Pharmacogenetics of antipsychotic treatment: Lessons learned from clozapine

Mario Masellis, Vincenzo S. Basile, Vural Özdemir, Herbert Y. Meltzer, Fabio M. Macciardi, James L. Kennedy*

*Corresponding author for this work

Research output: Contribution to journalReview article

78 Citations (Scopus)

Abstract

The reintroduction of clozapine, the prototype of atypical antipsychotics, in the late 1980s has led to significant advances in the pharmacological management of schizophrenia. Since then, there has been a rapid development of novel 'atypical' antipsychotic agents that have been pharmacologically modeled, to a certain extent, after their predecessor clozapine. As with all antipsychotics, there is variability among individuals in their response to these 'atypical' drugs. Pharmacogenetics can provide a foundation for understanding this interindividual variability in antipsychotic response. This review first provides a rationale for the pharmacogenetic investigation of this variable trait. Studies of pharmacokinetic and pharmacodynamic factors of antipsychotic therapy are considered in the development of this rationale. Next, the molecular genetic techniques used to study this interindividual variation in response are described. This is followed by a review and discussion of the published studies examining genetic factors involved in clozapine response. From this, several recommendations for future pharmacogenetic investigations of antipsychotic response are proposed. Although still in its early stages, psychiatric pharmacogenetics should provide a basis for individualized pharmacotherapy of schizophrenia, and may also lead to the development of newer, more efficacious antipsychotic agents. Copyright (C) 2000 Society of Biological Psychiatry.

Original languageEnglish (US)
Pages (from-to)252-266
Number of pages15
JournalBiological psychiatry
Volume47
Issue number3
DOIs
StatePublished - Feb 1 2000

Fingerprint

Clozapine
Pharmacogenetics
Antipsychotic Agents
Therapeutics
Schizophrenia
Genetic Techniques
Psychiatry
Molecular Biology
Pharmacokinetics
Pharmacology
Drug Therapy
Pharmaceutical Preparations

Keywords

  • Antipsychotic response
  • Clozapine
  • Pharmacodynamic
  • Pharmacogenetic
  • Pharmacokinetic
  • Polymorphism

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Masellis, M., Basile, V. S., Özdemir, V., Meltzer, H. Y., Macciardi, F. M., & Kennedy, J. L. (2000). Pharmacogenetics of antipsychotic treatment: Lessons learned from clozapine. Biological psychiatry, 47(3), 252-266. https://doi.org/10.1016/S0006-3223(99)00298-X
Masellis, Mario ; Basile, Vincenzo S. ; Özdemir, Vural ; Meltzer, Herbert Y. ; Macciardi, Fabio M. ; Kennedy, James L. / Pharmacogenetics of antipsychotic treatment : Lessons learned from clozapine. In: Biological psychiatry. 2000 ; Vol. 47, No. 3. pp. 252-266.
@article{8b0185083bd9443eab9483b9c882cc5b,
title = "Pharmacogenetics of antipsychotic treatment: Lessons learned from clozapine",
abstract = "The reintroduction of clozapine, the prototype of atypical antipsychotics, in the late 1980s has led to significant advances in the pharmacological management of schizophrenia. Since then, there has been a rapid development of novel 'atypical' antipsychotic agents that have been pharmacologically modeled, to a certain extent, after their predecessor clozapine. As with all antipsychotics, there is variability among individuals in their response to these 'atypical' drugs. Pharmacogenetics can provide a foundation for understanding this interindividual variability in antipsychotic response. This review first provides a rationale for the pharmacogenetic investigation of this variable trait. Studies of pharmacokinetic and pharmacodynamic factors of antipsychotic therapy are considered in the development of this rationale. Next, the molecular genetic techniques used to study this interindividual variation in response are described. This is followed by a review and discussion of the published studies examining genetic factors involved in clozapine response. From this, several recommendations for future pharmacogenetic investigations of antipsychotic response are proposed. Although still in its early stages, psychiatric pharmacogenetics should provide a basis for individualized pharmacotherapy of schizophrenia, and may also lead to the development of newer, more efficacious antipsychotic agents. Copyright (C) 2000 Society of Biological Psychiatry.",
keywords = "Antipsychotic response, Clozapine, Pharmacodynamic, Pharmacogenetic, Pharmacokinetic, Polymorphism",
author = "Mario Masellis and Basile, {Vincenzo S.} and Vural {\"O}zdemir and Meltzer, {Herbert Y.} and Macciardi, {Fabio M.} and Kennedy, {James L.}",
year = "2000",
month = "2",
day = "1",
doi = "10.1016/S0006-3223(99)00298-X",
language = "English (US)",
volume = "47",
pages = "252--266",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "3",

}

Masellis, M, Basile, VS, Özdemir, V, Meltzer, HY, Macciardi, FM & Kennedy, JL 2000, 'Pharmacogenetics of antipsychotic treatment: Lessons learned from clozapine', Biological psychiatry, vol. 47, no. 3, pp. 252-266. https://doi.org/10.1016/S0006-3223(99)00298-X

Pharmacogenetics of antipsychotic treatment : Lessons learned from clozapine. / Masellis, Mario; Basile, Vincenzo S.; Özdemir, Vural; Meltzer, Herbert Y.; Macciardi, Fabio M.; Kennedy, James L.

In: Biological psychiatry, Vol. 47, No. 3, 01.02.2000, p. 252-266.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Pharmacogenetics of antipsychotic treatment

T2 - Lessons learned from clozapine

AU - Masellis, Mario

AU - Basile, Vincenzo S.

AU - Özdemir, Vural

AU - Meltzer, Herbert Y.

AU - Macciardi, Fabio M.

AU - Kennedy, James L.

PY - 2000/2/1

Y1 - 2000/2/1

N2 - The reintroduction of clozapine, the prototype of atypical antipsychotics, in the late 1980s has led to significant advances in the pharmacological management of schizophrenia. Since then, there has been a rapid development of novel 'atypical' antipsychotic agents that have been pharmacologically modeled, to a certain extent, after their predecessor clozapine. As with all antipsychotics, there is variability among individuals in their response to these 'atypical' drugs. Pharmacogenetics can provide a foundation for understanding this interindividual variability in antipsychotic response. This review first provides a rationale for the pharmacogenetic investigation of this variable trait. Studies of pharmacokinetic and pharmacodynamic factors of antipsychotic therapy are considered in the development of this rationale. Next, the molecular genetic techniques used to study this interindividual variation in response are described. This is followed by a review and discussion of the published studies examining genetic factors involved in clozapine response. From this, several recommendations for future pharmacogenetic investigations of antipsychotic response are proposed. Although still in its early stages, psychiatric pharmacogenetics should provide a basis for individualized pharmacotherapy of schizophrenia, and may also lead to the development of newer, more efficacious antipsychotic agents. Copyright (C) 2000 Society of Biological Psychiatry.

AB - The reintroduction of clozapine, the prototype of atypical antipsychotics, in the late 1980s has led to significant advances in the pharmacological management of schizophrenia. Since then, there has been a rapid development of novel 'atypical' antipsychotic agents that have been pharmacologically modeled, to a certain extent, after their predecessor clozapine. As with all antipsychotics, there is variability among individuals in their response to these 'atypical' drugs. Pharmacogenetics can provide a foundation for understanding this interindividual variability in antipsychotic response. This review first provides a rationale for the pharmacogenetic investigation of this variable trait. Studies of pharmacokinetic and pharmacodynamic factors of antipsychotic therapy are considered in the development of this rationale. Next, the molecular genetic techniques used to study this interindividual variation in response are described. This is followed by a review and discussion of the published studies examining genetic factors involved in clozapine response. From this, several recommendations for future pharmacogenetic investigations of antipsychotic response are proposed. Although still in its early stages, psychiatric pharmacogenetics should provide a basis for individualized pharmacotherapy of schizophrenia, and may also lead to the development of newer, more efficacious antipsychotic agents. Copyright (C) 2000 Society of Biological Psychiatry.

KW - Antipsychotic response

KW - Clozapine

KW - Pharmacodynamic

KW - Pharmacogenetic

KW - Pharmacokinetic

KW - Polymorphism

UR - http://www.scopus.com/inward/record.url?scp=0033959580&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033959580&partnerID=8YFLogxK

U2 - 10.1016/S0006-3223(99)00298-X

DO - 10.1016/S0006-3223(99)00298-X

M3 - Review article

C2 - 10682223

AN - SCOPUS:0033959580

VL - 47

SP - 252

EP - 266

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 3

ER -