Schizophrenic effect

Revicki DA, Luce BR, Weschler JM et al (1990). Cost-effectiveness of clozapine for treatment-resistant schizophrenic patients. Hosp Community Psychiatry 850-69. 

Moller HJ, Muller H, Borison RL, et al (1995). A path analytical approach to differentiate between direct and indirect drug effects on negative symptoms in schizophrenic patients a re-evaluation of the North American Risperidone study. EurArch Psychiatry Clin Neurol243, 45—9. 

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. 

The mechanism by which 5-HT2 antagonism could ameliorate schizophrenic symptoms and what effect 5-HT has on mesolimbic and mesocortical pathways through A10 neurons is even less certain. It is more likely that 5-HT s action occurs postsynaptically in the limbic system or PFC. The probability that neuroleptics benefit from a particular balance of DA and 5-HT2A antagonism is developed later. 

Phencyclidine (PCP), a dissociative anesthetic agent, which is subject to abuse, produces behavioral effects in man that frequently resemble schizophrenia (Luisada 1978). Manifestations of persistent psychopathology frequently remain after the acute effects of PCP have diminished. With PCP, subjects may display autistic and delusional thinking typical of schizophrenics (Luby et al. 1959). A more striking link between schizophrenia and PCP comes from observations of cases in which PCP was given to hospitalized schizophrenics (Luisada 1978). After receiving PCP, these patients showed extreme exacerbation of their psychoses the reaction persisted for up to 6 weeks. By contrast, LSD produced no more severe effects in schizophrenics than in normal subjects. 

Psychoses, when they occur, appear to be due to drug effect interacting with a vulnerable personality organization (Luisada 1978). Our experience has been that some adolescents with borderline personality disorders, as well as adolescents at risk of schizophrenic decompensation, may have this vulnerability. Although we do not have hard data to support the hypothesis that patients with PCP psychoses that are most resistant to treatment have the poorest long-term prognosis (Erard et al. 1980), our observations have been that persistence of symptoms of psychosis after the first 2 to 3 weeks of treatment often correlates with extended periods of impai rment. 

To date, clozapine remains the only drug with proven and superior efficacy in treatment-resistant patients, and it is currently the only drug approved for the treatment-resistant schizophrenic. Studies have shown a response of approximately 30% to 50% in these well-defined treatment-resistant patients. Clinical trials have consistently found clozapine to be superior to traditional antipsychotics for treatment-refractory patients, and it is efficacious even after nonresponse to other SGAs and in partially responsive patients. It is often rapidly effective even in those who have had a poor response to other medication for years. Recent studies have demonstrated that it has a beneficial effect for aggression and suicidality, which led to the Food and Drug Administration (FDA) approval for the treatment of suicidal behavior in people with psychosis.41... 

Examples abound regarding the role of serendipity in the discovery of new therapeutic approaches, which on closer examination usually turned out to be the result of clinicians paying attention to unexpected clinical effects rather than discounting them. For example, lithium was tried first for hypertension, chlorpro-mazine was initially developed as an anesthetic, and imipramine was originally regarded as an antihistamine and an antipsychotic agent. Without astute clinical observations, these drugs would not have found their niche, nor would clozapine have been revived for the benefit of millions of the most difficult to treat schizophrenic patients. Other examples include the expanded indications of newer... 

While most schizophrenics maintain their medication for many years, it is often possible to gradually reduce the dosage. Kane and Marder (1993) noted that effective symptom control can often be achieved at low doses, which then reduces the incidence of side... 

The answer is c. (Katzung, pp 485-486.) In addition to its antipsychotic action, olanzapine diminishes emotional bluntness and social withdrawl that are seen in schizophrenic patients, without significant anticholinergic and extrapy rami dal effects. 

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