Improving Diagnosis and Symptoms in Patients With Bipolar Depression: Contemporary Strategies Discussion 1

Transcription

1 Discussion 1 The following is a transcript from a Web-based CME-certified multimedia activity. Interactivity applies only when viewing the activity online. This activity is supported by an educational grant from Sunovion Pharmaceuticals Inc. Slide 1 Dr. Sachs: Hello, this is Gary Sachs from Massachusetts General Hospital. Welcome to this educational activity on the diagnosis and management of bipolar disorder. Joining me in this discussion are Dr. Mark Frye from the Mayo Clinic and Dr. Terence Ketter from the Stanford School of Medicine. This activity comprises three separate panel discussions. and complete the post-test and evaluation for CME credit: 1

2 Discussion 1 Slide 2 Dr. Sachs: The slides, transcripts, audio, Practice Aids and other activity features are available for download for easy access anytime, anywhere This activity is also featured on OpenCME.org for use on a mobile device. Please search the itunes App Store for OpenCME to download the free app. and complete the post-test and evaluation for CME credit: 2

3 Discussion 1 Slide 3 Dr. Sachs: Let's start the conversation around the broad issue of diagnosis. I think we're all aware of the controversies here. Some people say this is an area where there is still a lot of under-diagnosis, some people say over-diagnosis, and I think everybody agrees there may be a lot of poor diagnoses. I wanted to ask each of you, how do you approach this so that you can feel confident when you make a diagnosis of bipolar disorder in general, and specifically bipolar depression? and complete the post-test and evaluation for CME credit: 3

4 Discussion 1 Slide 4 and complete the post-test and evaluation for CME credit: 4

5 Discussion 1 Slide 5 Dr. Frye: There is all of the above, under-diagnosis, over-diagnosis, poor evaluation. Particularly with residents and new clinicians in the field, it's really emphasizing the importance of doing a comprehensive evaluation, and sometimes that means more than one evaluation. Sometimes that means really waiting for some very critical corroborative information from family or friends to give you an accurate-enough picture to then make the diagnosis, recognizing that particularly for the depressive phase of bipolar disorder that may not be a simple 30- or 45-minute evaluation. and complete the post-test and evaluation for CME credit: 5

6 Discussion 1 Slide 6 1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., text revision. Washington, DC: American Psychiatric Association; Dr. Sachs: Are there particular content areas that you try to focus in on to convince yourself that you've got a case of bipolar disorder? Dr. Frye: The complexity is sometimes really challenging. So in many respects, confirming that, yes, there is an episode of depression and it meets criteria, and it has a disability that warrants treatment is going to be the first piece. I think what many people struggle with is confirming that there has been an episode of mania or hypomania that changes a unipolar condition to a bipolar condition, setting the stage for your next clinical list of to-dos. Dr. Sachs: Terry, how do you go about it? Dr. Ketter: It's really important to have information from a significant other. The patients themselves, if they happen to be depressed when they are presenting they may have and complete the post-test and evaluation for CME credit: 6

7 Discussion 1 some state-dependent memory and they can't even remember what it was like when they weren't depressed. They may see times that they re hypomanic as the times that they re normal. So having a significant other involved is very important. and complete the post-test and evaluation for CME credit: 7

8 Discussion 1 Slide 7 and complete the post-test and evaluation for CME credit: 8

9 Discussion 1 Slide 8 1. Based on: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., text revision. Washington, DC: American Psychiatric Association; Dr. Ketter: I think with the DSM-5 coming out next spring, this whole notion of mixity in depression is going to get more interesting. It's certainly not a slam dunk that everybody who has mixed depression would be considered to be bipolar, but it's probably one of those factors. Dr. Frye: Terry, I really like this idea of focusing on different types of depression, because I think often, unless it is classic euphoric mania or very discrete euphoric hypomania, sometimes these mixed manic or dysphoric hypomanic periods can be very difficult to clarify. That's where we really focus on different types of depression that might be linked to different neurovegetative patterns. Dr. Sachs: I think some of the ideas that we re touching on come to the evidence that we ve seen over the years that the single most common complaint during mania is actually depression. and complete the post-test and evaluation for CME credit: 9

10 Discussion 1 Dr. Ketter: Just to elaborate on what Mark is talking about, so if somebody comes in and you assess their current status and you get either an agitated or a shut-down depression or a pure depression versus a mixed depression, what I ll do during collecting the past history is just specifically ask them about the other the alternative flavor of depression to see if they've had it. and complete the post-test and evaluation for CME credit: 10

11 Discussion 1 Slide 9 1. Sachs G. Acta Psychiatr Scand. 2004;422(suppl):7-17. Dr. Ketter: The bipolarity index that Gary devised has the core, most important things in assessing the risk of bipolarity in a seemingly unipolar depression. So early onset, family history, medication responses are all important. The course of illness is important. I may try to tease out what happens right before and after depressions because maybe there will be something different. I try to tease out whether people have more than one type of depression because if somebody has a pure major depression, as well as major depressions with mixed features at other times, then this may be indicative of something that is a little bit more interesting than unipolar. and complete the post-test and evaluation for CME credit: 11

12 Discussion 1 Slide 10 and complete the post-test and evaluation for CME credit: 12

13 Discussion 1 Slide Based on: Akiskel HS. J Affect Disord. 2005;84: Dr. Sachs: Even within all of the phenotypes that we would call depression, looking for those that might be more classically associated with bipolar where there is hypersomnia, hyperphagia [the] presentation of depression I think we always think of as more characteristic of bipolar. Dr. Ketter: This leads us in towards the idea of mixed depressions. If they have the kind of depression you just described and they have a major depressive episode with mixed features, then I start thinking, "Well, maybe there is something interesting going on here." Dr. Sachs: If during the current episode they have some features suggestive of hypomania, that really is something that I think DSM has correctly drawn our attention to as a distinct entity. Dr. Frye: It's going to be very interesting as the field moves forward now that we have kind of a common set of criteria or a language as to how we are going to track symptoms, to then figure out what is the course of illness of these mixed depressive patients. and complete the post-test and evaluation for CME credit: 13

14 Discussion 1 Slide 12 BDI: Beck Depression Inventory; HAM-D: Hamilton Rating Scale for Depression; MADRS: Montgomery Åsberg Depression Rating Scale; MDD: major depressive disorder. 1. Hermens ML et al. Ann Gen Psychiatry. 2006;5:3. 2. McIntyre R et al. J Psychiatry Neurosci. 2002;27: Beck AT et al. Arch Gen Psychiatry. 1961;4: Miller CJ et al. Clin Psychol (New York). 2009;16: Depue J et al. Abnorm Psychol. 1981;90: Depue J et al. Abnorm Psychol. 1989;98: Altman EG et al. Biol Psychiatry. 1997;42: Shugar et al. Compr Psychiatry. 1992;33: Dr. Sachs: Terry mentioned our bipolarity index, which I think is a nice way to change the question from yes/no bipolar to how closely does this patient correspond to the classic presentation of bipolar. But I wonder, are there other tools that either of you use or want to suggest for clinical use? Dr. Ketter: I think the bipolarity index is good. I think the mood disorder questionnaire is reasonable. I think the most important point is, in some respects, not so much what the actual instrument is but that you re getting more information. What I think has been an and complete the post-test and evaluation for CME credit: 14

15 Discussion 1 unfortunate circumstance is for some people, the mood disorder questionnaire is where the diagnostic assessment ends. We think these tools are incredibly valuable, but they should not be the sole diagnostic assessment that someone is using. Dr. Sachs: Excellent point. We're not wanting to see screening be the endpoint of the assessment, maybe a beginning point. But moving on to a formal diagnosis I really think is one of the basic duties that we owe to our patients. Dr. Ketter: One of the things about the mood disorder questionnaire, I think it is as vulnerable as everything else we do to bias from the patients themselves who may not have insight into some of this stuff. So if I'm going to do that sort of thing, I am also relying on the objective report of a significant other. Dr. Sachs: Yeah, having that correlation from a different perspective is enormously helpful. I think a big part of it is asking every depressed patient about prior episodes or even current symptoms of mood elevation. If you do that systematically you can fill in from the patient and their other family members or supports enough to give you a pretty confident diagnosis. Dr. Frye: I agree. Dr. Ketter: I think this major depressive episode with mixed features is going to move clinicians to more routinely ask about the symptoms of opposite polarity in depressed patients who are presenting. and complete the post-test and evaluation for CME credit: 15

16 Discussion 1 Slide 13 Dr. Sachs: In summary, I don't think we would say that what's important is what tool you use, but that you have a systematic evaluation with outside corroborating interviews that you can conduct with family members or other supports. If you do that, you can be pretty confident of both the presence and potentially even the absence of bipolarity. Dr. Ketter: I guess with the proviso that in some places you're going to get something that s indeterminate and then the diagnosis will likely be informed by what you see over time. You may or may not capture hypomania along the way. Dr. Sachs: Diagnosis isn't really going to necessarily be a one-shot deal. This may be something that you come back to over several interviews at the beginning and possibly at intervals when you see what response has been over time or what the change in the course of illness has been. Dr. Frye: I think from the standpoint of really being as comprehensive as we can as diagnosticians, those serial evaluations are not infrequent in my practice. For some patients, they are important to really take that time and get that information and the longitudinal appreciation of what's going on. and complete the post-test and evaluation for CME credit: 16

17 Discussion 2 Slide 1 Dr. Sachs: Let's move on to discuss the treatments for bipolar depression. Just by way of overview, I like to start with what I think is an obligation that we have to our patients to present the proven treatments first. and complete the post-test and evaluation for CME credit: 17

18 Discussion 2 Slide 2 Dr. Sachs: That kind of requires that we define what a proven treatment is. If you think about the principles of evidence-based medicine, you might say that the highest level of quality is a double-blind, placebo-controlled trial with an adequate sample. An inadequate sample is probably less than 80 to 100 patients. Over 100, you may have higher confidence that you re there. and complete the post-test and evaluation for CME credit: 18

19 Discussion 2 Slide 3 and complete the post-test and evaluation for CME credit: 19

20 Discussion 2 Slide 4 ER: extended release; ERC: ER capsule; LAI: long-acting injectable formulation; XR: extended release. 1. Ketter TA (ed). Handbook of Diagnosis and Treatment of Bipolar Disorder. Am Psych Pub, Inc., Washington, DC, Dr. Sachs: If you simply apply that rule, what you find is that when it comes to bipolar depression, you really don't have that many options to talk about. At this point, only the combination of olanzapine-fluoxetine, and quetiapine have FDA approval, but these options are so limited we might want to think a little bit more broadly in terms of where this category A level evidence actually exists. How do you guys approach this? Dr. Frye: The first step is that we should be discussing medications that have an evidence-base, regulatory data, or just an FDA approval. The second part of that is we also want a drug to be safe and tolerable, and I think particularly for the depressive phase, that sometimes might be quite a challenge. and complete the post-test and evaluation for CME credit: 20

21 Discussion 2 Slide 5 NNH: number needed to harm; NNT: number needed to treat; wt: weight. 1. Srivastava S, Ketter TA. Clin Ther. 2011;33:B40-B Young AH et al. J Clin Psychiatry. 2010;71: Geddes JR et al. Br J Psychiatry. 2009;194: Tohen M et al. Arch Gen Psychiatry. 2003;60: Calabrese JR et al. Am J Psychiatry. 2005;162: Thase ME et al. J Clin Psychopharmacol. 2006;26: McElroy SL et al. J Clin Psychiatry. 2010;71: Suppes T et al. Affect Disord. 2010;121: Dr. Frye: We know that therapeutic levels of lithium can be a pretty good antidepressant. There is some data to suggest that higher-dose lamotrigine may have a better response than lower dose. So these are what we would think of as conventional mood stabilizers, and although much less robust, we ve got control data showing that we can get an antidepressant response with these drugs and we need to be thinking about them. Dr. Ketter: Certainly almost by definition the approved treatments have adequate efficacy, but I don't think they really have adequate tolerability. They are as likely to cause sedation or weight gain as they are to cause improvement. and complete the post-test and evaluation for CME credit: 21

22 Discussion 2 Slide 6 LTG: lamotrigine; OFC: olanzapine-fluoxetine combination; OLZ: olanzapine; QTP: quetiapine. 1. Tohen M et al. Arch Gen Psychiatry. 2003;60: Calabrese JR et al. Am J Psychiatry. 2005;162: Thase ME et al. J Clin Psychopharmacol. 2006;26: Calabrese JR et al. Bipolar Disord. 2008;10: Geddes JR et al. Br J Psychiatry. 2009;194:4-9. Dr. Ketter: So that leaves one in a position where the only two approved treatments are not particularly well tolerated. It leaves one in the position to start looking around for something else. Dr. Frye: Imagine a bipolar who has got depression with prominent atypical symptoms of hypersomnia, hyperphagia, and leaden paralysis, and we're using medications that have an adverse event profile that can make the disease symptom profile worse. This is sometimes very challenging in that regard, and I think quite often we end up going to medicines that may not have a regulatory approval. We re using them in an off-label and complete the post-test and evaluation for CME credit: 22

23 Discussion 2 condition, but they may have an evidence base that is reasonable, promising or a side effect profile that is more manageable. Dr. Sachs: I think that's exactly what our patients want us to do is to apply our clinical judgment to the evidence such as it is and then offer them treatment options that really are tailored to our understanding of them as individuals. and complete the post-test and evaluation for CME credit: 23

24 Discussion 2 Slide 7 IDS: Inventory of Depressive Symptomatology. 1. Frye M et al. Am J Psychiatry. 2007;164: Dr. Sachs: In the cases of the newer medicines it might be worth going back and talk a little bit about what has come out of the studies, let's say, with armodafinil and lurasidone. Mark, I know you've done some work with armodafinil and modafinil, so maybe I can turn to you for that. Dr. Frye: Sure, Gary. Our group was interested in looking at modafinil, which at the time was FDA-approved for daytime somnolence and fatigue associated with a number of sleep disorders. We were interested in the activating aspect or mechanism of action of the drug, thinking that would be helpful for alleviating depressive symptoms in bipolar disorder. We know that when many bipolar patients are depressed, they can have prominent atypical symptoms, and we were interested in looking at whether or not modafinil could treat those symptoms effectively and safely. and complete the post-test and evaluation for CME credit: 24

25 Discussion 2 In our first study, we enrolled 85 patients with bipolar depression who were on mood stabilizers. Many of them were on antidepressants. And over the course of 6 weeks, we did see significant improvement in depressive symptoms with modafinil in comparison to placebo. Our response rates were significantly higher in the modafinil group, but there was no difference in treatment-emergent mania, hypomania or hospitalization for mania. And we were impressed with this initial finding. and complete the post-test and evaluation for CME credit: 25

26 Discussion 2 Slide 8 and complete the post-test and evaluation for CME credit: 26

27 Discussion 2 Slide 9 IDS-C 30 : Inventory of Depressive Symptomatology Clinician-Rated. 1. Calabrese JR et al. J Clin Psychiatry. 2010;71: Accessed November 7, Dr. Frye: Shortly thereafter, armodafinil was developed. Armodafinil is the R enantiomer of modafinil. And Calabrese and colleagues looked at armodafinil in [an] 8-week, placebo-controlled, fixed-dose study. Patients who were randomized to armodafinil did show greater improvement in depressive symptoms in comparison to those patients randomized to placebo. No differences between treatment groups were observed in secondary outcome measures. Armodafinil adverse events were most commonly headache, diarrhea and insomnia, but armodafinil was not associated with any increased incidence and/or severity of suicidality, depression, or mania. and complete the post-test and evaluation for CME credit: 27

28 Discussion 2 In this proof-of-concept study, armodafinil appeared to improve depressive symptoms according to some, but not all measures, and it was generally viewed to be well tolerated in patients with bipolar depression. This proof-of-concept study was the main reason a larger study was completed. That data has been analyzed and will be presented at meetings later this year. I think it's an important advance in our potential bipolar pharmacopeia in that we see this medicine that is not an antimanic mood stabilizer, but it really doesn't look like it's a conventional antidepressant either. and complete the post-test and evaluation for CME credit: 28

29 Discussion 2 Slide 10 and complete the post-test and evaluation for CME credit: 29

30 Discussion 2 Slide 11 MADRS: Montgomery Åsberg Depression Rating Scale. 1. Loebel A et al. 165th Annual Meeting of the American Psychiatric Association (APA 2012). Poster Presentation NR4-58. Dr. Sachs: It really is exciting to think that we're going to have some new options. Terry, do you want to give us a rundown on lurasidone? Dr. Ketter: I think lurasidone could be viewed as a refinement of the two approved treatments, both of which involve an atypical antipsychotic, and so there are now a couple of trials. One is the monotherapy trial. and complete the post-test and evaluation for CME credit: 30

31 Discussion 2 Slide Loebel A et al. APA Poster Presentation NR4-29. Dr. Ketter: Another one is an add-on added to lithium or divalproex with lurasidone, which is a second-generation antipsychotic already indicated for schizophrenia. These trials are both positive. It's not the case the lurasidone is as well tolerated as say lamotrigine or armodafinil, but it's certainly better tolerated than the approved treatments. It looks like we ve got a refinement on the second-generation antipsychotic approach to bipolar depression as well, at the same time as we have this exciting advancement that Mark has described. and complete the post-test and evaluation for CME credit: 31

32 Discussion 2 Slide 13 and complete the post-test and evaluation for CME credit: 32

33 Discussion 2 Slide 14 ADT: antidepressant therapy. 1. Sachs GS et al. N Engl J Med. 2007;356: Dr. Sachs: One other piece of this puzzle relates to the use of so-called standard antidepressant medications. Of course, that was one of the main issues that was [the] focus for STEP-BD. I think, in summary, the fair thing to say is we have yet to show that adding any standard antidepressant to lithium or valproate is efficacious. That's not to say that you would never ever prescribe an antidepressant. I think in the way that we would approach personalizing care for people, it would mean you ve taken the time to do the kinds of things around the proven treatments, maybe working toward exploring the dose range that might be helpful with a drug like lithium or valproate, and if things aren t going well you might try other agents. I think the key to being successful with that approach is somehow integrating measurement into the management program, so that you can get that feedback about what's working, instead of layering on one treatment after another. and complete the post-test and evaluation for CME credit: 33

34 Discussion 2 Dr. Frye: This is a critical conversation to have with patients, and it's a concept that sometimes is very difficult to understand. Wait a minute; are you telling me that an antidepressant is not going to make my depression better? And this is a topic that's important to really address in detail so that they understand the dilemmas that we have here. Dr. Ketter: If you are considering an antidepressant, I guess part of it is looking at why you re considering that. Now if they've never had an antidepressant and you've tried some other things, then it seems to be that these are well-tolerated medicines and maybe the conversation ought to go in that direction. Dr. Frye: Sometimes when there is a comorbidity pattern, that can lead us one way or the other. So if there is a good deal of anxiety comorbidities, this is where there may be some rationale and some benefit of considering SSRI adjunctive therapy. and complete the post-test and evaluation for CME credit: 34

35 Discussion 2 Slide 15 Dr. Sachs: Are there any particular pearls of wisdom you want to pass on? Dr. Frye: I would say there are no clear guidelines here. These are all kind of general clinical recommendations. Dr. Sachs: But having that conversation with patients and letting them express their preference and their risk tolerance I think if you do that ahead of time you are really well served because as you go along in the treatment, the time to bring up these issues is early rather than late. and complete the post-test and evaluation for CME credit: 35

36 Discussion 3 Slide 1 Dr. Sachs: So let's move on to talk about a couple of cases so that we can highlight the issues around diagnosis and treatment decisions. Terry, you have something that you want to present. and complete the post-test and evaluation for CME credit: 36

37 Discussion 3 Slide 2 Dr. Ketter: The first one I want to discuss is a 20-year-old, single, female who was complaining of depression. She complained that the depression had worsened since she had stopped bupropion about a month ago. This is a person who's had several depressive episodes in the past, but actually has had a couple of hypomanic episodes as well and has a history of worsening of her mood symptoms around her menstrual period, but she has never been psychotic. and complete the post-test and evaluation for CME credit: 37

38 Discussion 3 Slide 3 Dr. Ketter: She has had some treatment before. She had lithium, which was ineffective, and she refused divalproex because of weight gain. She had tried aripiprazole and got akathisia and had refused quetiapine because of sedation. And she had tried sertraline, and actually developed suicidal ideation with that, and bupropion and had developed irritability. That's why she ended up stopping that. She has a mother who has bipolar I disorder with psychotic mania and a sister with bipolar II who was successfully treated with lamotrigine. and complete the post-test and evaluation for CME credit: 38

39 Discussion 3 Slide 4 Dr. Ketter: The kind of depressive symptoms that she has at this time include not only emotional symptoms of sadness and anhedonia, but it's one of these kind of shut-down depressions. So she's sleeping too much, weight gain, fatigue, sluggishness. Thankfully, the suicidal ideas that she does have are passive without intent, preparations, or plans. And currently she doesn't have mood elevation symptoms or anxiety symptoms. She is basically asking for some medication to help her relieve the depression. and complete the post-test and evaluation for CME credit: 39

40 Discussion 3 Slide 5 and complete the post-test and evaluation for CME credit: 40

41 Discussion 3 Slide 6 Dr. Ketter: So I guess the issue this case raises in my mind is just how advisable antidepressants would be in this kind of patient. Dr. Frye: These are complicated cases. To me, clearly an evidence base is the first discussion. But we have talked about the importance of tolerability, and she herself has a history of a poor track record difficulties with mood stabilizers, de novo suicidal ideation with SSRIs, sertraline, irritability or maybe even a hypomania surrogate with bupropion. So finding the right medication for her that s emphasizing efficacy and tolerability is really critical. The plus side is there doesn't seem to be a lot of comorbidity. There is no psychosis. There is no substance use. But she does have a cycle frequency that s moving along, and so the concern is will some of our treatments, while well-intentioned, potentially destabilize her further in that regard? The other piece of this is mom's got psychotic mania, and from a pharmacogenomic standpoint, the sister that has done very well with lamotrigine mood stabilization. So the picture here is she has evidence of poor tolerability with antimanic mood stabilizers, and and complete the post-test and evaluation for CME credit: 41

42 Discussion 3 poor tolerability or evidence of mood destabilization with the antidepressants, really leading me to think that working with mood stabilizers that have greater tolerability is probably going to be in order. Given a sister who has done well with lamotrigine, I d be inclined to figure out if that s really the first treatment for her. and complete the post-test and evaluation for CME credit: 42

43 Discussion 3 Slide 7 Dr. Sachs: I think one of the bottom line issues is how much risk is the patient comfortable with. If they said, "I just am terribly afraid of becoming like my mother in developing a psychotic episode," I would be right there with you. I don't think there is a better choice than that. On the other hand, if they said, "I've been through all these different medications you gave me they made me more suicidal. What is the treatment you could give me that might help my depression the most?" You may end up having a discussion about ECT, but there you would open up some options if the patient is willing to consider and accept some of the downside risk. Dr. Ketter: Looking at the patient s approach to risk management and just how much risk they re willing to endure that s important. And this particular patient is somebody who turned down divalproex because of weight gain, quetiapine because of sedation and ended up having a bad experience with an antidepressant. So this particular patient may be kind of risk averse by this stage. and complete the post-test and evaluation for CME credit: 43

44 Discussion 3 Dr. Sachs: It's very important in managing the therapeutic alliance to I think do more than pay lip service to the patient's preference. If they don't work, you may actually be in a position to come back to re-evaluate the next set of options for the patient, but having a much stronger alliance because you actually have honored their preferences. Dr. Frye: I would agree with you. Working through that just makes the alliance even stronger. and complete the post-test and evaluation for CME credit: 44

45 Discussion 3 Slide 8 Dr. Ketter: This next case is a 26-year-old single male graduate student. Interestingly, his chief complaint is anxiety and physical discomfort while teaching. He's taken on this job as a teaching assistant, and he's starting to have little mini panic attacks or limited symptom anxiety attacks when he's trying to teach. He gives a history of increased social anxiety, since he took on these duties a couple of months ago. And some creepage of dysphoria, so not actually meeting criteria for depression, but certainly anhedonia and some sadness and plenty of anxiety. He has increased his alcohol use to three drinks per day over the last couple of weeks. And he has increased his individual psychotherapy to weekly in the last month and actually had a group psychotherapy a couple of weeks ago. He has this history of social anxiety or dysphoria since his teenage years, major depressive episode treated with increased psychotherapy when he was 22, and a single clear, but untreated hypomania when he was 24. No history of psychosis or hospitalization. and complete the post-test and evaluation for CME credit: 45

46 Discussion 3 Slide 9 Dr. Ketter: He's got a mother with social anxiety who was successfully treated with citalopram, an older brother with social anxiety successfully treated with citalopram, a father with alcoholism who was in a 12-step program, and a grandmother with undiagnosed, untreated bipolar II disorder. So in contrast to the first case, there is no first-degree relative with full-on bipolar I disorder. His social history is the kind of thing you hear of in people with social anxiety. He had a girlfriend in high school and, briefly, a couple of years ago when his mood was somewhat elevated, but not since. He had given up on dating and attending parties about a year ago. He actually needs the money from this teaching job to pay for his living expenses. and complete the post-test and evaluation for CME credit: 46

47 Discussion 3 Slide 10 Dr. Ketter: He is currently having limited symptom anxiety attacks in pretty well every class he's trying to teach. They are not full-on panic attacks, but he's getting increasing anticipatory anxiety by teaching, and he's actually considering dropping out of the teaching assistant job. His current depressive symptoms involve fairly mild anhedonia, fatigue, and poor selfconfidence. There are no mood elevation symptoms, and he is currently asking for a medication that could help him with his anxiety but has a low abuse potential. This is somebody who is quite different from the first case and might lead to some different treatment options. Dr. Sachs: Right. It's not so much that he's depressed but more with a kind of anxious turmoil presentation. Dr. Ketter: A little secondary dysphoria, but he doesn't meet criteria for a major depressive episode right now. and complete the post-test and evaluation for CME credit: 47

48 Discussion 3 Dr. Sachs: It sounds like he's very upfront about the fact that he sees himself at risk for getting into trouble with self-administered psychoactives. and complete the post-test and evaluation for CME credit: 48

49 Discussion 3 Slide 11 and complete the post-test and evaluation for CME credit: 49

50 Discussion 3 Slide 12 Dr. Sachs: When you take his history and you see that there was that clear-cut hypomania, that does make you worry that if you gave him a reuptake inhibitor type treatment for his anxiety, that that could also lead to some problems. I think seeing the issue from his point of view, you might be able to hit the sweet spot for him if we have treatments that have less abuse potential, so atypicals, maybe even titrating a drug like valproate to a level that might help stabilize mood and for some people actually help anxiety quite a bit. That would be another consideration. But what would you offer to a patient like this, Terry? Dr. Ketter: This is actually somebody who I went with the two family members with a history of very good responses to citalopram and just put him on 5 [mg] of citalopram, with warning his mother and his brother. Dr. Sachs: You talked to them about the potential risks and they were acceptable, so you just gave him low starting dose and careful follow-up. and complete the post-test and evaluation for CME credit: 50

51 Discussion 3 Dr. Ketter: Yeah. And this was a couple of years ago. He's actually gone on to complete his graduate degree. He had a stellar response. He responded very well to it. Dr. Sachs: When you think about a guy who is bipolar II, if you're comfortable watching carefully, I think you can make that kind of an option available. Dr. Ketter: I guess one of the issues is say you get an acute response with the citalopram and at least the way I view the literature on antidepressants is that the switch risk is really the biggest deal in the longer-term. And so, would you try to minimize the exposure to the antidepressant once things have improved? Dr. Sachs: Yeah. That's the kind of thing that I will kick back and forth with the patient. Once they've shown that they have an acute response, the question of how long to continue any treatment, I think is important to talk through with them. For many patients, they would like to try to come off. If they do and they stay well, that's great. If not, I wouldn't hesitate to put them back and leave them. I think one of the best-proven principles of treatment is that stopping medications that were acutely effective often leads to deterioration, but not always. I think that's something that patients could certainly try. Since they re coming back for follow-up, at least for our patients where we really do use a lot of formal measures, it's possible to watch over this. I think that process, in and of itself, leads to a higher success rate, whichever decision you make. Dr. Ketter: There certainly are some clinicians who are really, really invested in avoiding antidepressants in bipolar patients. I worry that there are at least some people like this who end up getting shortchanged on a treatment that may end up being well tolerated and effective. Dr. Sachs: It's a very good option to have. I think if you rule that out, you've not given them the chance to have this great response. So it's good that you were open to that. So this assess, measure, reassess, and rethink the intervention process, I think that really gives you the best chance of managing in a way that is consistent with both an evidence base and the desire to personalize the treatment. and complete the post-test and evaluation for CME credit: 51

52 Discussion 3 Slide 13 Dr. Sachs: I think the important points are let's be systematic and thorough in our evaluation, not leave it to a screening instrument to make a diagnosis for us, but maybe have that be the starting point; being aware of the available treatments that have an evidence base that is compelling and also being aware of where FDA approvals have been granted, and winnowing down from that list the treatment options that are most appropriate for your patient, understanding their preferences and tolerance for adverse effects and other kinds of risks; and then, finally, I think we are talking about making sure that there is ongoing agreement between the clinician and the patient about their preferences and also what is an acceptable level of risk, and then integrating in the measurement and the management so that you can be watching over things and be assured that you re managing those issues around safety and efficacy in a close, responsible way. I thank you very much. and complete the post-test and evaluation for CME credit: 52

53 Discussion 3 Slide 14 Narrator: This activity has been jointly sponsored by Penn State College of Medicine and PVI, PeerView Institute for Medical Education. and complete the post-test and evaluation for CME credit: 53