Home » Drug Information » FDA Approved Drugs » 2002
Medical Areas: Psychiatry/Psychology
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Geodon (ziprasidone mesylate)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Approval Status: Approved June 2002
Treatment Area: Schizophrenia
Geodon for injection has been approved by the FDA to rapidly
control agitated behavior and psychotic symptoms (such as
hallucinations and delusions) in patients with acute exacerbations
of schizophrenia. Geodon is the first atypical antipsychotic
medication approved in the United States for intramuscular (IM)
Geodon blocks the action of serotonin and dopamine, two
mood-regulating chemicals found in the brain. An orally
administered form of this medication was approved by the FDA for
schizophrenia in February 2001. However, with acute agitation
(characterized by uncooperative or even violent behavior),
immediate intervention is required. Intramuscular delivery provides
a rapidly effective option for these emergency situations.
Intramuscular Geodon was evaluated for effectiveness in two
short-term, double-blind trials. These trials included
schizophrenic subjects who were considered by the study
investigators to be "acutely agitated" and in need of IM
antipsychotic medication. The subjects were also required to have a
score of three or more on at least three of the following items of
the Positive and Negative Syndrome Scale (PANSS): anxiety, tension,
hostility and excitement.
Both studies compared a 2 mg control dose to higher doses of
Geodon. In the first trial, the higher dose was 20 mg, which could
be given up to four times in the 24 hours of the study, with
intervals between dosing of no less than four hours. In the second
study, the higher dose was 10 mg. This dose could also be given up
to four times in 24 hours, but with interdose intervals of no less
than two hours.
The first trial (involving 20 mg or 2 mg doses of Geodon) was a
one-day, double-blind, randomized study (n=79). Results showed that
Geodon 20 mg was statistically superior to the 2 mg dose, as
assessed by area under the curve (AUC) of the Behavioral Activity
Rating Scale (BARS) at zero to four hours, and by Clinical Global
Impression (CGI) severity at four hours and study endpoint. The
BARS is a seven point scale with scores ranging from one (difficult
or unable to rouse) to seven (violent, requires restraint).
The second trial (involving 10 mg or 2 mg doses of Geodon) --
also a one-day, double-blind, randomized study (n=117) -- showed
that Geodon 10 mg was statistically superior to Geodon 2 mg
according to the AUC of the BARS at zero to two hours, but not as
assessed by CGI severity.
Testing has shown that ziprasidone (the active component of
Geodon) has a greater capacity to prolong the QT/QTc interval of an
electrocardiogram compared to several other antipsychotic drugs.
This effect is important because it is associated with torsade de
pointes-type arrhythmia, a potentially fatal polymorphic
ventricular tachycardia (rapid heart rate), and sudden death.
In clinical studies, adverse events associated with the use of
ziprasidone (incidence of 5% or greater) included somnolence
(drowsiness) (14%), extrapyramidal syndrome (5%) and respiratory
Mechanism of Action
The mechanism of action of ziprasidone, as with other drugs
having efficacy in schizophrenia, is unknown. However, it has been
proposed that this drug’s efficacy in schizophrenia is mediated
through a combination of dopamine type 2 (D2) and serotonin type 2
(5HT2) antagonism. Antagonism at receptors other than dopamine and
5HT2 with similar receptor affinities may explain some of the other
therapeutic and side effects of ziprasidone. (from Geodon