No association of a set of candidate genes on haloperidol side effects.
We previously investigated a sample of patients during an active phase of psychosis in the search for genetic predictors of haloperidol induced side effects. In the present work we extend the genetic association analysis to a wider panel of genetic variations, including 508 variations located in 96 genes. The original sample included 96 patients. An independent group of 357 patients from the CATIE study served as a replication sample. Outcomes in the investigation sample were the variation through time of: 1) the ESRS and UKU total scores 2) ESRS and UKU subscales (neurologic and psychic were included) related to tremors and 3) ESRS and UKU subscales that do not relate to tremors. Outcome in the replication sample was the presence vs absence of motoric side effects from baseline to visit 1 (~ one month of treatment) as assessed by the AIMS scale test. Rs2242480 located in the CYP3A4 was associated with a different distribution of the UKU neurologic scores through time (permutated p = 0.047) along with a trend for a different haloperidol plasma levels (lower in CC subjects). This finding was not replicated in the CATIE sample. In conclusion, we did not find conclusive evidence for a major association between the investigated variations and haloperidol induced motoric side effects.
Institute of Psychiatry, University of Bologna, Bologna, Italy.
Antonio
A
Drago
Ina
I
Giegling
Martin
M
Schäfer
Annette M
AM
Hartmann
Hans-Jürgen
HJ
Möller
Diana
D
De Ronchi
Hans H
HH
Stassen
Alessandro
A
Serretti
Dan
D
Rujescu
D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D006220:Haloperidol / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000235:genetics
D014150:Antipsychotic Agents; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D006220:Haloperidol