perseverance Complex situation with Mirtazapine and supplement interactions

[perseverance]

 

My current situation is complicated from past tapers/reinstatements so a little history first.  This is long.  Thank you moderators for reading.

 

When I reinstated Zoloft in 2015 (see signature) after being off 4 months, I had a severe adverse reaction.  I started have panic attacks, lightheadedness, heart palpatations and the strangest pounding feeling in my head that mimics my heartbeat.   My p-doc said to go down lower and titrate up.  I tried this to no avail.  Every increase, made those symptoms worse and added others like brain zaps so I quit it after 2 months.  I've never been the same since this incident.  I felt better quitting, but still had symptoms of anxiety, depression and the head pounding.  Three months later, I began having severe panic attacks and insomnia at night.  My doctor prescribed Ativan and Mirtazapine.  Withing 2 months, I was fully dependent on the Ativan and started having all kinds of side effects and interdose withdrawal.  It was bad!  Could not function.  Felt like I was in withdrawal 24/7.  I began tapering with help of Benzo Buddies.  Could only get halfway.  Got a new doctor who started prescribing other things like Gabapetin and and Vibrid.  Couldn't tolerate anything.  Anxiety so bad, we decided I should go back on Celexa ( a known) and a PPI (because the Celexa caused reflux).  I titrated up slowly to 7 mg of Celexa.  Doctor also crossed me over to Diazepam at my request.  

 

Unfortunately, I had two really severe interactions on the Diazepam with PPI's (Nexium/Prevacid).  Taking  the Nexium made the withdrawal worse.  After 4 days, I stopped it and was as high as a kite.  I mean I felt like I was on 10x the Diazepam.  That lasted 4 days and when I crashed, I was in withdrawal hell.  My doctor said, it was the Nexium and try Prevacid.  Same thing happened.  Could not recover afterwards and I was in acute the rest of my taper.  I was severely compromised and just about anything ramped my symptoms terribly.  Since I could no longer take the PPI, I had to quit the Celexa. I tried some other OTC antacids, but could not tolerate anything without huge symptom ramp and severe body burning.  I started reducing Celexa too.  Things got worse.  I had mutiple and severe symptoms.  Since I was already on a very low dose of Mirtazapine at this point, I slowly titrated up on that to help.  It alleviated some of the anxiety and other symptoms from reducing the Celexa.  I was still in acute for the rest of my Diazepam taper, but the Mirtazapine helped.  Finished taper (October 2017) and tried to take time to heal before tapering the Mirtazapine.  Three years later, I was still having 3 protracted symptoms (the body burning, tinnitus and the head pulsing - it's like having a heartbeat in your head that you can feel 24/7).   Many of the other symptoms resolved.

 

While trying to heal, I began to notice all kinds of interactions with the Mirtazapine and supplements I was on. (I was already on them during Benzo taper and addition of MIrtazapine).  The supplements as well as some foods seemed to either inhibit or induce the Mirtazapine and I learned over time that making any changes to the supplements were problematic.  I could easily go into withdrawal if I tried to remove them.  As a result, I just kept them in the routine an did not make any changes.   I tried not to add any new ones, except vitamin D when I became deficient.

However, a few times each year, I would go into withdrawal and not know why.  It was trial and error to figure out what I added to my diet to make it happen.

Things like potatoes, cheese, ginger, all became known interactions in addition to the supplements.  I realized that I needed to get off the drug so I began tapering in March 2020 (even though I was still compromised from the Benzo taper) and got to 4.5 mg.  I then hit a rough spot and held in the fall of 2020.  Had trouble getting any lower.  Then things got really bad.

 

 In January 2021, one of the supplements I take arrived and the formula had changed.  After 5 days on it, my body was burning up and terribly agitated.  I still had a bottle of the old and went back to it and stabalized.  I began to try other magnesiums, but nothing worked.  I went through a lot of trial and error and ultlimately found a few bottles of their older formula on eBay, bought them and switched over.  It was still inducing withdrawal, but I added in a food that I knew inhibited the Mirtazapine to stabalize.  However, it is not a forever solution.  Then just a little over a month ago another supplement came in .  I started taking it and same thing.  My body went into withdrawal.  Called the company and they changed suppliers or something making it different enough for me to react.  I ordered two of the older lot bottles and started to taper this supplement.  I made a 10% cut which put me in serious withdrawal ever since, but I need to keep cutting before I run out.  Then last week my new fish oil bottle came in and wham.  Took it and woke at 5 am with head pounding, heart palps, agitation and more - really bad day.  I had some of the old left so went back to it.  My CNS seems so compromised now that the slightest change is causing either withdrawal or just a ramping of symptoms.  Not sure which.  The fish oil company said they did not make any changes at all.  So it just must be enough variation in lot to cause my system to react.    The worst part is that in between the 2nd supplement and the fish oil, I went to get a new bottle of the Mirtazapine.  I hadn't picked it up in 3 months cause I had enough to last.  Right away I could tell the generic had changed.  It metabolized completely different.  I woke at 5 instead of 7 and was in terrible withdrawal.  So I went to a different drug store to get their version.  It metabolized more normally, but it was definitely much stronger and caused acid reflux.  In between these two I'm going back to my old supply of which I have some left.  I talk to my doctor and we decide to try the brand name to see if it works.  All I can say is that produced a neurological reaction. My body went into terrible burning mode with significant agitation throughout - hellish day.  

 

This reaction also happened during my benzo taper.  I could not add anything new without having this extreme burning and agitation.  However, it never happened with the med itself or the supplements my body was already used to.  Just anything new.  Now it is happening with both the medication and supplements I have been on if there is enough variation in the new formula.  I am running out of certain products and know I will be catapaulted into withdrawal because they act as an inhibitor and will mimic a large cut in the drug.  I have increased my mirtazapine to survivie the few supplement cuts I have made.  My body isn't liking that either - air hunger and lightheadeness trying to increase.  Obviously an increase isn't the same as what the supplements do. 

 

I feel like I am reinjuring what healing took place and I'm not tolerating anything.  I'm scared and unsure of what to do.  My PCP is my prescribing doctor for the Mirtazapine.  She is clueless.  I haven't a psychiatrist because the doctor who helped me with the Benzo taper retired and I just let my PCP take over the Mirtazapine prescription.  I've been trying to find one for the last 2 months and so far the ones I've talked to will not take my case beacuse they said they wouldn't know what to do.  I talked to someone today who said my symptoms were not withdrawal and probably psychosomatic.  I don't plan to see him again.

 

From all my research, this is a situation of suppplements actually sharing metabolite pathtways with the drug resulting in increased serum levels.  Removing them causes a significant drop- hence withdrawal.   It is also a situation of some sort of neruological injury and CNS aggravation from the trial and error to fix the problems.  Now even the slightest differences in formulations are causing significant reactions that mimic or ramp the withdrawal symptoms.  I haven't time to taper slowly.  I'm running out of things.  

 

Thank you for any wisdom you can provide.  Any help is appreciated.  If you know of any good doctors in the San Jose, CA area, please advise.  I cannot find one who understands this.

 

[Altostrata]

Welcome, @perseverance

 

What supplements are you taking, and why are you taking them? If you're having a bad reaction to any of them, please stop overthinking and discontinue them.

 

It sounds like your system may be hypersensitive due to your history of going on and off drugs, dating from your cold turkey of Celexa. The symptoms you attribute to drug interactions may be this hypersensitivity.

 

What do you mean when you say your new mirtazapine prescription metabolizes differently?

 

Please keep daily notes of times of day you take your drugs, their dosages, and your symptoms throughout the day. We need to know how you feel before and after taking each drug, and your symptoms in between. Post 24 hours of notes at a time in this topic, in a simple list format with time of day on the left and notation (symptom or drug and dosage) on the right. This can show if your symptoms are adverse effects from one of your drugs.

[perseverance]

Supplements:

Fish Oil - joint pain

phosphatidylserine - adrenal support

Magnesium- for regularity

B complex

Iberogast- motility

Vit D - deficiency 

 

Thank you for your response. I'm not trying to overthink supplements. I'm trying to survive their changes.  I have been on most of these supplements daily since I started taking the Mirtazapine. I learned early on if I try to remove the supplement, in a few days, I'm experiencing fierce withdrawal symptoms. So I can't just stop them easily.  When I reinstate the supplement, I stabilize.  I've been on these for the 4-5 years I've been on the mirtazapine.  

 

The magnesium and phos. made changes to their formulas this year, verified by the company (I think it's a COVID thing of supply shortages). When I tried the new lot, I had a severe reaction. It mimics my known withdrawal symptoms so it is either hypersensitivity (as you mention) or it is a response where the changes are impacting the drugs metabolism differently and reducing the serum levels thereby causing withdrawal. I did a lot of research on this when it started happening early on. Most drugs share the same metabolite pathway (CYP450) as supplements.  

Certain supplements are known to cause reactions by interfering with the enzymes that break the drug down.  Therefore the drug's serum levels build up in your system and increase its potency. This is referred to as an inhibitor since it inhibits the drugs metabolism from clearing your system.  It's the grapefruit effect.  There are also inducers. They do the opposite, clearing the drug from your system too fast and reducing its potency. I believe this is what is happening because I have experienced both - often with these supplements and sometimes with certain foods.  I have various experiences of adding something new to my diet, experiencing withdrawal, taking it out and stabilizing. 

 

Right now, I'm tapering what I have left of the old lot of phosphatidylserine.  I cut 10% of the capsule and was slammed with withdrawal symptoms worsening the ones that have remained with me from the benzo taper and causing new ones to surface.  I'm not stabilizing from it, but reinjuring the healing that occurred. Removing the phos. all together would feel rather like a cold turkey. So while I can't tolerate the changed formula (probably a hypersensitivity reaction), removing the old formula altogether creates a situation of withdrawal (probably from removing its inhibiting effect).

 

The same is true of the fish oil. It inhibits the drug so reducing it is like making a cut to the drug which results in withdrawal symptoms.  I've verified this by taking twice the dose of fish oil in a given day and I can feel like it's noticeably boosted the sedation effects of the Mirtazapine - almost like I took a benzo. This is what I mean by interactions.  

 

When the new formulas started with the magnesium in January, I tried several different magnesiums as a substitute and could not tolerate any of them. At this point, hypersensitivity was triggered from failed attempts at finding something that worked. So while there is hypersensitivity now occurring to even the smallest variations in formulas, there is also the inhibiting nature of the old formulas I have tolerated for three years without issue.  This is what I believe are the interactions. 

 

I hope I explained this more clearly in regards to my situation. This article speaks to it and there is plenty in the web that verifies inhibitors and inducers of metabolite pathways. I'm sure you are already familiar with this. I just want to clarify what I think is happening in addition to hypersensitivity, based on my experiences and why I just can't stop these supplements easily. 

 

https://withdrawal.theinnercompass.org/help-hub/drug-metabolism-substance-interactions-and-genetics-understanding-possible-implications

 

I did get a genetics test during my benzo taper. 

Mirtazapine uses 3 pathways, D26, 1A2 and 3A4/5.  I am a slow metabolizer of D26, a rapid metabolizer of 1A2, and normal for 3A4/5.  

 

I will respond to your other questions tomorrow.  Thank you for reading. 😊

 

[perseverance]

As for what I mean about the Mirtazapine metabolizing differently, that is how it felt based on the experience. Maybe it was a hypersensitive type of reaction instead, but it felt like it didn't kick in the same way.  I usually have enough of the med to last a few months so hadn't renewed in a while. When I went to pick up a new prescription of the same generic, I changed pharmacies due to insurance changes.  When I took the same dosing of the new bottle, I was jolted awake at 5:00 am (I was regularly sleeping at that point until 7:00-7:30) and experienced symptoms of acute withdrawal (head pulsing more pronounced, head pressure, heart palps, burning sensations throughout my body, inner vibrations and agitation to name the main ones). On a scale of 1-10 about an 8. This lasted all morning until about 1 pm. At that point, the symptoms lessened in severity or dissipated and I felt like the drug was then working more normally. This was the only change I made so I know it's the generic formula being different in some manner. Maybe they changed suppliers, or ingredients. Not sure. But I had a severe reaction to it and I've been using this generic for a couple years.  I went back to my previous pharmacy and got the same generic brand from them. The manufacturing bottle it comes in looks different too. I took this and woke at 8:30. It felt like it metabolized more normally, meaning, I didn't have withdrawal symptoms on it at a certain point in the day, but it was definitely stronger than the old lot I had been taking. I woke later, more groggy, and felt like overall I had increased the dose. It also triggered acid reflux the same day which would require me to take something to treat that. The reflux is something that I often experience with psych medications, but not with the older lot. When I went back to the old lot, after taking this new one, I noticed a difference in strength, waking time and how I felt on it. They have changed something for sure. However, the two pharmacies must be sourced from different suppliers because the first one was a nightmare reaction.  The second felt much stonger at the same dosing and caused acid reflux, but I didn't have the withdrawal symptoms.   Both felt problematic to some degree compared to the older lot. 

 

My doctor and I discussed and I decided to try the brand name. I did and I had the severe burning and agitation reaction to that upon waking.  It lasted all day and into the evening. On a scale of 1-10 about an 8 in symptom severity. At this point, I'm definitely having the hypersensitive response. Too many changes have occurred and the trial and error between the new supplement lots and now the medication has triggered the hypersensitivity. Even the smallest change seems to be cause a reaction now from both the med itself and the supplements. Adding anything new is now risky. I have some left of an old supply of the medication which I went back to for now. 

 

As for the log below, I try to take my supplements and Mirtazapine (only med) the same time each day. 

Vitamin B after breakfast every other day

Vitamin D after lunch every day

The rest in evening around 10:30 pm. 

 

I have had more severe symptoms since I started having the reactions to the new supplements in January.  Symptoms have worsened and become more prolonged throughout the day since trying the new Mirtazapines in April and especially since cutting the phosphatidylserine 10% on  May 13th (at which point symptoms worsened and became more 24/7 in nature). I held that cut for a time because I started having reactions to the new bottle of Fish oil the following week.

 

Before January, when the magnesium (1st changed supplement) came in with a new formula, I was much more stable.  I still had tinnitus, head pulsing (both 24/7) and the body burning that varied in degree of severity and duration. These never resolved after my Benzo taper. However, they were far less in severity than now and I was functional. Not so now. 

 

Here is Day 1 of the log:

 

Note:  Computer screen ramps the burning symptoms. 

Mornings are usually the hardest time with the most symptoms. 

 

Sunday eve 6/20

10:30 pm - take supplements

magnesium

phosphatidylserine- Day 5 of cutting 20% of cap

Iberogast

fish oil 

 

Midnight-take Mirtazapine 5.5 mg and go to bed

 

Monday - 6/21

7:30 am -Wake w/ mild anxiety, head pulsing, pressure in head is significant. 

 

8:15- Nose clogged, air hunger (these two symptoms started when I cut first 10% of Phosphatidylserine). 

 

9:05: Some burning through body, agitation in legs- all above symptoms still present

10:00- Breakfast

10:45:  Anxiety and agitation, anxiety in legs 

12:00- Fatigue, wave of sadness

12:30- More Air hunger

2:30- Lunch and Vit D

4:00- Head pulsing more like pounding. More severe. 

5:00-Check email, burning body Ramps. 

5:30- Rest, burning still pronounced. 

6:00 Toxic waking from small nap - Anxiety, head pulsing, burning, agitation

7:00- Tinnitus gets louder

7:30- Dinner

8:30-10:00 Time on computer OK (it can often ramp burning)

10:00-Shower Doing better

10:30-Take supplements same as above only make a cut to Phosphatidylserine to 22.5%. 

12:00 - email replies- burning

12:30 - take Mirtazapine 5.5 mg

1:00 am - Bed

 

Tuesday 6-22

8:00- Wake to major Head and whole body pulsing (meaning I can feel my veins pulsing in my extremities and in my head. Nausea, mild anxiety, air hunger, clogged nose. Everything's more severe probably from cut.

10:00- Breakfast, read, some dissipating of symptoms

11:00- Vit B

12:00 noon- Body burning and agitation really ramp up. 

12:30- Gets more severe

1:30- Time of prayer. Some relief of severity of burn and agitation. Now mostly legs burn and some nausea. 

2:30- Lunch

4:30- Rest- burn and agitation still present 

5:30-7:00 Start dinner-eat 

7:15- Online Bible study - struggle with screen time ramping burning symptoms, agitation

11:00 pm - take supplements

magnesium

phosphatidylserine- (25% cut Day 1)

Iberogast

fish oil

Vit D

11:30- 12:30 Write this out and body burning ramps badly. 

12:00- take Mirtazapine 5.5 mg

1:00 Am. Go to bed 

 

 

 

 

 

 

[Altostrata]

@perseverance, how are you doing?