who developed what looked very much like a steroid-induced psychosis, though, with manic-like features and mild delirium, shortly after starting efavirenz. It remitted following a short course of quetiapine and discontinuation of the efavirenz. Has anyone observed similar reactions?
Steve
Adriana Carvalhal
Tue, 9 Nov 2010 18:23:59 -0500
Subject: Re: Efavirenz and h/o depression?
I never had any case like that but I know that some of my colleagues had the same situation and it was a case report published a few years ago. I can find the reference if anyone is interested. Last year, based in these cases, it was a question in our Royal College exam board.
Adriana
Suad Kapetanovic
Tue, 9 Nov 2010 18:42:50 -0500
Subject: RE: Efavirenz and h/o depression?
A handful or more of my adult efavirenz-treated patients reported insomnia and/or very vivid dreams. The symptoms got more tolerable (or went away in some cases) after swithching from qhs to qam administration of efavirenz. I also had a 12 y/o perinatally infected boy with 2-year history of depression, which started very soon after his efavirenz was initiated (and he was still on it when he saw me). However, the initiation of efavirenz also co-incided with the diagnostic disclosure, and he was still having major probems dealing with that 2 years later when I met him, so its hard to know how much of it was efavirenz-related … They saw me only once, so I didn’t have the opportunity to test these clinical hypotheses …
Suad Kapetanovic, MD
Jordi Blanch
Wed, 10 Nov 2010 00:53:15 +0100
Subject: RE: Efavirenz and h/o depression?
I totally agree with Dr Carvalhal comments.
Jordi Blanch
Hospital Clinic Barcelona
Spain
Robert Bright
Tue, 9 Nov 2010 15:58:34 -0800
Subject: Re: Efavirenz and h/o depression?
I can’t say that I’ve seen clear cases of it inducing depression. Lots of patients with problems with nightmares and vivid dreams on it. Hope you are well by the way!
James Bourgeois
Wed, 10 Nov 2010 00:15:20 +0000
Subject: Re: Efavirenz and h/o depression?
Adriana. Thanks for responding. Stern and I used to be in the same dept in san antonio tx. He is still there. Jb
Jon Levenson
Tue, 9 Nov 2010 19:04:17 -0500
Subject: Re: Efavirenz and h/o depression?
I too concur with Drs Blanch and Carvalhal; I would add that we also not infrequently encounter other efavirenz induced side effects other than a depressive syndrome which can include vestibular dysfunction, emotional disinhibition and rarely a psychotic presentation. i would also add that even with patients who do not have any past psychiatric history, the first 6 weeks of treatment with efavirenz requires some serial mental status assessments as Dr Carvalhal also describes. It is also true that many patients tolerate this NNRTI quite well without psychiatric side effects…
Jon Levenson
Columbia University
Adriana Carvalhal
Tue, 9 Nov 2010 19:13:12 -0500
Subject: Re: Efavirenz and h/o depression?
I think that we could discuss this important matter and perhaps collect the data we have in all out patients on EFZ. it would be a great paper to publish since it remains a big unclear issue.
Adriana
Eric Hirsch
Tue, 9 Nov 2010 16:07:57 -0800
Subject: Re: Efavirenz and h/o depression?
In Costa Rica where I work, my patients on Efavirenz complain more about sedation (rather than insomnia) and vivid dreams than depression. The ones that are depressed, usually had a history of depression prior to the use of Efavirenz.
Eric Hirsch
Glenn Treisman
Tue, 9 Nov 2010 19:58:43 -0500
Subject: Re: Efavirenz and h/o depression?
i think the data for clear association between hx and efv precipitated depression is poor but i have had enough anecdotal cases that i am persuaded that patients with a history of depression are at higher risk
Jordi Blanch
Wed, 10 Nov 2010 08:39:12 +0100
Subject: Re: Efavirenz and h/o depression?
Good idea. A multicenter study is a good way to answer tk this kind of questions. I offer my collaboration to collect patients in Barcelona.
Jordi Blanch
Marshall Forstein
Wed, 10 Nov 2010 08:10:41 -0500
Subject: RE: Efavirenz and h/o depression?
My experience with EFV is similar to that of others: more nightmares and vestibular issues, anxiety about hose side effects, some more fatigued, some more energized. As for precipitating major depression, hard to tease out in high risk group for MDD and hard to know what is the psychological impact of going on ARVS. The lit search we did for the Practice guidelines gives limited good research data.
I think he idea of a practice based data collection system is fantastic, and I think the Office of HIV psychiatry could serve as a data collection point using the resources we have with the existing practice research network –
What it would be possible is a web based “Survey” of patients in the actual clinical setting. Let me suggest that each of you who are interested send me a list of questions that you would like to see as part of the data collection. We will work to put together a draft of a brief but hopefully useful study that clinicians could use and combine our numbers into a powerful clinical study.
For example, do we need to know if the EFV is in the FIRST ARV tried? Should we expand the study to include ALL ARV’s? Does a previous history of MMD, BPD, HEP C, etc help to sort out the confounding variables?
Should we use a standard tool for measuring depression to include a patient’s data in the study?
What time frame has to be included in the data ?
Anyway- I am copying the wonderful staff at our HIV Psychiatry office at APA to show them the interest you all have with this important issue.
Andrew Angelino
Wed, 10 Nov 2010 09:22:55 -0500
Subject: RE: Efavirenz and h/o depression?
Some time ago I had a conversation with Mark Sulkowski regarding depression/depressive symptoms caused by EFV and/or IFN. He did a small study (don’t know if he published it) that suggested that there was no connection between people who developed depression from IFN and those who had symptoms from EFV. He concluded that prior experience of depression from EFV did not predict depressive reaction to IFN.
Other than that, I can only add that Glenn and I have had a number of patients with early depressive symptoms that often resolve spontaneously. Nightmares and sleep disturbances seem to respond better to antipsychotics than anything else, and a few patients, usually with a pre-existing history of depression, develop an intractable depression that doesn’t respond well, even to aggressive treatment (although we have only had a couple of ECT patients, and these responded for a while). We have asked on a few occasions that the PCPs change the ARV regimen, with fair results. All of that said, and although I’m fairly convinced that EFV does cause depression for some people, I’d love to see a better study.
aa
Marshall Forstein
Wed, 10 Nov 2010 10:02:59 -0500
Subject: RE: Efavirenz and h/o depression?
What I think Andrew captures is what we all know: every medication can cause any side effect in some number of patients some of the time…..
Our task is to try to develop some risk ratios by gathering enough data from a variety of patients under a variety of circumstances to give the best guess as to the likelihood of such side effects in any one particular patient. In other words, even when you gather a lot of evidence, we have the task of determining how good the evidence is. I know none of us would ever say to a patient that EFV does not cause depression. We have to be more nuanced than that, and I think this is a great opportunity to add some knowledge to the field.
Adriana Carvalhal
Wed, 10 Nov 2010 13:02:58 -0500
Subject: Re: Efavirenz and h/o depression?
I think that the reference attached is a good example of the long-term impact of EFZ.
Just a quick clarification from my previous email yesterday and comparison with IFN. We didn’t find in our patients that use of EFZ increase the risk of depression during IFN treatment. I meant that we develop a model of care where the patients are assessed for depression before start on EFZ based regime.Dr. Marshall – I’d be interested to take part in this web-survey. I’ll work towards come up with some questions and will send it out soon.
Cheers,
Adriana
Mary Ann Cohen
Wed, 17 Nov 2010 05:47:53 -0500
Subject: Re: Efavirenz and h/o depression?
Dear Marshall, Jordi, Adriana, Jon, and Rob,
First of all, thank you to Bob for beginning this remarkable dialogue and asking the important question about whether persons with HIV and a history of depression should be treated with efavirenz.
My patients with depression and other mood disorders have had similar responses. I have had to ask for two of them to be taken off efavirenz because of relapses and unremitting suicidal ideation and an attempt in one patient.
I agree with Marshall and am grateful to you for offering help from the wonderful staff at the APA Office of HIV Psychiatry.
As you know, the APM AIDS Psychiatry SIG met last week and developed a task force to work on a study of efavirenz responses as a paradigm for a study of other ARVs including the newest ones being prescribed.
Thank you for inspiring this remarkable process and giving us a chance to collaborate again to answer some of the as yet unanswered questions in our care of persons with HIV and AIDS.
Warmly,
Mary Ann
