Hostname: page-component-586b7cd67f-gb8f7 Total loading time: 0 Render date: 2024-11-30T23:50:27.885Z Has data issue: false hasContentIssue false
  • English
  • Français

Classification of neuroleptic drugs - lack of relationship to effect on negative symptoms in schizophrenia

Published online by Cambridge University Press:  28 April 2020

Svein G. Dahl
Svein G. Dahl*
Affiliation:
Institute of Medical Biology, University of Tromsø, P.O. Box 977, N-9001Tromsø, Norway
Get access

Summary

There is both pharmacological and clinical support for a classification of the schizophrenic syndrome into negative and positive subtypes. For neuroleptics that act upon both types of symptoms, it appears that lower doses are required for treatment of negative than for positive symptoms. Successful drug treatment of negative symptoms may therefore depend upon the choice of a correct dosage for the individual patient. Due to variation in pharamacokinetic parameters, similar doses of a neuroleptic drug may result in different plasma levels in individual patients, especially after oral medication. Pharmacokinetic variations, if not under proper control, may easily disguise a concentration-dependent relationship, such as the effects of a neuroleptic drug upon negative and positive symptoms. In drug treatment of negative symptoms it may therefore be an advantage to individualize the doses as a function of plasma drug level measurements, when available. No general relationship has been demonstrated between the chemical properties or pharmacodynamics of neuroleptic drugs and their potential to act upon negative symptoms. Also, the drugs which have been demonstrated to have an “energizing” effect have widely different pharmacokinetic properties. A chemical or pharmacological classification of neuroleptics therefore does not seem to give any information about their possible efficacy in treating negative symptoms in schizophrenia.

Résumé

Résumé

Les données pharmacologiques et cliniques sont en faveur d’une classification du syndrome schizophrénique en sous types négatifs et positifs. Les neuroleptiques agissant sur les deux types de symptômes semblent nécessiter pour les symptômes négatifs des doses inférieures à celles qu'il convient d’utiliser pour traiter les symptômes positifs. Le succès du traitement médicamenteux des symptômes négatifs peut très bien dépendre du choix d’une posologie adaptée au cas individuel. En raison de la variation des paramètres pharmacocinétiques, des posologies équivalentes de neuroleptiques peuvent correspondre à des taux plasmatiques différents selon les individus, en particulier lors de traitements par voie orale. Les variations pharmacocinétiques, lorsqu’elles ne sont pas convenablement controlées, peuvent facilement provoquer à notre insu une notion qui serait liée à la concentration comme c’est le cas pour les effets d’un neuroleptique sur les symptômes négatifs et positifs. Dans le traitement médicamenteux des symptômes négatifs, il est parfois utile de déterminer la posologie à partir de la mesure des concentrations plasmatiques du produit, lorsque cela est réalisable. Aucune relation généralisable n’a été démontrée entre les propriétés chimiques ou pharmacocinétiques des médicaments neuroleptiques et leur efficacité potentielle sur les symptômes négatifs. Les produits pour lesquels l’effet désinhibiteur a été démontré ont des propriétés pharmacocinétiques très différentes. Une classification chimique ou pharmacologique des neuroleptiques ne semble donc pas rendre compte de l'efficacité de ces produits sur les symptômes négatifs de la schizophrénie.

Keywords

SchizophreniaNegative SymptomsNeurolepticsPlasma Drug LevelsPharmacological ClassificationPharmacokineticsMolecular structuresSchizophrénieSymptômes négatifsNeuroleptiquesConcentrations plasmatiques des produitsClassification pharmacologiquePharmacocinétiqueStructures moléculaires
Type
Research Article
Information
Psychiatry and Psychobiology , Volume 2 , Issue 4 , 1987 , pp. 289 - 294
Copyright
Copyright © European Psychiatric Association 1987

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References/Bibliographie

Alfredsson, G., Bjerkhnstedt, L., Edman, G., Härnryd, C., Oxenstierna, G., Sedvall, G., Wiesel, F.-A. - Relationships between drug concentrations in serum and CSF, clinical effects and monoaminergic variables in schizophrenic patients treated with sulpiride or chlorpromazine. Acta Psychiatr Scand 1984a; 69 (Suppl. 311): 49–74.CrossRefGoogle Scholar
Alfredsson, G., Härnryd, C., Wiesel, F.-A. - Effects of sulpiride and chlorpromazine on depressive symptoms in schizophrenic patients - relationship to drug concentrations. Psychopharmacology 1984b; 84: 237–241.CrossRefGoogle Scholar
Alfredsson, G., Härnryd, C., Wiesel, F.-A. - Effects of sulpiride and chlorpromazine on autistic and positive psychotic symptoms in schizophrenic patients - relationship to drug concentrations. Psychopharmacology 1985; 85: 8–13.CrossRefGoogle ScholarPubMed
Andreasen, N.C - Negative symptoms in schizophrenia. Definition and reliability. Arch Gen Psychiatry 1982; 39: 784–788.CrossRefGoogle ScholarPubMed
Andreasen, N.C., Grove, W.M. - Evaluation of positive and negative symptoms in schizophrenia. Psychiatrie & Psychobiologie 1986; 1,2: 108–121.Google Scholar
Angrist, B., Rotrosen, J., Gershon, S. - Differential effects of amphetamine and neuroleptics on negative vs. positive symptoms in schizophrenia. Psychopharmacology 1980; 72: 17–19.CrossRefGoogle Scholar
Carlsson, A., Lindquist, M. - Effect of chlorpromazine or haloperidol on formation of 3-methoxy-tyramine and normethanephrine in mouse brain. Acta Pharmacol Toxicol 1963; 20: 140–144.CrossRefGoogle ScholarPubMed
Dahl, S.G. - Pharmacokinetic aspects of new antipsychotic drugs. Neuropharmacology 1981; 20: 1299–1302.Google ScholarPubMed
Dahl, S.G. - Active metabolites of neuroleptic drugs: Possible contribution to therapeutic and toxic effects. Ther Drug Monit 1982; 4: 33–40.CrossRefGoogle ScholarPubMed
Dahl, S.G. - Plasma level monitoring of antipsychotic drugs - Clinical utility. Clin Pharmacokinet 1986; 11: 36–61.CrossRefGoogle ScholarPubMed
Dahl, S.G., Hough, E., Hals, P.-A. - Phenothiazine drugs and metabolites: Molecular conformation and dopaminergic, alpha adrenergic and nuscarinic cholinergic receptor binding. Biochem Pharmacol 1986; 35: 1263–1269.CrossRefGoogle Scholar
Ganguli, R., Reynolds, C.F. III, Kupfer, D. - Electroencephalographic sleep in young, never-medicated schizophrenics. Arch Gen Psychiatry 1987; 44: 36–44.CrossRefGoogle ScholarPubMed
Gerlach, J., Behnke, K., Heltberg, J., Munk-Andersen, E., Nielsen, H. - Sulpiride and haloperidol in schizophrenia: A double-blind cross-over study of therapeutic effect, side effects and plasma concentrations. Br J Psychiatry 1985; 147: 283–288.CrossRefGoogle ScholarPubMed
Hals, P.-A., Hall, H., Dahl, S.G. - Phenothiazine drug metabolites: Dopamine D2, α1 - and α2 - adrenoceptor binding. Eur J Pharmacol 1986; 125: 373–381.CrossRefGoogle Scholar
Hyttel, J., Larsen, J.-J., Christensen, A.V., Arnt, J. - Receptor-binding profiles of neuroleptics. In: Casey, D.E., Chase, T.N., Christensen, A.V. & Gerlach, J. eds.: Dyskinesia - Research and Treatment. Psychopharmacology Supplementum 2, 9–18, Springer-Verlag, Heidelberg, 1985.CrossRefGoogle Scholar
Jørgensen, A. - Metabolism and pharmacokinetics of antipsychotic drugs. In: Bridges, J.F. & Chasseaud, L.F. eds.: Progress in Drug Metabolism, vol. 9., 111–174, Taylor and Francis, London, 1986.Google Scholar
Lecrubier, Y. - Schizophrénie : La prescription des neuroleptiques antiproductifs et antidéficitaires en France. Psychiatrie & Psychobiologie 1986; 1,2: 139–147.Google Scholar
Meltzer, H. Y. - Effect of neuroleptics on the schizophrenic syndrome. In: Dahl, S.G., Gram, L.F., Paul, S.M. & Potter, W.Z., eds.: Clinical Pharmacology in Psychiatry. Selectivity in Psychotropic Drug Action - Promises or Problems? Psychopharmacology Series 3, 255–265, Springer-Verlag, Berlin Heidelberg, 1987.Google Scholar
Morel, E., Lloyd, K.G., Dahl, S.G. - Anti-apomorphine effects of phenothiazine drug metabolites. Psychopharmacology 1987; 92: 68–72.CrossRefGoogle ScholarPubMed
Sedvall, G., Farde, L., Persson, A., Wiesel, F.-A. - Imaging of neurotransmitter receptors in the living human brain. Arch Gen Psychiatry 1986; 43: 995–1005.CrossRefGoogle ScholarPubMed
Submit a response

Comments

No Comments have been published for this article.