Effects of antipsychotic drugs on memory functions of schizophrenic patients Eitan N, Levin Y, Ben-Artzi E, Levy A, Neumann M. Effects of antipsychotic drugs on memory functions of schizophrenic patients Acta Psychiatr Scand 1992: 85: 74-76.
I
In this research we investigated the effects of 4 antipsychotic drugs with different anticholinergic components on different memory functions of schizophrenic patients. Drugs were administrated in cumulative doses and memory was tested 90 min after each drug was administered. The results show that chlorpromazine and thioridazine impaired short-term verbal memory after 6 h of sequential administration. Trifluoperazine and haloperidol improved short-term verbal memory from the third to the fifth administration. Immediate memory, long-term memory and visual short-term memory were not impaired by any drug.
Since the late 1950s, evidence has indicated that antipsychotic drugs impair various memory and cognitive functions (1-3). Chlorpromazine, for example, was found to impair immediate memory in schizophrenic patients (4). Yet, other studies have not found phenothiazines to impair immediate memory in schizophrenic patients ( 5 , 6). Recent studies raise the possibility that memory impairment following antipsychotic treatment is partially caused by anticholinergic effects of antipsychotic drugs. It was found (7-11) that anticholinergic drugs used in the treatment of various parkinsonian side effects of antipsychotic drugs impair short- and long-term memory functions but not immediate memory. Moreover, Calev (3) reports that the addition of anticholinergic drugs to antipsychotic ones in schizophrenic patients caused an impairment of recall functions. The purpose of this study was to further investigate the effect of anticholinergic components of antipsychotic drugs on memory functions. In this study we investigated the effect on memory of different antipsychotic drugs, each representing a different class of antipsychotic drugs differing in their anticholinergic effect. The drugs were administrated several times to investigate the role of cumulative doses on memory functions. Material and methods Subjects and design
The subjects were 50 patients hospitalized in Shalvata Mental Health Center who consented to participate in the study. The sample consisted of 25 men 14
N. Eitan’, Y. Levin’,
E. Ben-Artzi‘, A. Levy M. Neumann
’
’,
’
Shalvatah Mental Health Center, Hod-Hasharon, Department of Psychology, Bar-llan University, Ramat-Gan, Israel
Key words: antipsychotic drug; memory; schizophrenia
Yosef Levin, D/Head Department A, Shalvatah Mental Health Center, P.O. B 94, Hod-Hasharon, 45 100 Israel Accepted for publication August 16, 199 1
and 25 women aged 19-46 years. All subjects met the DSM-111-R criteria for schizophrenia and were in a stable subacute phase of their illness as judged by the Brief Psychiatric Rating Scale (BPRS). Subjects were all in a good physical state, and had no history of central nervous system diseases, alcohol or drug abuse and intact kidney and liver functions. Subjects were assigned to 5 groups, 4 drugs and 1 placebo, and were tested using a battery of 5 cognitive tests. Groups did not differ in age, sex distribution and number of previous hospitalizations. Drugs
Four drugs were tested, each representing a different pharmacological group. The doses were adjusted according to the drugs’ relative potencies: chlorpromazine: 100 mg x 4; trioridazine: 100 mg x 4; trifluoperazine: 5 mg x 4; and haloperidol: 2 mg x 4. The placebo was sodium bicarbonate. Cognitive functioning tests
Cognitive functioning tests were administrated as previously reported (14) and included orientation: place, date, date of birth, country of birth and the name of the hospital and of the treating physician., Digit repetition. Pictures recall test: a set of 12 pictures of daily occurrences presented to the subjects simultaneously, after which they were withdrawn and the subjects were requested to describe them. Story repetition: recall of a story consisting of 20 sentences, and categorization: the subjects’ task was to
Antipsychotic drugs and memory
list as many objects as they could belonging to each of 5 categories (fruits, for example) within 30 s. For all tests, except for orientation, 5 different versions were used, each for a different time point. The different versions were the same used in a previous study (7). The similarity between stories was judged by 7 judges, all of whom speak Hebrew fluently. The judges ranked on a - 3 to + 3 scale (from completely different to completely the same) the perceived similarity between the stories for 7 categories: emotionality, understanding, difficulty, length, frequency of unusual and rare words, grammar and fluency. The mean scores between judges ranged between 2.28 and 3.00 for the different categories, indicating high similarity between stories. The choice of these tests was based on the conception according to which digit span reflects immediate memory, story test reflects short-term verbal memory, pictures test reflects short-term visual memory, and categorization as reflecting long-term semantic memory. Procedure
Subjects were drug-free for 48 h before the test day and were given only oxazepam (half-life 6-8 h) up to 80 mg. Oxazepam was discontinued 12 h before the onset of the study. During the test day, drugs and placebo were administrated 4 times with a 90-min interval in between. The cognitive functioning test battery was administered before drug or placebo administration and 90 min after the last one. Cognitive functioning tests, therefore, examined the pre-drug level and the cumulative effects on memory of 1-4 doses of drug. The study was cross-over doubleblind and all drugs and placebo were administered orally. Fig. 1 show the general design of the research. Variables
Since no norms exist, the main dependent variables were as follows: (a) 1-3 points for each category of orientation correctly remembered; (b) number of maximum digits recalled x 2 0 minus 2 points for each mistake; (c)number of pictures recalled: 2
1st dose
2nd dose
3rd dose
T1
T - time of testing.
Fig. I. General design
T2
T3
Statistics
Two-way analysis of variance (ANOVA) with one factor, time of testing (as measure by t l to t5) repeated, was applied to scores obtained in the different tests to examine possible effects of drug type and time of testing on cognitive functions. Results
Overall, for all tests, except for the story test, the main effects of drug type and time of testing were not significant. Interaction between drug type and time of testing were also not significant. The scores of story tests are shown in Table 1. Two-way ANOVA applied for the story scores revealed a group main effect for time of testing (F(4.225) = 2.48, P < 0.05), and an interaction between drugs and time of testing (F(16.225)= 1.89, P
I
In this research we investigated the effects of 4 antipsychotic drugs with different anticholinergic components on different memory functions of schizophrenic patients. Drugs were administrated in cumulative doses and memory was tested 90 min after each drug was administered. The results show that chlorpromazine and thioridazine impaired short-term verbal memory after 6 h of sequential administration. Trifluoperazine and haloperidol improved short-term verbal memory from the third to the fifth administration. Immediate memory, long-term memory and visual short-term memory were not impaired by any drug.
Since the late 1950s, evidence has indicated that antipsychotic drugs impair various memory and cognitive functions (1-3). Chlorpromazine, for example, was found to impair immediate memory in schizophrenic patients (4). Yet, other studies have not found phenothiazines to impair immediate memory in schizophrenic patients ( 5 , 6). Recent studies raise the possibility that memory impairment following antipsychotic treatment is partially caused by anticholinergic effects of antipsychotic drugs. It was found (7-11) that anticholinergic drugs used in the treatment of various parkinsonian side effects of antipsychotic drugs impair short- and long-term memory functions but not immediate memory. Moreover, Calev (3) reports that the addition of anticholinergic drugs to antipsychotic ones in schizophrenic patients caused an impairment of recall functions. The purpose of this study was to further investigate the effect of anticholinergic components of antipsychotic drugs on memory functions. In this study we investigated the effect on memory of different antipsychotic drugs, each representing a different class of antipsychotic drugs differing in their anticholinergic effect. The drugs were administrated several times to investigate the role of cumulative doses on memory functions. Material and methods Subjects and design
The subjects were 50 patients hospitalized in Shalvata Mental Health Center who consented to participate in the study. The sample consisted of 25 men 14
N. Eitan’, Y. Levin’,
E. Ben-Artzi‘, A. Levy M. Neumann
’
’,
’
Shalvatah Mental Health Center, Hod-Hasharon, Department of Psychology, Bar-llan University, Ramat-Gan, Israel
Key words: antipsychotic drug; memory; schizophrenia
Yosef Levin, D/Head Department A, Shalvatah Mental Health Center, P.O. B 94, Hod-Hasharon, 45 100 Israel Accepted for publication August 16, 199 1
and 25 women aged 19-46 years. All subjects met the DSM-111-R criteria for schizophrenia and were in a stable subacute phase of their illness as judged by the Brief Psychiatric Rating Scale (BPRS). Subjects were all in a good physical state, and had no history of central nervous system diseases, alcohol or drug abuse and intact kidney and liver functions. Subjects were assigned to 5 groups, 4 drugs and 1 placebo, and were tested using a battery of 5 cognitive tests. Groups did not differ in age, sex distribution and number of previous hospitalizations. Drugs
Four drugs were tested, each representing a different pharmacological group. The doses were adjusted according to the drugs’ relative potencies: chlorpromazine: 100 mg x 4; trioridazine: 100 mg x 4; trifluoperazine: 5 mg x 4; and haloperidol: 2 mg x 4. The placebo was sodium bicarbonate. Cognitive functioning tests
Cognitive functioning tests were administrated as previously reported (14) and included orientation: place, date, date of birth, country of birth and the name of the hospital and of the treating physician., Digit repetition. Pictures recall test: a set of 12 pictures of daily occurrences presented to the subjects simultaneously, after which they were withdrawn and the subjects were requested to describe them. Story repetition: recall of a story consisting of 20 sentences, and categorization: the subjects’ task was to
Antipsychotic drugs and memory
list as many objects as they could belonging to each of 5 categories (fruits, for example) within 30 s. For all tests, except for orientation, 5 different versions were used, each for a different time point. The different versions were the same used in a previous study (7). The similarity between stories was judged by 7 judges, all of whom speak Hebrew fluently. The judges ranked on a - 3 to + 3 scale (from completely different to completely the same) the perceived similarity between the stories for 7 categories: emotionality, understanding, difficulty, length, frequency of unusual and rare words, grammar and fluency. The mean scores between judges ranged between 2.28 and 3.00 for the different categories, indicating high similarity between stories. The choice of these tests was based on the conception according to which digit span reflects immediate memory, story test reflects short-term verbal memory, pictures test reflects short-term visual memory, and categorization as reflecting long-term semantic memory. Procedure
Subjects were drug-free for 48 h before the test day and were given only oxazepam (half-life 6-8 h) up to 80 mg. Oxazepam was discontinued 12 h before the onset of the study. During the test day, drugs and placebo were administrated 4 times with a 90-min interval in between. The cognitive functioning test battery was administered before drug or placebo administration and 90 min after the last one. Cognitive functioning tests, therefore, examined the pre-drug level and the cumulative effects on memory of 1-4 doses of drug. The study was cross-over doubleblind and all drugs and placebo were administered orally. Fig. 1 show the general design of the research. Variables
Since no norms exist, the main dependent variables were as follows: (a) 1-3 points for each category of orientation correctly remembered; (b) number of maximum digits recalled x 2 0 minus 2 points for each mistake; (c)number of pictures recalled: 2
1st dose
2nd dose
3rd dose
T1
T - time of testing.
Fig. I. General design
T2
T3
Statistics
Two-way analysis of variance (ANOVA) with one factor, time of testing (as measure by t l to t5) repeated, was applied to scores obtained in the different tests to examine possible effects of drug type and time of testing on cognitive functions. Results
Overall, for all tests, except for the story test, the main effects of drug type and time of testing were not significant. Interaction between drug type and time of testing were also not significant. The scores of story tests are shown in Table 1. Two-way ANOVA applied for the story scores revealed a group main effect for time of testing (F(4.225) = 2.48, P < 0.05), and an interaction between drugs and time of testing (F(16.225)= 1.89, P
