Amitriptyline Cocktail
Using tricyclic antidepressants (TCAs) as an euthanasia agent, the Amitriptyline Cocktail (AC) as shown in this article was first described in the book Guide to a Humane Self-Chosen Death written by Dr. Pieter Admiraal and a committee of medical professionals. The cocktail was further improved by knowledgeable members of ASM to be more reliable and act faster as well.
 The two versions of the cocktail
 Version #1: the original Amitriptyline Cocktail
This is the original Amitriptyline Cocktail as documented in the book Guide to a Humane Self-Chosen Death.
|Antiemetic drugs must be taken beforehand|
|Amitriptyline (Elatrol, Elavil, Endep, Laroxyl, Trepiline, Tryptanol, Tryptizol)||6 grams|
|Diazepam or other long-acting benzodiazepine||300 mg|
 Version #2: the improved Amitriptyline Cocktail
The original Amitriptyline Cocktail created by Dr. Admiraal had few issues:
- The estimated time to death, 36 hours, was far too much. For many people this parameter would be an issue.
- We were bothered regarding people who were overweight and how would that impact the potency of the cocktail.
- 1. Adding cimetidine, which is a cytochrome p450 inhibitor (see the description for cimetidine in this article), would almost double the amitriptyline blood levels and would potentiate it that much, that it would hasten death by far.
- 2. Adding midazolam would also act to significantly hasten death due to the drugs' interaction, as confirmed by Dr. Admiraal (he said in his book that adding 300 mg of another strong benzodiazepine would hasten death).
- 3. In cases of people over 100kg, following the data we gleaned from the sources mentioned above, we understood that increasing the needed amount would ensure death.
This table lists the components of the improved cocktail, depending on body weight:
|Drug||Body weight <100 kg||Body weight >100 kg|
|Antiemetic drugs must be taken beforehand|
|Amitriptyline (Elatrol, Elavil, Endep, Laroxyl, Trepiline, Tryptanol, Tryptizol)||7 grams||8 grams|
|Cimetidine||2 grams||2.5 grams|
|Midazolam||300 mg||300 mg|
|Diazepam (Valium)||300 mg||300 mg|
 Possible drug substitutions and changes to the cocktail
- Amitriptyline can be replaced with the following tricyclic antidepressants: clomipramine, desipramine, dosulepin, doxepin, imipramine, nortriptyline and trimipramine.
- If one cannot obtain midazolam (Dormicum), one had better use any other short-acting benzodiazepine, like lorazepam or temazepam. Alternatively, one can increase the amount of diazepam (Valium) to 500 mg. The use of two kinds of benzodiazepines would significantly hasten death.
- Do not use phenobarbital in this cocktail, due to unwanted (mainly unpredictable) drug interactions with the amitriptyline.
- Cimetidine can be replaced with encainide, flecainide or quinidine. It cannot be replaced with Ranitidine or any other antacid medication: see the description for cimetidine in this article.
- Other benzodiazepines could be usable too. One of the key parameters is the drug half life (how long the drug acts) which you can look up in the benzodiazepine equivalency table.
 Mechanism of action and roles of the drugs
Amitriptyline is the lethal component of the cocktail.
Tricyclic antidepressants (TCAs) exert their lethality mainly since they are sodium channel blockers.
Sodium channel blockers decrease the propagation and the magnitude of action potentials in the cardiac sytem. The principal effect of reducing the rate and magnitude of depolarisation by blocking sodium channels, is a decrease in conduction velocity (in atrial and ventricular muscle). The faster a cell depolarises, the more rapid adjacent cells will become depolarised, leading to a more rapid regeneration and transmission of action potentials between cells in the cardiac system. Therefore, blocking sodium channels reduces the velocity of action potential transmission within the heart.
This prolonges the QT interval, promoting phenomena like 'torsade de points' or other ventricular tachycardia, which mean that the ventricular muscle would twitch randomly, rather than contracting in unison, and so the ventricles would fail to pump blood into the arteries and into systemic circulation. If the arrhythmia continues, blood circulation will cease, and death (as in, ventricular fibrillation) will occur in a matter of minutes.
The cardiac impact is rather similar to an overdose of Darvon, since Darvon is a sodium channel blocker as well.
Cimetidine inhibits some of the group of liver isoenzymes named Cytochrome P450,or in short CYP450, which is responsible for the drugs' first phase metabolism. Also see the Wikipedia article for CYP2D6. Tricyclic antidepressants like amitriptyline require liver isoenzyme CYP2D6 (along with others of that group) to be metabolised, so inhibiting this enzyme increases the levels of amitriptyline in the blood.
Cimetidine achieves two goals in the cocktail:
- it hastens death;
- it eliminates any possibility of survival and renders the cocktail much more lethal.
Cimetidine is normally used to reduce gastric acidity, as a treatment for heartburn or peptic ulcers. But in the cocktail, this mode of action is not relevant; cimetidine is required because of inhibition of the CYP2D6 liver enzyme and not because of its effects on stomach acid. That is why it is not possible to replace cimetidine with ranitidine, or any other antacid medication that a pharmacy might offer to you as a replacement.
 Midazolam and diazepam
Midazolam (Dormicum) and diazepam (Valium) are powerful sedatives from the benzodiazepine class. They cause deep sleep before amitriptyline starts to act in overdose. Amitriptyline poisoning would be lethal on itself, but the death it causes would not be peaceful.
 How long does the cocktail take?
Since TCAs tend to slow the digestive process and the absorption from the intestines, death would occur within 12-24 hours.
 Is it recommended to use a plastic bag in addition?
The Amitriptyline Cocktail is reliable by itself, if done right. So, there is no reason to use a plastic bag. A plastic bag requires significant preparation and must be used correctly to be lethal. The main risk of combining both is that instead of focusing on doing one thing right, you will do two methods and both wrong.
 Comparison to other methods
 Evidence and medical reports attesting to the efficacy of the AC
Amitriptyline and other TCAs accounted for a very large number of death cases all over the globe (some were suicides and some were "accidents").
According to the book Guide to a Humane Self-Chosen Death, which summarises the decisions and inferences of a Dutch euthanasia group's research committee (which consists of Dr. Pieter Admiraal, who is a well-known anaesthetist, and 5 other experts in their fields), 6 grams of a tricyclic antidepressant has been proven in toxicity reports to be reliably lethal. The committee deemed that adding as little as 300mg of a benzodiazepine would render the death peaceful as well.
The conclusions mentioned above are also supported by the authors of the euthanasia book Beyond Final Exit (see its chapter "Tricyclic antidepressants: A new look"), all of whom possess medical and/or biochemical expertise.
Now, with the other ingredients in the cocktail that we have suggested here (such as cimetidine and two potent sedatives), it would provide for a much more lethal cocktail, one with a much faster and still peaceful demise.
These references document cases of amitriptyline overdose:
- One case in the ASM newsgroup, from the year 2008.
- "Deaths related to amitriptyline toxicity are relatively common and are typically related-to suicidal overdose." Source: Amitriptyline Abuse and Misuse. American Journal of-Forensic Medicine & Pathology. 26(1):86-88, March 2005. Prahlow, Joseph A. MD;-Landrum, Jeffry E. DDS
- "We report here an autopsy case of a 49-year-old woman with depression who died of-hyperthermia, probably due to amitriptyline intoxication." Source: A fatal case of-hyperthermia due to tricyclic antidepressant intoxication, Legal Medicine, Volume 2,-Issue 3, Pages 152-155 (October 2000)
- "Between the years 1992-2003 in the UK alone, TCA's were responsible for 2700-overdose related deaths where amitriptyline or another TCA was ingested." Source: click here.
- A Coroner's jury report (Drug Overdose of Amitriptyline). Source: Verdict of Coroner's - Jury into the Death of K. A. Rogers.
- "The tricyclic antidepressants amitriptyline and doxepin, the most commonly used-antidepressants in Norway, are also the two leading antidepressants causing death by-intoxication." Source: Death due to overdose of antidepressants: experiences from-Norway Acta Psychiatrica Scandinavica Volume 87 Issue s371 Page 28-32, May 1993
 Acquiring the required cocktail ingredients
 Where to obtain the drugs
The best place to find and share information about on-line pharmacies is the Drugbuyers.com forum.People often discuss their experiences with obtaining drugs on ASM and ASH. Publishing the Internet address of online pharmacies is strictly prohibited in these newsgroups, but it is considered acceptable to exchange this information over e-mail.
Also, please see the article Obtaining drugs for more information about this subject.
 Availability of the drugs
- Amitriptyline (Elavil) is a widely used drug and easily obtainable from on-line pharmacies. It is not on the controlled substance list and ordering it from the internet is legal in most countries. Amitriptyline is often used off-the-label to prevent migraines and tension headaches, so one can use this as an excuse, should any questions arise.
- Cimetidine (Tagamet) is a heartburn and ulcer medication, and is not a controlled substance. In the USA and many other countries it is sold over the counter (OTC), which means that it is available without a prescription. In some European countries cimetidine requires a prescription, so inhabitants of those countries have to buy it over the Internet.
- Midazolam (Dormicum) and Diazepam (Valium) are drugs from the benzodiazepine class that are commonly prescribed to treat insomnia and anxiety. One can order them over the internet, but keep in mind that benzodiazepines are controlled substances: thus ordering them over the Internet is a criminal offense in some countries. One can also get a prescription legally from one's doctor: if you complain about insomnia and tell your doctor that OTC sleeping pills are not working for you, then your doctor will most likely prescribe a benzodiazepine.
 Ingesting the cocktail
 Antiemetic regimen
It is very important to use drugs that prevent vomiting (i.e. antiemetic drugs) before one takes the cocktail. Important warnings:
- OTC antiemetics for motion sickness (Dramamine, Gravol) will not work well.
- Do not take more antiemetics, or take them more often. It might cause a serious and painful side effect named EPS (short for extrapyramidal symptoms). Have some diphenhydramine (Benadryl, Dimedrol) ready to treat EPS, should it happen to you.
Also, please read this page carefully.
 Is there a specific order in which to take the cocktail?
Yes, there is. Please see the quotation below.
Newsgroup: alt.suicide.methods From: SonOfTheLiving...@webtv.net (Son of the Sun) Date: Sat, 22 Mar 2008 17:57:18 -0700 Subject: Re: Is there an order to take the amitriptyline cocktail? After your antiemetic ingest in this order: * Amitriptyline * Cimetidine * Valium (Diazepam) * Dormicum (Midazolam)
 How to repackage the drugs in capsules
To reduce the number of tablets to be swallowed, you can repackage tablets in capsules. Below is a post from Son of the Sun explaining this process regarding the Amitriptyline Cocktail.
Newgroup: alt.suicide.methods From: SonOfTheLiving...@webtv.net (Son of the Sun) Date: Fri, 7 Dec 2007 04:25:06 -0800 Subject: ADVISE FOR THE WISE Purchase a mortar & pestle or a marble spice grinder and grind your amitriptyline tablets into a fine powder and tightly pack the powder into the largest size gelatin or vegetable capsules that you can comfortably swallow. The largest size available is "000" followed by "00" and "0". I don't know how small or large these tablets are, but if you are able to put 350 mg of powdered amitriptyline into one "000" size gelatin or vegetable capsule, then you will only need to swallow twenty "000" size capsules in order to ingest a total amount of 7 grams of amitriptyline. It might be a good idea to ingest these "000" size gelatin or vegetable capsules by the spoonful, using a slippery pudding or melted ice cream in order to make swallowing them a bit easier.
Also, please see the article Capsules for more information about this subject.
- ↑ Block of Human Heart hH1 Sodium Channels by Amitriptyline, Carla Nau, Margaret Seaver, Sho-Ya Wang and Ging Kuo Wang, Department of Biology, State University of New York, Albany, New York (M.S., S.-Y.W.); and Department of Anesthesia, Harvard Medical School and Brigham & Women's Hospital, Boston, Massachusetts (C.N., G.K.W.)| http://jpet.aspetjournals.org/cgi/content/full/292/3/1015