antipsychotics and hallucinations

   The term antipsychotic is used as a synonym for the terms neuroleptic and major tranquilizer. All three terms refer to a group of psy-chotropic substances with varying chemical structures that have a broad range of effects upon the CNS, the peripheral nervous system, and various other tracts. Among these effects is the potential to suppress the mediation of hallucinations and other " psychotic symptoms. The coiner of the term antipsychotic is unknown but it must have been intended to draw exclusive attention to the antipsychotic potential of these substances, thus suggesting a specificity of their action that was not warranted by their actual range of effects. The history of the antipsychotics starts with the alkaloid reserpine, a compound of the snakeroot plant Rauwolfia serpentina, which in Ayurvedic medicine has been used to treat 'madness' since ancient times, and the synthesis of chlorpromazine by the French chemist Paul Charpentier in 1950. The usefulness of chlorpro-mazine in the treatment of hallucinations and other symptoms characteristic of shock and postoperative " delirium was recognized in 1951 by the French surgeon Henri Laborit (1914-1995). The term neuroleptic was introduced in 1955 by the French psychiatrists Jean Delay (19071987) and Pierre Deniker (b. 1917), who were the first to test the efficacy and safety of chlor-promazine in individuals with a clinical diagnosis of "schizophrenia. In 1957, Delay and Deniker published a proposal for the biochemical action of chlorpromazine. A subsequent publication by the Swedish pharmacologists Arvid Carlsson (b. 1923) et al. in 1963, which designated the antipsy-chotics primarily as antidopaminergic agents, is generally regarded as an empirical corroboration of Delay and Deniker's biochemical thesis. In addition to their effects on the dopaminergic system, however, the antipsychotic substances also affect a variety of other neurotransmitter systems in the CNS. For example, they also have anticholinergic, antihistaminergic, and seroton-ergic effects, as well as an antagonistic effect on adrenergic receptors. On the basis of the antidopaminergic effects of chlorpromazine and other antipsychotics, in 1974 the group headed by the American psychiatrist and pharmacologist Solomon Snyder (b. 1938) proposed their " dopamine hypothesis of schizophrenia. Thus 3-hydroxytyramine or dopamine became a likely

   - although certainly not the only - candidate for biochemical models of hallucinatory experience in general. In spite of the high degree of sophistication that characterizes models like these, it should be noted that the elucidation of the neurophysiological correlates of hallucinatory experience and treatment is far from complete. The antipsychotics have been classified in various ways. Using their relative effect upon psychotic symptoms as a guiding principle, they are divided into low-potency and high-potency antipsychotics. In accordance with their molecular characteristics, they are divided into classical and atypical antipsychotics. The term classical antipsychotic has traditionally been used to denote the phenothiazine, thioxanthene, buty-rophenone, and diphenylbutylamine groups of antipsychotics, as well as the substance tiapride

   - all of which are believed to have the dopamin-ergic D2 receptor as their major site of action. The term atypical antipsychotic is used to denote substances such as aripiprazole, clozapine, olan-zapine, risperidone, sulpiride, quetiapine, and sertindole. The purported site of action of these substances is different for each substance, affecting one or more of the neurotransmitter systems listed above. The effects of antipsychotic substances upon hallucinations and other psychotic symptoms tend to differ somewhat across the various disease categories and across individuals within those categories. In the case of hallucinations due to any type of organic pathology, remission depends at least partly on an adequate treatment of the underlying disorder. Generally speaking, hallucinations occurring in the context of delirium or substance abuse tend to abate more quickly than those occurring in the context of any of the major psychotic disorders. Moreover, acute psychotic symptoms tend to diminish step by step. Symptoms such as sleeplessness, agitation, and aggression generally diminish within several days after the onset of antipsychotic treatment. The frequency and severity of hallucinations tend to diminish after 4-6 weeks of treatment. It has been suggested that the decline in hallucinatory behaviour often seen during the first few days of treatment is a sign that genuine antipsychotic effects kick in within hours after the onset of antipsychotic treatment. However, most authors attribute this initial effect to sedation and/or other aspecific therapeutic factors. In individuals with a major psychotic disorder, hallucinations - as well as delusions, formal thought disorders, catatonic symptoms, and negative symptoms - can disappear within several weeks to months. In many individuals with a clinical diagnosis of schizophrenia, however, these symptoms tend to linger on, although they often become less severe and incapacitating. Roughly speaking, a quarter to one-third of all individuals with a clinical diagnosis of schizophrenia attain a state comparable to complete remission. One-third to one-half of sufferers experience lifelong episodes of relapse and remission, generally with ongoing, though less severe psychotic symptoms during the periods of remission. The last quarter of the group remains psychotic throughout. This state of affairs was noted by the Swiss psychiatrist Eugen Bleuler (1857-1939) a century ago. And in spite of the advent of antipsychotic drug treatment, it has remained essentially unaltered up until the present day. It has even been argued that the surplus value of antipsychotic drug treatment is not its influence upon the long-term course of any of the major psychotic disorders, but rather its capacity to limit the duration of psychotic episodes and to reduce the severity of hallucinations and other psychotic symptoms. As is the case with any therapeutic, the antipsychotics tend to induce adverse effects. These include sedation, orthostatic hypotension, obstipation, urinary retention, changes in the electrocardiogram (ECG), hypersalivation, parkinsonism and other extrapyramidal symptoms, akathisia, metabolic syndrome, hyperprolactinaemia, disturbances of sexual function, agranulocytosis, a lowering of the threshold for epileptic seizures, tardive dyskinesia, and malignant neuroleptic syndrome. Alternative and/or adjuvant treatment forms for hallucinations include the use of lithium or other mood-stabilizing agents, psychotherapy, electroconvulsive therapy (ECT), and transcra-nial magnetic stimulation (TMS). In the past, many other alternatives have been explored, including sedation with the aid of substances such as chloral hydrate, paraldehyde, and acetyl-choline, alongside insulin coma treatment, drug-induced convulsive therapy, hydrotherapy, and psychosurgery. Conceptually, the term antipsy-chotic is used in opposition to the term "psychotic (which is employed as an equivalent of the term " hallucinogen to denote a group of substances with hallucinogenic properties).

   References

   Pilon, L. (1959). Contribution à la psychopathologie des hallucinations par l'étude de leur évolution sous chlorpromazine. Paris: Dactylo-Sorbonne.

   Snyder, S.H., Banerjee, S.P., Yamamura, H.I., Greenburg, D. (1974). Drugs, neurotrans-mitters, and schizophrenia. Science, 184, 1243-1253.

   Deniker, P. (1989). From chlorpromazine to tardive dyskinesia (brief history of the neurolep-tics). Psychiatry Journal of the University of Ottawa, 14, 253-259. Warner, R. (1994). Recovery from schizophrenia. Psychiatry and political economy. Second edition. London: Routledge. Carlsson, A., Lecrubier, Y., eds. (2004). Progress in dopamine research in schizophrenia. A guide for physicians. London: Taylor & Francis.