Comments: The Zyprexa Chronicles: Lilly Opens Defense Today
I'm glad to see the 2007 [possible? not sure if it's changed yet]label make a statement about weight gain and metabolic syndrome.
Posted by Stephany at March 17, 2008 11:52 PM
i was given the drug zyprexa, and went up to 218lbs
Posted by gary at March 18, 2008 01:16 AM
I have been studying antipsychotics for the last 7 to 8 years as many people calling the Prozac group had been diagnosed as 'bipolar' after taking their Prozac and were now on an antipsychotic. They would often ask me questions about their antipsychotics so I felt it was necessary to study this.
The first antipsychotic was chlorpromazine {Thorazine} and it was developed in France and began its use in 1953-54. Several years later the French did a big research study to ascertain exactly how many milligrams should be given to patients. Their answers were: 50 mg. for maintenance and as high as 100 [one hundred] mg. for an acute episode of schizophrenia. When the American doctors began using Thorazine, they followed the American principle of "More Is Better" and began prescribing dosages from 50 mg to 1500 [fifteen hundred] mg. The recommeneded dosage in the U.S. for schizophrenics was 350 mg. to 600 mg. all throughout the late 1950's until just recently.
Chlorpromazine is considered the 'benchmark' antipsychotic so all other antipsychotic dosages are converted into Thorazine milligrams. Zyprexa's 5 mg. is the equivalent of 100 mg. of Thorazine. So, if following the origianl French guidelines, the dosage for Zyprexa should be 2.5 mg. for maintenance and 5 mg. for acute espisodes. Of course, this was the dosage for adults as the French did not test this drug on children/adolescents back in the 1950's but children, according to the PDR, should be given from one-third to one-half the adult dosage.
Schizophrenics in mental hospitals before 1954 had a slightly higher rate of diabetes than the general population. Their rate was around 4% vs. 1.3% for the general population. By 1958 those hospitalized in psyciatric institutions had a rate of 17% for diabetes [but nobody cared].
Among the typical antipsychotics, Thorazine & Mellaril, as members of the 'low-potency' antipsychotics were more likely to cause weight gain and sedation than the high potency antipsychotics such as Haldol & Proxilin. The high potency antipsychotics were more likely to cause tardive dyskenesia [movement disorders] than the low potency although all could cause this disorder.
After 10 weeks of drug administration, the antipsychotic most likely to cause weight gain was clozapine, followed by Zyprexa, then Mellarail, Serentil, and then Thorazine. These were followed in descending order by Risperdal and Haldol.
The first atypical antipsychotic after Clozapine was Respirdal and, when it was being tested in clinical trials, it was tested at the equivalent of 200 mg. of Thorazine versus Haldol at 500 mg. of Thorazine value. When used below the equivqlent of 50 mg. of Thorazine, none of the antipsychotics have a propensity to cause tardive dyskenesia,although it can happen rarely in chlorpromazine equivalents as low as 30 mg.
About 4 years ago, it was discovered that Mellaril prolonged the QT interval of the heart and it was now considered a last resort antipsychotic. Mellaril has the smae equivalency rating as Thorazine so 50 mg. of Mellaril is also 50 mg. of Thorazine. At 50 mg.of Mellaril a person is likely to have a 1.12 increased risk of sudden death due to QT prolongation. At 500 mg. [which was the standard for over 40 years] the rate was 12.5.
The Canadians did some research in the last several years to see how much the dopamine receptors need to be blocked in order to quell a psychosis. They used Haldol in their study. They found that 1 to 3 mg. of Haldol was all that was needed to stop a psychosis. Converted to chlorpromazine equivalents this is 50 mg. to 150 mg. Converted to Zyprexa equivalents this is 2.5 mg. to 7.5 mg. These studies were all done on adults.
So for over 50 years, those in psychaitric hospitals were being overmedicated resulting in untold misery, suffering, zombishness and death. If the antipsychotics were going to work, they would work ina low dose. Otherwise, the patients were being medicated into a lobotomized state to turn them into zombies with a Thorazine shuffle so they would not disturb the hospital personnel.
So the story of the antipsychotics is one of the [many] great tragedies of modern medicine.
Posted by Rosie at March 18, 2008 11:39 AM
That's pretty fascinating about antipsychotics and standard dosages. It brings up a really important issue. A great deal of what's wrong in the use of these drugs relates to dosing. Antidepressants are routinely prescribed at doses substantially higher than lower ones that have been demonstrated to be effective and that's what often leads to the acute adverse effects. Glenmullen talks about this in Prozac Backlash. Of course higher doses means big pharma can charge more and they like to market a drug where "one size fits all". They don't want people to know tiny doses are actually often the most effective. I have heard of people doing well on 5mg of Paxil for instance who go berserk on 20mg. At one time 20mg was the smallest dose out there. Everyone assumed it was small but in reality even 20mg is a hefty dose of Paxil. Belatedly GSK started producing a 10mg tablet. I often tell people to stay on the lowest possible dose that seems to be working for them and not let their doctors talk them into ramping up to the "full" dose -- that is if I can't get them not to take it at all. Maybe this is presumptuous of me but in fact several people have successfully stayed on the tiny dose for a period of months and then not had much trouble coming off -- well worth it I would say.
Posted by Sara at March 18, 2008 04:37 PM
Comparing does of different drugs is tricky business. Seroquel, for example, hits numerous receptors although its greatest affinity is histamine (H1). It also hits dopamine (D2), serotonin (5HT2a,c), and alpha1. When you compare the receptor affinities between zyprexa and seroquel you'll see that the H1 and alpha1 (sedation and orthostatis) are much higher for seroquel. In fact, seroquel acts primarily as an antihistamine at low doses until H1 and alpha1 are "saturated".
I guess what I'm trying to say is that you can't easily convert so-called "therapeutic" doses. Going from 25 to 50 mg of seroquel has a huge sedation effect whilst going from 400 to 800 mg will not because H1 is already full saturated by the time you get past 300 mg or so. Of course, the numbers are different for each drug. The point is whilst 10mg zyprexa might equal 500mg seroquel, 5 mg zyprexa does not equal 250 mg seroquel.
The last psychiatrist has an excellent article on this point: http://thelastpsychiatrist.com/2007/07/the_most_important_article_on.html
Posted by Paul at March 18, 2008 09:15 PM
Iteresting posts about dosage. My son, killed by Zyprexa, was on 20 mg. I don't know why - perhaps the overworked Medicaid psychiatrist went by the more is better theory as the drug (I found out after my son's death) did not seem to be working. But I have an old friend who has been on Zyprexa since its beginning and of course now has diabetes. She became psychotic for months but when finally put up to 20 mg. lost the psychosis. However, she is now gaining weight again, and lacks the energy to work away at her diet.
Posted by Sorrowful at March 19, 2008 08:24 AM
So at what dose does seroquel hit serotonin?
Posted by Matt at November 12, 2008 11:07 AM