# Prodissociative Effects of Metyrapone



## S O L A R I S (Dec 24, 2009)

I was researching and found this article, its a cortisol reducer drug which supposedly brings on symptoms of DP. FYI
http://ajp.psychiatryonline.org/cgi/content/full/158/7/1159
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Prodissociative Effects of Metyrapone
MICHAEL KELLNER, M.D., MILDRED SCHICK, M.D., and KLAUS WIEDEMANN, M.D.
Hamburg, Germany

To the Editor: We present case vignettes of three patients with panic disorder (per DSM-IV) who underwent neuroendocrine testing of hypothalamic-pituitary-adrenocortical axis activity with the 11ß steroid hydroxylase inhibitor metyrapone (3 g given orally at midnight, i.e., 27.3-31.3 mg/kg of body weight). They were the first three patients in our hospital to participate in this single-blind, placebo-controlled study, and they unexpectedly developed transient dissociative symptoms after metyrapone administration but not after placebo ingestion. All patients had been free from psychotropic medication for at least 1 week and had negative urinary screens for illegal drugs.

Mr. A was a 30-year-old man who had suffered from panic disorder (without other lifetime axis I disorders) for 1.5 years. Thirty minutes after metyrapone ingestion, he felt dreamy and disconnected from his body and his surroundings, similar to how he felt right before losing consciousness during administration of general anesthesia. However, he did not feel panicky and did not experience the somatic symptoms of a panic attack.

Mr. B was a 57-year-old man who had suffered from panic disorder with agoraphobia for 28 years; he also had lifetime diagnoses of benzodiazepine abuse and major depression (both in remission for 1 year). Forty minutes after metyrapone ingestion, he felt unreal, developed tunnel vision, perceived objects as "swinging back and forth," and concurrently had a typical panic attack.

Mr. C was a 20-year-old man who had suffered from panic disorder with agoraphobia for 4 years and had comorbid secondary alcoholism; the latter had been in remission for 3 months. One hour after metyrapone ingestion, he developed tunnel vision, felt unreal and detached from his surroundings, and perceived objects as diminished in size. No other symptoms of a panic attack emerged.

These acute dissociative symptoms that developed shortly after metyrapone intake subsided completely in all three patients within 1 hour. Although all these patients regularly experienced derealization during their spontaneous panic attacks (as seen in about 70% of patients with panic disorder [1]), two of them reported experiencing only isolated dissociative symptoms after metyrapone administration and no simultaneous symptoms of panic. These unexpected prodissociative side effects of metyrapone were reported spontaneously by all three patients. After placebo ingestion, no side effects were experienced, with the exception of a slight transient stomach pain in one patient. Metyrapone administration remarkably elevated mean adrenocorticotropic hormone levels to 630% of baseline by 8:00 a.m.

Before further speculation about a potentially greater vulnerability of patients with panic disorder to the prodissociative side effects of metyrapone, a prospective double-blind study using standardized scales to measure acute dissociation is needed. Such an investigation should also include normal comparison subjects and other patient groups, since one patient with posttraumatic stress disorder has also been reported to have developed a dissociative episode approximately 1 hour after metyrapone ingestion (2).

References

1. Ball S, Robinson A, Shekhar A, Walsh K: Dissociative symptoms in panic disorder. J Nerv Ment Dis 1997; 185:755-760[Medline]
2. Yehuda R, Levengood RA, Schmeidler J, Wilson S, Guo LS, Gerber D: Increased pituitary activation following metyrapone administration in post-traumatic stress disorder. Psychoneuroendocrinology 1996; 21:1-16[CrossRef][Medline]


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## Guest (Jan 25, 2010)

Very interesting, and back to the theory that anxiety/panic/dissociation is related to a failure in the HPA Axis. I'm glad this is being replicated.
For those who say there is no research going on, there IS. Interesting is this could have initially been discovered by accident as I looked up the drug and it is used to test for poor adrenal function, Cushing's disease, etc. Not for DP/DR.
So, someone who got tested for one of these illnesses said they were feeling odd and that led to a neurological experiment.

*"Metopirone, metyrapone USP, is an inhibitor of endogenous adrenal corticosteroid synthesis, available as 250-mg capsules for oral administration. Its chemical name is 2-methyl-1, 2-di-3-pyridyl-1-propanone, and its structural formula is ..... etc....

Metopirone is a diagnostic drug for testing hypothalamic-pituitary ACTH function."*

This again, along with MANY other research studies leads me to believe that for various reasons those of us here have a MALFUNCTIONING Hypothalamus-Pituitary-Adrenal Axis ... or what helps control NORMAL HEALTHY ANXIETY and a NORMAL HEALTH FIGHT/FLIGHT response. We can find answers from this. Again, what amazes me is this was in a neurology journal. Have faith in neurological research, not necessarily psychiatric research. I've said 100 times, every neurologist I've come in contact with knows about "altered states of consciousness" and DP/DR. They may not know what to do for it, but they know what it is.

I'll print this out for my STUPID medical resident. My BRIGHT therapist can give it to him.
Curses on doctors who don't know what this VERY COMMON SYMPTOM is ... never have heard of it. IMPOSSIBLE. Emergency room physicians know what this is as they see individuals coming in thinking they have heart attacks and they are having severe panic attacks. The individual will also talk about feeling unreal. THIS IS COMMON.

Again, even though I came from an abusive home with no rec drug onset, I believe this is a MEDICAL problem I have. I deal with it the best I can. Depending on so many factors, many people can use many coping mechanisms to deal with this. I know of a number of people, my age (51) and older who have had chronic anxiety since childhood. Not necessarily DP/DR. Why? It is a medical condition. Some become chronic alcoholics because of this -- my father-in-law did. He had serious chronic anxiety (though he worked has an aerospace engineer in the 40s-70s). He smoked like a chimney and drank like a fish.

If I had been born in another century, I believe I would be an alcoholic ... self-medicating my anxiety.
Thank you for the post!

Best,
D


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## Guest (Jan 25, 2010)

PS -- note that follow up studies are needed. Only 3 participants were involved in this study. They had to go off their meds before the study.

It is difficult to have research studies like this. You need individuals to participate -- willing individuals. People who might have to travel some distance without getting payment. You need individuals who have been off medications for LONGER than a week which many can't tolerate.

When someone mentioned scans and "Why can't they figure something out right now from these scans?" -- well, there are ethics involved as well. The brain is the one organ in the body you must be careful experimenting with. You can't perform direct examination of brain tissue. Experimenting with a living brain can be dangerous. Researchers depend on the brains of deceased individuals. Brain research in other animals is NOT the same as in humans. Research on higher primates also brings in ethical questions as chimps, etc. are so like us.

There IS research out there, along with everything everyone is trying here on this board.

I have hope in this type of research, outside of the psychiatric profession. This research was coming from endocrinology! All research can teach us new things! And we can't "wait around for answers", but we can have hope. We each live our lives to the fullest, as best we can. Though I have to say it isn't easy. I'd say I'd take my depression and anxiety over the DP/DR any day.


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## Guest (Jan 25, 2010)

1. Ball S, Robinson A, Shekhar A, Walsh K: Dissociative symptoms in panic disorder.* J Nerv Ment Dis 1997;* 185:755-760[Medline]
2. Yehuda R, Levengood RA, Schmeidler J, Wilson S, Guo LS, Gerber D: Increased pituitary activation following metyrapone administration in post-traumatic stress disorder. *Psychoneuroendocrinology 1996*; 21:1-16[CrossRef][Medline]

Sorry, this is in a psychiatric journal, but the footnotes come from a "psychoneuroendrinology" write up and one in the Journal of Nervous and Mental Disorders.

There is work across all specialties that reveal new things about OTHER disorders. "Serendipitous discoveries."


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## S O L A R I S (Dec 24, 2009)

Thanks Dreamer for your comments, I too believe the answer is out there, and I am determined to find it!

I dont care what the hell people say, but I do not have DP because I think about it alot. Sure, everyones recovery method is different. But I feel you and I share the same story, both dysfunctional and traumatic upbringings, like way beyond what any child can handle. I never knew what DP was, I honestly thought I felt anxious and had low self confidence, and I worked towards making myself better w/no meds for years. I only found out recently I was DP'ed for my entire life, and now feel like ive been a pawn in the biggest joke of my life. I never knew reality, never had a chance to be DP free. I must've been pre puberty when this happened, and as you said, your mind gets conditioned to this way of reacting.

Im contemplating going off meds, and try a herbal approach, both brain supplements and adrenal supplements at once. I called pharmacies in my city, but metyrapone is not available, I would have otherwise given it a chance.

Ugh, Its out there! and blv me, the answer will be out sooner or later. I will assemble it, put it together, and do more for myself than any profession or medical field has done.

Cheers to the future!


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## S O L A R I S (Dec 24, 2009)

Just to comment further, I back up this story with my experience in EFFEXOR. It is the only story ive heard, of an anti depressant fully curing DP, and believe me, it did cure it completely in seconds.

From my research, EFFEXOR does have Adrenergic effects, which would somehow be related to adrenal glands and endocrine system. If you connect the dots, we can establish a common clue into the cause of this thing, and how to cure it.


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