Neuroleptics definition

Moller H-J (2000). Definition, psychopharmacological basis and clinical evaluation of novel/ atypical neuroleptics Methodological issues and clinical consequences. World Journal of Biological Psychiatry, 1, 75-91. 

In addition to the somatic side-effects of neuroleptics, there are a number of important psychiatric side-effects, such as demotivation or indifference (a direct effect of most drugs, actually part of the definition of the neuroleptic effect). This may mimic the negative features of the illness and may lead to prescriptions of an antidepressant when a reduction in dose or change of antipsychotic may be more appropriate. A second key problem is anxious activation or akathisia. This dose-dependent dysphoric state may lead to an apparent worsening in the clinical picture and accordingly an increase in antipsychotic dose rather than decrease and may be so intolerable as to lead on to suicide. 

In this context, Lilly (474) reported a meta-analysis of three controlled studies of patients with TD who were treated with olanzapine. These authors found an 11-fold decrease in TD on olanzapine versus haloperidol based on the AIMS scale. There were a few patients who developed TD in the first 6 weeks of olanzapine, but this could have been from previous drug exposure, now not suppressed by the neuroleptic. Interestingly, there were no new cases (0/375) of TD developing in patients on long-term olanzapine treatment, whereas there were three of 83 cases on haloperidol. It is very difficult to arrive at definitive evidence about TD because most patients have received previous neuroleptic therapy and because TD-like symptoms occur spontaneously, providing an alternative explanation. It is clear that it is difficult to prove that olanzapine causes TD but equally difficult to prove that it does not. The 11-fold decreased incidence, however, is strong evidence that at least it produces much less TD. 

As noted earlier, evidence indicates that atypical antipsychotics may also produce NMS ( 488). Several patients have developed NMS after treatment with clozapine, risperidone, or olanzapine. A few of these cases are classic NMS, with symptoms such as markedly elevated temperature and CPK levels. For each drug, approximately a dozen reported cases fulfill a reasonably stringent criteria for NMS, whereas the rest can be considered borderline. The number of NMS cases, however, appears low relative to use. In addition, some of the patients on clozapine who developed NMS were also receiving neuroleptics. There are cases of patients who had NMS on clozapine alone, however, and when rechallenged with clozapine experienced another NMS episode. Similarly, rechallenge with olanzapine- or risperidone-induced NMS has resulted in either questionable or definite reemergence of NMS. 

In addition to acute and chronic schizophrenia, the neuroleptics are sometimes used in the management of mania, delirium, and severe agitation, whatever the cause of these symptom complexes. It must be noted that unlike parkinsonism, where a definite dysfunction in the DA system has been established, for schizophrenia and other psychiatric diseases, no unequivocal evidence has yet been presented to prove that there is a disturbance of the DA system (e.g., dopaminergic overactivity or receptor hypersensitivity). In untreated schizophrenics the production of DA metabolites is normal. Conflicting results have been obtained in studies of the DA receptors in schizophrenics (11,12,13), but in the case of patients who have not received neuroleptics, the receptor density and affinity appear to be normal (13). The "dopamine hypothesis" in these disorders derives from the beneficial effects of drugs that block DA receptors. 

Animal autopsy data provide strong evidence that the neuroleptics frequently cause brain damage. Human autopsy studies are too few and contradictory to lead to a definite conclusion. Once again, interest in them has declined. 

Animal research provides definitive and apparently incontrovertible evidence that neuroleptics often cause irreversible brain damage. This is consistent with more recent studies reviewed earlier in the chapter that demonstrate how both older and newer atypical neuroleptics are highly toxic to living cells in animals. 

Shiloh R, Valevski A, Bodinger L, Misgav S, Aizenberg D, Dorfman-Etrog P, Weizman A, Munitz H. Precautionary measures reduce risk of definite neuroleptic malignant syndrome in newly typical neuroleptic-treated schizophrenia inpatients. Int Clin Psychopharmacol 2003 18 147-79. 

Of the 58 patients in the study (316), 34 were considered to have normal gag reflexes, nine to have variable responses to touching the posterior pharngeal wall, and 15 to have definitely Impaired gag reflexes. The last two groups were combined for the analysis of drug use. All 58 patients had been receiving neuroleptics and antlparklnsonlsm drugs 12... 

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