Second generation antipsychotics for schizophrenia: SECOND GENERATION ANTIPSYCHOTICS(12)


Ziprasidone has been submitted to the Health Protection Branch in Canada and the United States Food and Drug Administration, and is currently undergoing review for approval. It has been shown to be more effective than placebo for positive and negative symptoms of schizophrenia in four-and six-week, double-blind, randomized, fixed-dose trials using 80 to 160 mg/day. It has also been shown to be comparable to haloperidol in a four-week study (160 mg/day versus 15 mg/day). Its long term efficacy and safety have been evaluated during a one-year double-blind, randomized, placebo-controlled, parallel-group study that revealed a reduction in the risk of relapse and an improvement in negative symptoms over placebo. Studies remain in the preliminary phase, and data comparing ziprasidone with other second generation compounds are needed.

Noteworthy is its unique receptor binding profile in that it is an inhibitor of serotonin and norepinephrine reuptake in addition to the combined serotonin-dopamine antagonism shared among the newer agents. It is also an agonist at the 5-HT1A receptor and an antagonist at the 5-HT1D receptor. These actions may result in a clinical response different from what has been seen with other antipsychotics. Some potential claims attributed to its mechanism of action include both antidepressant and anxiolytic effects. levitra super active plus

Preclinical studies have shown it to be well tolerated, with somnolence and nausea being the most frequently reported side effects. The incidence of EPS was similar to that of placebo, as was orthostatic hypotension, anticholinergic effects and sexual dysfunction. The apparent lack of weight gain, which is a troublesome effect of other second generation an-tipsychotics, is promising. Another item of interest is that it will be the first atypical agent to be made available as a short acting intramuscular injection. Whether this will serve as an advantage over the others remains to be seen with clinical use.

The unique pharmacological properties and formulations make ziprasidone one of the more intriguing antipsychotics developed recently. However, its specific clinical characteristics have yet to be elucidated and reported from controlled trials and postmarketing experience. It is predicted that the protean pharmacological effects of ziprasidone will lead to variable clinical effects at different dosages.

This entry was posted in Antipsychotics and tagged Clozapine, Olanzapine, Risperidone, Schizophrenia, Ziprasidone.