badmeditator: second gen antipsychotics 20 years

[badmeditator]

Failed out of school several times because I would be in bed with depression for 3 weeks at a time every fall.  5 days in hospital -> major depression diagnosis.  5 years later -> bipolar II diagnosis. About 10 years of life lost to undiagnosed illness in total.

 

Took 1-2 mg of risperidone between 2001-2014.  Completed university, successful career, stable marriage since 1997.

In 2014, switched to lurasidone because of better metabolic profile.

 

I don't actually think the lurasidone is helping a lot.  I suffered from sleep apnea for at least 10 years but nobody screened me although there was a Health Canada warning about the connection between SGAs and sleep apnea.  My resting heart rate is 90 bpm.  Pretty sure I have heart damage from the sleep apnea.  My BMI is 27 which is not high enough to expect sleep apnea.

 

I will get zero support from my GP for my plan to taper according to my plan.

 

Very interested in anyone's experience with tapering from lurasidone with a diagnosis of bipolar II.

 

Also interested a recipe for making liquid lurasidone.  What to dissolve it in, does it require heating, etc.  I made a plan based on pill splitting - the last step looks terrible.

 

 

[badmeditator]

My tapering strategy is informed by the suggestion to follow the hyperbolic curve as given in this paper:

 

Horowitz, Murray, Taylor "Tapering Antipsychotic Treatment" JAMA Psychiatry Aug 5 2020

 

I fit a curve to 4 points in this paper to determine the curve for the drug I'm tapering:

 

Wong, Kuwabara et al. , Psychopharmacology (2013) 229:245-252 "Determination of dopamine D 2 receptor occupancy by lurasidone using positron emission tomography in healthy male subjects"

 

I find it hard to split the lurasidone pills past the 5 mg mark, and I can't locate a compounding pharmacy who will help me.

 

 

[Sunnyday]

Hi @badmeditator and welcome,

 

I don't know much about tapering off lurasidone, but this link might be helpful to you if you haven't seen it. It mentions making lurasidone into a liquid as well:

 

Tips for tapering off lurasidone (Latuda)

 

In your signature you say there are no problems so far which is great. Do you have any symptoms at all currently? And are you taking any other drugs or supplements apart from this? If so that's a good idea to put into your signature as well.

Sorry that I can't help you more right now, but I will ask other mods to see if they have more specific advice or input to give. 

[ChessieCat]

When to end the taper and jump to zero?

 

From Post #1 of the Tips for Tapering topic:

 

On 7/9/2015 at 12:14 PM, Altostrata said:

 

Make a liquid yourself from tablets or capsules

While lurasidone is only slightly soluble in water, you can make a liquid suspension, see How to make a liquid from tablets or capsules

Use an oral syringe to precisely measure out doses as small as .01mg.

 

Additional information about chemistry of making a lurasidone liquid http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381388/

 

Other data http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=88a244d1-eddb-499c-bee2-e1f49056e78f

 

Drugbank http://www.drugbank.ca/drugs/DB08815

 

 

[Altostrata]

Welcome,  @badmeditator

 

I would not be too anxious about keeping to a curve while tapering. Listen to your body, if you start to feel withdrawal or other odd symptoms, you may be tapering too fast. Please let us know how you're doing.

[badmeditator]

1 hour ago, Altostrata said:

Welcome,  @badmeditator

 

I would not be too anxious about keeping to a curve while tapering. Listen to your body, if you start to feel withdrawal or other odd symptoms, you may be tapering too fast. Please let us know how you're doing.

 

Thanks for your reply @Altostrata.

 

I revised the plan, see picture below.   Does this look like what Dr. Horowitz is suggesting, assuming my D2 calculations are correct?  Reason I am asking is that I had trouble going from 35 to 30 after 6 weeks on 35.    According to the plan I am going from 35 to 20 in the spring.  This is a much higher change!  But I am going to be on 35 for 5 months this time.

 

Also, my psychiatrist has told me that in his experience people have trouble in the fall and spring.  Have you ever heard of seasonal effects, and should I take them into account?

 

 

 

 

[ChessieCat]

I've provided the information above about making your own liquid suspension.  There is no reason to be making reductions larger than 10% when you can create the dose you need.

 

As Alto said it is important to listen to your body/symptoms and not rely on a formula or the calendar.  We do have members who have no choice but to make larger reductions but in your case you are able to go more slowly than your plan.

[badmeditator]

7 hours ago, ChessieCat said:

I've provided the information above about making your own liquid suspension.  There is no reason to be making reductions larger than 10% when you can create the dose you need.

 

 

Thanks.    Making a liquid is not a pressing practical concern because I don't have to get into that until Spring 2022.  I did read the post you referenced, and I confirmed that I can buy the Ora-Plus suspension solution.

 

There is only one step that is larger than 10%. This step is 13.7%, does not seem too bad?  10% is a pretty arbitrary number.

 

You are saying I can go more slowly.  It is already a 3 year plan - are you saying that because I've been on SGAs for 20 years, I should prolong even more?  This medication has caused very dramatic side effects in my case - I stopped breathing at night (!) and my heart rate is over 90 bpm all day long.

[ChessieCat]

13 hours ago, badmeditator said:

You are saying I can go more slowly.

 

What we are saying is that you need to let your brain and nervous system dictate how fast you go.  It's fine to have a plan but you need to understand that sticking to is dogmatically and not being flexible might cause problems.  Use the plan as a guideline.  For example if there are times when you experience additional stress or are sick it is better to hold for longer.  Some members find that traveling and/or returning home can cause an increase in their symptoms and at these times it is better to hold for longer until things settle back down to WDnormal.  We have members who have tried to go too fast and it has ended up taking longer to get off their drug than if they had done a careful taper.  Some have ended up on an additional drug which then also has to be tapered.

 

Stability

WDnormal

 

14 hours ago, badmeditator said:

There is only one step that is larger than 10%. This step is 13.7%, does not seem too bad?  10% is a pretty arbitrary number.

 

The idea is to get off the drug with minimal discomfort and disruption to our lives.

 

You have the ability to get the dose for the 10% or less reduction.  Why risk it?

 

The less than 10% reduction is a harm reduction method.  See the quote below.  If you reduce by a larger amount and get bad withdrawal symptoms it might take you a long time to stabilise.  Some members find that they don't go back to the stability they had before they got bad withdrawal symptoms.  This is because your nervous system can become sensitised.  It is better to go slower than risk going to quickly.  Any reduction is heading in the right direction and you will get off eventually.  It will take me 1 year to get off 0.5mg Pristiq.  But I'd rather go slowly and carefully than to risk upsetting the apple cart.  I've put in a lot of money and effort to get this far doing a nice and careful taper.  And I'm going to keep doing that until the end.  BTW I was hoping to get off by my 60th birthday and I've just turned 63 and won't be off until I'm 64.

 

  

On 8/6/2011 at 6:43 AM, Altostrata said:

 

Why decrease by such a small amount?

The risk of severe withdrawal is so great for some people, a very conservative approach to tapering to protect everyone is called for.

 

Do not assume you will be lucky, if your taper goes wrong, it can take a very long time for you to recover.

Many people seem to be able to taper off psychiatric medications in a couple of weeks or even cold-turkey with minor withdrawal symptoms perhaps for a month or so. Doctors therefore expect everyone can do this.

 

However, estimates dating from the 1990s suggested 20%-80% cannot go off quickly -- they suffer acute withdrawal symptoms and then post-acute withdrawal symptoms for much longer.. A recent paper, Davies and Read, 2019,  found about 45% experienced significant withdrawal symptoms.

 

You can't know how your nervous system will respond to a decrease in medication until you try it. If you go too fast, won't know if you're in the unlucky half until it's too late. It's a lot easier to taper slowly than to put your nervous system back together again after it's injured.

 

 

[badmeditator]

@ChessieCat  Thanks for typing all that.  I only ever viewed it as a plan, as you can see from my history I took a run at dose reduction and had to make a new plan when 6 weeks per step did not work out.  Plans rarely survive contact with the enemy.  And it's hard to make predictions, especially about the future.  My psychiatrist actually advised a much faster taper and in my ignorance I thought 6 weeks would be much longer than required. But what I'm finding out is that psychiatrists don't know a hell of a lot about tapering.

 

What I'm really concerned about is that the drop from 35 to 30 after 6 weeks caused effects that were very unpleasant.  The new plan, pictured below taking your advice into account, involves a drop from 35 to 20 next Spring -  this is a much bigger step in terms of absolute dose even if it's only supposed to be 9% in terms of D2 saturation.

 

Honestly if I could get down to 20 mg per day, I'd be very pleased and I could live with it even if I never made further gains.

 

I read what you wrote about being 3 years delayed several times.  That must be very hard.  May the best day of your previous tapering be the worst day of the coming year.

 

[ChessieCat]

6 hours ago, badmeditator said:

The new plan, pictured below taking your advice into account, involves a drop from 35 to 20 next Spring -  this is a much bigger step in terms of absolute dose even if it's only supposed to be 9% in terms of D2 saturation.

 

SA doesn't work with D2 saturation.  It's not measurable, whereas symptoms can be compared and can tell you whether your brain is managing to adapt after a reduction.

 

Have you seen the withdrawal symptom list?  Sometimes we have symptoms which we don't attribute to withdrawal.  I know I had an upset stomach for several days after reducing my Pristiq by half and just naturally assumed it was a tummy bug, but I think it was more than likely withdrawal.

 

Dr Joseph Glenmullen's WD Symptoms Checklist

 

6 hours ago, badmeditator said:

Honestly if I could get down to 20 mg per day, I'd be very pleased and I could live with it even if I never made further gains.

 

My original plan was to get to 50mg Pristiq and stay there.  I had been experiencing mild serotonin syndrome at 100mg.  However once I learned things here I decided to try and get as low as I could and I've just kept going.

 

[badmeditator]

I have been on 35 mg for 101 days now, have felt totally fine for months. 

 

[badmeditator]

I've been on 20 mg for 8 days and feel perfectly fine.  Yay!

[badmeditator]

After nine days at 20 mg I am alarmed by my level of anger/irritability, which is not super high, but is noticeably increased.

[badmeditator]

Days 9 and 10 were really tough but now that I'm in day 19 there are more good days than bad days.  I have felt totally euthymic for a few days now.

[badmeditator]

Having been on 20 mg from Mar 23 2021 to May 07 2021, I decided to adopt a micro taper approach that follows the hyperbolic descent advice from Dr. Horowitz in England.  I fit a hyperbola to the Latuda D2 saturation curve in Matlab.  The equation for a 60 week taper turned out to be y= -8.2697 + 660.1674/(x+22.3768).  It fit pretty well- the green dots are the points I got from the D2 sat paper I was referencing. I am following the same 6 week cycle suggested by brassmonkey, where you stick with the week 4 dose for weeks 5 and 6.   Those two week holds extended the taper period to 88 weeks, which for me is New Years Day 2023 (just by coincidence).

 

 

 

 

[badmeditator]

[badmeditator]

I have a true milligram scale (+/- 1 mg) but you don't really need one according to my compounding pharmacist.  The reason is that there are many many variables that affect absorption.

 

I split a bunch of 20 mg pills into halves and quarters.  The balance is made up with powder that I grind with a mortar and pestle - lurasidone turns into a nice powder very easily. I want to take as much of the dose in intact chunks as I can because I got a headache when I took 78 mg of powder stirred into tea.  My theory is that the surface area of the powder is super high compared to pills.

 

 

 

[brassmonkey]

By mixing the powder with hot tea you greatly changed the characteristics of the drug, this will affect the absorption rate, the way the body reacts to the drug and a variety of other things that would trigger a bad response. This drug needs to be stored and used at no more than 30C. Anything over that will degrade the medication and can render it useless.

 

Even though there are a lot of variables involved with absorption it is very important to keep the dose size and timing consistent. Some people are less susceptible to minor variations, but there is a lot of things going on in the background that can take time to develop and once they go wrong it takes a long time to get back on track. 

[badmeditator]

8 hours ago, brassmonkey said:

By mixing the powder with hot tea you greatly changed the characteristics of the drug,

 

Tea was not hot!  I let it sit on a counter for an hour.

 

Yesterday I got some rice paper and I dumped the dose onto it, wrapped it up and swallowed it. Worked pretty well.

 

8 hours ago, brassmonkey said:

Even though there are a lot of variables involved with absorption it is very important to keep the dose size and timing consistent.

 

Controlling the mass down to +/- 1 mg is not that important, the Amazon scales that are +/- 4 mg will be fine given that the filler ratio is around 4.   Timing is important mainly relative to meals, which double the absorption of this drug.

 

May I ask what theoretical basis you have for going down to homeopathic doses at the end of the taper?  Asking for information, not trying to start a fight. 

[brassmonkey]

The majority of a taper is based on the SERT Occupancy curves that you seem to be familiar with. When we get to the Endgame Taper and deciding on an Exit Dose, there is no theory about it, but rather hard won experience from working with many thousands of people. This has shown time and again that the smaller the Exit Dose the better. For many years it was considered the 1mgai (milligram active ingredient) was sufficiently low. Many top experts including Horowitz still think this way. If we were to analyze the data available on this site it would be found that 1mgai is still much too high. There is an ongoing debate about it. As a general target I look at "original dose X 0.000625= exit dose".

[badmeditator]

15 hours ago, brassmonkey said:

The majority of a taper is based on the SERT Occupancy curves that you seem to be familiar with. When we get to the Endgame Taper and deciding on an Exit Dose, ...As a general target I look at "original dose X 0.000625= exit dose".

In this case, it's a D2 curve.  This is what Horowitz is currently recommending (i just found this paper this morning)  for my class of drug, so I will revise my plan in light of it.

 

A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse

https://academic.oup.com/schizophreniabulletin/advance-article/doi/10.1093/schbul/sbab017/6178746

 

They are 10 step tapers and he seems to jump off earlier.  In my case, if I follow your advice and go down to 0.000625, it extends my taper by about 8 months - that is not actually too bad.  I have been on this stuff since 2001, I'm happy to accept another 8 months if I can actually be successful in getting off it.

 

 

 

 

Also, your descent seems to be slower?  I want to do it as efficiently as possible - this medication has adverse effects on brain structure according to papers going back to 2011, and most recently last year from CAMH in Toronto.  I was able to go from 35 mg to 20 mg very quickly.

 

https://www.camh.ca/en/camh-news-and-stories/anti-psychotic-medication-linked-to-potentially-adverse-changes-in-brain-structure

 

 

 

[brassmonkey]

First off the 0.000625 is not the target exit dose, but rather the multiplier used toe determine the target exit dose. The equation is

 

original dose X 0.000625 = target exit dose. Your original dose was 40mgai,  40X 0.000625 = 0.025mgai  So your target exit dose is 0.025mgai.

 

There are a lot of studies that show faster tapers are quite possible. For some people this is true. However, most of those studies don't do any follow up on the participants to document the post "0" experience. The studies that do, indicate that the majority of members return to their drug within a year because of a "return of their original condition". Which is doctor speak for "they are experiencing severe withdrawal". 

 

I won't argue the findings of the papers the you run into. For their data and with in the parameters of their testing they have reached a conclusion they are happy with. Their studies were probably conducted over a year or two and involved at most a few hundred members. The cases we have been working with go back over twenty years and are the combined experiences of over twenty thousand members. A much better sample. From those experiences we have come to the conclusion that slower is better. Let the body dictate the speed and take your time. 

 

Rushing a taper is a recipe for problems.  There is a huge amount of healing that goes on in the background that we are unaware of at the time. If that healing is not allowed to complete itself the unhealed portions add up and add up until the body reaches a breaking point.  That point manifests as a severe crash both physically and mentally. Once it happens it takes a year to 18 months to stabilize, and leaves the body in a highly sensitized state requiring very careful and very small reductions to continue to taper. As a result it frequently takes up to twice as long to do a fast taper than it would have to do a slow and controlled one.  The risk/reward of trying to get off the drugs as soon as possible are just isn't worth it, we see the results on a daily basis.

 

Any physical alterations to the body/brain will have been made well before a person decided to start to come off of the drugs. The additional time spent tapering should have very little effect on what has already happened. The physical trauma on the mind and body caused by a too fast taper would be much more debilitating than the additional exposure to the drug.

[badmeditator]

17 minutes ago, brassmonkey said:

First off the 0.000625 is not the target exit dose, but rather the multiplier used toe determine the target exit dose. The equation is

 

original dose X 0.000625 = target exit dose. Your original dose was 40mgai,  40X 0.000625 = 0.025mgai  So your target exit dose is 0.025mgai.

 

Thanks but I'm planning on using the more conservative 20 mg as the calculation basis, so it's really 0.0125 mgai. 

 

You have a log descent strategy that you're saying has been successful.   If it's unnecessarily slow, it extends the exposure for no reason. Horowitz's hyperbolic descent is faster and informed by a pharmacological principle viewed as obtained truth.  If it works, it's better.  But I am aware of no field trials of Horowitz's method.

 

I believe you that "fast is slow" but I'm hoping a 20 month Horowitz taper with an additional 0.0125 mgai step, will do the trick.

 

My compounding pharmacist wants to explain something called a "time taper" to me, which means you just extend the dose interval.  It sounds interesting but I think it might involve taking pills in the middle of the night.  I'll see what he has to say.

[badmeditator]

Also, you are saying "damage is already done."  I don't actually know what this means in the CAMH paper I linked, but it says "Across all participants who completed both a baseline and follow-up scan with useable neuroimaging data, we found a significant treatment-group × time interaction in relation to cortical thickness. "  which I am taking to mean that the damage keeps going the longer you take antipsychotic medication.

[Altostrata]

Horowitz thinks 1% receptor occupancy is low enough for the next step to be 0mg. Can you find some kind of receptor occupancy research for lurisidone?

 

Quote

 I was able to go from 35 mg to 20 mg very quickly.

 

This makes sense, because at higher doses, you can make larger cuts, receptor occupancy is reduced only a little. But as you get to lower doses, dosage decreases have proportionally larger and larger effects on receptor occupancy. All drugs follow that horizontal hockey stick curve, e.g.

 

[badmeditator]

On 5/12/2021 at 10:54 PM, Altostrata said:

Horowitz thinks 1% receptor occupancy is low enough for the next step to be 0mg. Can you find some kind of receptor occupancy research for lurisidone?

 

Yes.  I can post a picture of the hyperbola I fit to the data, if you will be so good as to raise my quota because I am unable to post it due to the limit you set.

 

On 5/12/2021 at 10:54 PM, Altostrata said:

 

This makes sense, because at higher doses, you can make larger cuts, receptor occupancy is reduced only a little. But as you get to lower doses, dosage decreases have proportionally larger and larger effects on receptor occupancy. All drugs follow that horizontal hockey stick curve, e.g.

 

 

 

For sure.  The contribution of your site cannot be overstated, and I'm not saying anything bad about your strong contributions at all. It's just that the recent work of Horowitz suggests that I can reduce hyperbolically at 10% D2 sat steps.   Your technique is not radically different, the curves are pretty similar.  It's just that his curve is supported by the law of mass action, so it has a theoretical basis that is pretty well accepted as far as I can tell.  (But it is not my field.)

[Altostrata]

The 10% exponential taper is close to 2-point receptor occupancy reduction.

 

We have to assume everyone's receptor occupancy hyperbola is individual and may deviate from the average that appears in the journal articles.

 

Please post a link from Google Drive or similar server to your lurisidone chart.

 

 

[badmeditator]

					pill weight (mg)	weeks	pill weight required (mg)	active ingredient (mg)
Sunday, May 30, 2021		69				2.5		1207				16.6
Sunday, June 20, 2021		63				1		438					15.1
Sunday, June 27, 2021		54				1		381					13.1
Sunday, July 4, 2021		49				1		342					11.8
Sunday, July 25, 2021		44				3		927					10.7
Sunday, August 1, 2021		40				1		277					9.6
Sunday, August 8, 2021		36				1		251					8.7
Sunday, August 15, 2021		32				1		225					7.8
Sunday, September 5, 2021	30				3		620						7.1
Sunday, September 12, 2021	27				1		188						6.5
Sunday, September 19, 2021	24				1		167						5.7
Sunday, September 26, 2021	21				1		148						5.1
Sunday, October 17, 2021	19				3		403						4.6
Sunday, October 24, 2021	18				1		123						4.2
Sunday, October 31, 2021	16				1		111						3.8
Sunday, November 7, 2021	14				1		100						3.4
Sunday, November 28, 2021	13				3		269						3.1
Sunday, December 5, 2021	12				1		81						2.8
Sunday, December 12, 2021	10				1		73						2.5
Sunday, December 19, 2021	9				1		63						2.2
Sunday, January 9, 2022	    8				3		172						2.0
Sunday, January 16, 2022	7				1		47						1.6
Sunday, January 23, 2022	6				1		42						1.4
Sunday, January 30, 2022	5				1		38						1.3
Sunday, February 20, 2022	5				3		95						1.1
Sunday, March 13, 2022	    4				3		79						0.9

 

 

The paper I found is pretty sketchy, only 4 patients per dose and the standard deviation is very high so you could fit pretty much any curve you want to it. 

 

Anyhow, the table shows what I'm running with right now.  I am not going to follow it slavishly, just going to see how I feel and I'll just stick with the same dose for a while if I feel unsettled.  I will add another few 3 week steps at the end, which are not shown.

 

The good news is that I have enough lurasidone on hand to complete the taper without ever renewing, but I will continue to renew the prescription since I am not paying for it and I don't want the medical people to get excited.  My view is that since they did not ever mention the brain shrinkage to me, they are not trustworthy and I don't want their advice.

 

I have quite strong akathisia about an hour after I take the pills, which I am doing at dinner.  Otherwise I feel great (euthymic) in the morning and afternoon.

 

Thanks for all the support I've found on this site, wish me luck.

 

 

 

[Thorin]

Hi, did you complete your taper? I’m curious as tapering Lurasidone also and not many people seem to take this med.