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The Treatment of Bipolar Depression: From Pills to ...
Presentation Q&A
Presentation Q&A
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So, let's go to some of the questions, and some of them are starting to roll in. I'm wondering if you can speak for a minute about any modifications you've made to your monitoring protocols during the COVID pandemic. Yeah, so one of the monitoring protocols relates to blood work for lithium. I have a lot of patients who take lithium, and because of the pandemic, initially, I checked lithium levels every six months, because we're looking at thyroid functioning, we're looking at kidney functioning, and, of course, the lithium level, and we had to take a break from that a little bit, initially, at least. Patients were not eager to go to phlebotomy clinics to get their blood work drawn, and I completely understood that, but now some of these phlebotomy sites have figured out ways to provide safety when they bring patients in for these lab draws. As far as the visits, I've been fortunate enough to be able to use telehealth, and thankfully, patients, most of my patients do have either smartphones or computers with cameras and good Wi-Fi, and so we've been able to continue our monthly appointments or every two-month appointments with the same frequency, so I'm very fortunate in that regard. Wonderful. Here's another sort of specific question. What do you think about a combination of Lamotrigine and Latuda for treatment? I think it makes sense. We often have to combine a stabilizer with a second-generation antipsychotic, and I've had patients on that combination. I see no reason why it wouldn't be a good combination to use, and I think it really speaks to the synergy of these medicines to help our bipolar patients because what we see is oftentimes when we start a medicine like Lamotrigine and we don't see enough improvement or any improvement at all, and then we add the second medicine like Latuda to that regimen, and all of a sudden we see improvement, then some of us might be inclined to try to get rid of that Lamotrigine because it wasn't helping, but what we see in some of those cases is that when we try to remove that Lamotrigine, that in fact the patient regresses, and so it proves that it really was the synergy of those two medicines together, so I think Lamotrigine and Latuda are a very reasonable combination. You've talked a lot about combining medications with such complex medication regimes. Have you found any success involving an individual's partner or family to help with adherence? Oh, absolutely. We really depend on family members and partners to help with this because when people are depressed, many of them have cognitive impairment, and the cognitive impairment can be so severe that you actually think they have dementia, and they don't, the cognitive impairment resolves once the depression resolves, but it's during that time where they're more likely than ever to forget doses or take more than they're supposed to, so the role of the family member is crucial in making sure that the patient takes the medicine every day and takes it at the correct time, so it's very important, especially when there are multiple pills and the patient has to keep track of. Do you have a recommendation regarding immediate release versus extended release lithium for treatment efficacy? Yeah, I've always, I always use extended release because the thinking is that the side effect profile might be a little more benign, less gastric irritation, maybe the tremors might be less severe. The only time where I don't use extended release is if the patient has had some sort of gastric bypass surgery, and they no longer have the full length of their, you know, their small intestines and large intestines, and so in those scenarios, you want to use the immediate release because if you use the extended release, then there's a chance that a lot of that lithium won't get fully absorbed. Can you say a little more about any clinical pearls or interview questions you like to use when assessing for unipolar versus bipolar depression? Yeah, this is an area of interest for me because we, you know, in clinical trials, when we run our major depression clinical trials, we do not want bipolar patients in those trials, so I really spend a lot of time with this, and I've developed a system, and what I do is I ask patients, I actually use the screening question from the SCID, so the Structured Clinical Interview for DSM-4 and 5, and the screening question, I think, is something along the lines of, was there ever a time in your life when you were feeling so good, so high, hyper, or excited that people around you thought you weren't your normal self? And if they say no to that, then I don't stop there, and I say, well, what about a time when you were feeling so good, so high, hyper, or excited that you knew you weren't your normal self, even if no one else took notice? Because sometimes patients will endorse that, actually. And then if they say no to that, then I'll focus on energy, and I'll say, well, what about a time when you were feeling so full of energy, more than normal for you, that you could go several nights without needing much sleep and feel fine the next day? And if they say no to that, then I try one more time with an energy question, and I say, well, what about a time when you were feeling so full of energy, you were just having bursts of energy, where you felt like you were on a caffeine high, or maybe you were on some drug? And the reason that I go through those different screening questions is because it can be really hard for someone with depression to remember a manic episode from 10 years, or a hypomanic episode from 10 years ago. Manic episodes may be easier to remember, but even then, patients still, especially if they're cognitively impaired during the depression, may not remember it much. Once they endorse one of those screening questions, then what I do is I drill down on the DIGFAST symptoms of mania, and I say, all right, well, during that time when you said that your mood was so high, hyper, or excited that people thought you weren't your normal self, describe your mood for me. What was it like? And then after that, I say, all right, well, during that time when your mood was elevated, was there a change in how distractible you were? And I let them explain, and then I go to the I in DIGFAST, which is the increased energy, and I say, all right, well, during that same time when you were elevated and you were more distractible, what was your energy like? And I get them to talk about that, and so on and so on, all the way through DIGFAST. And I do one symptom at a time, and I build up on it, just to help with the recall, because otherwise, like I said, it's hard to remember these details from the past. Another thing we sometimes do is we sometimes will talk to family if the patients allow us. Wonderful. Can you talk about the roles of gabapentin and trileptal as treatment options? Yeah. So gabapentin, I do use a lot, but not to treat bipolar depression or to treat mania. There's no good data in support of its use, certainly as monotherapy. I use gabapentin to help with anxiety in patients with bipolar disorder, whether they're depressed or not. And the reason I like gabapentin is because given the risk of antidepressant-induced mania, which the meta-analyses didn't show in a very obvious way, but which we see anecdotally, I'd rather avoid using an antidepressant to treat the patient's anxiety and instead use something like gabapentin. So I often will use it in that regard. Trileptal, with regards to bipolar depression, I'm not aware of any. You know, any, you know, robust studies, certainly not as monotherapy. I know there've been studies where it's been used as an adjunct for mania, and sometimes that can be helpful. But in terms of bipolar depression, it's not one of my go-to medicines. Sometimes a patient will come on already on it, and then if so, I may, you know, optimize it before looking for something else. Can you talk about using topiramate? Topiramate. Topiramate, yes. Topiramate. Thank you. So there's some data that suggests topiramate may be helpful for the ultra-rapid cycling patients. So those are the patients who are having multiple episodes of depression and mania within a month, you know, and they're not full criteria in terms of the duration, because if they're having these episodes within a month, it's hard to, you know, since a depressive episode has to be two weeks and a manic episode has to be at least one week. So when we say ultra-rapid cycling, we kind of do away with the time requirement, but either way, they're cycling in and out of mania, depression, mania, depression over the course of a month, sometimes within a day. There are some studies that suggest topiramate may be helpful for patients in that scenario, may be helpful for anxiety, certainly for patients with impulsivity, such as like binge eating or, you know, for, I think it's helpful for craving and addiction. So a lot of uses that may apply to a bipolar patient, but not any data that I'm aware of that suggests it's very useful for bipolar depression or mania for that matter. I know you mentioned we won't be talking about ketamine, but there is a lot of interest these days in using it. Can you say anything about the data on ketamine for bipolar depression, and is there any risk of treatment in emergent mania or psychosis? Yeah. So there is some data that shows that it is effective in bipolar depressed patients. It was part of one of the earlier trials that was published, I want to say maybe like in the mid to late 2000s, and in that group, it was shown to be effective. But you know, the issue with these ketamine infusions is we still haven't quite figured out how to bridge the effect, how to maintain the effect in the absence of the ketamine infusions. As far as risk of mania or risk of psychosis, there is a risk of psychosis, and we actually think you have to have a little bit of psychotic experience when you get the ketamine. Otherwise, the concern is you might not be getting enough ketamine if you don't at least have some sort of psychotic-like experience in the moment. But as far as developing full-blown mania or full-blown psychotic episodes, I can't remember exactly what the study showed. Yeah, I can't remember, but I would say the way we do it here is we always require the patient to be on a mood stabilizer just to mitigate that risk. Any special treatment considerations in patients with both Bipolar II and ADHD? Yeah, so the Bipolar II population is unique in that they may be able to receive antidepressant monotherapy and have benefit and not have the risk of becoming manic. But the studies that looked at that, they took an enriched sample of patients who were already tolerating antidepressant, and then they put them in the trial and either put them in the placebo group or the antidepressant group. And so I think the point is that there are some Bipolar II patients clearly who can tolerate antidepressants and get better, but we can't assume that they all can tolerate it. And as far as the treatment of ADHD and Bipolar disorder, there are studies that show that stimulants or at least the methylphenidate group of stimulants are effective and do not increase the likelihood of mania if used in conjunction with a mood stabilizer. And I will tell you, if you don't address ADHD in a Bipolar patient, you're not doing them justice because it's great if you can get them out of their depressive episode and keep them out of their manias. But if they're still wrestling with attentional problems, they may still have a hard time getting their life on track. And there are non-stimulant options that I usually will try first. So Guanfacine, Atomoxetine, and if those don't work, then I'll start moving to the stimulants. I'll usually start with the methylphenidate option first. And then if that doesn't work, then I'll go to the amphetamines, which would carry the higher risk, I think, for mania or psychosis. But I would still try it, assuming that there was a mood stabilizer on board and the patient was not having any manic symptoms. Wonderful. Dr. Rakofsky, thank you so much for this practical and evidence-based informed guidance you've given us during the question and answer.
Video Summary
In this video, Dr. Rakofsky discusses modifications to monitoring protocols during the COVID-19 pandemic, specifically regarding blood work for lithium levels. Initially, blood work was done every six months due to patients' reluctance to visit clinics. However, some clinics have found ways to safely provide lab draws. Telehealth has been utilized for patient visits, allowing for continued monthly or every two-month appointments. Dr. Rakofsky also discusses the combination of Lamotrigine and Latuda for bipolar treatment, the role of family members in helping with medication adherence, the use of extended-release lithium, and strategies for assessing unipolar versus bipolar depression. Gabapentin is recommended for anxiety in bipolar patients, while Trileptal is not commonly used for bipolar depression. Topiramate may be useful for ultra-rapid cycling patients. Ketamine has shown effectiveness in bipolar depression, but there is a risk of psychosis. Treatment considerations for Bipolar II and ADHD include the use of antidepressants with caution and the effectiveness of stimulants when used with a mood stabilizer. Non-stimulant options are also available for ADHD treatment in Bipolar patients.
Keywords
monitoring protocols
COVID-19 pandemic
blood work
Lamotrigine
Latuda
Funding for SMI Adviser was made possible by Grant No. SM080818 from SAMHSA of the U.S. Department of Health and Human Services (HHS). The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement by, SAMHSA/HHS or the U.S. Government.
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