How to treat ADHD in bipolar disorder without destabilizing mood part 2: non-stimulants and supplements.

Publication Date: 12/02/2024 

Duration: 11 minutes, 01 seconds 

KELLIE NEWSOME: Today, we continue with our full review of treatments for ADHD and bipolar.

CHRIS AIKEN: Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003. I’m Chris Aiken, the editor-in-chief of the Carlat Report.

KELLIE NEWSOME: And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue.

CHRIS AIKEN: Last week, you learned that the stimulants methylphenidate amphetamines are often used for cognitive problems in ADHD and bipolar disorder, despite a real 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 amphetamine 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 armodafinil 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 nonstimulants that have an antidepressant-like structure.

KELLIE NEWSOME: The other FDA-approved non-stimulants are atomoxetine (Strattera) and viloxazine (Qelbree), but these are controversial in bipolar disorder because they have antidepressant structures. Both are known to induce mania and while atomoxetine failed to gain approval as an antidepressant, viloxazine has been used for depression outside the US since the 1970s (Perugi G and Vannucchi G, Expert Opin Pharmacother 2015;16(14):2193-2204). 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.

CHRIS AIKEN: Yeah, atomoxetine is noradrenergic, which is one of the key pathways to mania among antidepressants, and viloxazine, Qelbree, is like an SNRI ( similar noradrenergic potential there).

KELLIE NEWSOME: 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 fish oil – omega 3.

CHRIS AIKEN: For patients who prefer a non-medication approach, omega-3 fatty acids are a good place to start. Thissupplement improved depression in bipolar disorder, and in children with ADHD, omega-3s improved both emotional and cognitive symptoms with a small effect size, that's according to meta-analyses of 7-8 placebo-controlled trials in each disorder (Kishi T et al., Bipolar Disord 2021;10.1111; Chang JP et al., Neuropsychopharmacology 2018;43(3):534-545). 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 mg a day of DHA + EPA.  So you add those two omega-3s together, and you also want the EPA amount to be at least twice as high as the DHA amount. That’s a bit complicated, so I’ve selected lab-tested products with the right ingredients on my website chrisaikenmd.com/supplements. 

KELLIE NEWSOME: 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 I disorder, where they prevented mania. What stands out in the depression trials is that probiotics also improved 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 thehealthy bacteria eat – and we have product recommendations with both pre and probiotics in them at chrisaikenmd.com/supplements.

CHRIS AIKEN: Here is what I do in practice. I usually start with alpha-agonists, particularly if the patient has insomnia, or the modafinils if they struggle more with depression and fatigue. I'm going for an agent that's gonna address residual symptoms in bipolar, which when you treat bipolar, residual symptoms are very common, of the two alpha-agonists, guanfacine has more evidence to improve executive functioning, while clonidine has more studies in related comorbidities that you often see in bipolar disorder, things like self-harm, clonidine prevents it. PTSD, clonidine helps nightmares and anxiety in sleep and opioid and nicotine use disorders. Where clonidine prevents that kind of substance use, clonidine is also more sedating, 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 modafinils, most patients prefer armodafinil, that's Nuvigil, for its steadier plasma levels, so there's less up and down, and a slightly longer duration of action, lasting about until 6 pm for its cognitive benefits if they take it in the morning, as opposed to about 2-4 pm for modafinil. The alpha-agonists take a few weeks to work for cognitive symptoms in ADHD you gotta give them some time. While the modafinil have same-day effects much like the stimulants, and they do very good at improving alertness and wakefulness, that's why 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 methylphenidate or amphetamine or even the modafinils (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 patience, and they're less reactive, less irritable on them. So a calming effect as 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, 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 or organize complex tasks like that? 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 stimulants and they don't actually have ADHD, well, the patient'sstill going to like the med,  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.

KELLIE NEWSOME: Let’s recap. About 10-20% of patients with bipolar disorder have genuine ADHD. To treat this comorbidity, stabilize mood first. Alpha-agonists and the modafinils are good options to start with, while the stimulantscarry 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 Carlat Psychiatry Report online. Want to keep up with the latest in psychiatric research? We post new studies in the Daily Psych feed. Search for ChrisAikenMD 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.