When Bipolar and ADHD Overlap: Treatment 2

Today, we return with a full review of treatments for ADHD and bipolar disorder. Welcome to the Carlisth Psychiatry Podcast, keeping psychiatry on a since-2003. I'm Chris Akin, the Editor-in-Chief of the Carlisth Psychiatry Report. And I'm Kelly Newsom, a psychiatric NP, and a dedicated reader of every issue. Last week, you learned that the stimulants, methamphetamine, are often used for cognitive problems in ADHD and bipolar disorder, despite a lack of evidence supporting them, despite animal models where they're used to worsen bipolar or cause bipolar, and despite other risks like mania, psychosis, and neurotoxicity. So we recommended that if you're going to use a stimulant, try to use methylphenidate in place of infetamine and bipolar, it's less risky, and try to keep the doses low, because those problems we mentioned are dose dependent. We then went on to list my top treatments for bipolar and ADHD, because there are two treatments that don't harm the brain and that treat both illnesses. Those are armadaphanyl for bipolar depression and for ADHD, or clonidine, which treats bipolar mania and ADHD. But there are many other options that you might consider. Let's get into them today, starting with those other non-stimulants that have an anti-depressant like structure. The other FDA-approved non-stimulants are adamoxetane, strutera, and philoxazine, quobri. But these are controversial in bipolar disorder because they have anti-depressant structures. Both are known to induce mania, and while adamoxetane failed to gain approval as an anti-depressant, philoxazine has been used for depression outside the US since the 1970s. Besides, these two have low effect sizes in ADHD anyway, so it's usually not worth the risk to add them in for a bipolar patient. Yeah, adamoxetane is noradgenurgic, which is one of the key pathways to mania among antidepressants. And philoxazine quailabri is like an SNRI similar noradgenurgic potential there. Now let's look at supplements. These probably aren't going to treat a full ADHD picture, but they can lessen the symptoms. And some of them have benefits for bipolar as well, starting with fisioil omega-3. For patients who prefer a non-medication approach, omega-3 fatty acids are a good place to start. This supplement improved depression in bipolar disorder, and in children with ADHD, omega-3s improved both emotional and cognitive symptoms with a small effect size. It's according to a meta-analysis of 7-8 placebo controlled trials in bipolar and in ADHD, so 7-8 in each of the separate disorders. In those ADHD trials, omega-3 tended to work better when the dose was brought closer to the range used in the mood trials, so brought a little higher. And that dose range is 1-3,000 milligrams a day of the addition of both DHA and EPA. So you add those two omega-3 together, and you also want the EPA amount to be at least twice as high as the DHA amount. That's a lot. That's a bit complicated. So to keep it simple, I have selected lab-tested products that have the right ingredients on my website, chrisacanmd.com/supplements. Probiotics are another option. These have two small trials in ADHD with mixed but promising results, and a lot of trials in major depression, including in bipolar disorder where they prevented mania. What stands out in the depression trials is that probiotics also improve cognition, making them a good choice for bipolar with cognitive symptoms, whether caused by ADHD or not. Probiotics work best with prebiotics, dietary fibers that the healthy bacteria eat, and we have product recommendations with both pre and probiotics in them at chrisacanmd.com/supplements. Here's what I do in practice. I usually start with one of the alpha agonists like clonidine, particularly if the patient has insomnia, or one of the medaphynils if they're struggling more with depression and fatigue. So I'm going for an agent that's going to address residual symptoms in bipolar, which when you treat bipolar, residual symptoms are very common. Of the two alpha agonists, wanfacine has more evidence to improve executive functioning while clonidine has more studies in comorbidities that you often see in bipolar disorder, things like self-harm clonidine prevents it, PTSD clonidine helps nightmares and anxiety and sleep, and opioid and nicotine use disorders where clonidine prevents that kind of substance use. clonidine is also more sedating than guanfacine. So I tend to go with clonidine. My patients have a lot of these comorbidities, but I've given you good reasons to go with guanfacine instead, such as if you don't want as much of a sedating med, or you just want one that has more evidence to improve executive functioning. Either one is good to start with. Now among the medaphynils, most patients prefer armadaphynil, that's new vigil, as it has steadier plasma levels, so there's less up and down, and a slightly longer duration of action lasting about until 6 p.m. for its cognitive benefits if they take it in the morning, as opposed to about 2 to 4 p.m. The alpha agonist take a few weeks to work for cognitive symptoms in ADHD. You gotta give them some time, while the medaphynils have same day effects, much like you see with the stimulants. And they do very good at improving alertness and wakefulness, that's what they're classified as, wakefulness promoting agents, but we want to see that they improve ADHD as well, which they did in the controlled trials in my own experience, they're not quite as successful as I'd like them to be, but they do make a difference, that's meaningful to many patients, in cognition. Now let's turn back to the stimulants, suppose you do go with methylphenidator, emphetamine, or even the medaphynils, the novel stimulants. One thing about these kinds of drugs is that it can be hard to assess the patient's response. It's a little tricky because these three drugs are controlled substances, so you have to be careful not just to ask the patient if they feel better, if they like the med, because hey, I mean that's how they know that these drugs are controlled substances, they give them to patients and ask if they have a liking if they'd like to take more of them, and they say yes. So let's go for other kinds of signs, and in my experience, these are the signs that point to a true ADHD benefit with stimulants. First, I'm going to look that they have a calming effect, that is that they actually improve hyperactivity, that the patient is less impatient on them, they have better patients and they're less reactive, less irritable on them, so a calming effect is opposed to a hyped up effect. Next, I'm going to look for actual improvements in executive functioning. And how can I tell? Well, I'm going to ask about questions about their ability to organize and prioritize complex tasks. So not are they just more energized and motivated to get out of bed? I mean, that's important, but if that's the only benefit they get, it tends to be short lived. But can they actually finish their term papers and organize and clean their entire room, organize complex tasks like that? And finally, I want to see that the benefits are sustained because many people have short lived benefits if they don't really have ADHD. So in contrast, what it looks like if you give a person a stimulant so they don't actually have ADHD, well, the patient's still going to like the med, but they're likely to talk about benefits in energy and motivation rather than organizational skills. They might also have a crashing fatigue as the stimulant wears off at the end of the day and the only benefit they were getting that boost of energy, falls away. And after a few months, these patients who don't really have ADHD tend to get some tolerance to those benefits, they tend to wear off prompting them to ask for higher and higher doses. Let's recap about 10 to 15 minutes. 20% of patients with bipolar disorder have genuine ADHD. To treat this comorbidity, stabilize mood first. Alpha agonists and the medaphineels are good options to start with, while the stimulants carry risks in bipolar disorder, particularly the amphetamines. If you'd like a table with all the treatments we've discussed and dosing tips, check out the November 2021 issue of the Carlates psychiatry report online. And to keep up with the latest in psychiatric research, we post new studies in the daily psych feed. Search for Chris Aiken MD on LinkedIn, Twitter, Facebook and threads. It's a first glimpse of the trials that inform this podcast. Thanks for tuning in and helping us stay free of industry support. [BLANK_AUDIO]