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....henylpiperazine
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.
trazodone (3-6 hrs) ---> mCPP (2-6 hrs) ---> other metabolites
per Wikipedia http://en.wikipedia.org/wiki/Trazodone
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, 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. However, scientific research has not supported this hypothesis, and mCPP may actually antagonize trazodone's efficacy as well as produce additional side effects....
mCPP is used to induce anxiety for study in the laboratory, e.g. http://www.ncbi.nlm....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.
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.
Department of Psychiatry, University of Vermont, Burlington, VT 05401, USA. rekast at email.com
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 ( 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..../pubmed/9616194
mCPP requires enzyme cyp 2D6 to leave your body Example: http://www.ncbi.nlm..../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...bel/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.../trazodone.html
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.
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.../trazodone.html
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....398a#nlm34089-3
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://survivinganti...dpost__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, 10 June 2015 - 11:31 AM.