Rasagiline and Depression

[jlmerten]

I have been taking Azilect and then the generic Rasagiline for 12 years after being diagnosed at 34. I also took generic Dopamine Agonists for ten years but had such pronounced OCD behavior that I finally quit cold turkey two years ago.

Today I take Rasagiline 1mg, 100mg Amantadine, and CL 25/100. I've noticed less interest in things, new anxiety, and growing general depression. I have run out of rasagiline numerous times (expensive and difficult to get) and for the first few days I feel my head clear, the depression leave like a light switch, and my very pronounced dyskinesia calm down. But when I have tried to titrate off completely, I notice I need more CL and sometimes get more intensive depression.

I stopped the rasagiline again this last week and the relief from depression (which has never been an issue for me before or after diagnosis) is so marked that I am committed trying again. I feel motivated to work and dyskinesia is better but I definitely am taking more CL. This is a long way of asking if anyone knows about the process of getting of Rasaginline/Azilect? I find it fascinating that depression is listed as a main side effect. I've also been told it takes 30+ days to clear your system. 12 years in I am doing better with fewer drugs and I would like to reduce further.

[rescuema]

I agree that it's fascinating that the MAO-B inhibitor is causing noticeable depression in you while it's supposed to help with the dopamine availability. Some people seem to experience opposite reaction with the drug while it helps others. Understandable that you'd require more l-dopa while weaning off the med. You might also want to try adding supplemental Mucuna (with green tea or EGCg) on top/addition of C/L to see if that helps while trying to slowly taper off the drug.

Before hashing that all out, I'm curious when was the last time you've checked your homocysteine level?

Vitamin B12, b9, b6 levels?

B12 is a methyl donor that's often deficient in PWP, and lack of it can cause significant depression and anxiety. I'd be curious to see how you'd react to trying a sublingual B12 while noticing depression? I'm wondering if rasagiline is contributing to your methylation issue.

[jlmerten in reply to rescuema]

I haven't had vitamin levels checked for awhile. I have been taking a multivitamin supplement regularly and add more B-6 and D3. Unfortunately, I cannot get health insurance right now--at least not until healthcare.gov does online enrollment again. I'll have to look into another screening option.

I have tried Mucuna but its efficacy is less predictable as I continue so I end up going back to my synthetic CL.

I described my symptoms as "depression" but they are also/more aligned with malaise or apathy. Usually I can manage, but lately have found myself unable to get work done and non-plussed about the consequences. That is frightening for me. Work is actually going well and I am freelance and need it!

One thing I have learned about PD, is that it takes a lot of experimentation to sort out symptoms and side effects...

[rescuema in reply to jlmerten]

Sublingual B12 is very inexpensive. B12 is poorly absorbed through gut absorption in most people. Get Jarrow's methyl sublingual and see if that helps you at all, you won't lose anything and more than likely to benefit.

[jlmerten in reply to rescuema]

Thank you. I will definitely do the sublingual B12. At one point my Vitamin D levels were so low they did an injection on the spot, but I've kept those up with large supplemental doses.

[rescuema in reply to jlmerten]

Yes low D3 will certainly exacerbate depression so you definitely need to keep your eyes on your serum value. For raising the D level safely, nothing works better than occasionally laying out in the sun.

[rescuema in reply to jlmerten]

oh, and I forgot to mention for your apathy - look up mannitol and see if that may help you. For some it is very effective for apathy. The Science Of Parkinson has a good article on it. I’m typing on my iPhone again. I’ll post the link a bit later.

[rescuema in reply to jlmerten]

Here's the mannitol article link.

scienceofparkinsons.com/201...

[Kia17]

That has happened because the MAO-B inhibitors reduce seretonin level which causes OCD and depression.

[rescuema in reply to Kia17]

I was wondering the same and did a targeted search on any induced serotonin deficiency but my quick research actually showed more of serotonin toxicity tied to Rasagiline. If a deficiency could be the issue for the OP, it may be worth looking into 5-HTP just as in combination with levodopa.

[Kia17 in reply to rescuema]

The mechanism is very complicated.

There are many other factors involved such as genetic tendency. For instance I have fast MAO-A snips ( faster than %75 of normal population ) but MAO-B gene performing normal therefore I am more sensitive to low seretonin. Other enzymes like COMT also interfere with the Seretonin/dopamine relations. In my experience, 5-htp supplements or foods contain Tryptophan can reduce level of dopamine and vice versa.

PS; ncbi.nlm.nih.gov/pmc/articl...

[rescuema in reply to Kia17]

Yes it is a balancing act with 5-HTP with the competitive inhibition, just as I’ve elaborated with levodopa recently. However the newer research certainly shows promising effect of the supplementation In dealing with the l-dopa toxicity and LID so it’s worth trialing with a very small dosage not more than 25mg at least for several weeks, especially to help with depression and lack of sound sleep. Any more than that or titrating up too fast may certainly risk depressing the dopamine production.

[MarionP in reply to Kia17]

This is quite an interesting little study.

Try to get as much sunlight as you can during the day, if your weather where you are permits, and you just do need to have lots of B Complex and additional b12, just can't replace it. Have you thought of trying a little St. John's Wort?

[rescuema in reply to MarionP]

I agree St. Joh's Wort is worth a try for the OP, especially combined with adequate dose of B3 (but not too much!). The only thing to watch out for is that SJW has drug interaction with myriad drugs so one must be careful.

jlmerten please visit the new post below on niacin - may be of interest to you. If you've already ordered PE B-Complex Plus as I've recommended on another thead, then you shouldn't need to supplement B3 on top.

healthunlocked.com/parkinso....

[MarionP in reply to rescuema]

I just realized that B3 is NOT in several B-Complex preparations, including the one I use. Doggone. How much would you consider a decent amount?

[rescuema in reply to MarionP]

I use Pure Encapsulation's B Complex Plus, which contains 103mg of B3. I'd put an initial upper limit at around 100mg or so to not tax the methylation, at least initially depending on your methyl or homocysteine status - I've elaborated more on the aforementioned niacin thread - I definitely recommend you read that article. I don't take my B-complex everyday, as I alternate and rotate all my supplements to limit the daily number of pills, and try to attain nutrients through well balanced food.

[KERRINGTON in reply to rescuema]

Hello...I was checking out this product in the question/answer section of Amazon, people seem to like it, but there were lots of references to it being synthetic. You seem well versed, I'd appreciate your thoughts. Thanks !

[rescuema in reply to KERRINGTON]

Recommending supplements online without seeing blood panels is akin to shooting blind out of a hope to fill deficiencies. The reason I recommend that formulation is because it is a clean well balanced active methyl B forms, and it'll help even those who're genetically compromised with absorption issue, not possible with natural formulations.

[KERRINGTON in reply to rescuema]

Hi, probably didn't make myself clear...I was wondering if you had an opinion in general re. synthetic vs food sourced vitamins. Thanks

[rescuema in reply to KERRINGTON]

I'm a major fan of attaining vitamins through natural food sources whenever possible. : ) I talk about this often including on the niacin thread. healthunlocked.com/parkinso....?

One of my multivitamin is organic food sourced, but I also alternate with others. However, when you're ramping up a nutrient such as B1 megadose, it's akin to applying it as a drug so supporting nutrients also need to be ramped up in balance. For people with genetic/degraded enzyme dysfunctions, supplementation is the only way. When fighting methylation imbalance for various reasons, extra methyl donors such as b12, b9, TMG, etc., can be invaluable and not always possible through the natural means.

[Smittybear7 in reply to rescuema]

What are the signs of too much B12? How often should you get your B levels checked?

[jlmerten in reply to rescuema]

Thank you. Such helpful advice. I have not tried St. John's Wort because I was told it was contraindicated but without the Rasagiline I imagine it would be fine.

[Kia17 in reply to MarionP]

Sorry for the belated reply.Tried St John’s wort a few years ago before diagnosis but it didn’t help.

[MarionP in reply to Kia17]

sorry I have never suggested St. John's wort. ???

[Kia17 in reply to MarionP]

Please see above your reply to me from last year;

“This is quite an interesting little study.

Try to get as much sunlight as you can during the day, if your weather where you are permits, and you just do need to have lots of B Complex and additional b12, just can't replace it. Have you thought of trying a little St. John's Wort?”

[MarionP in reply to Kia17]

I guess I did. 🙂

Might have been because, looking at the conversation, the things I know that work didn't work for you.

SJW It's an unrefined, thus last resort, very weak precursor to tryptophan with little credible effect on depression, except that in Europe they think more of it for some reason, hoping perhaps it might move up htp channel as opposed to things that work along the dopamine pathway...

...sjw works the alternate pathway which is the mechanism underlying amytriptilene and the other tricyclic prescription antidepressants, they all work along the serotonin pathway and increase serotonin...and if for some reason you were insensitive to dopamine pathway measures, DA and so forth, because you mentioned something about a genetic anomaly, then I think that was my idea, since you seem to have some hardwired problem with increasing your dopamine via trying to increase using the dopamine pathway. Thus, the sjw idea. You can see the reasoning.

I don't usually suggest stj because along with being relatively weak, it also has potential for some side effects and some of them can be not good. So if you were already taking measures along the dopamine pathway, (the dopamine agonists you mentioned), yes, you wouldn't want to double up on DA with a tryptohphan/htp/serotonin action unless the first wasn't helping and you needed an alternative route or an additional route, which would be the htp-5htp-serotonin pathway, i.e., St.JW and the tricyclic prescription antidepressants...since you weren't getting enough effect via the dopamine or DA pathway alone. And that's also what I was getting at with the idea of using vitamin D3 as well, when you don't have enough vitamin D the deficiency can contribute to depression and impede or counteract other efforts to lift depression.

It's all something you can confirm with a good neurologist or psychiatrist by the way, nothing new.

[Kia17 in reply to MarionP]

Thank you for your input.

[jlmerten in reply to Kia17]

I don't know if it is relevant, but when neurologists wanted to lower my DA they would suggest adding an anti-depressant/anti-anxiety drug during the titration down. Wellbutrin was the first and it made me abruptly and extremely depressed to the point of suicidal thoughts.

It looks like there are some good suggestions here for supplemental support but do you or anyone following this thread think leaving Azilect behind altogether is ok? I have watched the debate over Azilect's purported neuro-protective effects since my diagnosis in 2008 (my neuro told me to buy stock in TEVA LOL) and worry I am throwing out something I should suffer through despite the depression. But I also worry that long term RX use is its own side effect.

[rescuema in reply to jlmerten]

Whether Azilect is neuroprotective or not is unclear and very much debated, especially when you add in the variable that it allows you to reduce C/L dosage.

The below article should be in your interest.

scienceofparkinsons.com/201...

[alaynedellow]

I highly recommend mannitol for apathy. Get mine from syncolein.com.

[38yroldmale]

I stopped azilect After reading this post. I couldn’t shake depression and anxiety. I’ve been taking it since I was diagnosed. Last week I think I’ve had the best week since being diagnosed. I must have an issue with my serotonin. I’ve taken a few ssri antidepressants and it makes my symptoms worse. About three weeks ago I started St. John’s wort. Great decision. It’s helped immensely with my depression without worsening my physical symptoms. I really can’t tell the difference on my motor symptoms after getting off azilect. I thought it was a mild antidepressant but it did the opposite for me.

[jlmerten]

Hey there. I'm glad to hear you are feeling better. It's certainly not my place to make medical suggestions, but one thing I have learned after 12 years of being an Early Onset patient, is that my medical journey and drug reactions are unique to me and this is true for so many of us. There isn't a one size fits all version. I am now taking fewer drugs than I was 5 years ago.

In terms of the rasagiline--this is the longest I've gone without it -- a full month -- and I am finally feeling like I'm over the hump. Feel better than I did two weeks ago. I hope you continue to feel better as well.