Atypical Antipsychotic - History

History

The first major tranquiliser or anti-psychotic medication, chlorpromazine,a.k.a. Thorazine, a typical antipsychotic, was discovered in 1951 and introduced into clinical practice shortly after. Clozapine, a.k.a. Clozaril,an atypical antipsychotic, fell out of favor due to concerns over drug-induced agranulocytosis. With research indicating its effectiveness in treatment-resistant schizophrenia and the development of an adverse event monitoring system, clozapine reemerged as a viable antipsychotic. According to Barker (2003) the three most accepted atypical drugs are; clozapine, risperidone and olanzapine. However, he goes on to explain that clozapine is usually the last resort when other drugs fail. Clozapine can cause agranulocytosis (which is decreased number of white blood cells), Barker (2003) explains that a person on clozapine will have to go through rigorous blood monitoring. Despite the effectiveness of clozapine for treatment-resistant schizophrenia, agents with a more favourable side effect profile were sought after for widespread use. During the 1990s, olanzapine, risperidone and quetiapine were introduced, with ziprasidone and aripiprazole following in the early 2000s. The atypical anti-psychotic paliperidone was approved by the FDA in late 2006.

The atypical anti-psychotics have found favour among clinicians and are now considered to be first line treatments for schizophrenia and are gradually replacing the typical antipsychotics. In the past, most researchers have agreed that the defining characteristic of an atypical antipsychotic is the decreased propensity of these agents to cause extrapyramidal side effects (EPS) and an absence of sustained prolactin elevation.

The terminology can be imprecise. The definition of "atypicality" was based upon the absence of extrapyramidal side effects, but there is now a clear understanding that atypical antipsychotics can still induce these effects (though to a lesser degree than typical antipsychotics.) Recent literature focuses more upon specific pharmacological actions, and less upon categorization of an agent as "typical" or "atypical". There is no clear dividing line between the typical and atypical antipsychotics therefore categorization based on the action is difficult.

More recent research is questioning the notion that second generation anti-psychotics are superior to first generation typical anti-psychotics. Using a number of parameters to assess quality of life, Manchester University researchers found that typical anti-psychotics were no worse than atypical anti-psychotics. The research was funded by the National Health Service (NHS) of the UK. Because each medication (whether first or second generation) has its own profile of desirable and adverse effects, a neuropsychopharmacologist may recommend one of the older ("typical" or first generation) or newer ("atypical" or second generation) antipsychotics alone or in combination with other medications, based on the symptom profile, response pattern, and adverse effects history of the individual patient.