BRIAN R. APATOFF, MD: Hello and welcome to MS Conversations. I'm Brian Apatoff calling you from the MS Center at Cornell University, New York Presbyterian Hospital. This month's conversation is going to focus on multiple sclerosis, depression and the incidence of suicidality in multiple sclerosis. Joining me for a discussion today is Dr. James Miller from the Multiple Sclerosis Center at Columbia University, New York Presbyterian Hospital. Jim, thank you for joining us today. JAMES MILLER, MD: It's a pleasure, Brian. BRIAN APATOFF, MD: Before we begin, I would like to encourage everyone who is listening to send in questions via e-mail or telephone. And what I think I'd like to do is just kind of outline the general prevalence of depression in multiple sclerosis, really how common a problem is this, Jim, in your clinical practice and tell me what are your management strategies for depression and mood disorder in multiple sclerosis? JAMES MILLER, MD: Well, depression unfortunately is a very common problem. There are some people who believe it's directly related to the organicity of the disease. I'm not so sure about that. I think a fair number of people who come in with the -- and just receive the diagnosis or already have signs and symptoms of depression in their own lifestyle. But certainly learning that you have a chronic disease doesn't make that any better. And then as we'll probably talk about in a bit is the question of whether some of the medications may not augment that. But even without the medications, even the days before medication, the prophylactic medications, the interferons, there was still plenty of depression in the MS population that had to be handled. My strategy is to try and be alert to that. Ask people directly about depression symptoms and ask them directly about suicidal thoughts if I think it's indicated. And then to either arrange for them to get appropriate treatment in therapy or by medication and sometimes with more modest cases, start the medications myself. BRIAN APATOFF, MD: So what you're saying is there some element of reactive depression perhaps in receiving a diagnosis of multiple sclerosis, but also a fair percentage of patients that have depression as really just an underlying component of their disease. JAMES MILLER, MD: It's certainly common enough in the population that that's an issue, I think. BRIAN APATOFF, MD: Do you feel there are MS patients whose primary manifestation or their presenting symptoms are psychiatric; i.e., depression as opposed to other visual motor sensory complaints. JAMES MILLER, MD: That I'm not so sure about. It's certainly possible because I certainly have seen people, for example, with other more obvious cognitive deficits that one would have immediately assumed couldn't be related to underlying mood problems. And so the presenting patient with depression wouldn't surprise me. BRIAN APATOFF, MD: In your clinical practice and perhaps even from your review of the literature, do you have some percentage of patients -- just how prevalent depression or other sort of mood disorders are thought to be? JAMES MILLER, MD: I don't really have a good sense. My estimation is it's probably running about 30-40% in my practice in terms of some signs of depression that need to be addressed. BRIAN APATOFF, MD: And would you say that similar numbers are on -- are either in some type of therapy or counseling or all on antidepressant medication? JAMES MILLER, MD: Yeah. I like to get people into counseling at the very least and then sometimes that's sufficient and sometimes medication is necessary. You've done a little bit more of the research literature review, and do you think my impression is pretty much what people are finding? BRIAN APATOFF, MD: Yeah, I think people have this in terms of ongoing depression -- it could be anywhere from 30-40%. The lifetime prevalence is thought to be much higher. In other words, people -- patients with MS tend to go through cycles of depression so that any point in the course of the disease, there are periods of significant depression. But certainly at least a third could have a significant, clinically significant mood disorder, depression at any point in time. JAMES MILLER, MD: It's certainly true also that there are things that happen to people with MS that provoke the depression symptoms and even questions of suicidality, such as the people who live in isolation are certainly more prone to these kinds of problems. And it's not infrequent that I see break-up in marriages over the issues of multiple sclerosis and the difficulty of the spouse coping with it that then leads the patient into further problems. BRIAN APATOFF, MD: So you might identify certain risk factors, patients that are a little bit more socially isolated or people who don't have the social supports that would help with depression. Those people might be at higher risk for depression and suicidal behavior. JAMES MILLER, MD: It certainly seems so. There's some literature that bears that out. BRIAN APATOFF, MD: Yeah. You know, I think the -- one of the questions that has come up and has been throughout the course of two or three controlled clinical trials on interferon-beta therapy in multiple sclerosis is how interferons might contribute to mood disorder, might aggravate depression and contribute to suicidal behavior. What's your understanding of the literature and your expressions in --? JAMES MILLER, MD: I think you know my impression that this is mainly an old wives' tail which got started for unfortunate reasons back with the first release of the Betaseron information in 19 -- early 1990s by Berlix. I think they pointed out to a slight increase in the numbers of patients depressed in the treatment group as opposed to the non-treatment group in their first study. This wasn't by any means statistically significant. I think there were mainly psychological reasons why this was pushed to the forefront. As I mentioned to several people, this came out at the time when Prozac was being taken over the coals for causing suicides and, more importantly, that Lily was hiding the data from the public. Now neither of those assertions were true, but I think that led Berlix to bend over backwards to stress this non-significant finding. And since then, it seems to have taken off despite the fact that virtually every other study has never shown association between taking a beta-interferon and depression. And certainly there are some people who seem to become more depressed after taking medicine, but I think there are good psychological reasons for that. They're faced with the diagnosis of a lifelong disease that may be debilitating and also the fact that they have to take these medicines which are given by injection, often have side effects, it certainly could lead to depression. And Don Goodkin did a study which shows that this seems to be the case that the correlation with depression after taking interferon was related to depression before taking interferon and not much more. BRIAN APATOFF, MD: Yes, I see. So -- so really there's no good statistical evidence that interferons can in a significant way contribute to depression or suicidal behavior. As you mentioned, this just is a patient population that's at risk in general. So the numbers were quite small and probably not clinically relevant. JAMES MILLER, MD: And anecdotally I'm going to say I haven't really found this to be major feature in my practice. Certainly there are people who are dealing badly with the whole concept and become more overtly depressed after starting the medication. But I've never been able to attribute it to the medication itself. BRIAN APATOFF, MD: And those are patients that you might just reasonably start on antidepressant medication or -- JAMES MILLER, MD: Absolutely. I think the main feature about depression in multiple sclerosis that has to be emphasized even in the face of whether or not causes -- the medicines cause depression or anything else contributing to depression -- that they respond to treatment, treatment for depression. So every effort has to be made to identify these people and help them. BRIAN APATOFF, MD: Yes, so I think the issue is -- yes, depression does exist in multiple sclerosis. It's really not evident that interferon contributes to that depression but regardless you're just going to treat them aggressively, try and identify depression whenever it occurs and use appropriate clinical interventions whether it's medication or some other type of counseling. JAMES MILLER, MD: Exactly. BRIAN APATOFF, MD: What about your use of other medications in the incidence of depression and mood disorder? For example, treating patients with acute corticoid steroid intervention for major relapses, do you modify therapy, antidepressant therapy for patients that are undergoing high-dose steroids for extended periods of time? JAMES MILLER, MD: I don't routinely modify the antidepressant medications, although in a few patients who I think have bipolar issues, I tend to increase them. And some people who seem to have gotten depressed on steroids before, I certainly -- excuse me -- I would certainly increase. I may lessen them for people who seem to be getting an upper effect. BRIAN APATOFF, MD: So patients with a touch on the manic depressive or bipolar effected disorders, which are also slightly higher -- there is a slightly higher incidence in MS, you feel that those people you might take some special precautions and -- JAMES MILLER, MD: Well, I mean if -- there are times, of course, when you have to repeat steroid treatment and if you know the patient has had problems with it before, I frequently use lithium starting a few days before I plan to use the steroids -- if I can. But certainly starting them with the medication and then carry it on during whatever taper you provide the patient. BRIAN APATOFF, MD: So lithium just prophylactically offset the mania component from the steroids. JAMES MILLER, MD: I've found that to be very effective and it's even useful if you've missed a patient and want to start it later. I seem to prefer it to the other newer drugs that the psychiatrists are using to manage manic episodes. BRIAN APATOFF, MD: Yeah, I think that some of the precautions and concern around interferon-beta came from some of the established literature on interferon-alpha which is used in certain oncologic situations and for viral hepatitis at much higher doses. JAMES MILLER, MD: Certainly the dose may be well a consideration because there it seems clearly related to the medication but it also may be some type of differences that we don't understand between the two interferons. BRIAN APATOFF, MD: Exactly. Yes. So they are similar but not identical interferons. They might have at particularly different doses, different risks for depression. And I think the important effects of treatment in managing depression are perhaps underutilized in clinical practice. And are there -- would you estimate a percentage of patients that you feel you typically have on one type of antidepressant medication and you find that there are typical categories of antidepressants that you use for depression but also for other symptomatic relief of fatigue or cognitive complaints. What is your general strategy or algorithm in patient care? JAMES MILLER, MD: This is entirely anecdotal. I tend to -- if fatigue is a major issue, I tend to prefer Prozac or Zoloft which seem to be more energizing. If it's not, I like Celexa very much as a relatively mild antidepressant which seems to make people comfortable -- sometimes augmenting with Wellbutrin will bring back activity in people who are feeling very blah -- even if their depression is relieved. So these are really three or four drugs I use most frequently. BRIAN APATOFF, MD: So tend to be activating, help with fatigue and potentially some cognitive complaints. JAMES MILLER, MD: Yeah. BRIAN APATOFF, MD: Good. What about other antidepressants for complicated symptoms of pain or other sensory disturbance? JAMES MILLER, MD: Well, certainly you always hope -- and the people who are clearly depressed and have a lot of dysesthesias or pain sensations that you'll get a twofer effect with the tricyclics and sometimes that's come true. But sometimes I haven't hesitated to use both the tricyclics for this sensory management and add an SSRI as well. BRIAN APATOFF, MD: Yeah, so it sounds like a little polypharmacy sometimes necessary and just empiric trial and error to hopefully arrive at the right combination of medication. JAMES MILLER, MD: I certainly don't think there is a fixed medication that works in patients with MS and like most depression you have to figure out the one that seems to be best for your patients. BRIAN APATOFF, MD: I think I'm also in our practice sometimes Effexor has been helpful for mood as well as some of the chronic pain issues that many patients experience. But it is just a trial and error depending on how patients tolerate medication. JAMES MILLER, MD: I haven't used Effexor much myself, but I think it has a role as well. BRIAN APATOFF, MD: Good. Okay, well I think you know that we have seen that it is really a central component in MS symptomatology. Obviously mood disorder, depression impacts greatly on quality of life issues for patients. And as you said initially, I think to inquire about depression since many patients aren't going to volunteer elements of mood disorder, some patients might not even recognize certain symptoms as reflecting depressed moods. Certain vegetative signs and symptoms of sleep disturbance and other complaints might not be -- they might not have a clear interpretation of what is underlying those symptoms. And you find that sometimes you have to pull the diagnosis out of patients and educate them about it or are people -- JAMES MILLER, MD: I'm sorry Brian. BRIAN APATOFF, MD: Go ahead. JAMES MILLER, MD: I think that's certainly true. I recall one particular man who had moderate deficits who was leaping for disability because he was distressed that he couldn't perform his job. And clearly he wasn't -- from a physical point of view and I don't even think from a cognitive point of view was that depressed -- was that disabled, but still I think his underlying depression which he had a very tough time recognizing was giving him the sense of hopelessness in not being able to do his job and functioning correctly. I'm still not sure I've worked that one out satisfactorily, but that certain is, I think, what you mean when you really have to sometimes really work with people to recognize that this is an important aspect of what's going on. Some people think they have a right to be depressed because they have multiple sclerosis. I can't say that they don't have the right. But I can say that if we can address it, it will be treatable. BRIAN APATOFF, MD: Exactly. It's not something that you have to accept as a component of the disease and patients certainly don't need to endure. So I think just an active recognition and treatment as you're stating is really the best plan and just recognizing that the depression can be episodic. Patients can be fine at one point in their disease, but then have mood variations for a variety of reasons. JAMES MILLER, MD: I usually find it's best to try and convince people to stay on antidepressants once they've improved. Because I find the drift down can be fairly rapid with people who don't think they need the medication anymore -- they're all through. And then it comes back again. BRIAN APATOFF, MD: So the likelihood of needing to maintain medication indefinitely is certainly going to be higher in this patient population, with an underlying brain disease. Well, Dr. Miller, thank you very much. I think that your comments have been very helpful in outlining the high prevalence and significance of this clinical issue. Or anything else that you would like to add? JAMES MILLER, MD: I think I've managed to squeeze everything that I think is important into it. And again I want to leave the message that no matter what is at the basis of the depression, the important thing is to get at it, recognize it and treat it. BRIAN APATOFF, MD: Well, thank you again, Dr. James Miller, from the New York Presbyterian Hospital at Columbia University. This has been Dr. Brian Apatoff at Cornell University, signing off for healthology.