Posted by Sunnely on November 11, 2001, at 19:50:39
In reply to Re: Paxil interaction? » Elizabeth, posted by Cam W. on November 9, 2001, at 22:36:56
>Still Mellaril is fairly safe; especially when you consider the number of doses that have been taken without incident since it was first released.
Actually, there have been serious incidents of thioridazine (Mellaril)-induced arrhythmias. In 1992, Donatini et al., reviewed 22 cases in the literature of Mellaril-induced arrhythmias plus 155 cases reported to Mellaril's manufacturer, Sandoz.
They found out that cases of life-threatening arrhythmias and even deaths have occurred with the use of Mellaril. The most life-threatening are ventricular arrhythmias including ventricular tachycardia, ventricular fibrillation and "torsades de pointes." These arrhythmias are more likely to occur with higher doses of Mellaril and not correlated with the duration of treatment. They also found out that patients who overdosed on Mellaril remained vulnerable to ventricular tachycardia or fibrillation for up to 10 days after Mellaril was discontinued. In patients who were on Mellaril 800 mg/day (maximum dose allowed/day), 14 cases of ventricular tachycardia or fibrillation occurred. Five of 10 patients who suffered complete heart block died. Six cases who developed first or second-degree heart blocks from doses of 800 mg/day, always led to ventricular tachycardia.
IMHO the seriousness of Mellaril-induced arrhythmias was not widely talked about until at least 2 events occurred: 1) several (heart) sudden deaths reported to the FDA from the use of Seldane, Hismanal, and Propulsid, and 2) the Geodon study. Like Seldane, Hismanal, and Propulsid, Mellaril can also prolong QTc on electrocardiogram (ECG) which could potentially lead to serious ventricular tachycardia, in particular, "torsades" and even death. Experts consider the presence of prolonged QTc on ECG as a "harbinger" for "torsades."
During clinical trials, Geodon was found to cause prolonged QTc. This was the reason why Geodon was delayed (about 2 years) in its release to the US market. To convince the FDA that Geodon is safe, Pfizer conducted a study comparing Geodon with other antipsychotics with regard to their potential to prolong QTc. Among the antipsychotics involved, only Mellaril was found to prolonged QTc to a clinically significant proportion. While Geodon was also found to prolonged QTc, it was considered not clinically significant to be of concern, hence, its subsequent FDA approval. Although doing a pre-treatment and maintenance treatment ECG is not required during Geodon treatment, the FDA required that Geodon's labeling include a "Warning" about QT prolongation and risk of sudden death.
Incidentally, as a consequence of the Geodon study, Mellaril got clocked. Subsequently, the US FDA required that Novartis (formerly Sandoz) revise Mellaril's labeling to include a "black box" about risk of serious heart arrhythmias and risk of sudden death. Also, the revised label now indicates that Mellaril is no longer considered a "first-line" drug for the treatment of schizophrenia and other psychoses. Finally, a pretreatment and maintenance treatment ECG should be done on patients who are on Mellaril. For patients who are already on Mellaril, if ECG shows prolonged QTc that is greater than 450 msec but less than less 500 msec, CONSIDER a switch to a different antipsychotic; if ECG shows prolonged QTc that is 500 msec or greater, MUST switch to a different antipsychotic.
poster:Sunnely
thread:83603
URL: http://www.dr-bob.org/babble/20011104/msgs/83932.html