New neuroleptics

Despite its novel therapeutic profile, it was soon evident that clozapine occasionally caused agranulocytosis, a potentially fatal immune condition, in approximately 3% of patients. The use of clozapine was therefore restricted largely to patients who suffered severe side effects with the typical neuroleptics, who were resistant to conventional neuroleptics or who had a high proportion of negative symptoms. Thus, clozapine has served as a useful prototype for the development of new neuroleptics and these will be briefly described. 

The Collaborative Working Group has also drawn attention to the interpretation of certain results from clinical trials with novel neuroleptic drugs (10). It has been stated, for instance, that when extrapyramidal signs are not significantly different from those with placebo, it does not necessarily mean that a new neuroleptic drug absolutely lacks extrapyramidal effects. Patients who enter studies of new neuroleptic drugs may have been... 

Of 524 inquiries received by the National Poisons Information Service concerning new neuroleptic drugs over 9 months, only 45 cases involved overdose with a single agent (olanzapine, n = 10 clozapine, n = 8 ... 

Of 524 inquiries received by the National Poisons Information Service concerning new neuroleptic drugs over 9 months, only 45 cases involved overdose with a single agent (olanzapine, n — 10 clozapine, n — 8 risperidone, n — 10 sulpiride, n = 16) (503). There were no deaths or cases of convulsions. Cardiac dysrhythmias occurred only with sulpiride. Symptoms were most marked with clozapine most patients had agitation, dystonia, central nervous system depression, and tachycardia. Most of the patients who had taken risperidone were asymptomatic. 

A survey of potential new neuroleptics reported during the year shows that the large majority are variations on well-known drug classes. A Hoechst-Roussel group has reported a group of 9 new butyrophenones, of which 1 is the most interesting. It is orally effective in blocking... 

The new neuroleptic (which also demonstrates that the keto group is not essential for activity) fluspirilene (IXb) has been shown to be an extr iely potent and long acting drug... 

Chlorpromazine had been shown to produce a tranquil state in animals and since it had a similar effect in humans it became known as a major tranquiliser but the term is rarely used today. Sometimes the drugs used to treat schizophrenia are called anti-psychotics but more commonly neuroleptics. Leptic means to activate (take hold of) and in animals these compounds produce a state of maintained motor tone known as catalepsy. This is an extrapyramidal effect and in schizophrenics the neuroleptics can cause a number of extrapyramidal side-effects (EPSs) including Parkinsonism. The new term neuroleptic is unsatisfactory as a description of clinically useful drugs. It really describes a condition (catalepsy) seen in animals and is more indicative of a compound s ability to produce EPSs than to treat schizophrenia. Antipsychotic is more descriptive but could imply a more general efficacy in psychoses than is the case. It would seem more appropriate to call a drug that is used to treat schizophrenia an antischizophrenic just as we use the terms antidepressant or antiepileptic irrespective of how the drug works. Despite such personal reservations, the term neuroleptic will be used in this text. 

BickeboeUer-Friedrich J, Maurer H. 2001. Screening for the detection of new antidepressants, neuroleptics, hypnotics... 

As a group, these medications have been known by several names. They have been called major tranquilizers. This is not altogether inaccurate these medications do calm or tranquilize. Physicians still use this name sometimes, especially when they re reluctant to use the word psychotic in a discussion with a new patient or his/her family. These medications have also been called neuroleptic, literally meaning seize the nerve cell, in the original Greek. This term is derived from the potential for the medications to cause extrapyramidal side effects. Finally, and most accurately we contend, these medications are called antipsychotics. 

Besides the poor specificity of many of the assays used to determine plasma drug concentrations, another problem which has arisen from these studies has been the length of the "wash-out" period necessary before the patient is given the neuroleptic under investigation. As a result of the prolonged duration of blockade of dopamine receptors in the brain by conventional neuroleptics and their metabolites, it is necessary to allow a wash-out period of several weeks before the patients are subject to a pharmacokinetic study. This raises serious ethical questions. Perhaps with the advent of new imaging techniques it may be possible in the near future actually to determine the rate of disappearance of neuroleptics from the brain of the patient. This may enable the relationship between plasma concentration and clinical response to be accurately determined. 

Atypical neuroleptics. Because of the limited effectiveness and safety of conventional neuroleptics in TS, clinicians have turned to a new generation of neuroleptics that have been introduced for the treatment of schizophrenia. Risperidone, a member of a class of antipsychotics that blocks both DA and serotonin receptors, has been established as superior to placebo and equal, or superior, to haloperidol in the treatment of schizophrenia (Chouinard et al. 1993 Marder and Meibach 1994]. Risperidone has a more favorable side-effect profile than that of conventional neuroleptics and may have less potential for producing tardive dyskinesia. Compared with haloperidol, fewer extrapyramidal side effects are observed with risperidone in doses of 6 mg/ day or less. As encouraging reports appear in the literature (Lombroso et al. 1995 Stamenkovic et al. 1994 van der Linden et al. 1994], risperidone is currently being widely used by clinicians to treat tic disorders. 

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