Recognition and Treatment of Bipolar Depression

Recognition and Treatment of Bipolar Depression

hello I'm dr. Sloane Manning I'm from the University of North Carolina at Chapel Hill I co-direct the mood disorders clinic at the family medicine residency program in Greensboro North Carolina the following audio is part of a certified educational activity titled recognition and treatment of bipolar depression exploring a patient's journey from diagnosis to treatment access the entire activity and complete the post-test @ww peer review press comm /b w/e downloadable slides and practice aids are also available today I want to share a story with you about a patient in my practice who has bipolar disorder but was originally misdiagnosed with major depressive disorder this is actually a pretty common state of affairs in outpatient psychiatry and in primary care because of the nature of the illness and I'd like to tell you the story today of a particularly instructive patient that patients name is Sally so bipolar disorder as many of you know is a neuropsychiatric condition that's quite severe it's characterized by fluctuations in mood and energy levels it consists of manic or hypomanic episodes usually with recurring major depressive episodes although the age of onset for bipolar disorder is typically set at twenty-one people who first start experiencing the illness usually beginning their teens with an index episode that's usually depression so you usually experience a series of major depressions before you have your first manic episode and you can be formally diagnosed as having bipolar disorder it's a challenge to diagnose in primary care and in psychiatry because depressions outnumber manic episodes and also it's just hard to think in different waise sometimes when the patient is presenting with depression but you have to decide what kind of depression you're looking at there are multiple mood states there's a lot of comorbidities so when Sally first presented to my clinic she was 26 years old and had been experiencing recurring depression since about age 13 she's a political science major within a few weeks of graduating she had a minor in art she was graduating from one of our local universities in Greensboro she was referred to me by therapists that she had been seeing through the Department of Psychology at the University and I never forget the day that she walked into my office because she was immediately engaging me in conversation she was not hard to talk to she's very intelligent very bright looking very happy rather chatty as a matter of fact I became so involved in the friendly conversation that I had to remind myself that we had some business at hand when I had got her to go ahead and tell me a little bit about her college experience she said well I'm on the eight year plan and I said well I've heard about the five year plan but I don't know about the eight year plan tell me about that she said well I've stopped and started college three times I've had five changes in my major I you know started with history then I went to palasa fiy elementary education finally sided on political science but I kept my art minor so I said you know we have to talk about why you're here what were you hoping to gain from our conversation from our meeting today and at that point Sally broke into tears I mean a sobbing mess that we you know took several Kleenexes it took a couple of minutes for her to compose herself and she said you know I've been dealing with depression my whole life medicines have never really helped me but my therapist thinks I really need to give medicine another try what is the typical story someone who has bipolar disorder how does it differ how do the stories of a major depressive illness differ from the story of a bipolar illness and in medicine at least we learned initially the phrase all that wheezes is not asthma I mean you know wheezing can be asthma but it also could be pulmonary edema and another series of diagnoses in this case all that is depression is not major depressive disorder so if you're presenting with depression and you're looking at a differential diagnosis of depression the underlying depressive diagnosis might be major depressive disorder could be bipolar disorder could be a premenstrual dysphoric disorder or a substance use mood disorder or maybe a mood disorder from another general medical condition like stroke or thyroid or some other brain injury or it could be a chronic dis timing disorder and the dsm-5 criteria for a major depressive disorder are the same as the DSM 4tr criteria for a major depressive disorder involves two weeks of persistent depressed mood or anhedonia with enough other symptoms to make five total symptoms that are clinically impairing and that are not due to anything else and so I think all of us are familiar with the diagnosis for major depression it turns out that the criteria for a bipolar depression and the criteria for a major depressive disorder in terms of a major depressive episode are not different so bipolar disorder is often misdiagnosed as depression and it was a very well known study published ten or fifteen years ago were a series of individuals with bipolar disorder were asked the question in a survey how long did it take you to get properly diagnosed with bipolar disorder and the average time to be properly diagnosed was about 10 years and most people were misdiagnosed with major depression initially and the average number of healthcare professionals needed to make the diagnosis was between three and four there have been a few studies actually we were one of the first to publish such a study back in the 1990s about depression presenting in primary care settings and in our study and that looked at what percentage of people with depression in primary care have a bipolar disorder we found about 25 26 percent in that study has been replicated a number of different times now what you're looking for to make the differential diagnosis is a manic episode of course it's a distinct period of abnormal or persistently elevated or irritable mood people become expansive in their mood or extremely irritable psychosis is not uncommon getting in the hospital is not uncommon so you're looking for a period of time before a manic episode when your energy and mood is someplace very different elated energetic or a severely irritable and the wheels are starting to fall off of your life because you can't get anything done a hypomanic episode is a milder manic episode they don't last as long typically four days is required for the diagnosis but you're looking at the same sorts of symptoms you're just looking for a milder shorter duration of the manic symptoms one of the most important things that you can learn about manic and depressive episodes in bipolar disorder is that it's not necessary to be either manic or depressed in the dsm-5 you can have manic episodes that are mixed with depressive features and you can have depressed episodes that are mixed with manic features and so the mixed features specifier is a particularly important thing to recognize in terms of what symptoms people have so what makes a diagnosis any diagnosis what's in a diagnosis actually there are five elements five elements of a diagnosis the first element is phenomenology which is the symptoms that you see the second element is the longitudinal course of the illness how did it begin how did it change over time the third element of diagnosis is pedigree or family history is it inheritable is there a genetic connection the fourth element of diagnosis is treatment response because different types of illnesses do respond differentially to different kinds of treatment and the fifth category of evidence or classification for a diagnosis is biologic markers now we don't have biologic markers for bipolar disorder or major depressive disorder really yet in a very clinically useful fashion but it's getting there but we don't have that yet so we were talking about Sally right and Sally's story sounds like this she had her first major depressive episode at about age 13 for bipolar women this is not uncommon at all because there's something about menarche or beginning the reproductive cycle that opens the door for mood issues in women and when I asked her to tell me about the nature symptoms in her depressive episodes first of all she said I've had so many episodes I don't know how many episodes I've had so TNT see too numerous to count some of the episodes were very agitated painfully agitated and there was some cutting behaviors during those agitated depressions other depressions were more atypical overeating over sleeping arms and legs feeling like lead rejection sensitivity reaction to positive stimuli except that when the stimulus has gone the depression comes right back she did one previous suicide attempt in the past it was an overdose at age 16 after the breakup with her girlfriend she was treated at the emergency department referred to a therapist interestingly when we talked about her previous suicide attempt she said you know I haven't any suicide pact with a close friend of mine and I said really and she said yeah I'm really wanting to be different from the rest of my family I I want to live but there have been a lot of deaths in my family so a little more history for Sally she's graduating college in a couple of weeks but she has no career plans well she waits tables at a very upscale restaurant in the area she had hopes of becoming a sommelier but she said I don't do alcohol well being don't miss that my question after that was tell me about not doing alcohol well she has a history of binge drinking had one DUI in the past she said I finally decided that alcohol was a dead end for me no pun intended but I mean look at my family history she smokes cannabis socially not twice a month you know at a party a couple of times a month really produces anxiety and some true paranoia if she goes beyond just a little social sort of participation in terms of cannabis and this is a general rule that you should understand that everyone should understand about mood disorders and bipolar disorders in particular when you mix bipolar disorder with substance use disorders you release the Beast so I asked her about significant relationships and particularly intimate significant relationships and Sally is sexually ambivalent she describes herself as having eight total sexual partners in her life some male some female when I asked her to place herself in an LGBTQ category she de Muir's she's like yeah no thanks I'm not really interested in sex right now and I took that to mean let's move on and we did so she gets an exercise bug now and then again she goes sometimes in these depressions into very very you know sort of leaden paralysis and what she said was well I remember one summer after my sophomore year at school when my interest in exercise and art were just off the scale and I said well off the scale what do you mean well I spent a lot of money on art supplies I mean a lot of money I was exercising constantly I only needed one or two hours of sleep at night I was calling people up in the middle of the night and and demanding that they come over and see my latest art project my latest ceramic or paint or whatever and again I'm calling people at 3:00 a.m

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and saying I can't believe you don't want to come over and see what I've done it's beautiful or I'm heading to the gym and it's 3 a.m. and I want you to come with me and what what do you mean you won't come with me I can't believe this she also said that her head was so full of thoughts that she fantasized about drilling a hole in her head to let all of the excess thinking out and so that to me was whoa we've got decreased need for sleep we've got boundless energy we've got some behaviors that are negative and consequence and I'm thinking you know what's going on and she even said that she broke that cycle by going into a drinking binge so sally's talked about her family history a couple of times remember so let's go to Sally's family history a maternal grandmother who was institutionalized and actually ultimately treated with the frontal lobotomy a maternal aunt with serious depression who was treated with antidepressants who got bad enough ill to be treated with ECT electroconvulsive therapy shock therapy who died by suicide her mother severe postpartum depression alcoholism with eventually a formal diagnosis of bipolar one an older brother with ADHD substance use disorders we don't know where he is he hasn't been seen in a while and a younger brother who was alcoholic and died suicide by hanging that's a serious family history one of the things that differentiates unipolar major depressive disorder from bipolar disorder is that bipolar disorder as a more heritable psychiatric illness the family histories look sicker so Sally's been treated a couple of times again when she came in antidepressants have never worked for me but my therapist really wanted me to try one more time because my depression was getting more serious she's tried nothing's really helped her except one antidepressants that she remembers taking we're in about a week she felt like she had been cured of her depression she was active talkative she was back into exercise and practicing for half marathons and that lasted about six weeks and then the benefit was gone she crashed back into the depression and no matter what her provider did with the dose of the antidepressant that could not recreate her recovery well what happened in that situation was most likely that the antidepressant triggered a hypomania that looked like relief from her major depression but in fact was switching her it was a switch into a hypomanic episode she's never had a trial of a mood stabilizer or an atypical antipsychotic so I don't know about you but I measure depression so in my practice we used the phq-9 and we gave salad the phq-9 and she scored 20 out of 27 with nothing for suicidal ideation which is nice and it basically extremely difficult for the tenth question so she's got a severe depression going on with some anxiety on the G 87 which is the instrument we use for measuring anxiety symptoms she scores about an eighth when we use a screener for bipolar disorder which is the CD 3.0 she's positive on both the stim questions for expansive mood and irritable mood and she endorses every one of the nine manic symptoms so she would score in a very high risk for bipolar disorder so the screener is backing up what I've already heard already so we're really looking for associated features we got some blood work panel lipid panel TSH CBC urine analysis all of that was normal so as we might have mentioned in the earlier part are you've surmised by now bipolar disorder comes mixed with a lot of other things it's very rarely pure in terms of other dsm-5 diagnosis most people have come ability on axis one usually substance use disorders but anxiety disorders such as generalized anxiety panic disorder PTSD not uncommon at all you'll find people with bipolar disorder with OCD you'll find lots and lots of comorbidities so once you find one thing you're more likely to find others and the complete assessment of somebody like Sally with bipolar disorder you're going to assess for depression anxiety mania substance use you want to make sure that you know who you are engaged with and treating before you move on bipolar disorder is associated with higher rates of diabetes with migraine with the tendency toward chronic pain disorders with cardiovascular disease so in order to truly treat someone like Sally you have to be looking for metabolic issues and the mood issues and you might be you know Co managing you know a migraine disorder and if she has a strong family history of coronary artery disease you want to make sure you factor in her bipolar disorder as a risk factor for her coronary artery disease so you're establishing the diagnosis and you're really doing a very nice risk assessment and chronic disease management that's the mindset that you need to be in and that particularly Sally needs to be in because she's not getting over this illness he's gonna need to manage this illness and it is her illness and you you will need to to engage her and to probably need a team of people including her therapist to help engage in that activity you so based on our assessment of Sally what do we have we have recurring early onset major depressions we have the family history that's chock-full significantly mentally ill individuals several suicides a mother who hasn't established bipolar one diagnosis and she's had manic episodes that meet criteria for bipolar disorder so she has bipolar one disorder meaning she's had a manic episode she is currently in a depression and major depression with some mixed features the talkativeness the distractibility the tangential Ness the racing thoughts you know it's depressed but it's a little manic and it took 13 years to get her from when she began to be ill until now and that's tragic incredibly tragic so when you're treating bipolar disorder here's a summary of what we're thinking about so you're looking for efficacy convenient safety tolerability something that the patient will adhere to because that's the way you get to a robust sustained remission of symptoms and it's only in that robust sustained period of wellness that sally has a chance to think clearly and plan clearly and move on with life and that's what we want Sally to do we want to alleviate depression and we want to provide a long-term mood stabilization because life lived with an unstable mood is the life that she has it's you know eight years of college and five different majors and a risk of suicide and not knowing what you want to do with a degree in political science and a minor in art and your waiting tables bipolar disorder unfortunately in both psychiatric and non psychiatric settings is very poorly treated in a couple of studies in the literature the most commonly prescribed medication for an episode of bipolar depression is an antidepressant and we know that antidepressants as mono therapy and even antidepressants when combined with mood stabilizers are not the appropriate treatment for bipolar depression so there are treatments for acute mania there are treatments for acute bipolar depression and there are treatments that have been approved and are used for maintenance therapy we're going to focus really on the acute depression and the maintenance aspect and again the unmet needs in in the area of treatment of bipolar depression are treatments that are well tolerated and effective and are efficacious in the long haul because the illness is a lifelong illness at least in reference to the science that we have today so here's a graph showing the first study the first medication approved for bipolar depression olanzapine fluoxetine in combination and again significant separation from placebo beginning at about two weeks and lasting through the study of eight weeks here's the second medication that was approved for bipolar depression quetiapine and again two different studies builder one Boulder - showing that doses of both 300 milligrams and 600 milligrams quo type and were effective in separated from placebo in treating bipolar depression and again because 600 milligrams of Co type and yields more adverse effects than 300 you typically think about the antidepressant dose of khatai panas 300 milligrams here's the most recent medication that's been approved for the treatment of bipolar depression larezo Doane and again there's a mono therapy study on the left-hand side of the graph is your madras scores compared to placebo the montgomery osburgh depression rating scale on the other side is the cgi the clinical global improvement for bipolar depression severity scale basically showing that larezo Donen mono therapy separates nicely from placebo and randomized control trials for the treatment of bipolar depression some additional therapy on Lozado mono therapy indicates that two weeks in a post hoc analysis of the larezo time studies you can typically tell when you've got a positive signal and for that reason when we are seeing people in active management of both major depressive disorder and bipolar disorder we're seeing people about every two to three weeks because there's typically an assessment and an action plan that needs to be instituted for that the other thing that has been noticed for the resident in studies is there were significant improvements in both depression severity and our secondary measures of anxiety and quality of life and functioning and Laura's adone is fairly well tolerated medication for bipolar depression another nice thing about Laura's adone in the treatment of bipolar disorder is that since bipolar disorder treatment is very often polypharmacy irrational polypharmacy larezo Doane looks like a good combination with both lithium a standard mood stabilizer and divalproex which is an antiepileptic which is also a mood stabilizer so you could Adler acid own based on established literature to people who are already on maintenance therapy so the second generation antipsychotics are being used more and more in the treatment of bipolar disorder also as adjunctive z' for other conditions and here's a list of potential warnings and precautions that we want to draw your attention to the need to monitor from metabolic adverse effects remember I told you that when Sally started therapy we got a metabolic panel and a lipid panel and a hemoglobin a1c and we'll be monitoring that for her periodically to make sure that we are in the safety zone around metabolic or glycemic control for her and the other is the potential for cognitive and motor impairment tardive dyskinesia is still an issue it is less prevalent on the newer second-generation antipsychotics but it is not absent on these drugs and the full assessment the proper assessment of anyone who's taken any kind of antipsychotic where their first or second generation involves assessing and documenting for abnormal involuntary movements and evidence of this in Asia every time you see them so another way of looking at the efficacy safety tolerability equation is the number needed to treat and number needed to harm I'm sure many of you are familiar with that way of an been analyzing control trials we like for a number needed to treat in a randomized trial to be less than 10 that helps identify an efficacious treatment we like number needed to harm to be greater than 10 that helps us identify treatments that are more tolerable and more safe and I would just point here there's information for the olanzapine fluoxetine combination for quetiapine for lamotrigine versus placebo and again lamotrigine is not fda-approved for bipolar depression but there are a couple of positive studies in the literature and so it is sometimes used by experienced clinicians in this illness but I wanted to point out the Laura's adone data versus placebo with a number needed to treat a 5 and a number needed to harm in the low dose range 20 to 60 milligrams per day which is the dose range you'll usually use a la razón if you do the number needed to harm for akathisia was 18 for extrapyramidal symptoms was 40 and for weight gain greater than 7% from baseline was 58 and then you have your adjunctive lore acid own meaning Laura's adone with lithium or acetone with divalproex there your numbers there so we talked about antidepressants and bipolar depression we talked about in referenced a couple of times the fact that although they are often used in the treatment of bipolar depression based on good scientific data from multiple studies they're not effective so we would like to move away from treating as first order treatments adding antidepressants to mood stabilizers or using antidepressants alone for people with bipolar depression first of all the potential risks would be it's not usually going to work the second potential issue is it might make them worse it might induce manic episode rapid cycling other kinds of things now there are a few people that might do well with an antidepressant added to a mood stabilizer or a couple of mood stabilizers the the illness can be challenging to diagnose challenging to manage and sometimes antidepressants can play a positive role but when you're initiating treatment for bipolar depression you want to use a specific evidence-based intervention and that's not antidepressants alone or antidepressants combined with mood stabilizers Sally came from a therapist therapy has an established benefit psychotherapy has an established benefit in bipolar depression social rhythm therapies family therapies cognitive behavior behavioral therapies particularly dialectic behavioral therapies therapy is as good as a pill in many studies and so the therapy is going to be really important for Sally because she said such pervasive mood disruptions early in her life that she's missed a lot of the milestones for maturing and developing into stable adulthood so now we're back to Sally we know about her illness we know about her diagnosis we know about her family history and we've taken a look at treatment in a general kind of way now we have to match Sally's illness to a rational treatment strategy and what do we know well she has a history of significant manic episodes and hypomanic episodes that we are going to have to prevent she is in a severe current depressive episode that's enough severe enough to require immediate specific therapy she has high recurrent depressive episodes and so we need prophylaxis a you know for prevention of depression and there's no single pharmacologic agent that currently fills the entire prescription so you know based on a nice view of Sally's illness she's gonna need more than one medication more than one strategy so here's what we did we put her on lithium at a small dose 900 milligrams a day that's kind of low standard therapy last level she came in with when we were checking levels was 0.7 meq per liter that's the low end of the therapeutic range or renal function thyroid function was fine that's for prevention of mania probably also has some prophylaxis against depression but I want to sort of mention here part of the art of treatment people with bipolar disorder live with very passionate emotions and they live in their emotions and if you don't understand that you might push the levels of some of these medicines too high so you can't mood stabiliser one like Sally with a high dose of lithium and her be comfortable because she lives in her emotions and her emotions are part of her authenticity and so what you want is not to damp all of the emotional movement out you want to put boundaries around the emotions larezo don't at 20 milligrams a day was used to treat acutely the bipolar depression and she had no adverse metabolic changes and follow up we also use lamotrigine as an agent known to and approved for prevention of bipolar depression and she continued with her psychotherapist as we talked about six months in Sally's very stable very happy very pleased if she takes her lithium without a meal she remembers that you really should take lithium on a full stomach that's just part of the rules around taking lithium but the plan is since she is now in what I would call a robust sustained remission a full functional remission some people say she's engaged in her psychotherapy she's on three medications that are working well after a year of stable youth amia probably planning on discontinuing the la razón and then looking at the lithium and lamotrigine and the psychotherapy as her maintenance strategy so everything's a journey okay in diabetes care and hypertension care in the care of the bipolar patient early identification of the bipolar disorder is critical to optimal treatment remember she went 13 years improperly diagnosed had several non-productive treatments if she had been properly diagnosed five or ten years earlier perhaps some of these these difficulties in college and this sort of you know sort of erratic kind of life plans could have been avoided the rationale polypharmacy we've mentioned several times we want to maximize efficacy safety and tolerability and stable emotions promote thoughtful decisions and self-efficacy and again we want to use our medicines in a way that eliminates episodes but allows these highly emotional highly intelligent and emotionally intelligent individuals to have that authentic range of emotions that they're going to be comfortable with otherwise they won't participate in treatment because their emotions are part of who they are the patient gets to set the agenda it's their illness it's their life our role as clinicians is to inform and to engage and to collaborate and to help get to the the to get the goals the patient wants in ill in the illness control the therapeutic alliance is always patient oriented and psychotherapy is essential I think for a successful outcome because as I've said a couple of times before there's no wisdom and a pill so I thank you and hope this has been very helpful this activity has been jointly provided by medical learning institute incorporated and PVI peer view institute for medical education thank you for listening download materials and complete the post-test for instant credit at wwp review press comm /b w/e this activity is supported by an educational grant from synovium pharmaceuticals incorporated