Interactions or counteraction between Mirtazapin and Guanfacine (+ Vyvanse) in treatment of comorbid ADHD/OCD/Anxiety/Depression et al? Possible alternatives?
I'm a 24M masters student, ~68kg, 188cm, of Western European descent. Diagnosed in last 18 months with ADHD, OCD; suspect ASD; suffer from anxiety, agitation, tics, depression, insomnia, fatigue. Consume no recreational drugs, and very little alcohol infrequently. But I am currently very sedentary. I know how to cook and eat very healthily, but struggle with my nutrition/desire to eat regardless.
When first diagnosed with ADHD (October 2022), tried variety of methylphenidate based drugs, and hated them. Only experienced side effects, including weight loss. Been on Elvanse/Vyvanse for past year roughly. Titrated up and down, and settled on 30mg (taken after breakfast). It helps with the ADHD immensely, it allows me to function. But it sadly also worsens my appetite and my tics/anxiety/agitation, and my pulse and BP have suffered as a consequence.
End of 2023 I was prescribed Mirtazapin (taken before bed) to help with the depression/anxiety/sleep, initially titrated from 15mg to 30mg. It also helped immensely, especially reducing my tics and intrusive thoughts as well as allowing me to eat better, but the effect fell off somewhat. Whether because of tolerance, or because I upped the dose, I don't know. We decided I would try 45mg, but I honestly didn't feel that much of a benefit and if anything felt a little worse, less calm, and it was worse for sleep. Back to 30mg and it's fine. It doesn't knock me out like 15mg did, but I nevertheless manage to fall asleep consistently.
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But the tics/agitation/anxious & intrusive thoughts are becoming debilitating, and my psych and I have been discussing changing or adding something else into the mix. I've read many anecdotal accounts of people combining Guanfacine with stimulant meds to great effect in the treatment of their ADHD, addressing their focus/inattention and emotional dysregulation both, while somewhat cancelling out each others' side effects.
So I mentioned it to my psych, and they decided it would be worth trying. I have just been prescribed 1mg Intuniv (XR, taken mornings before breakfast), to titrate up to 1mg per week. Since starting it, I have felt less anxious, less in my head, and physically more calm and comfortable. I have been eating more. I will be buying a BP cuff and pulse-oximeter today (replacing the ones I lost before), and while I have no reliable numbers, they both feel lower. I do feel a bit more tired, but that's inevitable, and also usually passes after the first week or so.
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Out of curiosity I decided to read up on their respective pharmacologies, and have now found that Guanfacine acts as an alpha–2a agonist, and Mirtazapine in part as an alpha–2a antagonist. So by my (very limited) understanding... they should in essence be highly counterproductive, right?
My question then is if there's any point in taking the two together? They're both expensive, they both come with side effects, and I don't want to be wasting my time if they're not only counterproductive, but in some ways counteract each other fully. I do take them at different times of day, but they still have long half lives, and will overlap. I definitely mean to discuss this with my psych and will be giving him status updates, but felt it worth asking here too, not least because I fear they might not be that familiar with the subject given they put me on the two in the first place.
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Mirtazapin + Vyvanse alone isn't working as it stands, but I also can't do without their effects. I need the Vyvanse most of all, and doubt non-stimulants on their own would do the trick (especially as I struggle with fatigue already), but I need something to manage their side-effects, my depression and especially the anxiety which is becoming paralysing. I am in therapy, and am trying to make lifestyle changes, but they take time and are currently insufficient.
My psych preferred me to try Mirtazapin before others, such as SSRIs, changing only if necessary. It has worked well for me, with few side effects, so I'm hesitant to drop it. But if it and Guanfacine won't work together, then one of them has to change or go. I do worry about the impact of coming off the Mirtazapin and of starting a new antidepressant, especially during the interim before benefits are felt and because of potential worse side-effects. And I worry of the impact to my sleep. There are also my academic obligations to consider, so I want to avoid destablising things as much as possible.
I still want to see how things go on the Guanfacine as I've been on it for less than a week and it does seem to be helping a bit (unless that's simply placebo; and I have pinned no small amount of hope on this). But I'm just now wondering what alternatives might be available to me in the event I find it not to work, if it's just not meant to. I have though of beta-blockers in the past, as well as maybe cannabis-derivations (thankfully just legalised), but I'm not a medical professional. I don't want to drug myself into a stupor or try to solve all my problems through pharmaceuticals alone, but as it stands I do need them. I'm just struggling to find the right balance that works for my issues.
Thanks.
P.S. I've tried to be comprehensive, but please let me know what, if any, salient information I've left out.