Recognition and Treatment of Bipolar Depression

Hello, I'm Dr. Sloane Manning I'm from the University of North Carolina at Chapel Hill. She co-directs 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 Exploring the Recognition and Treatment of Bipolar Depression. a patient's journey from diagnosis to

treatment

access the entire activity and complete the posttest @ww peer review press comm /b w/e downloadable slides and practice aids 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 as having major depressive disorder, this is actually a fairly common situation in outpatient psychiatry and primary care due to the nature of the illness and today I would like to tell you the story of a particularly instructive case.

The patient that the patient calls is Sally, so

bipolar

disorder, as many of you know, is a fairly serious neuropsychiatric condition that is characterized by fluctuations in mood and energy levels. It consists of manic or hypomanic episodes, usually with recurrent major depressive episodes, although the age of onset of bipolar disorder is usually set at twenty-one people who begin to experience the illness for the first time, usually beginning in adolescence with an index episode that It's usually

depression

, so you usually experience a series of major

depression

s before you have your first manic episode and can be formally diagnosed.

Bipolar disorder is challenging to diagnose in primary care and psychiatry because depressions outnumber manic episodes and it is also difficult to think differently sometimes when the patient presents with depression, but you have to decide what type of depression you are seeing . there are multiple mood states and there are many comorbidities, so when Sally first came to my clinic she was 26 years old and had been experiencing recurrent depression since she was 13, she is majoring in political science and within weeks of graduating, she had a specialization in art. She was graduating from one of our local universities in Greensboro, the therapists she had been seeing through the University's Department of Psychology referred her to me and I never forget the day she walked into my office because she immediately started engaging me in conversation it wasn't difficult to talk to she is very intelligent very bright she looks very happy quite talkative in fact I got so involved in the friendly conversation that I had to remind myself that we had some issues on our hands when I got her ahead and tell me a little about her college experience she said well I'm on the eight year plan and I said well I heard about the five year plan but I don't know about the eight year plan tell me about she said well I left and started college three times I had five changes in my major, you know, I started with history, then I went to palasa fiy primary education, finally I decided on political science, but I kept my art major, so I said you know we need to talk about why you're here, what you were hoping to get from our conversation from our meeting today and at that moment Sally burst into tears, I mean a sobbing mess that, you know, grabbed several tissues, took a couple of She took a few minutes to compose herself and told me : "You know, I've been dealing with depression my whole life." Medications have never really helped me, but my therapist thinks I really need to give meds another chance.

What is the typical story of someone who has bipolar disorder? As? How are stories of a major depressive illness different from a story of bipolar illness and in medicine at least we initially learned the phrase everything that wheezes is not asthma? I mean, you know, wheezing can be asthma but it can also be pulmonary. edema and another series of diagnoses, in this case everything that is depression is not a major depressive disorder, so if you have depression and are looking for a differential diagnosis of depression, the underlying depressive diagnosis could be a major depressive disorder, it could be bipolar disorder. it could be a premenstrual dysphoric disorder or a substance use mood disorder or maybe a mood disorder due to another general medical condition like stroke or thyroid or some other brain injury or it could be a chronic weather disorder and the DSM-5 criteria for a major depression disorder are the same as the DSM 4TR criteria for a major depressive disorder: it involves two weeks of persistent depressed mood or anhedonia with enough other symptoms to make a total of five symptoms that they are clinically harmful and that they are not due to anything else, so I think that we all As we are familiar with the diagnosis of major depression, it turns out that the criteria for a bipolar depression and the criteria for a major depressive disorder in terms of an episode Major depressive disorders are no different, so bipolar disorder is often misdiagnosed as depression and was a very A well-known study published ten or fifteen years ago in which a number of people with bipolar disorder were asked in a survey how long it took to get a proper diagnosis of bipolar disorder and the average time to be properly diagnosed was about 10 years and most people were initially misdiagnosed with major depression and the average number of health professionals needed to make the diagnosis was between three and four; some studies have been done; in fact, we were one of the first to publish such a study in the 1990s on the presentation of depression. in primary care settings and in our study and we looked at what percentage of people with depression in primary care have bipolar disorder, we found that about 25 to 26 percent in that study has been replicated several different times, now what you're looking for making the differential diagnosis is a manic episode, of course, it is a distinct period of abnormal, persistently elevated or irritable mood, people become expansive in their mood or extremely irritable psychosis, it is not uncommon to go to the hospital, no It's rare, so you're looking for a period of time before a manic episode when your energy and mood are very different, euphoric, energetic, or severely irritable and the wheels of your life are starting to fall off because you can't do anything, A hypomanic episode is a milder manic episode that doesn't last as long, it usually takes four days to diagnose, but you see the same type of symptoms, just look for a milder, shorter duration of manic symptoms.

One of the most important things you can learn about mania. and depressive episodes in bipolar disorder is that you do not have to be manic or depressed in dsm-5, you can have manic episodes that mix with depressive traits and you can have depressive episodes that mix with manic traits and therefore the traits mixed The specifier is a particularly important thing to recognize in terms of the symptoms that people have, so what makes a diagnosis any diagnosis, what is in a diagnosis, there are actually five elements, five elements of a diagnosis , the first element is phenomenology, which are the symptoms that are seen, the second.

The element is the longitudinal course of the disease, how it started, how it changed over time, the third element of the diagnosis is the pedigree or family history, whether it is heritable, whether there is a genetic connection, the fourth element of the diagnosis is the response to

treatment

, because different types of diseases do it. respond differentially to different types of treatment and the fifth category of evidence or classification for a diagnosis is biological markers. Now we still don't have biomarkers for bipolar disorder or major depressive disorder in a very clinically useful way, but we're getting there.

I 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 around age 13 for bipolar women. This is not at all unusual because there is something about menarche or the beginning of the reproductive cycle that opens the door to mood problems in women and when I asked her to tell me about the natural symptoms of her depressive episodes, first of all said he had had so many episodes I don't know how many episodes I have had so TNT See too numerous to count some of the episodes were very agitated painfully agitated and there was some cutting behavior during those agitated depressions other depressions were more atypical overeating while sleeping arms and legs feeling of rejection of lead sensitivity reaction to positive stimuli except when the stimulus has gone depression returned immediately she made a previous suicide attempt in the past she overdosed at age 16 after the breakup with her girlfriend she was treated in the emergency department referred to a therapist interestingly when we talked about her previous suicide attempt she said You know, I don't have any suicide pact with a close friend and I said really and she said yes, I really want to be different from the rest of my family.

I want to live, but there have been many deaths in my family, so a little more history for Sally. She will graduate from college in a couple of weeks, but she has no career plans. Well, she waits tables at a very exclusive restaurant in the area. She had hopes of becoming a sommelier, but she said I wouldn't. alcohol well being, don't miss my question after that was telling me about not taking alcohol well, she has a history of binge drinking, she had a DUI in the past she said, I finally decided alcohol was a alley no outlet 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, it's really anxiety-producing and some paranoia if it goes beyond a small social participation in terms of cannabis and this.

It's a general rule that you should understand and that everyone should understand about mood disorders and bipolar disorders, especially when you mix bipolar disorder with substance use disorders, you release the Beast, so let's I asked about meaningful relationships and particularly meaningful intimate relationships, and Sally is sexually ambivalent. she describes herself as having eight total sexual partners in her life, some men, some women, when I asked her to put herself in an LGBTQ category, she says, from Muir, yes, no, thank you. I'm not really interested in sex right now and I took that to I mean, let's go ahead and do it, so every once in a while he gets an exercise bug, sometimes he gets these depressions, a kind of leaden paralysis, you know , and what he said was good.

I remember one summer after my sophomore year in school when my interest in exercise and art was off the scale and I said very off the scale. What do you mean? I spent a lot of money on art supplies, I mean a lot of money. He exercised constantly. He only needed an hour or two of sleep. At night I would call people in the middle of the night and demand that they come see my latest art project, my latest pottery or painting or whatever, and again I called people at 3:00 a.m. m. and I told them I could.

I can't believe you don't want to come and see what I've done, it's beautiful or I'm heading to the gym and it's 3am. and I want you to come with me and what do you mean you won't come? I can't believe this with me, she also said that her head was so full of thoughts that she fantasized about drilling a hole in her head to let all the excess thoughts out and that to me was wow, we have less need! To sleep we have unlimited energy, we have some behaviors that are negative and have consequences and I think you know what's going on and she even said that she broke that cycle by drinking excessively, so Sally talked about her family. story a couple of times remember so let's go to Sally's family history a maternal grandmother who was institutionalized and eventually treated with frontal lobotomy a maternal aunt with severe depression who was treated with antidepressants who became sick enough to be treated with electroconvulsive therapy ECT shock therapy who died by suicide his mother severe postpartum depression alcoholism with eventually a formal diagnosis of bipolar an older brother with ADHD substance use disorders we don't know where he is they haven't seen him in a while and a younger brother who was an alcoholic and he committed 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 is a more hereditary psychiatric illness the family history seems sicker so Sally hasbeen treated a couple of times again when she came antidepressants have never worked for me but my therapist really wanted me to try it one more time because my depression was getting more severe.

She tried and nothing really helped except an antidepressant which she remembers taking. We are in about a week. She felt like she was cured of her depression, she was talking actively, she started exercising again and did half marathons and that lasted about six weeks and then the benefit went away, she fell back into depression and no matter what her provider did with the dosage of the antidepressant that could not recreate his recovery well, what happened in that situation was most likely that the antidepressant triggered a hypomania that seemed like a relief from his major depression but was actually changing it, it was a change towards a hypomanic episode that never has had a test. of a mood stabilizer or an atypical antipsychotic so I don't know about you but I measure depression so in my practice we use the phq-9 and we gave Salad the phq-9 and she got a 20 out of 27 without nothing for suicidal ideation. which is good and basically it's extremely difficult for the tenth question so you have severe depression with some anxiety on the G 87 which is the instrument we use to measure anxiety symptoms you score about an eighth .when we use a screener for bipolar disorder, which is the CD 3.0, she tests positive on both the expansive mood and irritable mood stimulation questions and endorses each of the nine manic symptoms, so that you would get a very high risk score for bipolar disorder, so the evaluator is supporting what I already heard, so we are really looking for associated characteristics.

We got some blood work. Lipid panel. TSH. CBC. Urine analysis. All of that was normal. As we could have mentioned in the previous part. At this point we have already assumed that bipolar disorder comes mixed with many other things; very rarely is it pure in terms of other dsm-5 diagnoses. Not at all, you will find people with bipolar disorder with OCD, you will find many, many comorbidities, so once you find one thing, you are more likely to find others and the full evaluation of someone like Sally with bipolar disorder will do that. To screen for depression, anxiety, mania, substance use, you need to make sure you know who you are interacting with and who you are dealing with before proceeding.

Bipolar disorder is associated with higher rates of diabetes with migraine prone to chronic pain disorders with cardiovascular disease. In order to truly treat someone like Sally, you have to look for metabolic and mood issues, and you may know Co-managing, you may know a migraine disorder, and if she has a strong family history of coronary artery disease, you need to make sure you consider their bipolar disorder as a risk factor for their coronary artery disease, so you're establishing the diagnosis and you're really doing a very good risk assessment and chronic disease management, that's the mindset you need to have. and that Sally particularly needs. be because she is not getting over this illness, he will need to manage this illness and it is her illness and you will need to involve her and you will probably need a team of people, including her therapist, to help engage in that activity that you need.

Based on our assessment of Sally, what do we have? We have recurrent early-onset major depression. We have a family history filled with people with significant mental illness. Several suicides. A mother who has not established a diagnosis of bipolar disorder and has had manic episodes that meet the criteria. for bipolar disorder, so she has bipolar one, which means she has had a manic episode. She is currently in depression and major depression with some mixed characteristics. The talkativeness, the distraction, the tangential. Ness, racing thoughts. You know she's depressed, but she's a little manic and took it. 13 years to get her back from when she started getting sick to now and that's tragic, incredibly tragic, so when you're treating bipolar disorder, here's a summary of what we're thinking so you're looking for efficacy, convenience, safety, tolerability, something that The patient will comply because that is the way in which a solid and sustained remission of symptoms is achieved and it is only in that solid and sustained period of well-being that Sally has the opportunity to think clearly, plan clearly and move forward with the life, and that's what we want Sally to do.

Do we want to relieve depression and do we want to provide long-term mood stabilization because the life lived with an unstable mood is the life she has? 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 bachelor's degree in political science and a minor in art and your wait tables bipolar disorder unfortunately, in both psychiatric and non-psychiatric settings, is treated very poorly in a couple of studies in the literature, the most frequently prescribed medication for an episode of bipolar depression is an antidepressant and we know that antidepressants as monotherapy 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 really focus on acute depression and the maintenance aspect and again the unmet needs in the area of ​​bipolar depression treatment.

They are treatments that are well tolerated, effective and effective in the long term. because the disease is a lifelong disease, at least in reference to the science that we have today, so here is a graph showing the first study, the first drug approved for bipolar depression, olanzapine fluoxetine in combination and again a significant separation from placebo starting about two weeks and lasting an eight-week study, here's the second drug that was approved for bipolar depression, quetiapine, and again two different studies, one from Boulder, showing that doses of 300 milligrams and 600 milligrams of the type quo were effective separate from placebo in the treatment of bipolar depression. and again because 600 milligrams of type Co produces more adverse effects than 300, what you normally think about khatai panas antidepressant dosage 300 milligrams.

Here is the latest medication that has been approved for the treatment of bipolar depression. Larezo Doane and again there is a monotherapy study. On the left side of the graph are your madras scores compared to placebo, the montgomery osburgh depression rating scale, on the other side is the cgi, clinical global improvement for bipolar depression severity scale which basically shows that monotherapy with Larezo Donen separates very well from placebo and randomized control trials for the treatment of bipolar depression some additional therapy with Lozado monotherapy indicates that two weeks in a post hoc analysis of Larezo time studies typically You can tell when you have a positive sign and for that reason, when we are seeing people in active treatment for both major depressive disorder and bipolar disorder, we see people approximately every two to three weeks because there is usually an evaluation and a treatment plan. action that needs to be instituted for that, the other thing that the resident has noticed in According to the studies, there were significant improvements in both the severity of depression and our secondary measures of anxiety and quality of life and functioning, and Laura's Adone is a medication Fairly well tolerated for bipolar depression.

Another good 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 seems like a good match with lithium, a standard mood stabilizer, and divalproex, which is an antiepileptic that is also a mood stabilizer, so you might have Adler acid based on established literature for people who already They are under maintenance. therapy so second generation antipsychotics are increasingly used in the treatment of bipolar disorder and also as an adjunct for other conditions and here is a list of possible warnings and precautions that we want to draw your attention to the need to control the metabolic adverse effects.

Remember I told you that when Sally started therapy, we got a metabolic panel, a lipid panel, and a hemoglobin A1c test, and we'll monitor that periodically to make sure we're in the safe zone around metabolic or glycemic control for her. . and the other is the potential for cognitive and motor impairment, tardive dyskinesia remains a problem; It is less common with the newer second generation antipsychotics, but is not absent with these medications and the complete evaluation, proper evaluation of anyone who has taken any type of antipsychotic where their first or second generation involves evaluating and documenting abnormal involuntary movements and there is evidence of this in Asia every time you see them, so another way to look at the equation of efficacy, safety and tolerability is the number needed to treat and the number needed to harm.

I'm sure many of you are familiar with that way of analyzing control trials that we like the number needed to treat in a randomized trial to be less than 10, which helps identify an effective treatment. We like the number needed to harm to be greater than 10. That helps us identify treatments that are more tolerable and safer and I would just like to point out here that there is information for the combination of olanzapine fluoxetine with quetiapine for lamotrigine versus placebo and again lamotrigine It is not approved by the FDA for bipolar depression, but there are a couple of positive studies in the literature and that is why it is sometimes used by doctors experienced in this disease, but I wanted to point out the data of Laura's Adone versus placebo with a number needed to treat a 5 and a number needed to harm in the low dose range of 20 to 60 milligrams. per day, which is the dosage range you will generally use to reason, if you do, the number needed to damage akathisia was 18, extrapyramidal symptoms were 40, and weight gain greater than 7% from baseline was 58 and then it has its complement. 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 that we talked about in reference a couple of times to the fact that, although they are often used in the treatment of Bipolar depression based on good scientific data from multiple studies is not effective, so we would like to stop treating adding antidepressants to mood stabilizers or using antidepressants alone as first-line treatments for people with bipolar depression.

First of all, the potential risks would be that it's generally not going to be like that. the second potential problem is that it could make them worse it could induce a manic episode rapid cycles other types of things now there are some people who could do well with an antidepressant added to a mood stabilizer or a couple of mood stabilizers The illness can be challenging to diagnose and sometimes antidepressants can play a positive role, but when starting treatment for bipolar depression it is necessary to use a specific evidence-based intervention that is 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 behavioral therapies particularly dialectical behavioral therapies the therapy is as good as a pill in many studies, so therapy will be really important for Sally because she said that there were such pervasive mood disturbances in the early years of her life that she had missed many of the milestones necessary to mature and develop into a stable adulthood, so now we return to Sally , we know about her illness, we know about her diagnosis, we know her family history, and We've looked at treatment in a general way, now we need to match Sally's illness with a rational treatment strategy, and what do we know well?

She has a history of significant manic and hypomanic episodes that we are going to have to look into. prevent her from being in a current major depressive episode that is severe enough to require immediate specific therapy. She has very recurrent depressive episodes, so we need prophylaxis to prevent depression and notThere is only one pharmacological agent that currently fills the entire prescription, so we know that, based on a good view of Sally's illness, she will need more than one medication, more than one strategy, so this is what we did: we prescribed lithium in a small dose of 900 milligrams a day, which is a low standard therapy with which it reached the last level. when we were checking the levels it was 0.7 meq per liter which is the low end of the therapeutic range or kidney function, thyroid function was fine, it's for mania prevention, it probably also has some depression prophylaxis, but I want to 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 can increase the levels of some of these medications too much so that you can't stabilize the mood, one like Sally with a high dose. of lithium and she feels comfortable because she lives in her emotions and her emotions are part of her authenticity, so what she wants is not to dampen all the emotional movement, she wants to put limits on the emotions .

Larezo does not do it with 20 milligrams. It was used one day to treat acute bipolar depression and she had no adverse metabolic changes and at follow up we also used lamotrigine as a known and approved agent for the prevention of bipolar depression and she continued with her psychotherapist as we spoke for six months at Sally's . very stable very happy very pleased if you take lithium without eating, remember you really have to take lithium on a full stomach, that's just part of the rules about taking lithium, but the plan is that you are now in what I would call a solid state. sustained remission a complete functional remission some people say he is participating in his psychotherapy he is taking three medications that are working well after a year of stable youth amia probably plans to discontinue reason and then consider lithium and lamotrigine and psychotherapy as a maintenance strategy for Let everything be a smooth journey in the care of diabetes and hypertension in the care of the bipolar patient.

Early identification of bipolar disorder is essential for optimal treatment. Remember that she was incorrectly diagnosed for 13 years and had several non-productive treatments. properly diagnosed five or ten years earlier, perhaps some of these difficulties in college and these types of erratic life plans could have been avoided, the fundamental reason for polypharmacy that we have mentioned several times is that we want to maximize effectiveness, safety, tolerability and promote stable emotions. thoughtful decisions and self-efficacy and again we want to use our medications in a way that eliminates episodes but allows these highly emotional, highly intelligent, emotionally intelligent individuals to have that authentic range of emotions that they will feel comfortable with, otherwise they will not engage in treatment. because their emotions are part of who the patient is. setting the agenda is your illness it is your life our role as doctors is to inform, get involved, collaborate and help achieve the goals that the patient desires in the control of the illness the therapeutic alliance is always oriented to the patient and I believe that psychotherapy is essential for a successful outcome because as I said a couple of times before, there is no wisdom or pill, so I thank you and I hope this has been of great help.

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