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When chlorpromazine was first recognized for its antipsychotic properties in 1952 and became the prototype of treatment for schizophrenia, we in psychiatry began a journey that nearly a half century later has taken a promising turn. Granted, chlorpromazine started the revolution and generated a long succession of conventional treatments that led to the more atypical drugs now reaching the market.
Jane Eyre's description of the madwoman in the Rochesters' attic in 1847 was typical of what society thought of mental illness. Since then, tremendous progress in medicine has validated a biological basis of schizophrenia and delineated its neuropathology. Regardless, a century passed before chlorpromazine loosened the bindings and helped patients with schizophrenia regain their places in society. But even now, many individuals continue to be locked out socially because of mental illness-about 35% of individuals treated do not respond to current therapies.
In the year and a half since I last discussed the management of schizophrenia in this column, the search for agents with improved efficacy for the more treatment-resistant negative symptoms has led to three new drugs being marketed in the United States. These agents have acquired the label "atypical" antipsychotics. This article explores the meaning of this label and the characteristics denoted by placement in the atypical category.
What Are Atypical Antipsychotic Agents?
Antipsychotic agents may be categorized based on their effects on two neuroreceptors in the central nervous system: 5-hydroxytryptophan or serotonin (5-HT) to dopamine receptors. Most experts would agree that a 10:1 ratio of 5-HT to dopamine should be present for an agent to be categorized as atypical.
Another term sometimes used to describe the atypical agents is serotonin-dopamine antagonist. Other characteristics common in the atypical agents are the following:
Compared with conventional agents, atypical antipsychotic agents have a much clearer separation between treatment effects and side effects. Mesolimbic blockade of dopamine relates to the antipsychotic effects of these agents, while nigrostriatal blockade of dopamine results in the EPS side effects. Researchers seek limbic selectivity with striatal-sparing effects. The net result is then a more distinct separation between drug effects, receptor binding, and side effects. Conventional agents demonstrate more of an overlap between the adverse effects and efficacy curves.
Available Atypical Antipsychotic Agents
Three atypical agents are currently marketed in the United States. Clozapine (Clozaril, Novartis) began the atypical age in 1990. It has definite efficacy in the treatment-resistant patient. Its potential for agranulocytosis and seizures has limited its use, and even though its potential for extrapyramidal symptoms is far less than that of conventional agents. The second agent marketed in the United States was risperidone (Risperdal) in 1994. It also has established efficacy and causes fewer extrapyramidal symptoms than do conventional agents. In 1996, olanzapine (Zyprexa) was introduced. Its efficacy and side effect profiles are very good, and the drug is being rapidly incorporated into many patients' therapy. It appears that sertindole (Serlect) may reach the market in 1997.
Switching Patients from Conventional to Atypical Antipsychotic Agents
With these newer agents hitting the market, practitioners are beginning to discuss the best way to switch patients from conventional agents to atypical drugs. The mnemonic SWITCH has been used to demonstrate a concise recommendation for converting patients:
This may be a useful tool for clinicians to use in the difficult process of changing such an important treatment of schizophrenia.
Conclusion
Even though pharmacotherapy has come a long way in the past 50 years in the treatment of schizophrenia, some 35% of patients do not respond to therapy-and another 35% only do so partially. The introduction of the atypical agents has certainly brought new hope. Each new agent has taught practitioners more about the neurobiology of the disease and confirmed the role the various neurotransmitters play in the illness.
Even with the advent of these new agents, we continue to seek
alternative treatments-the art of psychiatry needs many arrows
in its quiver.
Phyllis M. Parks-Veal, PharmD
103 Cambridge Drive North
Milledgeville, GA 31061