Mirtazapain: introduction - my mirtazapine taper

[Mirtazapain]

Hi there, 

I am new to this forum, but not, unfortunately, new to mirtazapine withdrawal. This is my intro story. 

 

In 2015 I experienced a very rapid onset major depression. Within two weeks I was hospitalized. I was put on 22.5 mg mirtazapine and within 3 weeks I was out of the hospital and no longer suicidal. This drug saved my life. 

 

A year later I was feeling better and frustrated with the weight gain associated with this medication. I also have chronic fatigue syndrome and a sedating medication was not helping with my fatigue. 

 

I began a taper (10%/month) and in 6 months I reached 15 mg. What I recall about this taper was on about day 4 at the new lower dose I experienced agitation, irritability, and anxiety. This levelled out by about the 2nd week. Anyway, I stayed at 15 mg for a year. 

 

Then, in the spring of 2018 I started my 2nd taper, again at 10%/month. When I reached 7.5 mg I stopped. Withdrawal symptoms were the same (irritability, agitation and anxiety). 

 

I stayed at 7.5 mg until 2022. My cholesterol has skyrocketed and as this can be a side effect of mirtazapine, my doctor and I agreed that I should lose 15 lbs, come off the drug, and see if my cholesterol comes down. I really don't want to start taking statins if my high cholesterol is due to mirtazapine. I've lost 10 lbs (not easy on mirtazapine!) and now I am starting my taper. 

 

So here I am. I began my first reduction 2 weeks ago (again at 10% / month). So I am taking 6.75 mg at the moment. 

 

What I am noticing is that the withdrawal symptoms are worse and lasting longer. I have my usual trifecta of agitation, irritability and anxiety, but also tachycardia, tinnitus, and "ear worms." Basically, I get a song stuck in my head and it plays all day. I remember this from when I went on the drug. So irritating!

 

A few other people on this forum mentioned ear worms as a withdrawal symptom (also with mirtazapine) and I found a few articles on the internet also mentioning this with mirtazapine. Very weird. Withdrawing from this drug clearly messes with our heads. 

 

Anyway, I reached out to my doctor and my new plan is to stay on 6.75 mg for an extra month and then slow my taper down to 5% / month. 

 

Thanks for welcoming me and I will update on my progress. I appreciate being able to read other people's experiences. There is not a ton of mainstream help out there. 

 

Thanks! 

 

****

2015-2016: 22.5 mg mirtazapine 

2017: 10% taper/month to 15 mg

2017: 15 mg mirtazapine 

2018: 10% taper/month to 7.5 mg

2018-2022: 7.5 mg mirtazapine 

Begin taper 03-2022: 6.75 mg

 

Other meds:

- Trazadone 12.5 mg or 2.5 mg Zoplicone, as needed, for sleep 

Supplements: omega-3, CA Mg Zn, vitamin D. 

 

[Mirtazapain]

On 3/24/2022 at 11:04 AM, Mirtazapain said:

2015-2016: 22.5 mg mirtazapine 

2017: 10% taper/month to 15 mg

2017: 15 mg mirtazapine 

2018: 10% taper/month to 7.5 mg

2018-2022: 7.5 mg mirtazapine 

Begin taper 03-2022: 6.75 mg

 

Other meds:

- Trazadone 12.5 mg or 2.5 mg Zoplicone, as needed, for sleep 

Supplements: omega-3, CA Mg Zn, vitamin D

 

Hi there, 

I'm now 3 weeks in to my taper from 7.5 mg to 6.75 mg. My withdrawal symptoms (agitation, anxiety, dissociation, "ear worms") have definitely been more difficult than my previous two tapers (22.5 to 25 mg @ 10%/month; and 1 year later 15 mg to 7.5 mg @ 10% / month). So much so that my doctor and I agreed that I should switch to a slower taper. 

 

Last night was the first time my sleep has been impacted by withdrawal. I was swimming in anxiety, bordering on panic for most of the night. These are not the symptoms that I was originally treated for. 

 

Now I am wondering if I should:

 

a) go back to 7.5 mg, stabilize and then start a slower taper;

b) go up 5% (to 7 mg), stabilize and then start a slower taper;

c) grind it out at this dose for another month (or longer), then start tapering at 5% / month. 

 

Any thoughts or suggestions? It's so infuriating. I've been on this drug for 6 years, but trying to get off it for half of that time. 

 

Thanks for listening. 

[getofflex]

Hello, and welcome to SA.  We are a volunteer-run community of people who have been or are getting off of psychiatric drugs.  It sounds like you have been doing a proper and slow taper.  I'm sorry you are running into difficulties now.  Thank you for giving us your drug history.  As we get lower and lower in our taper, it can get more challenging.  I'll go into this more, but first let me share some basic info with you.

 

Here is some information about how these drugs actually work.   This explains why we get symptoms from going off of these medications, and why it's so important to taper slowly and carefully, and be very cautious about changing our doses: 

 

How Psychiatric Drugs Remodel Your Brain

 

 

This helps you understand what withdrawal syndrome is: 

 

Video on Recovery from Psych Drugs

 

Windows and Waves Pattern of Stabilization

 

Here is a link with checklists of common WD symptoms: 

 

Dr Joseph Glenmullen Withdrawal Symptom Checklists

 

 

Here are some techniques to cope with symptoms: 

 

Non Drug Ways to Cope with Withdrawal Symptoms

 

Stability is really important when we are tapering off psych meds.  Please read the link about stability:

 

Keep It Simple, Slow, and Stable

 

 

We don't suggest many supplements, but 2 that many of us find helpful are magnesium and omega-3 fish oil. Here are the links for info about those. It is suggested to add one at a time, and start with a low dose to see how it affects you. 

Magnesium

Omega 3 Fish Oil

 

The reason it gets harder as we get lower in the taper, is because even at low doses, the drug tends to affect a high number of receptors.  This link will explain it better than I can.  Take a look a the chart - over to the left, the curve is almost vertical, showing that even very small decrements in drug dose cause significantly larger changes in occupancy of the receptors in the brain.  This is why we suggest an exponential taper.  However, we are each unique, and some of are affected differently, so some of u may need to slow down our taper even more.  

 

SERT Transporter Occupancy Studies

 

You could do what is called a micro taper. This link describes it well.  It is gentler on the nervous system.  

 

Brassmonkey Slide Method of Micro Tapering

 

[getofflex]

38 minutes ago, Mirtazapain said:

Now I am wondering if I should:

 

a) go back to 7.5 mg, stabilize and then start a slower taper;

b) go up 5% (to 7 mg), stabilize and then start a slower taper;

c) grind it out at this dose for another month (or longer), then start tapering at 5% / month. 

If it were me, I would do option b).  Updose to 7 mg.  I say this because your brain has probably already made some adjustments, being as how you made the reduction 3 weeks ago. I believe there is a good chance this will help to ameliorate your withdrawal symptoms.  Then, I would hold on this for a while, until you stabilize.  After you are stable, still stay on this for a couple of weeks just to really let things settle.  This link explains what we mean by stability:  

 

Stability

 

I use a system where I listen to my body before each dose reduction.  Instead of having a set schedule, like reducing every 4 weeks, I reduce when my body tells me I'm ready to reduce. Sometimes that is 6 week, or 8 weeks, or even longer.  

 

Please let us know what you decide to do, and hang in there.  It will get better. 

[marie123]

Hello. I would also go with option b. I find 5% a tolerable way to cut Mirtazapine. More than that a month I find symptoms ramp up and others show up. Marie.

[Gigi68]

Hi Mirtazapine, I love your name, so fitting. It is a pain isn’t it. I don’t have any advice about whether you should updose or not but it seems that many people do and it helps. I have been dropping 6% of my current dose for quite awhile and find it works well for me. 
 

Also as I have gotten lower, I feel better and better. The anxiety symptoms I had have been gone for nearly 3 months. So hang in there. It does get better. 

[Mirtazapain]

Thanks everyone.

 

It was helpful to read that mirtazapine withdrawal can actually peak 3 weeks into a taper, as that is exactly what happened to me. Which was hard because I'd just had 2 pretty good days and thought I had turned the corner at this dose.

 

Then last night I spent most of the night, wide awake in a state of panic, followed by a morning laying on the floor shaking, tremoring, and crawling with anxiety. Now I am exhausted AND restless. Not a great combo.

 

The idea of a year or more struggling with withdrawal at this intensity fills me with dread.

Clearly 10% was too much of a drop. I see why, now that I understand that the brain uses the lower doses of ADs much more effectively.

 

Thank you for providing a safe space to talk about this. I will report back once I figure out my next steps. 

 

It sounds Iike both of you (gigi68 and marie123) are  successfully tapering down from 7.5 mg at much slower rates than me. And very successfully. This fills me with hope. 

[Mirtazapain]

As an update, I'm clearly riding the windows and waves at this first 10% reduction. A terrible day, then one good day. Rinse. Repeat. Today was horrible in the morning but got better as the day progressed....

 

I spoke to my doctor this afternoon and decided to grind it out at 6.75 mg (rather than go up 5%, or all the way back to 7.5mg). I really don't want to lose ground, and from what I've read, going back up is not always a cakewalk, either. 

 

So, in the end, I decided to stay at this dose for an extra month, then start again with a 5% taper next time. 

 

Thanks for listening. 

[marie123]

This is a good plan Mirtazapain. Do you still take the trazodone and zoplicone? Marie.

 

[Mirtazapain]

Yes, I alternate 12.5 mg Trazadone (which is so tiny a dose it probably does nothing) one night, and 2.5 mg Zoplicone the next. I'd like to get off these, too, or just use them as needed. But, mirtazapine first... 

[marie123]

Hello. I did take trazodone and ambien like you. Be careful of zoplicone as it's like a benzo. I found trazodone a little less potent than ambien. Good luck with your taper.

[Faure]

Hello, sorry to hear you are having nasty withdrawal effects. I am on a mirtazepine taper too, using the BrassMonkey slide of 2.5% a week for 4 weeks then a 2 week hold. Generally this works very well for me with minimal WD effects. I am just through a little blip brought on by stress.  Interesting that irritability is a WD effect I am often very irritable with my closest friend, but fortunately this doesn’t tip over into my work which would be a problem as it’s with children. Do look into the BrassMonkey slide, it is a very gentle taper method. I hope you feel better soon ☺️

[Mirtazapain]

Thanks for this. If my next 5% taper is too much I will give brassmonkey's plan a try. Whatever it takes, right? 

[Faure]

Yep, even though it takes what seems like forever. I do feel better and better the lower I go so that helps a lot.

[getofflex]

@Mirtazapainthis sounds like a prudent solid plan.  Good for you for being willing to tough it out.  I’m glad you have some good periods too. This should slowly level out and improve over the weeks.  Be sure to take your same dose every day at the same time. Avoid alcohol and other mind altering stuff.  

[Mirtazapain]

16 minutes ago, getofflex said:

Avoid alcohol and other mind altering stuff.  

It's funny you should say that. I'm not a huge drinker, but when I am tapering I lose my taste for alcohol. My body just says, "Nope." Ditto coffee. I tried dinking a half-caff coffee one morning in the midst of a taper and what a *mistake* that was. As if my agitated hyper-aroused body needed caffeine 😂

 

I am a yoga and meditation teacher and if I have learned anything it's, "Listen to your body. It knows."

 

Today is a better day. A window, I guess, as opposed to yesterday's wave. I feel wobbly and vulnerable but at least I am not nauseaus and shaking. 

 

[getofflex]

I'm glad you are having a window today, Mirt!  Things will gradually improve.  

[Mirtazapain]

I thought I would give an update. I'm now almost 28 days into my 10% drop from 7.5 mg to 6.75 mg. No shaking, profuse sweating, or nausea for 3 days, so I take that as a win. My chief symptoms now are tinnitus, ear worm (song stuck in my head in a loop, all day, same song for 2 weeks 😬), headache, tension, and some agitation. I'm managing to sleep, but I sure spend a lot of time in REM. 

 

I've added acupuncture and a low histamine diet to my self-care, and will continue with twice daily meditation, and walking. 

 

I will continue to take this dose for an extra month. Or more. 

[getofflex]

You are definitely on the right track!  I'm happy to hear that you are feeling better in the past 3 days.  It is wise to stay on this dose for an extra month.  And it's good that you are trying acupuncture and a low histamine diet, let us know if that helps.  It's a good thing you are getting sleep.  

 

You may want to consider a gentler tapering method, such as a micro-taper.  This link talks about what that is, and how to do it.  

 

Brassmonkey Slide Method of Micro Tapering

 

Here is a very good post that will help you know more about stability, and when to do another dose reduction: 

 

WD Normal

[Mirtazapain]

I'm definitely riding windows and waves, daily, hourly even. Today has not been good. Agitated. Frustrated. Shaking. Tinnitus. Headache. Depersonalized.

 

I'm feeling so sad and demoralized that this 10% drop has hit me so hard. What did I do wrong? This did not happen when I tapered 10% / month from 22.5 to 15, then 15 to 7.5 mg. Both of my previous tapers were pretty smooth so I was sure 10% would be okay this time as well. Nope. Not by a long shot. 

 

Now I am afraid that I will be feeling crappy forever and this is my new normal. 

 

One month ago I was happy, stable and after much hard emotional work, ready to begin my (hopefully final) taper. One month into this my taper and my life has taken a nose dive. I don't know if I should updose to 7.1, keep holding at 6.75 mg, or what.

 

I thought for sure things would have levelled out by now. I can't believe this pill has such a strong hold on me. I've done years of therapy, trauma work; I've gotten through a severe depression, a marital crisis, the death of my mom, but this is harder.

 

I even teach meditation and thought I knew how to settle my body. Meditation does help, so does walking, but honestly, not for long. Any thoughts? Thank you! I so appreciate that there is a place to share our stories.

 

No one IRL seems to get it. Certainly not my (new) doctor, who'd never heard of mirtazapine, nor antidepressant withdrawal, nor about slow tapers. At least he is supportive and writing me prescriptions for holds, smaller tapers, etc. 

 

Thanks for listening 💜🙏

[Gigi68]

Hi Mirtazapain, I’m so sorry to hear that you have hit such a rough patch so far into your last drop. People say that it gets harder below 7.5mg. I have read that the lower you get, there are more receptors freed up to experience WD. If it was me, I would ride it out. Thinking of you today. Hugs!

[Mirtazapain]

I'm not entirely sure where to put this question, but here goes.

 

After holding at 7.5 mg mirtazapine for the past 3 years (after tapering from 22.5 to 7.5 @ 10% / month with manageable symptoms), I began my (hopefully final) taper just over 4 weeks ago. I followed the 10% rule and am on 6.75 mg. The capsules were made by a local compounding pharmacy.

 

This taper has been really grim. Much harder than my previous tapers, though I understand now that the lower doses can be harder to taper off. So, I decided to hold at this dose until I stabilize. 

 

Four nights ago I began taking my second batch of 6.75 mg capsules, made by the same pharmacy. 

 

Last night, about 2 hours after taking my capsule, I was hit with intense nausea, insomnia, and I've been shaking pretty constantly for 10 hours. 

 

This also happened a couple of weeks ago but my symptoms have been stabilizing day by day. 

 

Anyway, here's my question.  

 

Is it conceivable that the dose in this batch of 6.75 mg capsules is somehow different than the previous batch of 6.75 mg capsules? 

 

I ask because I've read that it takes 4 days for a new steady state to be reached. The change was immediate and intense. 

 

Or, is this just another wave washing over me? I've been on a slow uptrend, and so this has shaken me up quite a bit. I don't plan to shift my dose until I stabilize, but I am now worried that I can't rely on the stability of my doses across batches. 

 

I had success previously with liquid suspensions and I'm wondering if I should switch to that delivery method. But then again, switching from capsule to liquid can be destabilizing. 

 

Any feedback would be greatly appreciated. Thank you for listening. 

 

 

[Altostrata]

Hello, @Mirtazapain. If I were you, I'd ask the pharmacy how they compounded the capsules and if there's a possibility of error. You might ask them not to put fillers that might cause an allergic reaction in the capsules.

 

2 hours ago, Mirtazapain said:

This also happened a couple of weeks ago but my symptoms have been stabilizing day by day. 

 

Was this also when you started a new batch of compounded capsules?

[Mirtazapain]

No, my first round of insomnia, sweating and shaking was 3 weeks into the first batch of capsules. This round of shaking etc started on day 4 of the new batch of capsules. It's been really awful. 

[Altostrata]

58 minutes ago, Mirtazapain said:

This round of shaking etc started on day 4 of the new batch of capsules.

 

Is this your pattern of withdrawal symptoms? About 4 days is what it would take for a change in mirtazapine dose to fully register.

 

It's possible that your irregular use of zopliclone and trazodone might be involved.

 

Other than that, have you recently taken an antibiotic or drunk alcohol? 

[Mirtazapain]

I don't really have a usual pattern yet. When I tapered from 22.5 to 7.5 @ 10% / month I had mild agitation, anxiety, and irritability (day 4-14), then stable. 

 

This time it was kind of the same day 4-14, but then the wheels came off on day 21. I had a few windows last week, yesterday I was calm and feeling like I was stabilizing. 

 

But then last night (day 4 into the new batch, same dose) I started shaking after taking my mirtazapine and I have not really stopped for 12 hours. This feels really not good. 

 

I wondered about the Trazadone, tbh. 

 

And thank you so much for responding to me. 

[Altostrata]

Please put ALL your drugs in this Interactions Checker and post the report or a link to it in this topic.

[Mirtazapain]

Major: trazodone  mirtazapine

Using traZODone together with mirtazapine can increase the risk of a rare but serious condition called the serotonin syndrome, which may include symptoms such as confusion, hallucination, seizure, extreme changes in blood pressure, increased heart rate, fever, excessive sweating, shivering or shaking, blurred vision, muscle spasm or stiffness, tremor, incoordination, stomach cramp, nausea, vomiting, and diarrhea. Severe cases may result in coma and even death. You should seek immediate medical attention if you experience these symptoms while taking the medications. Talk to your doctor if you have any questions or concerns. Your doctor may already be aware of the risks, but has determined that this is the best course of treatment for you and has taken appropriate precautions and is monitoring you closely for any potential complications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

 

trazodone  zopiclone

Using traZODone together with eszopiclone may increase side effects such as dizziness, drowsiness, confusion, and difficulty concentrating. Some people, especially the elderly, may also experience impairment in thinking, judgment, and motor coordination. You should avoid or limit the use of alcohol while being treated with these medications. Also avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medications affect you. Talk to your doctor if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

[Mirtazapain]

The symptoms of serotonin syndrome overlap almost entirely with withdrawal. And how come my doctor said it was ok to take them together?? 

[Altostrata]

Your doctor is wrong, as they so often are when it comes to psychiatric drugs. Your bad days may be the ones following a trazodone dose. Suggest you stop taking trazodone.

[Mirtazapain]

@Altostrata, Oh my goodness, thank you so much!  I am actually freaking out a little because I did not know about this interaction, or even pick up on the pattern. Yet, when I looked over my symptom diary and read my little notebook, the pattern was immediately clear. Every day after I took a small crumb of trazodone, I had a horrible wd day. More out of it, headaches, all the shaking and trembling, high agitation and sweating. I would write things like, "this has categorically been the worst day," or "massive headache that I could not shake all day," etc. And looking back on last night, I started to feel nauseous, panicky and shaky about an hour after I took the trazodone.  So, there you go.

 

The days after I took nothing, or a small dose of zopiclone, I wrote things in my journal like, "feel more myself today," or "more in my body today," or "less shaky and jangly." 

 

I never would have picked out the pattern if not for you.  I can't begin to thank you enough. 

 

It's very weird because I have been pairing mirtazapine and v. low doses of trazodone for years.  I wonder why this taper (7.5 to 6.75) resulted in this interaction?  

 

I spoke to a doctor today who told me that he has treated hundreds of patients with mirtazapine, and gotten hundreds more off without incident.  He told me that there is no such thing as mirtazapine withdrawal, and that my symptoms must be "something else," (i.e., in my head).  He also said that mirtazapine and trazadone can be taken together.  So, another terrible bit of insight from the medical profession. 

 

I am not sure what I (and so many others like me) would do without your tireless efforts on our behalf.  Much gratitude to you. 🥰

[Altostrata]

6 minutes ago, Mirtazapain said:

I wonder why this taper (7.5 to 6.75) resulted in this interaction?  

 

You have become sensitized to mirtazapine and trazodone -- probably trazodone's active metabolite, mCPP, which would emerge the day after a dose.

[Mirtazapain]

That is so interesting. Thank you. 

 

Even the pharmacist didn't warn me when I picked up my Trazadone and mirtazapine prescriptions (on the same day). 

 

 

[Mirtazapain]

I'm happy to report that this morning I feel like a human being again, as opposed to a terrified, shaking wreck.

 

@Altostrata, I owe you a huge debt.

 

I will check back in as my taper at this dose continues. Hopefully the horrific, uncontrolled shaking and sweating will fall by the wayside now that I have eliminated trazodone from my life.

 

With deep gratitude. 

[Mirtazapain]

I thought I'd share an update on my situation now, 5 days post-giving up the 12.5 mg trazodone I was taking every couple of nights to help with sleep, alongside my regular nightly dose of mirtazapine.

 

Looking back on the past three weeks, I can clearly see that I was experiencing some kind of toxic potentiation between the 2 drugs.  But while it was happening, I had no idea what was going on.

 

This 10% drop, from 7.5 to 6.75 started out following the same trajectory as my previous 10% drops.  By day 4 I noticed heightened anxiety, agitation, and irritability, but unlike my previous drops, things did not settle or stabilize after a couple of weeks.  Instead, by week 2, I was experiencing DP/DR.  My agitation and anxiety got worse and worse, and I just did not feel "right."  My brain felt the way it did after my concussion. By day 21 I had started experiencing nausea, dizziness, loss of appetite, prolonged shaking and sweating. But only every couple of days.  Except for the 3 week headache that I could not shake.  I just assumed that I was going through extreme withdrawal from a too-quick drop.  I valiantly struggled along with a low histamine diet and meditation.

 

I spoke to several doctors.  One told me I was experiencing severe withdrawal, and I should probably hold at this dose until I stabilize.  Another told me that there was no such thing as mirtazapine withdrawal and that my symptoms were in my head and/or my depression coming back. Um, no.  My own doctor told me that he knows nothing about mirtazapine, or antidepressant wd, but he would at least support my slow taper.  Even the pharmacist who prescribed the two meds together did not mention the risk.

 

Finally, last Friday (6 days ago), I had my worst day yet.  I shook all night uncontrollably, and into the next day, for 16 straight hours.  I was nauseous, had diarrhea, my blood pressure spiked, I was sweating profusely, and I had this odd, jerky gait when I walked.  Not a heart attack, so I did not go to the hospital.  Also, I was terrified of adding more meds to the mix. 

 

Thankfully @Altostratanoticed that I was taking trazodone and mirtazapine and that my symptoms were worse the day after I took them together. (This is why it is soooo important to list all your meds in your signature!) She alerted me to the potential risk of serotonin syndrome, of which I had every single symptom, short of convulsions and a fever.  My doctor finally confirmed this diagnosis when I spoke to him a couple of days ago.  I'd never even heard of serotonin syndrome.  It is no joke.  It is potentially fatal.

 

I stopped the trazodone CT, and I am back in wd land: anxiety, foggy-head, trouble sleeping, tinnitus and ear worm.  But thankfully the scary physiological symptoms symptoms (particularly the shaking, sweating, BP spikes, tachycardia, nausea, diarrhea, and the 3 week long headache) are gone.  It was a terrifying experience, and I am still recovering emotionally.

 

How is it that 2 medications that I had taken together for years without incident, suddenly became a toxic brew?  What is going on in my brain?  Doctors have no clue.  It is deeply humbling to realize that when we embark on this journey we quite literally have no idea what will happen to us; how we will react to cutting our dose, how long it will take us, what will happen to us.  The medical profession is not a source of help.  Instead, we step into uncharted territory, relying on the kindness of perfect strangers to guide us and sound the alarms when they need sounding. As altostrata did for me last weekend.  At the risk of being overly melodramatic, I believe she saved my life. 

 

I am going to hold at 6.75 mg until I feel back on track, however long that takes  It's still a bit of a roller coaster.  But once the ground feels firmer, then I am more committed than ever to continuing to taper off this medication.

 

Thank you all so much for simply being here.

 

 

[getofflex]

On 4/13/2022 at 8:24 PM, Mirtazapain said:

How is it that 2 medications that I had taken together for years without incident, suddenly became a toxic brew?  What is going on in my brain?  Doctors have no clue

The way our system responds to the drugs may change over time.  I've seen a pattern of people's systems becoming very sensitive to drugs, drug combinations, foods, etc, as time goes on.  Here are some links that can help understand this: 

 

Kindling and Nervous System Hypersensitivity

 

Drug Interactions

 

Indirect Factors that Influence Withdrawal Difficulties