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Re: Geodon really works and I won't shut up about it Bob

Posted by SLS on October 5, 2001, at 23:05:03

In reply to Re: Geodon really works and I won't shut up about it, posted by Bob on October 5, 2001, at 16:22:21

Dear Bob,

I have been taking Geodon (ziprasidone) for about three weeks. Given my history of extreme refractoriness to treatment, that Geodon helps at all might be an indicator of its potential to exert an antidepressant effect. It has been helping a bit as an adjunct to Effexor + nortriptyline + Lamictal. I am currently taking 40mg/day in divided doses. I was gratefully greeted by insomnia for the last few nights. Historically, this has been a good prognosticator for me.

1. I have experienced transient improvements with Risperdal and Zyprexa.

2. Risperdal was somewhat sedating at first, and later produced some cognitive impairments at 1.5mg and higher; dosages that were necessary to sustain an improvement.

3. Zyprexa was cleaner than Risperdal and somewhat more robust. I did experience some increase in appetite as well as a slurring of speech over the first two weeks that later dissipated. I would experience occasional somnolence during the afternoon. I experienced diminishing returns in the second week.

4. So far, the antidepressant effect produced by Geodon has not reached the degree that I saw early in the Zyprexa trial, but it seems to be more consistent and stable. It has not increased my appetite nor produced any slurring of speech. So far, I would say that Geodon is well worth consideration. I have not experienced EPS with any of these three neuroleptics. Of note is the fact that all three have been observed to induce mania. It is my impression that Geodon is more liable to produce mania than either Risperdal or Zyprexa. I see the relative maniogenic potential as Geodon > Zyprexa > Risperdal. > Stelazine.

Regarding pharmacology, all three are mild to moderate antagonists at DA2 receptors, and moderate to potent antagonists at the 5-HT2a receptor. Geodon, unlike Risperdal and Zyprexa, displays considerable agonism at the 5-HT1a receptor. In this respect, it is similar to buspirone, gepirone, ipsapirone, and flesinoxan, all drugs known to display mild to moderate antidepressant effects. In addition, Geodon is often *cited* as capable of inhibiting the reuptake of both serotonin and norepinephrine. However, I am not so confident that this is accurate, although I have no reason to believe otherwise. I have yet to see the investigations that are said to have yielded this conclusion. Were this to be so, Geodon would then possess five pharmacological properties associated with drugs known to possess antidepressant properties:

1. DA2 antagonism if it is preferential to presynaptic autoreceptors at low dosages.

2. 5-HT2a antagonism

3. 5-HT1a agonism

4. NE reuptake inhibition

5. 5-HT reuptake inhibition.

It is a very interesting drug. It probably has the second lowest risk of producing EPS, Seroquel being perhaps lower. This might be due to its high ratio of 5-HT2a / DA2 binding ratio. It is without the H1 receptor antagonism displayed by Zyprexa and Clozaril. One notable detraction is that it can affect cardiac function, as it prolongs the QT interval in a manner similar to Mellaril, albeit less robustly. However, it is significant enough as measured in the laboratory to take into consideration when making a decision.

Some people on Psycho-Babble have reported Geodon to have produced excitation, insomnia, manic-like symptoms, and various presentations of EPS, including lingual dystonias.

I hope this helps.


P.S. Im in Minnesota right now. I had to wear my winter jacket today. I just thought youd like to know.




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