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Altostrata

Tips for tapering off trazodone (Desyrel)

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Altostrata   
Altostrata

Aka Oleptro, Beneficat, Deprax, Desirel, Molipaxin, Thombran, Trazorel, Trialodine, Trittico, and Mesyrel

Trazodone (trazodone hydrochloride) is a nasty drug often added to antidepressants and other "activating" drugs to aid sleep.

It's nasty because it has an evil active metabolite, meta-Chlorophenylpiperazine (mCPP), and a huge number of interactions with other drugs that can make you feel very sick.

First, carefully read the below to see if you have any adverse effects from trazodone.

Trazodone's evil byproduct, mCPP
Trazodone's active metabolite, mCPP, does the opposite of aiding sleep -- it's very, very activating, often in an unpleasant way.

Wikipedia on mCPP http://en.wikipedia.org/wiki/Meta-Chlorophenylpiperazine

 

Quote

Meta-chlorophenylpiperazine is a major metabolite of the psychotropic drug trazodone, and may be responsible for some of its side-effects, such as headaches and migraines induced many hours after initial consumption.


per Wikipedia http://en.wikipedia.org/wiki/Trazodone

Quote

The mean blood elimination half-life is biphasic: the first phase's half-life is 3–6 hours, and the following phase's half-life is 5–9 hours. The drug is extensively metabolized with 3 or 4 major metabolites having been identified in the human body, particularly mCPP,[39] which may contribute to the side effect profile of trazodone.

....mCPP, a non-selective serotonin receptor agonist and serotonin releasing agent, is an active metabolite of trazodone and has been suggested to possibly play a role in its therapeutic benefits.[31][32][33] However, scientific research has not supported this hypothesis, and mCPP may actually antagonize trazodone's efficacy as well as produce additional side effects....

 

Half-lives
trazodone (8-15 hrs) ---> mCPP (2-6 hrs) ---> other metabolites (inactive)

 

The metabolism of trazodone is highly variable among individuals. mCPP can be produced during the initial 8-15 hours; its clearance from the body can be blocked by other drugs (see explanation below).
 

mCPP is used to induce anxiety for study in the laboratory, e.g. http://www.ncbi.nlm.nih.gov/pubmed/20828578

For some people, mCPP produces not only anxiety but headaches and a hallucinatory effect. So while trazodone may help you sleep at night, mCPP might make you feel sick, anxious, and out of control during the day.
 
http://www.ncbi.nlm.nih.gov/pubmed/19384678

Quote

World J Biol Psychiatry. 2009;10(4 Pt 2):682-5. doi: 10.1080/15622970902836022.
Trazodone generates m-CPP: in 2008 risks from m-CPP might outweigh benefits of trazodone.
Kast RE.

Source
Department of Psychiatry, University of Vermont, Burlington, VT 05401, USA. rekast at email.com

Abstract
Since deleterious effects of m-CPP, the primary catabolic metabolite of trazodone, were last reviewed 2 years ago, research data continue to accrue showing that clinically significant levels of m-CPP (a) are generated in patients using trazodone for sleep and ( B) are present 24 h a day and © have potentially serious ill effects. This commentary argues that the documented potential for harm and multiple risks of m-CPP outweigh potential benefits of trazodone, given the development and marketing of many safer alternatives since trazodone's introduction in the 1980s.

 

Traffic jams with antidepressants in the liver
While trazodone is metabolized by liver enzyme P450 cyp 3A4 http://www.ncbi.nlm.nih.gov/pubmed/9616194

mCPP requires enzyme cyp 2D6 to leave your body Example: http://www.ncbi.nlm.nih.gov/pubmed/9836023

Liver enzyme enzyme cyp 2D6 also is necessary for metabolization of most antidepressants, such as Prozac and Paxil, and all tricyclic antidepressants.
 

If two or more drugs try to use cyp 2D6 in the liver, a "traffic jam" occurs and one or both of the drugs backs up, causing adverse reactions and possibly liver damage.

 

Additionally, about 10% of the population are cyp 2D6 "poor metabolizers" and particularly prone to this type of adverse reaction.

When trazodone is taken with another drug utilizing liver enzyme CYP2D6, the "traffic jam" in the liver can cause increased levels of mCPP, the other drug, or both in the blood stream, increasing the incidence of adverse events.

Special problems with Abilify (aripiprazole)
Abilify conflicts with trazodone via two liver pathways, cyp 3A4 and cyp 2D6. See https://www.pharmgkb.org/label/PA166104839

 

This can cause 1) delay of trazodone metabolism via cyp 3A4 and a backup of trazodone, increasing side effects or 2) delay of mCPP metabolism via cyp 2D6 and a backup of mCPP, or 3) both.

 

Huge number of drug interactions with trazodone
Major drug interactions with trazodone http://www.drugs.com/drug-interactions/trazodone.html
include:

5-HTP (5-hydroxytryptophan)
amitriptyline
BuSpar (buspirone)
Celexa (citalopram)
Cymbalta (duloxetine)
doxepin
Lexapro (escitalopram)
lithium
Luvox (fluvoxamine)
mirtazapine
Nardil (phenelzine)
nefazodone
nortriptyline
Prozac (fluoxetine)
Savella (milnacipran)
Wellbutrin (bupropion)
Zoloft (sertraline)
and on for 138 drugs, and that's just the major interactions.

Danger of serotonin syndrome
Trazodone and mCPP are serotonergics. Taking trazodone with antidepressants can cause serotonin overload or serotonin syndrome.

At the extreme, serotonin syndrome is a life-threatening condition. But even an increased serotonin level of serotonin in the bloodstream can be dangerous.

Unnecessary polypharmacy
If your doctor has given you a benzo to help with adverse effects caused by trazodone, mCPP, or drug interactions, you are taking two medications to counter the adverse effects of another drug: Trazodone to counter insomnia from the antidepressant and a benzo to counter the effects of trazodone.

Should I go off trazodone first?
If you are having any of the above adverse effects of trazodone, you might consider reducing trazodone first.

BUT -- if you're taking trazodone because your antidepressant keeps you awake, what should you do?

You might reduce the antidepressant first, part way. If it's interacting with trazodone, this may enable the trazodone and mCPP to be metabolized faster, and reduce the adverse effects of trazodone.

To see if reducing your antidepressant (or other medication) will help reduce adverse effects of trazodone, look here to see if your antidepressant is a substrate or inhibitor of cyp 3A4 or cyp 2D6, the liver enzymes needed to metabolize trazodone and mCPP.

Trazodone tablet dosages
Official FDA information (with NDC codes for ordering): http://www.drugs.com/pro/trazodone.html
 

Quote

Trazodone HCl is supplied for oral administration in 50 mg, 100 mg and 150 mg tablets.

....
Peak plasma levels occur approximately one hour after dosing when Trazodone hydrochloride is taken on an empty stomach or two hours after dosing when taken with food.

 

Reduce trazodone by 10% per month to start
The 10% rule holds for trazodone, just like other antidepressants: Reduce by 10% per month, calculated on the last dosage. (The amount of the reduction gets progressively smaller.)

See Why taper by 10% of my dosage?

Cutting up tablets to taper
If you're taking more than 50mg trazodone, you might ask your doctor or pharmacy to fill your prescription with 50mg tablets (i.e. instead of 30 100mg tablets, 60 50mg tablets per month).

Then you can cut a piece from a 50mg tablet to reduce your dosage by 10%.

Weighing your tablets with a digital scale will enable accurate dosage.

Get trazodone oral solution from the pharmacy
In the UK, trazodone is available in liquid form, each 5ml containing 50mg trazodone.

Use an oral syringe for dosing.

Order a liquid from a compounding pharmacy
Compounding pharmacies can make a liquid from medications that do not have special extended-release coatings or Cymbalta.

Your doctor will have to write a prescription specifying how the drug is to be compounded.

Use an oral syringe for dosing.

Dissolving trazodone in water to make a liquid
According to the US National Library of Medicine http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=42836232-a71f-4e4b-8060-2bdbd853398a#nlm34089-3
 

Quote

It is a white to off-white crystalline powder which is sparingly soluble in chloroform and in water.

On the other hand, according to this Material Safety Data Sheet (pdf) from ScienceLab, it may be "partially soluble in cold water."

Our member Rhi has made suspensions from drugs that are technically insoluble in water, see http://survivingantidepressants.org/index.php?/topic/2883-tips-for-tapering-off-trazodone-desyrel/page__view__findpost__p__45161

I haven't personally done this and I don't know of anyone who has, so if you do it, please post your experience in this topic.

Also see How to make a liquid from tablets or capsules

Use an oral syringe for dosing.

 

Using a combination of tablets or capsules and liquid

Rather than switch directly to an all-liquid dose, you may wish to take part of your dose in liquid and part in lower-dose tablets or capsules, gradually converting to all liquid as you get to lower dosages. This can be very convenient and reduce any problems switching from one form of the drug to another.

 

If your doctor prescribes liquid and tablets or capsules at the same time, most likely he or she will have to indicate "divided doses" in the prescriptions to get the drugs covered by insurance.

Edited by Altostrata
updated

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primrose   
primrose

Hi Alto

 

After seeing my doctor today and discussing some problems with her regarding trazodone, we both decided that it would be best for me to take 75mgs every 6 hours instead of the 100mgs every 8 hours, because 100mgs started to make me feel zombied and didn't seem to last until my next dose was due.

 

As we know, tablets don't come in 75mgs only 150, 100 and 50, and my doctor said she was unable to prescribe me a liquid version because of the cost, and the liquids were only reserved for people with feeding tubes or otherwise unable to take a tablet.

 

My intention was to make 100mg : 100ml solution and draw off 25mgs leaving me with 75mgs each dose time.

When I went back to my jar of trazodone solution, however, it looked uneven, as if something had not dissolved. The water was cloudy and there seemed a deposit on the bottom.

Whilst doing a google search to see how to get around this problem, I came up with this link which says trazodone is insoluble.

http://www.sigmaaldrich.com/united-kingdom.html

 

I went and spoke to a pharmacist at our local chemists, and she advised me not to try to get 75mg trazodone from a 100mg capsule as capsules were not designed to be tampered with, and there was a high chance I would not be giving my self the correct dose, because of the uneven distribution of the trazodone in the liquid.

She never said anything about solubility or insolubility.

She was really helpful and phoned my surgery and got a doctor to issue me with 150mg pills, as I can split them into 75mg pieces.

 

It seems opinions on trazodones solubility is divided, as I read another post from a trazodone user who also said it did not dissolve, but they were not scientifically qualified.

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Altostrata   
Altostrata

primrose, if you want to take 75mg trazodone, splitting a 150mg tablet seems as good a way as any.

 

Apparently trazodone is "sparingly soluble" in water, meaning not so much. The FDA info I had from drugs.com was incorrect. I've corrected post #1.

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primrose   
primrose

Hi Alto and thanks.

 

What does sparingly soluble mean please?

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flower   
flower

Doc told me the other day Traz comes in a powder. Don't know what that would be measured with but I'll find out next visit..

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primrose   
primrose

Hi Alto and flower, that would be useful to know.

 

Luckily, my 150mg tablets were ready to pick up yesterday, so I am now on two of them a day (chopping them up to make 75mgs 4 x a day)

 

This link seems to suggest that light degrades trazodone and to keep in a light sensitive container http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=33648

It's relevant for me because I have my pills split in half so the powder is exposed.

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flower   
flower

Hi Alto and flower, that would be useful to know.

 

Luckily, my 150mg tablets were ready to pick up yesterday, so I am now on two of them a day (chopping them up to make 75mgs 4 x a day)

 

This link seems to suggest that light degrades trazodone and to keep in a light sensitive container http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=33648

It's relevant for me because I have my pills split in half so the powder is exposed.

 

that's good to know, are you preparing to taper?

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primrose   
primrose

 

Hi Alto and flower, that would be useful to know.

 

Luckily, my 150mg tablets were ready to pick up yesterday, so I am now on two of them a day (chopping them up to make 75mgs 4 x a day)

 

This link seems to suggest that light degrades trazodone and to keep in a light sensitive container http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=33648

It's relevant for me because I have my pills split in half so the powder is exposed.

 

that's good to know, are you preparing to taper?

 

Not yet Flower

 

I was tapering my valium and held the taper due to symptoms. When things got better, I cut 112.5mg off my seroquel last week, so am holding things again at the moment.

I will then taper my valium again.

 

Not looking forward to the traz taper. Beleiving it to be water soluble, I thought there would not be a problem, but discovered that it is not fully water soluble.

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Altostrata   
Altostrata

As near as I can tell, trazodone powder is available only for experimental purposes. If you find you can get it by prescription, please let us know.

 

From Children’s Hospitals and Clinics of Minnesota http://www.childrensmn.org/manuals/pfs/med/018920.pdf

 

Trazodone comes in pill form. It can also be

made into liquid by your pharmacist.

 

Give it at regular times, to keep a steady

level in the bloodstream. It may take 1-4

weeks for effects to be seen.

 

If using the liquid form, shake well right

before using. ....

 

For children who cannot swallow pills:

 

• Crush it between 2 spoons or crush it

inside a plastic bag or in folded paper.

 

• Mix the powder with a very small

amount (about 1 teaspoon) of soft food,

such as applesauce, chocolate syrup, ice

cream, jelly, or yogurt. Make sure your

child takes all of the mixture.

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primrose   
primrose

*Woops* I made a mistake above

 

I cut from 112.5mg seroquel to 100mgs, sorry for the confusion.

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Altostrata   
Altostrata

About solubility or insolubility, Rhi has made many, many homemade liquids:

 

I'm kind of out of it right now and need to go to bed, but I just wanted to toss in my usual bit on the subject of making preparations for liquid tapering, which is: I personally don't worry about solubility.

 

None of the meds I'm tapering are actually soluble in water. But the pills dissolve into small enough particles that I can stir them up and keep them suspended in water while I measure them out, and that seems to work for me. I stir well before I measure, I stir a little while pipetting them up; I dissolve the pills in glass and pipette out of glass so that I can see visually how evenly everything is suspended, and that's good enough for me.

 

I use water as a medium because I like it that I can easily see for myself how evenly the little particles are suspended or if they seem to be settling out. Also because it's handy and cheap and I don't have to carry it with me if I travel.

 

Mostly I would just say, I don't think it really matters if the medication is soluble in whatever vehicle you're using, as long as it can be evenly distributed. What really matters is that it be evenly distributed and that your method be repeatable and consistent.

 

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sassy   
sassy

I am on trazodone 50 mg and want to come off

can somebody suggest the best way to taper

each time i try i hit total sleeplessness

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flower   
flower

If you figure this out Sassy let me know..I too take 75mgs.. How long have you taken it? I will watch your progress.

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GiaK   
GiaK

the general rule... 10% of current dose tapers...every 2 to 4 weeks... I've seen work just fine...

 

also it seems, in general, that most people have less problems with trazadone causing other symptoms besides insomnia...so just going really slow and easy, allowing the body to adapt to the change, seems to work quite well.

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anna7887   
anna7887

I apologize if this was addressed in a previous post but I can't seem to find it.

 

I was thinking of using a mg scale to measure my Trazadone reductions but not sure if it makes sense: are medications assigned a mg based on the weight of the pill or the amount of active medication? In other words, can I use a pill cutter to weigh 20mg traz, etc.

 

Thank you!

 

Anna

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lanah   
lanah

I updosed last night to 50 mgs and will stay there for a few months, not going to make the same mistake twice (made a 20% cut and had horrible withdrawal sx) 
But I would like to read other people's experiences and get as much information as possible.

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Amygdala   
Amygdala

I had no problem cutting from 150 mg --> 50 --> 25 but I made the mistake of going from 25 to 0. The withdrawal took a couple of days to hit but was quite pronounced when it did come. Tremors, confusion, akathisia, ataxia and lots of aches and pains. I went back to 25 mg but it did not help so I tried going back to 50 mg and the relief was almost immediate, I could not believe the difference.

 

So I started over a couple of months later and I am back down to 25 mg where I will hold for at least 2 months before making about a 10% reduction this time. I made the mistaken assumption that Trazodone would be easier to stop than my other meds, maybe the initial cuts were far easier but CT from 25 mg was just as bad as other things I have stopped.

 

BTW I also had a severe psychotic reaction within a couple of hours of taking 50 mg of Trazodone after cutting Zopiclone by 50% based on my doctor's recommendation.

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blackhawks89   
blackhawks89

Hi,

I was put on trazodone 3 weeks ago 50mg. I tried to cut a quarter off to taper and felt horrible the next day. I  had to go back to 50mg. I'm going to get a pill cutter and just take a little off. I don't want to be on something that causes so much pain when you don't take it.

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Wondering   
Wondering

I get the 10% taper, but specifically what would be the tapering amounts for tapering off 300mg of Trazodone. I can't figure out the math and the other posts were about 50 or 150 Trazodone. Thanks for any specific advice or maybe there is someone on this forum that helps people with their tapers?

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Amygdala   
Amygdala

300-->270-->243-->218.7-->196.8-->177.2-->159.4-->143.5-->129.1-->116.2-->104.6-->94.2-->84.7-->76.3-->68.6-->61.8-->55.6-->50-->45-->

 

40.5-->36.4-->32.8-->29.5-->26.5-->23.9-->21.5-->19.3-->17.4-->15.7-->14.1-->13.0-->11.7-->10.5-->9.5-->8.5-->7.7-->6.9-->6.2-->5.6-->5-->

 

4.5-->4.1-->3.7-->3.3-->3-->2.7-->2.4-->2.2-->2-->1.8-->1.6-->1.5-->1.3-->1.2-->1.1-->1

 

Numbers are less accurate the smaller they get but this should still be a good guideline.

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lanah   
lanah

If you get really pronounced symptoms, do you need to updose or wait it out? I'm confused about this. 

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Altostrata   
Altostrata

Thank you, Amygdala.

 

lanah, if you get really pronounced withdrawal symptoms, you are tapering too fast. If you have been reducing by more than 10% for a while, thus risking withdrawal symptoms, you may need to updose.

 

If you have just made a 10% decrease and experience really pronounced withdrawal symptoms for the first time, you might try waiting it out and make a smaller decrease the next time. There's no way to predict if waiting it out will work. It's up to you if you want to go back to the previous dose at which you were stable.

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Magnolis   
Magnolis

Does Trazadone ( a non-Ssri) have the same risks of causing The protracted withdrawal syndrome caused by SSRI's, when it is discontinued at a slow taper?

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Altostrata   
Altostrata

We have people here who have had problems going off trazodone and took quite a while to recover. It's difficult to tell if the risk of withdrawal syndrome is the same as the SSRIs, trazodone isn't prescribed as often.

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Rob66   
Rob66

My GP handed me a prescription for Trazadone a year ago for sleep issues. I used to work swing shift and had many sleep issues. He knew I was already on Zoloft but handed them out to me anyway. He said "It probably will even help with your depression"....Ugh!! Of course at that time I didn't know any better and used them on a as needed basis. So basically popping a 20mg pill once or twice a week when my bad sleep periods would hit. I used them like sleeping pills because I didn't know any better. I quit using them months ago but never tapered, just CT'd. I haven't experienced anything negative after quitting. That may be due to the short sporadic time I was using them. I know better now. The complete ignorance that some doctors have is very disturbing to me. It's hard for me to have trust in doctors anymore.

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Stormstrong   
Stormstrong

Trazodone and Zoloft is also the combination that is the bane of my existence..... 

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street129   
street129
On 10/5/2017 at 3:33 PM, Stormstrong said:

Trazodone and Zoloft is also the combination that is the bane of my existence..... 

im in new york , did you got stable on trazodone. im tapering it and stuck at 225mg now going on 2 months.

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street129   
street129
On 3/7/2017 at 8:20 PM, Altostrata said:

We have people here who have had problems going off trazodone and took quite a while to recover. It's difficult to tell if the risk of withdrawal syndrome is the same as the SSRIs, trazodone isn't prescribed as often.

is it ok for me to post to you here. i dont know if im causing any harm .. 4 days now on my compounding tablet of trazodone at 225mg and i woke every half an hour, before compounding , i had no problem sleeping.. can you tell me any of your thoughts on this . thanks altro.i will continue to hold. 

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street129   
street129

4 days now on my compounding tablet of trazodone at 225mg and i woke every half an hour, before compounding , i had no problem sleeping.. can you tell me any of your thoughts on this . will continue to hold. 

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