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Assessing memory function after single oral doses of buspirone and alprazolam in young healthy subjects
421 being greater and longer lasting with increasing doses, the highest showing a peak effect on the 2nd hour which lasted until the 4th, mostly in central regions. Brain maps of drug-induced pharmaco-EEG changes as compared to placeboinduced alterations (univariate analysis) demonstrated typical 'anxiolytie pharmaco-EEG patterns' after DZP, characterized by a decrease of total power, attenuation of alpha activity and augmentation of beta activity, as well as by an increase of the centroid and centroid deviation of the total activity. Furthermore, a decrease of the eentroid of combined delta and theta activity and an increase of the centroid of alpha activity were seen. In contrast, BUS produced an increase of theta activity with an acceleration of the centroid of the combined delta-theta activity, no modification of alpha activity but slowing down its centroid and a tendency to reduce beta activity. The centroid of the total activity was also reduced. Although both compounds have proven their ability to reduce anxiety in patients, their opposite neurophysiological profiles point to their different neurobioiogical mechanism of action after acute intake. This work has been financed with a grant (FIS 90/0432) from the Spanish Ministry of Health. aFellowship 'Severo Ochoa' awarded by Ferrer Research Foundation.
Buspirone effects in adolescent psychiatric disorders
S i m e o n , J.G. Royal Ottawa Hospital, 1145 Carling Avenuue, Ottawa, Ontario, Canada KIZ 7K4 Thirteen adolescents 12-20 years old (mean 16 years), with diagnosis of attention deficit and/or conduct disorders (n = 4), anxiety and/or depressive disorders (n ~ 5), obsessive compulsive disorders (n ~ 2), and psychosis (n = 2), received buspirone alone or in combination with other drugs in daily dosages from I0 to 40 mg (mean 25 mg) from one to four months (mean 2.5 months). These adolescents had shown poor or no clinical response to prior drug therapy. With the addition of buspirone, clinical global improvement was marked in seven cases, moderate in three, mild in two and none in one. The gratest improvement occurred in their mood (n = 9), anxiety (n ~ 6), social interaction (n ~ 6), sleep (n ~ 4), aggression (n ~ 3), concentration (n ~ 3), irritability (n = 1). These preliminary single ease trials suggest the usefulness of buspirone in the treatment of various adolescent psychiatric disorders. Further controlled trials with buspirone are recommended.
Assessing memory function after single oral doses of buspirone and alprazolam in young healthy subjects
Baygs, M.C., Barbanoj, M.J., Gea, C.G., Torrent, J., Gich, I. and Jan~, F. Clinical Pharmacology Unit, Department of Pharmacology and Psychiatry, Sant Pau Hospital, Autonomous University of Barcelona, Spain Although impairment of mnesic processes by benzodiazepines in certain type of patients would be desirable, amnesia in anxious out-patients may raise problems. The aim of the present double-blind, randomized, cross-over, placebocontrolled trial was to investigate the effects of single oral equipotent anxiolytie doses of buspirone (15 mg) and
422 alprazolam (1.5 mg) on memory function and their relation with vigilance level in 16 healthy young volunteers of both sexes.
Before and +1, +2.5 and 5 hours after drug intake, short- and long-term verbal memory (anterograde amnesia: learning phase and delayed recall and recognition) as well as objective (critical flicker-fusion frequency, simple reaction time, cancellation and fine motoric tests) and subjective (analogue, numerical and descriptive scales) assessments of vigilance level were performed. Additionally, retrograde amnesia was investigated at +2.5 and +5 hours. In order to avoid bias in terms of learning and habituation phenomena, individual training periods as well as an initial experimental day with placebo in single blind conditions were performed. Alprazolam produced a clear peak impairment of short- and long-term memory at + 1 hour, delaying storage processes and disrupting intrinsic mechanisms underlying memory, resulting in anterograde amnesia, mainly to recall but also to recognition. Conversely, buspirone could not be differentiated from placebo at any time. Aiprazolam but not buspirone or placebo induced retrograde 'promnesia'. Vigilance level remained significantly reduced after alprazolam from +1 to +2.5 hours, both objectively and subjectively, but was not affected after buspirone. These results further support the possibility of separating the ancillary cluster effects of anxiolytic drug therapy, making the attainment of an "anxioselective' alternative feasible.
The selectivity of anterograde amnesia caused by single doses of ethanol, lorazepam, and scopolamine in young volunteers
Satzger, W. and Engel, R.R. Psychiatric Hospital, University of Munich, Nussbaumstr. 7, 8000 Munich 2, F.R.G. Drags that modulate the memory system in a specific way are of practical and theoretical interest. Several strategies have been proposed to distinguish more general drag-induced sedation or attention effects from 'pure' memory effects: determining changes for memory and for attention by separate measures, including measures of attention as covariate in anova analysis for memory measures or manipulating the time-delay in visual decision tasks (matching-to-sample paradigm). These strategies were compared for ethanol, Iorazepam and scopolamine using the same memory and attention measures in each drag group. 36 volunteers (mean age 24 years) were divided in three parallel groups. The design for each study group was double-blind, radomised and cross-over. In the first group 0.4 and 0.8 g/kg ethanol p.o., in the second group 1 and 2 mg lorazepam p.o., and in the third group 0.3 and 0.6 mg scopolamine s.c. were given. Additionally subjects received two placebo conditions in each of the three groups. Simultaneous vs. delayed visual matching-to-sample tasks (Satzger et al, 1990) were used to separate attention and episodic memory components. Three continuous recognition memory tests, free recall of word-lists, a continuous performance test (CPT) and an observer rating of vigilance (ORV) were further performed as separate measures for memory and attention. Free recall was measured four times (3 min prae drug and 82, 137 and 213 min post drug), all other tests were measured twice (block I: 90-159 min post drug; block II: 179-223 min post drug). While ethanol had no effect on simultaneous or delayed matching-to-sample tasks, Iorazepam impaired during block I(Ft3,24~=5.26, p=.006) and scopolamine during block II(F(3,24)=5.16, p=.007) selectively the delayed matching-to-sample performance. Thus, the result of a selective memory impairment in matching-to-sample tasks shown for lorazepam in an earlier study could be replicated (Satzger et al, 1990). Another indicator for a selective memory impairment, an enhancement of recall for words learned before the drug (e.g. Curran et al, 1987), was found for lorazepam only (F(3,24)-3.70, p*.026). The memory impairment caused by scopolamine could still be demonstrated, when CPT or ORV were included as covariates in anova analyses. In general, drug effects on memory tests were only short-time lasting and weak for ethanol, more pronounced for Iorazepam and obvious for scopolamine. Results indicate a selective anterograde amnesia for scopolamine and lorazepam, bot not for ethanol.
Buspirone effects in adolescent psychiatric disorders
S i m e o n , J.G. Royal Ottawa Hospital, 1145 Carling Avenuue, Ottawa, Ontario, Canada KIZ 7K4 Thirteen adolescents 12-20 years old (mean 16 years), with diagnosis of attention deficit and/or conduct disorders (n = 4), anxiety and/or depressive disorders (n ~ 5), obsessive compulsive disorders (n ~ 2), and psychosis (n = 2), received buspirone alone or in combination with other drugs in daily dosages from I0 to 40 mg (mean 25 mg) from one to four months (mean 2.5 months). These adolescents had shown poor or no clinical response to prior drug therapy. With the addition of buspirone, clinical global improvement was marked in seven cases, moderate in three, mild in two and none in one. The gratest improvement occurred in their mood (n = 9), anxiety (n ~ 6), social interaction (n ~ 6), sleep (n ~ 4), aggression (n ~ 3), concentration (n ~ 3), irritability (n = 1). These preliminary single ease trials suggest the usefulness of buspirone in the treatment of various adolescent psychiatric disorders. Further controlled trials with buspirone are recommended.
Assessing memory function after single oral doses of buspirone and alprazolam in young healthy subjects
Baygs, M.C., Barbanoj, M.J., Gea, C.G., Torrent, J., Gich, I. and Jan~, F. Clinical Pharmacology Unit, Department of Pharmacology and Psychiatry, Sant Pau Hospital, Autonomous University of Barcelona, Spain Although impairment of mnesic processes by benzodiazepines in certain type of patients would be desirable, amnesia in anxious out-patients may raise problems. The aim of the present double-blind, randomized, cross-over, placebocontrolled trial was to investigate the effects of single oral equipotent anxiolytie doses of buspirone (15 mg) and
422 alprazolam (1.5 mg) on memory function and their relation with vigilance level in 16 healthy young volunteers of both sexes.
Before and +1, +2.5 and 5 hours after drug intake, short- and long-term verbal memory (anterograde amnesia: learning phase and delayed recall and recognition) as well as objective (critical flicker-fusion frequency, simple reaction time, cancellation and fine motoric tests) and subjective (analogue, numerical and descriptive scales) assessments of vigilance level were performed. Additionally, retrograde amnesia was investigated at +2.5 and +5 hours. In order to avoid bias in terms of learning and habituation phenomena, individual training periods as well as an initial experimental day with placebo in single blind conditions were performed. Alprazolam produced a clear peak impairment of short- and long-term memory at + 1 hour, delaying storage processes and disrupting intrinsic mechanisms underlying memory, resulting in anterograde amnesia, mainly to recall but also to recognition. Conversely, buspirone could not be differentiated from placebo at any time. Aiprazolam but not buspirone or placebo induced retrograde 'promnesia'. Vigilance level remained significantly reduced after alprazolam from +1 to +2.5 hours, both objectively and subjectively, but was not affected after buspirone. These results further support the possibility of separating the ancillary cluster effects of anxiolytic drug therapy, making the attainment of an "anxioselective' alternative feasible.
The selectivity of anterograde amnesia caused by single doses of ethanol, lorazepam, and scopolamine in young volunteers
Satzger, W. and Engel, R.R. Psychiatric Hospital, University of Munich, Nussbaumstr. 7, 8000 Munich 2, F.R.G. Drags that modulate the memory system in a specific way are of practical and theoretical interest. Several strategies have been proposed to distinguish more general drag-induced sedation or attention effects from 'pure' memory effects: determining changes for memory and for attention by separate measures, including measures of attention as covariate in anova analysis for memory measures or manipulating the time-delay in visual decision tasks (matching-to-sample paradigm). These strategies were compared for ethanol, Iorazepam and scopolamine using the same memory and attention measures in each drag group. 36 volunteers (mean age 24 years) were divided in three parallel groups. The design for each study group was double-blind, radomised and cross-over. In the first group 0.4 and 0.8 g/kg ethanol p.o., in the second group 1 and 2 mg lorazepam p.o., and in the third group 0.3 and 0.6 mg scopolamine s.c. were given. Additionally subjects received two placebo conditions in each of the three groups. Simultaneous vs. delayed visual matching-to-sample tasks (Satzger et al, 1990) were used to separate attention and episodic memory components. Three continuous recognition memory tests, free recall of word-lists, a continuous performance test (CPT) and an observer rating of vigilance (ORV) were further performed as separate measures for memory and attention. Free recall was measured four times (3 min prae drug and 82, 137 and 213 min post drug), all other tests were measured twice (block I: 90-159 min post drug; block II: 179-223 min post drug). While ethanol had no effect on simultaneous or delayed matching-to-sample tasks, Iorazepam impaired during block I(Ft3,24~=5.26, p=.006) and scopolamine during block II(F(3,24)=5.16, p=.007) selectively the delayed matching-to-sample performance. Thus, the result of a selective memory impairment in matching-to-sample tasks shown for lorazepam in an earlier study could be replicated (Satzger et al, 1990). Another indicator for a selective memory impairment, an enhancement of recall for words learned before the drug (e.g. Curran et al, 1987), was found for lorazepam only (F(3,24)-3.70, p*.026). The memory impairment caused by scopolamine could still be demonstrated, when CPT or ORV were included as covariates in anova analyses. In general, drug effects on memory tests were only short-time lasting and weak for ethanol, more pronounced for Iorazepam and obvious for scopolamine. Results indicate a selective anterograde amnesia for scopolamine and lorazepam, bot not for ethanol.