A COMPARATIVE-STUDY OF ACUTE AND SUBCHRONIC EFFECTS OF DOTHIEPIN, FLUOXETINE AND PLACEBO ON PSYCHOMOTOR AND ACTUAL DRIVING PERFORMANCE

1 The acute and subchronic effects of dothiepin 75-150 mg and fluoxeti ne 20 mg on critical fusion frequency (CFF), sustained attention and a ctual driving performance were compared with those of placebo in a dou ble-blind, cross-over study involving 18 healthy volunteers. Drugs and placebo were administered for 22 days in evening doses. Fluoxetine do ses were constant but dothiepin doses increased on the evening of day 8. Performance was assessed on days 1, 8 and 22 of each treatment seri es. Subjective sleep parameters and possible side effects were recorde d on visual analogue scales on alternate treatment days. 2 Dothiepin r educed sustained attention on day 1 by 6.7% (95% confidence interval ( Cl): -12.0 to -1.3%) and CFF on day 22 by 1.1 (CI: -2.2 to -0.1) Hz. F luoxetine reduced sustained attention days 1, 8 and 22 of treatment by 7.4, 6.7 and 6.5% respectively (CI: -11.3 to -3.6; -14.3 to -1.5 and -9.5 to -3.4). CFF decreased linearly over days during fluoxetine trea tment and significantly differed from placebo on day 22 with 1.2 Hz (C I: -2.3 to -0.2). Neither drug significantly affected driving performa nce. Whilst receiving dothiepin, subjects complained of drowsiness on days 1-3 of treatment (mean rank 5.6; CI: 2.0 to 9.2) and slept 43 min longer (CI: 8.2 to 76.2). After receiving fluoxetine, they reported d izziness (mean rank 2.8; CI: 0.1 to 5.5), shakiness (mean rank 1.9 and 4.2; CI: 0.5 to 3.3 and 1.5 to 6.9), nausea (mean rank 3.5 and 4.1; C I: 0.1 to 6.9 and 0.9 to 7.4) and concentration problems (mean rank 2. 4; CI: 0.4-4.9) in the second or third week of treatment. Spontaneousl y reported adverse events resembled the side effects recorded on visua l analogue scales but differed less between drug treatments. 3 It is c oncluded that both drugs possess similar but apparently small potentia ls for impairing performance.