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THE MANAGEMENT OF PSYCHOGERIATRIC PATIENT
Arch. Gerontol. Geriatr. Suppl. 9 (2004) 465–470 0167-4943/$ – see front matter # 2004 Elsevier Ireland Ltd. All rights reserved
THE MANAGEMENT OF PSYCHOGERIATRIC PATIENT
G. ZANNINO, A. GARGIULO*, F. LAMENZA, M.G. MAROTTA, T. BARZOTTI, A. SILVESTRI, E. ETTORRE and V. MARIGLIANO
Department of Aging Science, Policlinico Umberto I, University "La Sapienza", Viale de Policlinico, 155, I-00161 Rome, Italy *Corresponding author at address: Via P.A. Micheli, 90, I-00197 Roma, Italy Tel.: +(39-348)-0447-724; Fax: +(39-06)-445-6316; E-mail: [email protected]
SUMMARY The exponential growth in the prevalence of cognitive impairment of old patients leads the physicians to deal with a larger incidence of behavioral disorders (such as excitement, aggressiveness), and psychotic symptoms (such as delirium and visual hallucinations). The presence of psychotic troubles in dementia causes a remarkable distress to caregivers and involves higher difficulties in the patient management. The estimates of such troubles range between 15 and 75 %. Geriatric assessment and the management of behavioral troubles require a prompt evaluation of all their possible causes. As a matter of fact, their appea rance often reveals a physical disturbance (pain, fever, etc.), or adverse environmental conditions, or it could also be a consequence of a multiple drug therapy. For this reason, the use of antipsychotics should always be preceded by an accurate clinical diagnosis. Anxiolytic, anti-depressive, anti-convulsive and anti-psychotic drugs are among the therapeutic strategies for the management of the psychogeriatric patient. Atypical antipsychotics seem to be able to decrease the psychotic symptoms, with low levels of therapeutic failure. They also reduce extrapyramidal effects and the growth of prolactine hormone, which is quite useful when dealing with very old patients. Risperidone and olanzapine are two atypical anti-psychotics, which already proved to be adequate and well tolerated during the treatment of schizophrenia and of acute maniacal disorders. Our experience, with a population of patients followed by our Alzheimer Evaluation Unit (AEU), confirms that a low dose of olanzapine (5mg/day) and risperidone (0.5-1.0 mg/day) are effective in lowering behavioral disturbances, and psychotic symptoms due to dementia. Even in the long run, low doses of these drugs are still well tolerated. Higher levels of risperidone (>1 mg/die) often caused extra-pyramidal symptoms such as rigidity and dyskinesia, whereas higher levels of olanzapine (> 5 mg/day) lead to an exceeding sedation. The management of behavioral disturbances is one of the most important goals in the global treatment of patients affected by dementia, to the extent of improving the quality of life. Atypical antipsychotics are preferable compared to old-generation drugs, therefore, they are the key therapeutic strategy we cannot renounce. Keywords: behavioral psychiatric symptoms of dementia (BPSD), atypical antipsychotics, olanzapine. risperidone
466
INTRODUCTION The management of behavioral disturbance appearing with dementia (behavioral psychiatric symptoms of dementia: BPSD) evaluated with the neuropsychiatric inventory (NPI) (Cummings, 1997) is performed in several ways. First of all, it is essential to make a careful evaluation of the determining factors. Frequently their appearance could denote an organic illness (pain, constipation, retention of urine, hunger, thirst, fever) or environmental disturbance. The patient who will not adapt to new situations (e.g., home change) or cannot catch different complexities of the surrounding reality (too much lights or too strong sounds), could express his/her difficulty and dysadaptation with an incongruous action (a fit of anxiety, aggressiveness). Even conditions of polyphannacotherapy, very common in old patient with dementia, could cause psychotic disturbances. In presence of visual or auditory hallucinations it should be considered, whether there is an uncorrected sensorial deficit. The pharmacological treatment of psychiatric disorders is based on the use of neuroleptic drugs: even if sometimes it could be useful to use other classes of drugs like antide pressants, anticonvulsants or beta blockers (Shneider, 1999). Not all of the psychiatric disorders are susceptible to pharmacological treatment (repetitive behavior and wandering); in those cases it is possible to control the determining factors, or to manage the situation, in order to reduce the risk factors for the patient. Considering the changes the organism goes through with aging, and the alterations in the pharmacokinetics and pharmacodynamics, it is necessary to adopt for the elderly patient lower dosages, starting from a minimum dose and increasing slowly (“start low, go slow”), till the achievement of the desired result, in order to avoid as much as possible of side effects. Up to now, neuroleptic drugs are the most common used drugs for behavioral distur bances. They are divided in two classes: typical and atypical, distinguishing them by the special action on the dopaminergic receptor. Both of them stoop D2 receptors, even though by different mechanisms on the central nervous system. In particular, atypical neuroleptics have less specificity for D2 receptor on the nigrostriatal and tubero-infundibular systems, and better affinity for receptors of mesolimbic and mesocortical systems, and for serotonin ergic receptors 5HT2A (Brunello and Racagni, 1997). The pharmacodynamic characteris tics of these drugs should determine, in clinical practice, a reduced induction of neurological side effects, mainly extrapyramidal disorders, and late dyskinesia, when compared to the typical neuroleptic drugs. Objective of this study is to verify within our ambulatory experience, the efficacy and safety of atypical antipsychotics, with particular attention to risperidone and olanzapine in
467
the control of behavioral disturbances, trying to identify the target dose able to conciliate the needs of maximum efficacy with less side effects. PATIENTS AND METHODS We selected, in the period from January and to June 2002, 46 patients affected by Alzheimer disease (AD), followed in our ambulatory Alzheimer Evaluation Unit (AEU) at the Department of Aging Science of University of Rome “La Sapienza”. AD diagnosis was made following the NINCDS-ADRDA criteria (McKhann et al., 1984). The other types of dementia, e.g., the mixed one (vascular -degenerative), were excluded, and so were all the clinical cases of AD associated with any heavy chronic illness, or history of psychiatric disorders, like schizophrenia, bipolar disorders or major depression, and all the other neurological diseases different from AD, which could contribute to the onset of dementia or psychosis. To be included in the study, patients had to have at the initial screening, a score > 3 for each item of NPI (Cummings, 1997) forming the basic core of behavioral disturbance in AD patients: agitation, aggressiveness, hallucinations and delusions (NPI-core). We obtained a sample of 14 males and 32 females affected by AD associated with BPSD, with an average age of 75.4 ± 6.9 (range 59-90) years. Each person underwent a complete evaluation of the 3 symptomatic areas characterizing AD: cognitive, functional and psychi -atric -behavioral ones. Cognitive function was investigated with the mini mental state examination (MMSE) (Folstein et al., 1975) and with a complete battery of tests with the aim to identify and quantify the cognitive impairment in the diverse superior cognitive areas, such as the Babcok story recall, Raven’s standard progressive matrices, Rey complex figure test copy and memory, phonological fluency testing, semantic fluency testing (Raven, 1947, 1960; Rey, 1958, 1968; Spinnler and Tognoni, 1987). Functional assessment was evaluated by using the activities of daily living (ADL) (Katz et. al., 1963) and the instrumental activities of daily living (IADL) (Lawton and Brody, 1969). Psychiatric and behavioral diseases were investigated with the NPI, being a diagnostic instrument for psychiatric diseases in patients with dementia. We used also the NPI distress scale (NPI-D) for measuring the level of distress caused to the caregivers from the psychiatric-behavioral conditions of the AD patients. At the first evaluation (time-0, t0) all the patients showed some behavioral disturbance requiring antipsychotic treatment. We used risperidone (20 patients) and olanzapine (26 patients), and the choice between the two drugs was made basically on the presence of sleep disorders or extrapyramidal troubles. In presence of such symptoms we used olanza-
468
pine utilizing the advantage of the sedative effect of the drug, and also in consideration of its lower pro-parkinsonian action. The dosage was personalized in each patient according to the sensibility to the medicine. The starting dosage for risperidone was 0.50 mg once or twice daily, up to a maximum of 2 mg/day; for olanzapine the minimum dose was 2.5 mg once a day in the evening, till a maximum of 10 mg/day. The MMSE, ADL, IADL and NPI analyses were repeated after 3 months of treatment with antipsychotic drugs (time-1, t1). Statistical analysis was carried out to evaluate the efficacy of the treatment with the paired Student’s t-test, detecting the presence of a statistically relevant difference between the score obtained from the patients at t0 and t1. RESULTS AND DISCUSSION The cognitive impairment of the AD patients we considered was from mild to moderate level, with an average MMSE score of 17.3 ± 5.1 ranging 4.4-23.9. Of the 46 patients enrol led, 12 withdrew from the study, 5 in treatment with risperidone, because of the appearance of severe rigidity, 4 in treatment with olanzapine because of the appearance of hyper somnia, and 3 were lost to follow up: 2 in treatment with olanzapine, 1 with risperidone. The appearance of extrapyramidal disorders and orthostatic hypotension occurred with risperidone at the increase of the dosage to 2.0 mg/day. The excessive sedation due to olanzapine was observed in the patients taking the higher doses (7.5-10.0 mg/day), only 2 people had weight increase more than 4 kg (in average). Statistically significant differences were observed in the average NPI scores for both antipsychotic drugs. Regarding the single items, treatment with risperidone caused signifi cant variations in 5 items: delusions, hallucinations, agitation/aggressiveness, peevishness, anomalous motor activities. On the other hand, with olanzapine significant improvements were observed in 6 items of 12: agitation, aggressiveness, delusions, peevishness, anxiety, sleep disorders, appetite. Regarding depression, all the patients we examined presented an important reduction of the mood’s tone (90 %), but the utilization of the antipsychotics only, was not enough to control such symptoms. For several patients it was necessary to add, after an unsettled time from 5 to 8 weeks, another drug such as antidepressant, mainly belonging to the family of selective serotonin reuptake inhibitors (SSRI), mostly citalopram and sertraline. Our experiences confirm the efficacy and tolerability of the two antipsychotic drugs we utilized. The majority of our patients (75 %) treated with risperidone, took a dose of 1.0 mg per day in double administration, 21.5 % assumed 1.5 mg per day, only 4 % received a
469
dose of 2.0 mg/day. The most widely used dose of olanzapine was 5 mg/day (70 %) in single administration at the evening, and for the remaining 30 % it was necessary to increase the dose to 10 mg/day (20 % 7.5 mg, 10 % 10 mg). Risperidone was the most effective in controlling properly the psychotic symptoms (hallucinations and delusions), meanwhile olanzapine showed a better effect on behavioral disturbance like aggressive ness, agitation, peevishness, anxiety and sleep disorders. In 15 % of the patients treated with risperidone we observed extrapyramidal adverse effects (dosage 1.5-2.0 mg/day) mainly rigidity and oral dyskinesia; a lower percentage of patients (7 %) showed also orthostatic hypotension. The most frequent side-effect observed with olanzapine administration (34 %) was excessive sedation. Other adverse effects like gastrointestinal disease and cutaneous rush were observed in a small percentage (3 %). IADL showed a natural decline that is typical of the illness, but in the meanwhile we observed a certain stability of cognitive status and in basic ADL. We have not observed any significant changes in electrocardiographic (Q-T interval) or hematological parameters. Only in one patient treated with olanzapine we noticed an important increase of glycemia. In our experience, low doses of risperidone (1.0 mg/day) and olanzapine (5.0 mg/day) showed positive results in controlling behavioral disturbances in AD patients, without the appearance of major adverse events, like extrapyramidal and anti-cholinergic effects, which could be observed during the utilization of typical antipsychotic molecules. This fact reflects a better management of the patient, with an important improvement in the quality of life of both the patients and the caregivers. A pharmacological intervention able to reduce quickly and effectively the behavioral disturbances in AD patients, as well as the negative impact occurring in the families of the patients, can reduce or delay the moment of hospitalization. This latter event always has a negative psychological effect on both the patients and the caregivers. REFERENCES Brunello, N. and Racagni, G. (1997): Meccanismi d’azione degli psicofarmaci. In: Bellantuono, C. and Balestrieri, M. (Eds.): Gli psicofarmaci. Farmacologia e terapia. II Pensiero Scientifico Editore, Roma, pp. 38-46 (In Italian). Cummings, J.L. (1997): The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology, 48, S6-S10. Folstein, M.F., Folstein, S.E. and McHigh, P.R. (1975): Mini-Mental State: a practical method for grading the cognitive status of patients for the clinician. J. Psychiatric Res., 12, 189-198. Hermann, N. (2001): Recommendations for the management of behavioral and psychological symptoms of dementia. Can. J. Neurol. Sci. 28 (Suppl. 1), S96-S107. Lawton, M.P. and Brody, E.M. (1969): Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist, 9, 179-186.
470
Katz, S., Ford, A.B., Moskowitz, R.W., Jackson, B.A. and Jaffe, M.W. (1963): Studies of illness in the aged. The index of ADL: a standardized measure of the biological and psychosocial function. J. Am. Med. Assoc., 185, 914-919. Katz, I., Jeste, D.V., Mintzer, J.E. Clyde C, Napolitano J, Brecher M. (1999): Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double blind trial. J. Clin. Psychiatry, 60, 107-115. McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. and Stadlan, E.M. (1984): Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA work group under the auspices of Departement of Health and Human Services Task Force on Alzheimer’s disease. Neurology, 34, 939-944. Raven, J.C. (1947): Sets A, AB, B Board and Book Forms of Progressive Matrices. Lewis, London. Raven, J.C. (1960): Changes in productive and reproductive intellectual activity between 60 and 90 years of age. J. Gerontol., 8, 760-767. Rey, A. (1958): Mémorisation d’une série de 15 mots en 5 répétition. In : Rey, A. (Ed). L’examen clinique en psychologie. Presses Universitaires de France, Paris, (in French). Rey, A. (1968): Reattivo della figura complessa. Manuale. (Complex Figure Task). Organizzazioni Speciali, Firenze (in Italian). Spinnler, H. and Tognoni, G. (1987): Taratura e standardizazione ltaliana di test neuropsicologici. Ital. J. Neurol. Sci., Suppl. 8, pp.: 7-120 (in Italian). Schneider, L.S. (1999): Pharmacologic management of psychosis in dementia. J. Clin. Psychiatry, 60 (Suppl. 8). 54-60.
THE MANAGEMENT OF PSYCHOGERIATRIC PATIENT
G. ZANNINO, A. GARGIULO*, F. LAMENZA, M.G. MAROTTA, T. BARZOTTI, A. SILVESTRI, E. ETTORRE and V. MARIGLIANO
Department of Aging Science, Policlinico Umberto I, University "La Sapienza", Viale de Policlinico, 155, I-00161 Rome, Italy *Corresponding author at address: Via P.A. Micheli, 90, I-00197 Roma, Italy Tel.: +(39-348)-0447-724; Fax: +(39-06)-445-6316; E-mail: [email protected]
SUMMARY The exponential growth in the prevalence of cognitive impairment of old patients leads the physicians to deal with a larger incidence of behavioral disorders (such as excitement, aggressiveness), and psychotic symptoms (such as delirium and visual hallucinations). The presence of psychotic troubles in dementia causes a remarkable distress to caregivers and involves higher difficulties in the patient management. The estimates of such troubles range between 15 and 75 %. Geriatric assessment and the management of behavioral troubles require a prompt evaluation of all their possible causes. As a matter of fact, their appea rance often reveals a physical disturbance (pain, fever, etc.), or adverse environmental conditions, or it could also be a consequence of a multiple drug therapy. For this reason, the use of antipsychotics should always be preceded by an accurate clinical diagnosis. Anxiolytic, anti-depressive, anti-convulsive and anti-psychotic drugs are among the therapeutic strategies for the management of the psychogeriatric patient. Atypical antipsychotics seem to be able to decrease the psychotic symptoms, with low levels of therapeutic failure. They also reduce extrapyramidal effects and the growth of prolactine hormone, which is quite useful when dealing with very old patients. Risperidone and olanzapine are two atypical anti-psychotics, which already proved to be adequate and well tolerated during the treatment of schizophrenia and of acute maniacal disorders. Our experience, with a population of patients followed by our Alzheimer Evaluation Unit (AEU), confirms that a low dose of olanzapine (5mg/day) and risperidone (0.5-1.0 mg/day) are effective in lowering behavioral disturbances, and psychotic symptoms due to dementia. Even in the long run, low doses of these drugs are still well tolerated. Higher levels of risperidone (>1 mg/die) often caused extra-pyramidal symptoms such as rigidity and dyskinesia, whereas higher levels of olanzapine (> 5 mg/day) lead to an exceeding sedation. The management of behavioral disturbances is one of the most important goals in the global treatment of patients affected by dementia, to the extent of improving the quality of life. Atypical antipsychotics are preferable compared to old-generation drugs, therefore, they are the key therapeutic strategy we cannot renounce. Keywords: behavioral psychiatric symptoms of dementia (BPSD), atypical antipsychotics, olanzapine. risperidone
466
INTRODUCTION The management of behavioral disturbance appearing with dementia (behavioral psychiatric symptoms of dementia: BPSD) evaluated with the neuropsychiatric inventory (NPI) (Cummings, 1997) is performed in several ways. First of all, it is essential to make a careful evaluation of the determining factors. Frequently their appearance could denote an organic illness (pain, constipation, retention of urine, hunger, thirst, fever) or environmental disturbance. The patient who will not adapt to new situations (e.g., home change) or cannot catch different complexities of the surrounding reality (too much lights or too strong sounds), could express his/her difficulty and dysadaptation with an incongruous action (a fit of anxiety, aggressiveness). Even conditions of polyphannacotherapy, very common in old patient with dementia, could cause psychotic disturbances. In presence of visual or auditory hallucinations it should be considered, whether there is an uncorrected sensorial deficit. The pharmacological treatment of psychiatric disorders is based on the use of neuroleptic drugs: even if sometimes it could be useful to use other classes of drugs like antide pressants, anticonvulsants or beta blockers (Shneider, 1999). Not all of the psychiatric disorders are susceptible to pharmacological treatment (repetitive behavior and wandering); in those cases it is possible to control the determining factors, or to manage the situation, in order to reduce the risk factors for the patient. Considering the changes the organism goes through with aging, and the alterations in the pharmacokinetics and pharmacodynamics, it is necessary to adopt for the elderly patient lower dosages, starting from a minimum dose and increasing slowly (“start low, go slow”), till the achievement of the desired result, in order to avoid as much as possible of side effects. Up to now, neuroleptic drugs are the most common used drugs for behavioral distur bances. They are divided in two classes: typical and atypical, distinguishing them by the special action on the dopaminergic receptor. Both of them stoop D2 receptors, even though by different mechanisms on the central nervous system. In particular, atypical neuroleptics have less specificity for D2 receptor on the nigrostriatal and tubero-infundibular systems, and better affinity for receptors of mesolimbic and mesocortical systems, and for serotonin ergic receptors 5HT2A (Brunello and Racagni, 1997). The pharmacodynamic characteris tics of these drugs should determine, in clinical practice, a reduced induction of neurological side effects, mainly extrapyramidal disorders, and late dyskinesia, when compared to the typical neuroleptic drugs. Objective of this study is to verify within our ambulatory experience, the efficacy and safety of atypical antipsychotics, with particular attention to risperidone and olanzapine in
467
the control of behavioral disturbances, trying to identify the target dose able to conciliate the needs of maximum efficacy with less side effects. PATIENTS AND METHODS We selected, in the period from January and to June 2002, 46 patients affected by Alzheimer disease (AD), followed in our ambulatory Alzheimer Evaluation Unit (AEU) at the Department of Aging Science of University of Rome “La Sapienza”. AD diagnosis was made following the NINCDS-ADRDA criteria (McKhann et al., 1984). The other types of dementia, e.g., the mixed one (vascular -degenerative), were excluded, and so were all the clinical cases of AD associated with any heavy chronic illness, or history of psychiatric disorders, like schizophrenia, bipolar disorders or major depression, and all the other neurological diseases different from AD, which could contribute to the onset of dementia or psychosis. To be included in the study, patients had to have at the initial screening, a score > 3 for each item of NPI (Cummings, 1997) forming the basic core of behavioral disturbance in AD patients: agitation, aggressiveness, hallucinations and delusions (NPI-core). We obtained a sample of 14 males and 32 females affected by AD associated with BPSD, with an average age of 75.4 ± 6.9 (range 59-90) years. Each person underwent a complete evaluation of the 3 symptomatic areas characterizing AD: cognitive, functional and psychi -atric -behavioral ones. Cognitive function was investigated with the mini mental state examination (MMSE) (Folstein et al., 1975) and with a complete battery of tests with the aim to identify and quantify the cognitive impairment in the diverse superior cognitive areas, such as the Babcok story recall, Raven’s standard progressive matrices, Rey complex figure test copy and memory, phonological fluency testing, semantic fluency testing (Raven, 1947, 1960; Rey, 1958, 1968; Spinnler and Tognoni, 1987). Functional assessment was evaluated by using the activities of daily living (ADL) (Katz et. al., 1963) and the instrumental activities of daily living (IADL) (Lawton and Brody, 1969). Psychiatric and behavioral diseases were investigated with the NPI, being a diagnostic instrument for psychiatric diseases in patients with dementia. We used also the NPI distress scale (NPI-D) for measuring the level of distress caused to the caregivers from the psychiatric-behavioral conditions of the AD patients. At the first evaluation (time-0, t0) all the patients showed some behavioral disturbance requiring antipsychotic treatment. We used risperidone (20 patients) and olanzapine (26 patients), and the choice between the two drugs was made basically on the presence of sleep disorders or extrapyramidal troubles. In presence of such symptoms we used olanza-
468
pine utilizing the advantage of the sedative effect of the drug, and also in consideration of its lower pro-parkinsonian action. The dosage was personalized in each patient according to the sensibility to the medicine. The starting dosage for risperidone was 0.50 mg once or twice daily, up to a maximum of 2 mg/day; for olanzapine the minimum dose was 2.5 mg once a day in the evening, till a maximum of 10 mg/day. The MMSE, ADL, IADL and NPI analyses were repeated after 3 months of treatment with antipsychotic drugs (time-1, t1). Statistical analysis was carried out to evaluate the efficacy of the treatment with the paired Student’s t-test, detecting the presence of a statistically relevant difference between the score obtained from the patients at t0 and t1. RESULTS AND DISCUSSION The cognitive impairment of the AD patients we considered was from mild to moderate level, with an average MMSE score of 17.3 ± 5.1 ranging 4.4-23.9. Of the 46 patients enrol led, 12 withdrew from the study, 5 in treatment with risperidone, because of the appearance of severe rigidity, 4 in treatment with olanzapine because of the appearance of hyper somnia, and 3 were lost to follow up: 2 in treatment with olanzapine, 1 with risperidone. The appearance of extrapyramidal disorders and orthostatic hypotension occurred with risperidone at the increase of the dosage to 2.0 mg/day. The excessive sedation due to olanzapine was observed in the patients taking the higher doses (7.5-10.0 mg/day), only 2 people had weight increase more than 4 kg (in average). Statistically significant differences were observed in the average NPI scores for both antipsychotic drugs. Regarding the single items, treatment with risperidone caused signifi cant variations in 5 items: delusions, hallucinations, agitation/aggressiveness, peevishness, anomalous motor activities. On the other hand, with olanzapine significant improvements were observed in 6 items of 12: agitation, aggressiveness, delusions, peevishness, anxiety, sleep disorders, appetite. Regarding depression, all the patients we examined presented an important reduction of the mood’s tone (90 %), but the utilization of the antipsychotics only, was not enough to control such symptoms. For several patients it was necessary to add, after an unsettled time from 5 to 8 weeks, another drug such as antidepressant, mainly belonging to the family of selective serotonin reuptake inhibitors (SSRI), mostly citalopram and sertraline. Our experiences confirm the efficacy and tolerability of the two antipsychotic drugs we utilized. The majority of our patients (75 %) treated with risperidone, took a dose of 1.0 mg per day in double administration, 21.5 % assumed 1.5 mg per day, only 4 % received a
469
dose of 2.0 mg/day. The most widely used dose of olanzapine was 5 mg/day (70 %) in single administration at the evening, and for the remaining 30 % it was necessary to increase the dose to 10 mg/day (20 % 7.5 mg, 10 % 10 mg). Risperidone was the most effective in controlling properly the psychotic symptoms (hallucinations and delusions), meanwhile olanzapine showed a better effect on behavioral disturbance like aggressive ness, agitation, peevishness, anxiety and sleep disorders. In 15 % of the patients treated with risperidone we observed extrapyramidal adverse effects (dosage 1.5-2.0 mg/day) mainly rigidity and oral dyskinesia; a lower percentage of patients (7 %) showed also orthostatic hypotension. The most frequent side-effect observed with olanzapine administration (34 %) was excessive sedation. Other adverse effects like gastrointestinal disease and cutaneous rush were observed in a small percentage (3 %). IADL showed a natural decline that is typical of the illness, but in the meanwhile we observed a certain stability of cognitive status and in basic ADL. We have not observed any significant changes in electrocardiographic (Q-T interval) or hematological parameters. Only in one patient treated with olanzapine we noticed an important increase of glycemia. In our experience, low doses of risperidone (1.0 mg/day) and olanzapine (5.0 mg/day) showed positive results in controlling behavioral disturbances in AD patients, without the appearance of major adverse events, like extrapyramidal and anti-cholinergic effects, which could be observed during the utilization of typical antipsychotic molecules. This fact reflects a better management of the patient, with an important improvement in the quality of life of both the patients and the caregivers. A pharmacological intervention able to reduce quickly and effectively the behavioral disturbances in AD patients, as well as the negative impact occurring in the families of the patients, can reduce or delay the moment of hospitalization. This latter event always has a negative psychological effect on both the patients and the caregivers. REFERENCES Brunello, N. and Racagni, G. (1997): Meccanismi d’azione degli psicofarmaci. In: Bellantuono, C. and Balestrieri, M. (Eds.): Gli psicofarmaci. Farmacologia e terapia. II Pensiero Scientifico Editore, Roma, pp. 38-46 (In Italian). Cummings, J.L. (1997): The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology, 48, S6-S10. Folstein, M.F., Folstein, S.E. and McHigh, P.R. (1975): Mini-Mental State: a practical method for grading the cognitive status of patients for the clinician. J. Psychiatric Res., 12, 189-198. Hermann, N. (2001): Recommendations for the management of behavioral and psychological symptoms of dementia. Can. J. Neurol. Sci. 28 (Suppl. 1), S96-S107. Lawton, M.P. and Brody, E.M. (1969): Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist, 9, 179-186.
470
Katz, S., Ford, A.B., Moskowitz, R.W., Jackson, B.A. and Jaffe, M.W. (1963): Studies of illness in the aged. The index of ADL: a standardized measure of the biological and psychosocial function. J. Am. Med. Assoc., 185, 914-919. Katz, I., Jeste, D.V., Mintzer, J.E. Clyde C, Napolitano J, Brecher M. (1999): Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double blind trial. J. Clin. Psychiatry, 60, 107-115. McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. and Stadlan, E.M. (1984): Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA work group under the auspices of Departement of Health and Human Services Task Force on Alzheimer’s disease. Neurology, 34, 939-944. Raven, J.C. (1947): Sets A, AB, B Board and Book Forms of Progressive Matrices. Lewis, London. Raven, J.C. (1960): Changes in productive and reproductive intellectual activity between 60 and 90 years of age. J. Gerontol., 8, 760-767. Rey, A. (1958): Mémorisation d’une série de 15 mots en 5 répétition. In : Rey, A. (Ed). L’examen clinique en psychologie. Presses Universitaires de France, Paris, (in French). Rey, A. (1968): Reattivo della figura complessa. Manuale. (Complex Figure Task). Organizzazioni Speciali, Firenze (in Italian). Spinnler, H. and Tognoni, G. (1987): Taratura e standardizazione ltaliana di test neuropsicologici. Ital. J. Neurol. Sci., Suppl. 8, pp.: 7-120 (in Italian). Schneider, L.S. (1999): Pharmacologic management of psychosis in dementia. J. Clin. Psychiatry, 60 (Suppl. 8). 54-60.