Absence of effect of sertraline on time-based sensitization of cognitive impairment with haloperidol.
This double-blind, randomized, placebo-controlled study evaluated the effects of haloperidol alone and haloperidol plus sertraline on cognitive and psychomotor function in 24 healthy male subjects.


METHODS
All subjects received placebo on Day 1 and haloperidol 2 mg on Days 2 and 25. From Days 9 to 25, subjects were randomly assigned to either sertraline (12 subjects) or placebo (12 subjects); the sertraline dose was titrated from 50 to 200 mg/day from Days 9 to 16, and remained at 200 mg/day for the final 10 days of the drug administration period. Cognitive function testing was performed before dosing and over a 24-hour period after dosing on Days 1, 2, and 25.


RESULTS
Impairment of cognitive function was observed 6 to 8 hours after administration of haloperidol on Day 2 but was not evident 23 hours after dosing. When single-dose haloperidol was given again 25 days later, greater impairment with earlier onset was noted in several tests in both treatment groups, suggesting enhancement of this effect. There was no indication that sertraline exacerbated the impairment produced by haloperidol since an equivalent effect also occurred in the placebo group. Three subjects (2 on sertraline and 1 on placebo) withdrew from the study because of side effects. Ten subjects in each group reported side effects related to treatment. The side effect profiles of sertraline and of placebo were similar.


CONCLUSIONS
Haloperidol produced a clear profile of cognitive impairment that was not worsened by concomitant sertraline administration.
Williams
S A
SA
Pfizer Central Research, Sandwich, Kent, United Kingdom.
Wesnes
K
K
Oliver
S D
SD
Rapeport
W G
WG
D015057:1-Naphthylamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D004357:Drug Synergism; D006220:Haloperidol / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011581:Psychological Tests; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D020280:Sertraline
D015057:1-Naphthylamine; D006220:Haloperidol; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline