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The effects of haloperidol on visual search, eye movements and psychomotor performance
380
P-3 Psychotic Disorders and Neuroleptics
The effects of haloperidol on visual search, eye movements and psychomotor performance
D.J. King", G. Lynch~', M.F.
M a n n i o n ~' a n d W. B y t h b
~'Queen's University Department ~[ Therapeuties and Pharmacology, Bel[ast BT9 7BL, Northern Ireland anal ~'School ~7[Psvehology, Queen's University, Be[l~lst, Northern Ireland Key words." Haloperidol; Eye movements: Visual search: Normal volunteers Human volunteer studies are important to identify the cognitive effects of antipsychotic drugs (King, 1990). Calvert and Troscianko (1992) showed that patients with Parkinson's disease (PD) had impaired parallel processing on a visual search task. The purpose of this study was to determine if single doses of haloperidol (HPL) would replicate this effect in healthy volunteers. We also looked for evidence of a dose dependent effect of HPL on eye movements, sustained attention and subjective feelings. HPL (2, 4 and 6 rag) was compared to lorazepam (L) (2.5 lng) and placebo in 15 healthy male volunteers, in a double-blind study using a balanced latin-square design. Saccadic eye movements (SEM), smooth pursuit eye movements (SPEM), digit symbol substitution test (DSST) and visual analogue ratings of subjective feelings (VARS) were measured at baseline and at 2. 4 and 6 h after drug administration. The visual search (VS) and continuous attention tasks (CAT) were assessed tit baseline and 4 h. The results were analysed by Friedman and Wilcoxon non-parametric statistics comparing differences from baseline with placebo. Single doses of HPL did not cause impairment of parallel search. L caused a significant overall increase in reaction time, but this did not depend on the number of distractors (see Table 1). L and all doses of HPL caused impairment of all saccade parameters except latency, error and acceleration/deceleration ratio, which were unaffected by any drug. The effect was maximal at 4 h. L and HPL (4 and 6 nag) impaired all measures of SPEM (position error, velocity error and saccadic intrusions). The effect of HPL on eye movements appeared to be dose dependent. The peak of the dose-response curve was at 4 mg for all measures except for saccadic intrusions where the effect peaked at 6 rag. The CAT and DSST and VARS (Alert) were all significantly impaired by L and HPL 4 and 6 rag. Clinically significant dysphoria with or without akathisia occurred in 12 volunteers (80%) after HPL 6 mg and in 9 volunteers (60%) after HPL 4 rag. We conclude that: (1) single doses of HPL did not replicate the visual search abnormalities seen in PD; (2) SEM measures were sensitive to the effects of HPL at all doses used: (3) both HPL (4 and 6 rag) and L caused SPEM abnormalities similar to those seen in chronic schizophrenia: (4) none of the above tests will qualitatively distinguish between the psychomotor effects of neuroleptic and benzodiazepine drugs: (5) the psychomotor effects of HPL appear to peak tit 4 ing.
Table l. Visual search 4 h (reaction time) (medians) No. of distractors (target absent)
Placebo HPL 2 mg HPL 4 mg HPL 6 mg L 2.5 mg
4
9
16
36
64
657.4 571.4 615.6 6(12.2 778.0**
597.8 558.2 635.2 565.9 740.6**
595.6 608.7 604.4 581.3 650.5**
602.2 626.4 637.4 585.7 839.6**
6(14.4 606.6 593.4 547.2 7t)9.9'*
**Difference from placebo: P<0.01. References
Calvert, J. and Troscianko, T. (1992) The role of dopamine in visual attentional processes. J. Psychopharmacol. 6, 103. King, D.J. (1990) The effect of neuroleptics on cognitive and psychomotor function. Br. J. Psychiatry 157, 799 811.
P-3 Psychotic Disorders and Neuroleptics
The effects of haloperidol on visual search, eye movements and psychomotor performance
D.J. King", G. Lynch~', M.F.
M a n n i o n ~' a n d W. B y t h b
~'Queen's University Department ~[ Therapeuties and Pharmacology, Bel[ast BT9 7BL, Northern Ireland anal ~'School ~7[Psvehology, Queen's University, Be[l~lst, Northern Ireland Key words." Haloperidol; Eye movements: Visual search: Normal volunteers Human volunteer studies are important to identify the cognitive effects of antipsychotic drugs (King, 1990). Calvert and Troscianko (1992) showed that patients with Parkinson's disease (PD) had impaired parallel processing on a visual search task. The purpose of this study was to determine if single doses of haloperidol (HPL) would replicate this effect in healthy volunteers. We also looked for evidence of a dose dependent effect of HPL on eye movements, sustained attention and subjective feelings. HPL (2, 4 and 6 rag) was compared to lorazepam (L) (2.5 lng) and placebo in 15 healthy male volunteers, in a double-blind study using a balanced latin-square design. Saccadic eye movements (SEM), smooth pursuit eye movements (SPEM), digit symbol substitution test (DSST) and visual analogue ratings of subjective feelings (VARS) were measured at baseline and at 2. 4 and 6 h after drug administration. The visual search (VS) and continuous attention tasks (CAT) were assessed tit baseline and 4 h. The results were analysed by Friedman and Wilcoxon non-parametric statistics comparing differences from baseline with placebo. Single doses of HPL did not cause impairment of parallel search. L caused a significant overall increase in reaction time, but this did not depend on the number of distractors (see Table 1). L and all doses of HPL caused impairment of all saccade parameters except latency, error and acceleration/deceleration ratio, which were unaffected by any drug. The effect was maximal at 4 h. L and HPL (4 and 6 nag) impaired all measures of SPEM (position error, velocity error and saccadic intrusions). The effect of HPL on eye movements appeared to be dose dependent. The peak of the dose-response curve was at 4 mg for all measures except for saccadic intrusions where the effect peaked at 6 rag. The CAT and DSST and VARS (Alert) were all significantly impaired by L and HPL 4 and 6 rag. Clinically significant dysphoria with or without akathisia occurred in 12 volunteers (80%) after HPL 6 mg and in 9 volunteers (60%) after HPL 4 rag. We conclude that: (1) single doses of HPL did not replicate the visual search abnormalities seen in PD; (2) SEM measures were sensitive to the effects of HPL at all doses used: (3) both HPL (4 and 6 rag) and L caused SPEM abnormalities similar to those seen in chronic schizophrenia: (4) none of the above tests will qualitatively distinguish between the psychomotor effects of neuroleptic and benzodiazepine drugs: (5) the psychomotor effects of HPL appear to peak tit 4 ing.
Table l. Visual search 4 h (reaction time) (medians) No. of distractors (target absent)
Placebo HPL 2 mg HPL 4 mg HPL 6 mg L 2.5 mg
4
9
16
36
64
657.4 571.4 615.6 6(12.2 778.0**
597.8 558.2 635.2 565.9 740.6**
595.6 608.7 604.4 581.3 650.5**
602.2 626.4 637.4 585.7 839.6**
6(14.4 606.6 593.4 547.2 7t)9.9'*
**Difference from placebo: P<0.01. References
Calvert, J. and Troscianko, T. (1992) The role of dopamine in visual attentional processes. J. Psychopharmacol. 6, 103. King, D.J. (1990) The effect of neuroleptics on cognitive and psychomotor function. Br. J. Psychiatry 157, 799 811.