The behavioral and psychological symptoms of dementia (BPSD) are common serious problems that are a major contributor to caregiver burden. Despite their significance, the underlying neurobiology of these disturbances is still unclear. This review examines the role of norepinephrine (NE) on BPSD, including depression, aggression, agitation and psychosis. A number of lines of evidence suggest that NE dysfunction leading to BPSD may result from increased NE activity and/or hypersensitive adrenoreceptors compensating for loss of NE neurons with progression of Alzheimer's disease (AD). With greater appreciation of the underlying neurobiology of behavioral and psychological symptoms of dementia (BPSD) more effective, rational, targeted pharmacotherapy will hopefully emerge.

The Role of Norepinephrine in the Behavioral and Psychological Symptoms of Dementia

Recommandations pour la prise en charge des symptomes comportementaux et psychologiques de la demence. Introduction: Les symptomes comportementaux et psychologiques de la demence (SCPD) sont des problemes frequents et serieux qui alterent la qualite de vie du patient et de l'aidant. Une revue qualitative de la litterature a ete effectuee afin de fournir des recommandations basees sur les donnees scientifiques disponible. Methodes: Une recherche de la litterature medicale de langue anglaise publiee entre 1966 et 2000 a ete effectuee. La qualite des etudes a ete evaluee en considerant les sujets, le plan de l'etude, l'analyse et les resultats. Les recommandations finales ont ete fondees sur la qualite des observations disponibles. Resultats: La prise en charge des SCPD commence par une evaluation minutieuse pour rechercher les causes sous-jacentes du changement de comportement. Les maladies concomitantes devraient etre traitees et les deficits sensoriels ameliores. Des approches non pharmacologiques devraient etre instituees avant de prescrire une medication. Ces interventions incluent la musicotherapie, la phototherapie, les changements dans le niveau de stimulation et l'utilisation de techniques comportementales specifiques. Les antipsychotiques constituent l'intervention pharmacologique la mieux etudiee pour traiter l'agitation et l'agressivite. Ils ont demontre une efficacite modeste mais constante. Les antidepresseurs tels le trazodone et les inhibiteurs selectifs de la recaptation de la serotonine de meme que des anticonvulsivants tels la carbamazepine et l'acide valproique sont egalement efficaces. Les benzodiazepines peuvent etre utilisees a court terme, p.r.n. La pharmacotherapie doit etre surveillee etroitement tant au point de vue de son efficacite que de ses effets secondaires, avec reevaluation de sa pertinence. Conclusion: La prise en charge des SCPD peut ameliorer significativement la qualite de vie du patient et des aidants, Leur evaluation et leur prise en charge sont des composantes essentielles du traitement de la demence.

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Recommendations for the Management of Behavioral and Psychological Symptoms of Dementia

OBJECTIVE: To evaluate the use of newer psychotropic agents in nursing home residents in the era of new Health Care Financing Administration (HCFA) guidelines.



DESIGN: Retrospective chart review of referrals to an on-site geriatric psychiatry service in seven Eastern Massachusetts facilities during 1995–1996.



SUBJECTS: The 298 patients examined included 226 women and 72 men with a mean (SD) age of 81.9 (9.4) years.



MEASUREMENTS: Patient demographics, psychiatric history and medical diagnoses, prescribed medication information, and mental status examination results were recorded systematically. Descriptive statistics of demographics, medication use, and dosing were generated, and comparative analyses were performed by chi-square, ANOVA, and Tukey's tests.



RESULTS: Overall, 69% of subjects were taking at least one psychotropic medication. Although benzodiazepines (32%) and antipsychotics (42%) were used by a large portion of subjects, antidepressants (61%) were the most commonly prescribed psychotropic, with 53% taking serotonin reuptake inhibitors. The atypical antipsychotic, risperidone, accounted for more than 30% of antipsychotic prescriptions. Low rates of anticholinergic use and low doses and rates of tricyclic antidepressant use were found in Alzheimer's disease patients. Mean dosing of the psychotropic agents fell within HCFA guidelines.



CONCLUSIONS: Newer-generation psychotropics have had a significant impact on the prescribing practices of primary physicians in treating nursing home residents. Of clinical importance is the high rate of antidepressant use in a population that has traditionally received inadequate pharmacotherapy for depression. More studies are needed to examine a shift to the use of other psychotropic drugs in this population in the post-HCFA area.

Newer psychotropic medication use in nursing home residents.

Background

Indications for serotonergic medications in the treatment of behavioral disorders associated with Alzheimer's disease (AD) remain to be established.



Method

Sertraline (100 mg OD) was evaluated in a double-blind, randomized, placebo-controlled cross-over study in 22 nondepressed patients with severe probable AD and significant behavioral disturbance. Each subject was given a fenfluramine challenge to evaluate central serotonergic tone.



Results

Eight of 21 (38%) completers responded to sertraline. Drug responsive behaviors included aggression/agitation, irritability and aberrant motor behavior. Low aggression, female gender and large prolactin increase were associated with a better response. There was a trend for decreased aggression during sertraline versus placebo (p = 0.08).



Conclusion

Aggression, gender and serotonergic function were associated with sertraline response. Larger randomized controlled trials are needed to clarify the profile of responders. Copyright © 2002 John Wiley & Sons, Ltd.

Gender, aggression and serotonergic function are associated with response to sertraline for behavioral disturbances in Alzheimer's disease.

Neuroleptics remain the mainstay for the treatment of behavioral disturbance and psychotic symptoms in demented patients. The limited available data suggest that low-dose neuroleptics are significantly more efficacious than placebo, though the magnitude of the effect is moderate in most published studies. Demented patients are particularly prone to neuroleptic side effects, and individualized dose titration may be necessary to achieve the optimal trade-off between efficacy and side effects. Target behavioral symptoms and side effects, including effects on cognition and activities of daily life, should be identified and assessed serially during neuroleptic treatment. The choice of neuroleptic depends more on likely side effects than differential efficacy, and non-response or intolerable side effects should lead to dose adjustment or a switch to an alternative class of neuroleptic (or an alternative type of medication). Further studies of optimal neuroleptic dosage, the optimal duration of continuation neuroleptic treatment, and placebo-controlled studies comparing neuroleptics to other classes of medications are needed.

Trait shyness in the elderly: evidence for an association with Parkinson's disease in family members and biochemical correlates.

This study clarifies the methodological pitfalls of using cross-sectional data to characterize episodic and continuous patterns of prescribing psychotropic medications in nursing homes. Although more than half of the residents in a teaching nursing home received a psychotropic drug during their 5 years of residence, less than one-quarter were continuously medicated. The authors conclude that although the rates of psychotropic prescriptions are an important entry point f or concerns about quality and appropriateness of psychotropic administration to older nursing home residents, longitudinal studies including the prescribing pattern, indications, and efficacy are needed to determine more clinically meaningful indicators of quality care. (AmJ Psychiatry 1990; 147:1637-1639)

Gail Lowenstein

Papers

A longitudinal study of psychotropic prescriptions in a teaching nursing home.