Antidepressants, alcohol and psychornotor perf omance n
Tiller JWG. Antidepressants, alcohol and psychomotor performance. Acta Psychiatr Scand 1990: Suppl 360: 13-17. The acute psychomotor effects of moclobemide, a reversible inhibitor of MAO-A antidepressant (100 and 300 mg) compared with amitriptyline (25 and 75 mg) showed that moclobemide caused no significant impairment in contrast with amitriptyline, which caused significant impairment at both doses. Two other studies are reviewed. One study reported the acute effects of moclobemide (100 and 300 mg), trazodone (100 mg), placebo, and alcohol (0.5 g/kg) or placebo in an elderly group: moclobemide caused little impairment or alcohol potentiation and may reverse some alcohol impairment, whereas trazodone caused substantial impairment and alcohol potentiation. Another study of the acute and chronic effects of moclobemide (200 mg 3 times daily) or clomipramine (25 mg twice daily) and their interactions with alcohol (blood alcohol concentration 0.6 g/l) showed that alcohol caused significant impairment, whereas clomipramine tended to enhance and moclobemide to reduce some impairment. Moclobemide appears to be an antidepressant with few psychomotor effects and minimal alcohol potentiation and may reduce some alcohol I impairment.
Many antidepressants, such as the tricyclic antidepressants amitriptyline and clomipramine, and atypical antidepressants such as trazodone, impair psychomotor performance, particularly in elderly people (1-5). Consequently, patients need to be warned of the risks, including those of handling machinery and driving. Moclobemide is a benzamide reversible inhibitor of monoamine oxidase A (RIMA) antidepressant. In preclinical and clinical studies, including studies at the University of Melbourne, in atypical depression and in depression in elderly people, moclobemide has not shown a significant sedative effect (6, 7). Patients taking antidepressants might also take alcohol. Sedative drugs tend to enhance the effect of alcohol, with the prospect of alcohol potentiating the sedative effects and psychomotor impairment caused by antidepressants. These sedative effects especially occur when treatment is initiated, although they may persist with chronic use. This article reports one study (study 1) by the author on the acute psychomotor effects of moclobemide (100 and 300 mg) compared with those of amitriptyline (25 and 75 mg). Two other studies are reviewed. Study 2 (8) reports the acute effects of moclobemide (100 and 300 mg), trazodone (100 mg) and alcohol (0.5 g/kg) or placebo in an elderly group. Study 3 (9) reports the acute and chronic effects of moclobemide (200 mg 3 times daily) or
J. W. 6. tiller University of Melbourne, Melbourne, Australia
Key words: moclobemide; trazodone; clomipramine; alcohol; psychomotor Dr. J. VI! G. Tiller, Associate Professor, Department of Psychiatry, University of Melbourne, 7th Floor, Clinical Sciences Building, Royal Melbourne Hospital, Parkville,Victoria, 3050 Australia
clomipramine (25 mg twice daily) and their interactions with alcohol to a blood alcohol concentration (BAC) of 0.6 g/l. These comparisons are between drugs of 3 classes with differing chemical structures. All 3 studies were conducted according to the provisions of the Declaration of Helsinki and Tokyo as amended in Venice 1983, and received the approval of the appropriate institutional ethics committees. The Australian study was also performed in accordance with the National Health and Medical Research Council guidelines for human experimentation. Study 1: acute psychomotor effects of moclobemide vs amitriptyline Material and methods
Moclobemide (100 and 300 mg), amitriptyline (25 and 75 mg) and placebo were administered, in turn, on a weekly basis to 5 male and 5 female, healthy, drug-free tertiary students, using a double-blind, balanced, crossover, latin-square design. Each subject was assessed, trained at the psychomotor tasks, and attended, once a week, or no more frequently than 3 days apart for a total of 5 test days, receiving one of the test drugs or placebo on each occasion. The order of presentation of the first drug was 13
randomized, as was the order of administration of tests. A stepwise regression analysis was performed, eliminating covariates that were not significant, relating each outcome to the particular treatments. A power analysis was also effected. Because of the number of statistical tests carried out, there is a chance that some of the P values less than 0.05 will be false positives. Thus, in this report, only results for which P is less than or near 0.01 are reported. The psychomotor tests were assessments of critical flicker fusion frequency and choice reaction time, assessing both liftoff time and total response time with a Leeds Psychomotor Tester, a complex choice reaction time task, digit symbol copying assessments, time estimation, Maddox wing, and lateral gaze nystagmus assessments (10). The test schedule on each test day was for the subject to attend the laboratory, have a urine sample taken for a benzodiazepine screen, have baseline psychomotor testing, receive the test medicine or placebo, and have repeat psychomotor tests 2 h and 6 h after ingesting the medication. Five male and 5 female students participated. Their mean age was 25 years (range 20-32), mean height 171 cm (range 153-188) and mean weight 68 kg (range 45-79). All were benzodiazepine-free.
Results
For the individual drugs there was no significant difference between the weeks of the study on which the medicine was administered, nor were there any statistically significant differences between subjects. No differences emerged between the effects of moclobemide at either dose and placebo, nor were there significant differences from baseline. Because there was no effect for any test for moclobemide, power calculations were carried out using alpha = 0.05, beta=0.2 (giving a power of 80%) and n= 10 (the number of subjects). For this study it should have been possible to detect differences in effects approximately equal to the standard deviation of the errors with 80% power. The power of the study thus appears to be adequate. The results following amitriptyline (25 mg) showed significant, acute impairment for the 10 subjects, compared with placebo after 2 h in complex choice reaction time (difference= 0.1 1 s, P
Tiller JWG. Antidepressants, alcohol and psychomotor performance. Acta Psychiatr Scand 1990: Suppl 360: 13-17. The acute psychomotor effects of moclobemide, a reversible inhibitor of MAO-A antidepressant (100 and 300 mg) compared with amitriptyline (25 and 75 mg) showed that moclobemide caused no significant impairment in contrast with amitriptyline, which caused significant impairment at both doses. Two other studies are reviewed. One study reported the acute effects of moclobemide (100 and 300 mg), trazodone (100 mg), placebo, and alcohol (0.5 g/kg) or placebo in an elderly group: moclobemide caused little impairment or alcohol potentiation and may reverse some alcohol impairment, whereas trazodone caused substantial impairment and alcohol potentiation. Another study of the acute and chronic effects of moclobemide (200 mg 3 times daily) or clomipramine (25 mg twice daily) and their interactions with alcohol (blood alcohol concentration 0.6 g/l) showed that alcohol caused significant impairment, whereas clomipramine tended to enhance and moclobemide to reduce some impairment. Moclobemide appears to be an antidepressant with few psychomotor effects and minimal alcohol potentiation and may reduce some alcohol I impairment.
Many antidepressants, such as the tricyclic antidepressants amitriptyline and clomipramine, and atypical antidepressants such as trazodone, impair psychomotor performance, particularly in elderly people (1-5). Consequently, patients need to be warned of the risks, including those of handling machinery and driving. Moclobemide is a benzamide reversible inhibitor of monoamine oxidase A (RIMA) antidepressant. In preclinical and clinical studies, including studies at the University of Melbourne, in atypical depression and in depression in elderly people, moclobemide has not shown a significant sedative effect (6, 7). Patients taking antidepressants might also take alcohol. Sedative drugs tend to enhance the effect of alcohol, with the prospect of alcohol potentiating the sedative effects and psychomotor impairment caused by antidepressants. These sedative effects especially occur when treatment is initiated, although they may persist with chronic use. This article reports one study (study 1) by the author on the acute psychomotor effects of moclobemide (100 and 300 mg) compared with those of amitriptyline (25 and 75 mg). Two other studies are reviewed. Study 2 (8) reports the acute effects of moclobemide (100 and 300 mg), trazodone (100 mg) and alcohol (0.5 g/kg) or placebo in an elderly group. Study 3 (9) reports the acute and chronic effects of moclobemide (200 mg 3 times daily) or
J. W. 6. tiller University of Melbourne, Melbourne, Australia
Key words: moclobemide; trazodone; clomipramine; alcohol; psychomotor Dr. J. VI! G. Tiller, Associate Professor, Department of Psychiatry, University of Melbourne, 7th Floor, Clinical Sciences Building, Royal Melbourne Hospital, Parkville,Victoria, 3050 Australia
clomipramine (25 mg twice daily) and their interactions with alcohol to a blood alcohol concentration (BAC) of 0.6 g/l. These comparisons are between drugs of 3 classes with differing chemical structures. All 3 studies were conducted according to the provisions of the Declaration of Helsinki and Tokyo as amended in Venice 1983, and received the approval of the appropriate institutional ethics committees. The Australian study was also performed in accordance with the National Health and Medical Research Council guidelines for human experimentation. Study 1: acute psychomotor effects of moclobemide vs amitriptyline Material and methods
Moclobemide (100 and 300 mg), amitriptyline (25 and 75 mg) and placebo were administered, in turn, on a weekly basis to 5 male and 5 female, healthy, drug-free tertiary students, using a double-blind, balanced, crossover, latin-square design. Each subject was assessed, trained at the psychomotor tasks, and attended, once a week, or no more frequently than 3 days apart for a total of 5 test days, receiving one of the test drugs or placebo on each occasion. The order of presentation of the first drug was 13
randomized, as was the order of administration of tests. A stepwise regression analysis was performed, eliminating covariates that were not significant, relating each outcome to the particular treatments. A power analysis was also effected. Because of the number of statistical tests carried out, there is a chance that some of the P values less than 0.05 will be false positives. Thus, in this report, only results for which P is less than or near 0.01 are reported. The psychomotor tests were assessments of critical flicker fusion frequency and choice reaction time, assessing both liftoff time and total response time with a Leeds Psychomotor Tester, a complex choice reaction time task, digit symbol copying assessments, time estimation, Maddox wing, and lateral gaze nystagmus assessments (10). The test schedule on each test day was for the subject to attend the laboratory, have a urine sample taken for a benzodiazepine screen, have baseline psychomotor testing, receive the test medicine or placebo, and have repeat psychomotor tests 2 h and 6 h after ingesting the medication. Five male and 5 female students participated. Their mean age was 25 years (range 20-32), mean height 171 cm (range 153-188) and mean weight 68 kg (range 45-79). All were benzodiazepine-free.
Results
For the individual drugs there was no significant difference between the weeks of the study on which the medicine was administered, nor were there any statistically significant differences between subjects. No differences emerged between the effects of moclobemide at either dose and placebo, nor were there significant differences from baseline. Because there was no effect for any test for moclobemide, power calculations were carried out using alpha = 0.05, beta=0.2 (giving a power of 80%) and n= 10 (the number of subjects). For this study it should have been possible to detect differences in effects approximately equal to the standard deviation of the errors with 80% power. The power of the study thus appears to be adequate. The results following amitriptyline (25 mg) showed significant, acute impairment for the 10 subjects, compared with placebo after 2 h in complex choice reaction time (difference= 0.1 1 s, P
