Polymorphic drug metabolism (CYP2D6) and utilisation of psychotropic drugs in hospitalised psychiatric patients: a retrospective study.
OBJECTIVE
The aim of the current retrospective study was to assess the influence of polymorphic drug metabolism as assessed by genotyping, on the on the utilisation of psychotropic drugs in hospitalised psychiatric patients. The utilisation of psychotropic drugs was assessed using pharmacy records with emphasis on the number of prescriptions and prescriptions for possible side effects.


METHODS
CYP2D6 genotype was assessed in 241 psychiatric patients by investigation for the five most common allelic variants ( CYP2D6*3, *4, *6, *7, *8) and the presence of gene duplication using allele-specific polymerase chain reaction. Data concerning the pharmacotherapy of the patients were retrieved from the pharmacy information system. Data was analysed on differences observed in pharmacy records concerning the different metabolic classes: ultra rapid metabolisers (UMs), extensive metabolisers (EMs) and poor metabolisers (PMs).


RESULTS
For CYP2D6, 2.5% was UM (95% CI: 0.5-4.5%, n=6) and 8.3% was PM (95% CI: 4.8-11.8%, n=20). Drugs metabolised by CYP2D6 were less frequently prescribed in PMs than EMs (21.1% vs 33.6%, P=0.023). The average duration of prescriptions was significantly lower in PMs than EMs (54 days vs 106 days, P=0.010). Between UMs and EMs, no significant differences were found, although a similar tendency was observed. With regard to dose, no consistent differences were observed between the CYP2D6 genotype classes. Drugs against Parkinsonian-like side effects were given twice as frequently in PMs as EMs (6.9% vs 3.4%, P=0.045).


CONCLUSIONS
Patients with impaired CYP2D6 metabolism received fewer CYP2D6 drugs. PMs were more prone to Parkinsonian-like side effects as evidenced by more prescriptions for drugs combating these side effects. Dose titrations were not often used to compensate for genetic polymorphisms. Pharmacy records might be a useful tool to detect differences related to polymorphic metabolism.
Tamminga
Wim J
WJ
Pharma Bio-Research Group BV, Science Park, NL-9471 GP Zuidlaren, The Netherlands. wtamminga@PBR.nL
Wemer
Johan
J
Oosterhuis
Berend
B
de Boer
Anthonius
A
Vranckx
Stan
S
Drenth
Ben F H
BF
de Zeeuw
Rokus A
RA
de Leij
Lou F M H
LF
Jonkman
Jan H G
JH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000378:metabolism / Q000627:therapeutic use; D016022:Case-Control Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism*; D017723:Drug Utilization Review; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D016347:Medical Records Systems, Computerized; D001523:Mental Disorders / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D019338:Polypharmacy; D011619:Psychotropic Drugs / Q000378:metabolism / Q000627:therapeutic use*; D012189:Retrospective Studies
D000978:Antiparkinson Agents; D011619:Psychotropic Drugs; D019389:Cytochrome P-450 CYP2D6