Possible drug induced Parkinsonism

About Parkinson's and health Newly diagnosed
1

I wanted to share my experience to see if anyone else is aware of anything similar.


I was diagnosed with idiopathic Parkinsons disease in February 2013, aged 49. My initial symptoms were loss of arm swing in my right arm, slight dragging of the right foot, tiredness and a history of  sleep apnoea. I had no tremor. At the time of diagnosis I was taking 10mg Ramipril (for high blood pressure), 10mg Amlodipine (for high blood pressure) and 10 mg Escitalopram (antidepressant – generalised tiredness was diagnosed by my GP as depression).


The specialist put me on Sinemet (25/100) three times a day. I did initially see some improvement in my symptoms, but this did not last long and the symptoms returned. The specialist replaced the Escitalopram with 10mg Selegiline daily. Again, there was some improvement, but it was not long lasting. The specialist then increased my sinemet dose to 5 times daily (dose 25/100). Again, I saw some limited improvement for a short period just for the symptoms to return again. The next step was to drop the Selegiline, reintroduce the Escitalopram and increase the Sinemet dose to 5 tablets @ 25/100 and 5 tablets @12.5/50. I continued to take the high blood pressure medications throughout.


Over the last couple of years, my symptoms continued to worsen, with speech affected some days, loss of clarity of thinking and other Parkinsonian symptoms. Worst of all, I had to take medical retirement from a career that I enjoyed immensely as I just was not able to function.


Earlier this year, my symptoms seem to be progressing more rapidly and I started with dystonia in my arms.
As the medication did not seem to be effective, I always wondered if my initial diagnosis was correct and having researched the subject thoroughly, I did wonder if I may have Multiple System Atrophy as I was starting to display a number of red flag symptoms for this.


I had also read some research papers on drug induced Parkinsonism and that certain groups of drugs were known to cause this. These two groups of drugs were SSRI’s (Selective Serotonin Reuptake Inhibitors) which includes Escitalopram that I was taking and Calcium Channel blockers which includes Amlodipine that I was also taking.


I decided that the only way to really understand what was going on was to get a baseline whilst un-medicated. I researched very carefully how to safely reduce my medication regime as I was acutely aware of the dangers of suddenly stopping some of the medications.


Firstly, I carefully titrated my sinemet dose down until I stopped completely. Surprisingly, I did note a small improvement is some symptoms, but I wasn’t sure if I was experiencing a ‘placebo’ effect.


The next one to stop was the Escitalopram, I had been on this for 7 years. Again I thoroughly researched how to stop taking this and titrated down until I was off this drug. I did have some slight side effects for a couple of weeks that caused some light headiness, but it was nothing too bothersome and from my research, I knew to expect this. I noticed a very significant change in cognitive functioning, I hadn’t felt as clear headed for years. No change to PD symptoms at this stage. One thing that did change significantly is that after stopping this drug, I no longer woke up during the night to go to the toilet. I have had nocturia for several years 3 or 4 times a night and I haven’t had it once  since stopping the Escitalopram (about 4 weeks now).


Next was my blood pressure medication, I have been taking these medications for about 10 years. I needed to be very careful here and started to monitor my blood pressure at home as I titrated off these medications. I reduced the dose of Amlodipine by taking half a tablet for a week and then coming off it completely. I have observed a very slight increase in average blood pressure, but it is only small. I haven’t  altered my Ramipril dose at the moment and still take this.


What happened next is hard to believe. Within a couple of days of stopping the Amlodipine, my Pakinsons symptoms improved significantly. By day five my dystonia had gone completely, by day seven my arm swing had returned in both arms and all the symptoms I had associated with Parkinsons were all gone.


It has been two weeks now of no symptoms, so all I can assume is that my Parkinsons was drug induced and whilst normally, drug induced Parkinsons would normally reveal itself soon after starting the offending drug, I have read some research that indicates these drug side effects can come much later as is my case, although this is more unusual.


Hopefully, things will continue, but I will update this post if there are any significant changes. I will of course reply to any comments and observations.


Sorry that this is a long post, but I wanted to share my story in case there is anyone else looking for information on this subject.


Please be aware that stopping prescribed medications can be very dangerous and should not be undertaken without great care and most sensibly, medical advice and support from your doctor. I took the decision to undertake this myself but I researched every aspect of it very carefully and cross referenced my research to ensure that it was properly validated.

2

That's very interesting to read!  All these months later, how are you getting on?

3

I am pleased to report that I remain symptom free and I was signed off by the specialist in December 2015 with my final diagnosis being drug induced Parkinsonism (caused by Amlodipine). The specialist arranged a DATScan late last year and this confirmed that dopamine levels were normal and this confirmed the drug induced diagnosis.

As I mentioned in my first post, I would not recommend changing any medication (particularly the Parkinsons drugs) without the support of your specialist or GP as there can be some very serious side effects of stopping or changing these drugs suddenly.

I do hope that my experience may help someone in similar circumstances in the future.

4

Howie, my wife came upon your posting during a Google search regarding CCBs and PD. Very interesting report with good attention to details. 

I'm a physician myself, and was recently told by a neurologist that the twitching in my left hand thumb and digits 4/5 indicated a PD-like tremor to him. He basically told me I had early PD. I show no other signs and I had thought initially it was an ulnar neuropathy. The EMG and ultrasound of the nerve were normal, however.

Of note, my symptoms began about a week after initiation of amlodipine at 2.5 mg/day. Since I thought I had an ulnar neuropathy. I paid it no mind. After my symptoms continued, however, and seeing the neurologist last week, I'm having different thoughts. Since my BP has been under good control with improved diet and weight loss, I stopped the amlodipine 4 days ago. My symptoms come and go, but are generally improving. I will wait a month to reassess (the published case reports and your report indicate a month is generally the right time frame.

In light of this, I have deferred starting my dopa medications to see if this continues to improve. The twitching and occasional tremor I had were more annoying than anything else really.

Have you investigated the possible mechanisms of the effect of amlodipine on the substantia nigra? Considering the Danish retrospective study indicating a protective effect, the population results conflict with animal models and the few case reports. On the other hand, the Danish study results have not been well-confirmed in other population studies.

One animal model I found (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087208/) appears interesting in that L-type DHP CCBs may have some inhibitory effect on the L-type calcium channels in substantia nigra cells in the aged mouse. I wonder if certain genotypes or phenotypes in humans are particularly more prone to these effects?

Cheers,

Tim

5

Tim
Thank you for your comments and the research paper link. This looks a fascinating piece of research and I am going to study it carefully. I don’t have any medical training or background, but I find that with these technical papers, if I take a small section at a time (with google at my side!) I can slowly decode the information. There is often other very interesting research cited within these papers and I enjoy the learning opportunity!


Once I have got it decoded and translated into ‘Howie’ language (i.e. very simple!), I will post my thoughts.


Having not posted an update since January 2016 (can’t believe it has been that long), it is probably worth me providing an update.


Current medication:
Indapamide 2.5mg 1 tablet a day (blood pressure)
Ramipril 10 mg 1 tablet a day (blood pressure)
Blood pressure is well managed and has been consistently so for last couple of years on the above tablets.


I don’t take any other medication.


The last time I saw my neurologist was December 2015 and his final opinion was drug induced Parkinsonism caused by Amlodopine.


He did say that the Amlodipine may have uncovered subclinical Parkinson’s disease. For those unfamiliar with the term subclinical, this in simple terms means the denoting of a condition that is not currently severe enough to present symptoms or be readily observable.


So, nearly 2 years later, how am I? Some neurological symptoms have returned slowly, but I am not completely convinced that it is Parkinsons. I have dystonia in my hands at rest with my fingers making tight fists, but I can still play the piano as well as I have all my life. I can use my hands normally. In fact, the more I relax, the tighter my fists become!


My gait is poor and I shuffle and stumble when I am out walking, yet I can run on my running machine for 20 mins without any problems or balance issues whatsoever.

I get very tired and have to stop what I amdoing to sleep, but after 10 to 15 mins sleep I am fully refreshed and ready to go again.
No tremor, no loss of sense of smell
Some very mild postural hypotension but certainly not bad enough to be any issue whatsoever.
Complete loss of arm swing (both arms)
Writing is a bit smaller than it used to be, but much better than when I was on the Amlodipine.
No changes to speech/voice
No muscle rigidity


I am convinced that regular exercise is helping to ward off the advance of my symptoms. I exercise every day in my home gym. My usual routine is 20 minutes on the running machine, 10-15 minutes on the cross trainer and 30 minutes on an exercise bike (sometimes I swap 15 minutes on the bike for 15 minutes on a rowing machine). So around an hour each day of cardio. I do have a weight machine that doesn’t get as much use as it should! – I need to work on that.


I treat exercise like medication and don’t allow anything to get in the way of it. I am convinced that it helps me greatly. Whether it does or whether it is a mental thing, doesn’t really matter to me, as long as I know it helps.


So, in summary, I know that there is something wrong and it is very likely neurological in nature. Is it Parkinsons? I am honestly not sure. Did taking Amlodipine for years cause some damage in the brain? Again, I don’t know.


If my symptoms worsen significantly in the future, I will go back to the neurologist, but for now I know my limitations and will continue with my exercise regime. I certainly do not want to take any medication until I absolutely have to after my previous experience.


Sorry for the long post, but if my experiences help someone else, I have done some good!
Time to study that research paper now…………

6

Hello, hope you are well.
I know it’s been a while since you last posted but I was wondering how you are doing? A relative of mine is on the exact same medication as you. And I suspect they might have drug induced Parkinsonism caused by Amplodipine. If you have any updates or advice, please do share!

7

It has been a long time since my last post, but actually very little has changed. I still have a very similar set of symptoms as described in my last post. Certainly in my case, the Amlodipine was the cause of the drug induced Parkinsonism. I have continued with my exercise regime. I still see the neurologist every couple of years and at my last visit we discussed drug induced Parkinsonism and I got the impression that it is perhaps a little more widely considered by neurologists now, but I have yet to speak to a GP who has ever heard of it.

8

Oh brilliant, glad to hear symptoms haven’t gotten worse.
My relative saw the GP a few days ago and is off amlodipine, so am hoping his symptoms begin to improve.
The GP did take into account that is could possibly be drug induced Parkinsonism!
Thank you for you reply and i wish you well!