Efficacy of fluvoxamine as a treatment for behavioral symptoms in frontotemporal lobar degeneration patients

Patients with frontotemporal lobar degeneration (FTLD) present a profound personality change, social misconduct, overeating, and stereotyped behavior. We examined the hypothesis that many of the behavioral symptoms of FTLD will respond to selective serotonin reuptake inhibitors (SSRIs). Sixteen FTLD patients were treated with an SSRI (fluvoxamine maleate) in an open 12-week trial. Treatment responses for stereotyped behavior and other neurobehavioral symptoms were evaluated by the Stereotypy Rating Inventory and the Neuropsychiatric Inventory. The behavioral symptoms, especially stereotyped behaviors of FTLD, significantly improved after treatment. Randomized, placebo- and other SSRI-controlled trials may improve available treatments.     

Efficacy of metrifonate in improving the psychiatric and behavioral disturbances of patients with Alzheimer's disease.

Neuropsychiatric and behavioral symptoms are frequent and problematic components of Alzheimer's disease (AD). In two previously reported studies, metrifonate was shown to benefit behavioral symptoms as assessed by the Neuropsychiatric Inventory (NPI). In this post hoc analysis, detailed studies were completed to determine the effects of metrifonate on individual symptoms. This study was a retrospective analysis of pooled NPI data from two double-blind, placebo-controlled, multicenter 26-week studies of metrifonate that had achieved similar levels of cholinesterase inhibition. Mild-to-moderate probable AD patients received placebo (n = 222) or metrifonate (n = 450) 30 to 60 mg by weight or a 50-mg fixed dose once daily. At 26 weeks, metrifonate-treated patients had significantly reduced NPI total scores (P = .001) and fewer neuropsychiatric symptoms when compared with placebo-treated patients, including hallucinations (P = .004), agitation/aggression (P = .006), depression/dysphoria (P = .011), apathy (P = .019), and aberrant motor behavior (P = .008). Metrifonate reduced or stabilized neuropsychiatric disturbances in 60% of symptomatic patients. Almost 40% of metrifonate-treated patients had a clinically relevant reduction (> or = 30% decrease in NPI score) in their neuropsychiatric disturbances (P = .002). High proportions of metrifonate-treated patients manifested clinically relevant reductions in anxiety (58%, P = .009), apathy (51%, P = .020), and depression/dysphoria (50%, P = .021) compared to placebo. The metrifonate-associated reductions in NPI scores were evident by week 12 and were maintained for the 26-week study period. There was an overall effect size of metrifonate of approximately 15% on total NPI scores when compared to placebo. Metrifonate significantly reduced many of the psychiatric and behavioral symptoms of AD. The observations suggest that enhancement of cholinergic functions in AD has beneficial effects on behavior.     

The utility of the Cambridge Behavioural Inventory in neurodegenerative disease

We investigated the utility of the Cambridge Behavioural Inventory (CBI), a carer-completed questionnaire, in a large cohort with Parkinson's disease (PD) (n = 215). In a sub-cohort of 112 patients with PD, the CBI was found to be a valid instrument compared with the Neuropsychiatric Inventory, PDQ-39 and UPDRS, with high internal consistency. Furthermore, in the whole cohort, the CBI was sensitive to changes in behaviour with disease progression. Comparison between CBI scores in PD and other neurodegenerative diseases, including Huntington's disease (HD) (n = 75), Alzheimer's disease (AD) (n = 96) and frontal variant frontotemporal dementia (fvFTD) (n = 64), revealed distinct profiles for each disease. Predominant deficits were "sleep"' and "self care" in PD; "memory" in HD and AD; and "motivation" and "stereotypic behaviours" in fvFTD. The CBI is a robust, easy-to-use and valid instrument, which has the capacity to discriminate between neurodegenerative diseases, and may be of value in monitoring therapeutic interventions.     

Buspirone for stereotypic movements in elderly with cognitive impairment

Repetitive and stereotypic behavioral disturbances in patients with dementia are common; however, little is known regarding successful treatments. The authors describe six cases of elderly cognitively impaired patients exhibiting repetitive and stereotypic behaviors who were treated successfully with buspirone. The cases demonstrate that buspirone may be an effective and safe treatment for patients with dementia who demonstrate repetitive and stereotypic behavior disorders.     

Neuropsychology of frontal type dementia]

The clinical conceptual change in frontal type dementia is reviewed in discussing its relationships to several related concepts such as Pick's disease, frontotemporal dementia (FTD), semantic dementia (SD) and frontotemporal lobar degeneration. We analyzed frontal type dementia selected from a consecutive series of our outpatients as to the details of neuropsychological symptoms, psychiatric symptoms, and abnormal behaviors. In our series of 143 patients with primary degenerative dementia, there were 16 cases of FTD and 6 cases of SD. Patients with two types of FTD and patients with SD were not distinguishable by neuropsychological examinations, behavioral abnormalities and psychiatric symptoms assessed with the Neuropsychiatric Inventory except for aphasia. The clinical picture of frontal type dementia involves frontal lobe symptoms such as disinhibition, apathy and stereotypy. Semantic memory loss for words, objects or faces suggestive of temporal lobe involvement developed only in patients with SD, and not in patients with FTD. Certain behavioral symptoms seen in frontal type dementia may respond to selective serotonin reuptake inhibitors. In care for patients with frontal type dementia, behavioral disturbances can be diminished and the quality of life can be improved by using their preserved procedural memory, pathological stereotypic behavior and stimulus-bound behavior such as utilization behavior and environmental dependency syndrome.     

Neuropsychiatric symptoms, functional impairment and executive ability in Thai patients with Alzheimer's disease

BACKGROUND: Instrumental activities of daily living (IADL) depend on executive planning and procedural memory mediated by the frontal lobes. Planning and judgment are involved in clock drawing. Neuropsychiatric symptoms are also mediated by frontal lobes, and a relationship between ADL, clock drawing and neuropsychiatric symptoms was hypothesized. OBJECTIVE: To investigate the relationship between behavioral disturbances, ADL, and executive function. METHODS: Seventy-three Thai patients with Alzheimer's disease (AD) were evaluated. Neuropsychiatric symptoms and behaviors were assessed with the Nevropsychiatric Inventory (NPI). The Thai version of the Mini-mental State Examination (TMSE) was utilized as a global cognitive assessment. A clock-drawing test (CDT) and both category (animals) and letter (ko, so in Thai) verbal fluency were used as executive measures. Thai ADL scale, Barthel Index (BI), and Functional Assessment Questionnaire (FAQ) were ADL measures used in this study. RESULTS: There were statistically significant correlations between CDT and the frontally-mediated behaviors of agitation (r = -0.367), apathy (r = -0.273) and disinhibition (r = -0.247). Verbal fluency correlated with agitation (r = -0.341). There were significant correlations between Thai ADL scores and agitation (r = 0.350), apathy (r = 0.441), and disinhibition (r = 0.417). FAQ correlated with the same three behaviors. After controlling for TMSE, a significant correlation remained between Thai ADL scores and agitation (r = 0.291) and apathy (r = 0.342). CONCLUSIONS: We demonstrated correlations between ADL and behavioral changes in Thai elderly with AD. Our results emphasize the important relationships among behavioral changes and impaired ADL.     

Hospital admission circumstances and prevalence of frontotemporal lobar degeneration: a multicenter psychiatric state hospital study in Germany

Frontotemporal lobar degeneration (FTLD) is a heterogenous, non-Alzheimer's disease, dementia complex with variable clinical presentation. We carried out a prospective nationwide hospital-based clinico-epidemiologic study in geriatric psychiatry to estimate the prevalence and admission circumstances of patients with FTLD. During a 4-week period 33 patients with clinical FTLD were prospectively ascertained in 36 psychiatric state hospitals in Germany with a total catchment area of >20,000,000 people. The relative portion of FTLD patients within the primary dementia population accounted for 1.9%. The estimated prevalence of FTLD in Germany was 47.9/100,000 population aged between 45 and 79 years. The admission circumstances were mainly behavioral disturbances (54.5%), unclear syndromes of dementia (18.1%) and further remarkably heterogeneous psychiatric syndromes. FTLD is a common cause of dementia in geriatric psychiatry with a variable clinical presentation that could mimic most of the major psychiatric diseases. Patients with FTLD may be older than previously assumed (mean age at admission 63.9 years) and show their maximum age-related prevalence between 60 and 70 years (78.7/100,000).     

A 3-month, randomized, placebo-controlled, neuroleptic discontinuation study in 100 people with dementia: the neuropsychiatric inventory median cutoff is a predictor of clinical outcome

BACKGROUND: Although few placebo-controlled neuroleptic discontinuation studies have been conducted in people with dementia, such studies are essential to inform key clinical decisions. METHOD: A 3-month, double-blind, placebo-controlled, neuroleptic discontinuation study (June 2000 to June 2002) was completed in 100 care-facility residents with probable or possible Alzheimer's disease (according to National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria) who had no severe behavioral disturbances and had been taking neuroleptics for longer than 3 months. The Neuropsychiatric Inventory (NPI) was used to measure changes in behavioral and psychiatric symptoms. Quality of life was evaluated using Dementia Care Mapping. RESULTS: Eighty-two patients completed the 1-month assessment (36 placebo, 46 active). The number of participants withdrawing overall (N = 14 [30%] placebo, N = 14 [26%] active treatment) and because of exacerbation of behavioral symptoms (N = 6 [13%] placebo, N = 5 [9%] active treatment) was similar in the neuroleptic- and placebo-treated patients. As hypothesized, patients with baseline NPI scores at or below the median (< or = 14) had a particularly good outcome, with a significantly greater reduction of agitation in the patients receiving placebo (Mann-Whitney U test, z = 2.4, p =.018), while patients with higher baseline NPI scores were significantly more likely to develop marked behavioral problems if discontinued from neuroleptics (chi(2) = 6.8, p =.009). There was no overall difference in the change of quality of life parameters between groups. DISCUSSION: A standardized evaluation with an instrument such as the NPI may be a clinical indicator of which people with dementia are likely to benefit from discontinuation of neuroleptic treatment.     

The spectrum of behavioral responses to cholinesterase inhibitor therapy in Alzheimer disease.

BACKGROUND: Behavioral abnormalities are common in Alzheimer disease (AD); cholinergic treatment reduces the behavioral disturbances of some patients with AD. Characterizing the pretreatment profile of patients who are likely to respond to cholinergic therapy will aid the efficient use of clinical resources. OBJECTIVE: To determine the baseline behavioral profile for 86 patients with AD treated with the cholinesterase inhibitor donepezil hydrochloride. METHODS: Open-label retrospective study of treatment-related behavioral assessments. Based on previous double-blind placebo-controlled experience using the Neuropsychiatric Inventory (NPI), patients were divided into responder (> or =4-point total NPI score decrease, indicating improvement), unchanged (+/-3-point total NPI score change), or nonresponder (> or =4-point total NPI score increase, indicating worsening) groups. The Mini-Mental State Examination assessed cognitive response. RESULTS: Behavioral improvement was seen in 35 patients (41%), worsening in 24 (28%), and no change in 27 (31%). Comparison of profiles in behavioral responders vs nonresponders revealed significantly worse delusions (P = .04), agitation (P = .04), depression (P = .006), anxiety (P = .02), apathy (P = .003), disinhibition (P = .02), and irritability (P<.001) at baseline in responders. Five behaviors changed significantly from baseline, improving for the responders and worsening for the nonresponders: delusions (P = .003 for nonresponders, P = .004 for responders), agitation (P = .01), anxiety (P = .006 for nonresponders, P = .004 for responders), disinhibition (P = .02 for nonresponders, P = .05 for responders), and irritability (P = .003 for nonresponders, P = .001 for responders). The behavioral changes were dose dependent. Cognition did not change significantly with donepezil treatment within any group. CONCLUSIONS: Donepezil has psychotropic properties, and pretreatment behaviors help predict patients' responses to treatment.     

Growth hormone response to clonidine predicts aggression in Alzheimer's disease

OBJECTIVE: The neurobiology of aggression in Alzheimer's Disease (AD) remains unknown. The objective of this study was to determine if altered central noradrenergic (NE) responsiveness is related to aggression in AD. METHODS: Fifteen institutionalized, non-depressed elderly (11 males, four females, mean age 81.5 +/- 5.5) with probable AD, severe cognitive impairment (MMSE mean 3.3 +/- 4.6) and significant behavioral disturbances (Neuropsychiatric Inventory (NPI) score > or = 8) were studied. Growth Hormone (GH) response to clonidine challenge (5 microg/kg) was used as an index of central alpha(2)-adrenergic function. RESULTS: When patients were divided into those with preserved GH response (GH maximum change from baseline > 0, n = 6) and those with blunted GH response (GH maximum change from baseline < or = 0, n = 9) there were significant differences in levels of aggression as measured by the Cohen-Mansfield Agitation Inventory (CAMI) physical aggression subscale (p = .026). Patients with blunted GH response also had significantly higher levels of aggression against others on the retrospective Overt Aggression Scale (p = 0.027). CONCLUSIONS: Certain types of physically aggressive behaviors are associated with a blunted GH response to clonidine challenge. This finding is consistent with compensatory down-regulation of post-synaptic alpha(2)-adrenergic receptors in response to enhanced NE outflow in aggressive AD patients.     

Cerebrospinal fluid tau in frontotemporal lobar degeneration: clinical, neuroimaging, and prognostic correlates

Frontotemporal lobar degeneration (FTLD) refers to heterogeneous clinical and biological conditions. In FTLD, cerebrospinal fluid (CSF) tau levels have been reported highly variable. The aim of the present study was to evaluate whether CSF tau might be the hallmark of a distinct FTLD phenotype. Fifty-five FTLD patients, who underwent CSF analysis, were considered in the present study. In each patient, a wide standardized neuropsychological evaluation, and CSF tau, phospho-tau, and amyloid-β (Aβ) dosages were performed. Each patient was followed-up to five years, and outcomes carefully recorded. In a subgroup of patients (n = 24), magnetic resonance imaging scanning was performed, by using voxel-based morphometry, for grey matter investigation. The higher the CSF tau levels, the worse the neuropsychological and neuroimaging pattern, mainly characterized by greater language disturbances and left temporal grey matter loss. The same pattern, even if less significant, was associated with CSF phospho-tau, while CSF Aβ levels did not play any influence on FTLD phenotype. FTLD patients with high CSF tau showed poor prognosis compared to those with low CSF tau (p = 0.031). In FTLD, CSF tau levels might be considered a marker of neurodegeneration, associated with a specific clinical and neuroimaging picture, and significantly related to poor outcome. Further studies aimed at defining the biological underpinnings of these findings are warranted.     

A study of stereotypic behaviours in Alzheimer's disease and frontal and temporal variant frontotemporal dementia

OBJECTIVE: To document the prevalence and pattern of stereotypic behaviour in patients with Alzheimer's dementia and frontal and temporal variants of frontotemporal dementia. Secondly, to examine the relationship between stereotypic and other neuropsychiatric behaviours. METHODS: Patients with the following were studied; Alzheimer's disease (n=28), frontal variant frontotemporal dementia (fvFTD, n=18), and semantic dementia-the temporal lobe variant of FTD (n=13). All patients were assessed using the Neuropsychiatric Inventory (NPI), the Mini-Mental State Examination, Addenbrooke's Cognitive Examination, and the Clinical Dementia Rating scale. Patients were also rated on the newly devised Stereotypic and Ritualistic Behaviour (SRB) subscale, which was designed as an addendum to the NPI. RESULTS: There was no significant difference across diagnostic groups in terms of age, sex, or severity of cognitive deficits. The overall NPI was significantly higher in patients with fvFTD compared with the other two groups, but fvFTD and semantic dementia showed a similar, and significantly increased, prevalence of stereotypic behaviours on the SRB subscale. Within the FTD group as a whole these behaviours were more likely to be complex, whereas in Alzheimer's disease, when present, such behaviours tended to be more simple stereotypies or stimulus bound repetitive behaviours. Stereotypic behaviours were not correlated with either disease severity or the extent of cognitive impairment in the fvFTD group, but were in the other two diagnostic groups. CONCLUSION: Complex stereotypic behaviours are a core feature of the dementing syndrome in FTD and may reflect early and specific deficits in orbitofrontal circuitry and basal ganglia involvement.     

The brain-derived neurotrophic factor Val66Met polymorphism is associated with reduced hippocampus perfusion in frontotemporal lobar degeneration

Brain-derived neurotrophic factor (BDNF) promotes several functions in neurons and modulates neurotransmissions, especially in hippocampal regions. Frontotemporal lobar degeneration (FTLD) has a strong genetic background, but genetic risk factors associated with sporadic disease are unknown. Hippocampal involvement is frequently observed in FTLD. The aims of this study were: i) to evaluate if BDNF genetic variations are associated with an increased risk of developing FTLD; and ii) to assess the neuroimaging profiles associated with BDNF polymorphisms. Ninety-one FTLD patients who underwent SPECT imaging and blood sampling entered the study, and clinical, cognitive, and behavioral examinations were performed. A larger group of FTLD patients (n = 194) and controls (n = 396; 162 healthy subjects and 234 Alzheimer's disease (AD) patients) underwent genetic analyses, considering BDNF polymorphisms (Val66Met, rs2049045 C/G, G11757C). A significant different distribution of G11757C genotype in FTLD (GG 53.1%, GC 42.8%, CC 4.1%) compared to controls (G/G 55.6%, G/C 34.6%, C/C 9.8%, p = 0.020) was found. No other significant differences in genotype and allele distributions were detected. The effect of BDNF polymorphisms on brain perfusion was analyzed. BDNF Val66Met A* carriers (A/A or G/A) showed a significant greater hypoperfusion parahippocampal regions as compared to G/G carriers (p < 0.005). No effect of G11757C polymorphism on brain perfusion was found. rs2049045 C/G was not considered as in linkage disequilibrium with Val66Met polymorphism. BDNF Val66Met polymorphism may play a role as a modulator of the FTLD expression and may drive a selective damage in specific brain region affected by the disease.     

Behavioral disturbances in the course of frontotemporal dementia

BACKGROUND: Behavioral disturbances are prominent in frontotemporal dementia (FTD), and their occurrence has been the topic of several investigations. Nonetheless, the prevalence and severity of behavioral disturbances of patients with FTD in different degrees of dementia severity have rarely been studied. Objective: The aim of this study was to assess and compare the prevalence and severity of behavioral disturbances in patients with mild FTD and in patients with moderate/severe dementia. METHODS: We included 21 outpatients with mild FTD [Clinical Dementia Rating (CDR) = 1] and 19 patients with moderate or severe dementia (CDR = 2 or 3) in this study. Behavioral disturbances were assessed using the Neuropsychiatric Inventory (NPI). RESULTS: We found a statistically significant difference in the total NPI scores between patients with mild FTD and patients with moderate or severe FTD, the latter scoring higher. Apathy was the most prevalent symptom in both patient groups (90.5 and 100%). Except appetite and eating disturbance, which appeared in 77.8% of the patients with moderate/severe dementia, all other symptoms were clearly less common (<50%). CONCLUSION: The results highlight the variability of behavioral disturbances in mild and moderate/severe stages of FTD.     

Psychological and behavioral factors in patients with comorbid obstructive sleep apnea and insomnia

Objective

Insomnia symptoms in patients with obstructive sleep apnea (OSA) are commonly assumed to be secondary to respiratory disturbances. Previous studies, however, showed that insomnia might persist after treatment for OSA. Higher levels of emotional disturbances were reported in OSA patients with insomnia than those without insomnia, which suggests that psychological factors may play an important role for their sleep difficulties. This study aimed to further explore sleep-related psychological/behavioral factors that may contribute to insomnia in OSA patients.

Methods

This study included 88 men, of which 33 had OSA (OSA group); 29, primary insomnia; (Insomnia group); and 26, both OSA and insomnia (OSA+Insomnia group). All subjects underwent polysomnography (PSG) overnight and completed a package of questionnaires, including the Insomnia Severity Index (ISI), Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS), Sleep Hygiene Practice Scale (SHPS), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Pre-Sleep Arousal Scale (PSAS).

Results

The OSA+Insomnia and Insomnia groups had significantly more dysfunctional sleep beliefs, more arousal-inducing sleep-related behaviors, and higher levels of pre-sleep arousal, anxiety, and depression than did the OSA group. The respiratory indices and arousal index were higher for OSA and OSA+Insomnia groups than for the Insomnia group.

Conclusion

Although OSA patients with insomnia showed a similar degree of respiratory disturbances as patients with OSA only, their psychological and behavioral profiles resembled the features of primary insomnia patients. The results support the concept of comorbid insomnia and suggest the importance of evaluating and treating both physiological and psychological factors in these patients.     

Behavioural measures in frontotemporal lobar dementia and other dementias: the utility of the frontal behavioural inventory and the neuropsychiatric inventory in a national cohort study

BACKGROUND: Distinguishing between patients with frontotemporal lobar dementia (FTLD) and other dementing illnesses remains a difficult task for many clinicians. In this study, we aimed to provide further evidence for the construct validity of the frontal behavioural inventory (FBI) and assess its utility in differentiating FTLD patients from other groups using data from the Canadian Collaborative Cohort of Related Dementias (ACCORD) study. METHOD: Baseline scores on the FBI and neuropsychiatric inventory (NPI) were compared among several clinical groups (n = 177). RESULTS: The FBI discriminated a higher percentage of FTLD patients (>75% correct classification) from Alzheimer's disease and other groups compared to the NPI (54.2%). CONCLUSION: This study provides good evidence for convergent validity between the FBI and NPI (r = 0.72), indicating that both measures capture similar psychopathology in this nationwide cohort.     

Patterns of referring of patients with frontotemporal lobar degeneration to psychiatric in- and out-patient services. Results from a prospective multicentre study

Dementia with frontotemporal lobar degeneration (FTLD) is clinically characterized by the occurrence of various psychiatric symptoms. In a recent study, the hospital-based prevalence of FTLD and the circumstances of the patients' admission to German psychiatric state hospitals were estimated. On the basis of further continuous assessment, this original FTLD group (n = 33) has been enlarged to 58 patients. The authors here present demographic and clinical data, and reasons for admission to geriatric psychiatry hospitals in comparison with 17 patients, who primarily attended the Memory Disorders Clinic of the University of Regensburg. The results implicate that both institutions see patients with different clinical syndromes: (1) patients were primarily referred to the Memory Disorders Clinic presenting memory and/or speech difficulties as the leading symptoms; (2) major reasons for hospitalisation of patients with FTLD in geriatric psychiatry hospitals were behavioural disturbances; (3) late-onset FTLD (>65 years) was more common than previously assumed in both institutions, and (4) increasing age at admission increased the likelihood to obtain a limited diagnostic approach of brain imaging (only cranial computer tomography) to evaluate the cause of dementia.     

Neuropsychiatric inventory workshop: behavioral and psychologic symptoms of dementia in Asia

The Neuropsychiatric Inventory (NPI) was introduced in 1994 and has since become a standard instrument for clinical trials and other types of behavioral research in dementing disorders. Its reliability and validity have been confirmed. The NPI was the subject of a workshop in Asia in conjunction with the International Workgroup on Dementia Drug Guidelines (IWG). Investigators using the NPI from 4 Asian areas--Taiwan, Hong Kong, Japan, Thailand--presented conclusions from their research. A high prevalence of behavioral disturbances across Asian countries was found and the rates are similar to those observed in Western countries. Apathy is more difficult to detect and characterize in Asian populations. Neurobiologic studies show an excess of some serotonin receptor gene polymorphisms in patients without behavioral disturbances and positron emission tomography reveals reductions in frontal lobe metabolism in patients manifesting depression as measured by the NPI. Studies in Thailand show relationships among verbal fluency, activities of daily living, and neuropsychiatric symptoms particularly agitation, apathy, and disinhibition. This suggests a triad of symptoms of behavioral abnormalities, executive dysfunction, and abnormalities of activities of daily living that impugn frontal lobe function. The NPI is a reliable and useful instrument to characterize behavioral changes in Asian and Western populations.     

The relationship between donepezil and behavioral disturbances in patients with Alzheimer's disease.

The authors tested the hypothesis that behavioral disturbances are reported at significantly lower rates by caregivers of Alzheimer's disease (AD) patients receiving the antidementia drug donepezil, compared with a group of patients receiving no antidementia drug treatment. Patients administered donepezilfor 6 months (n=84) were compared with patients not on donepezil (n=248). Patients taking donepezil had significantly lower levels of behavioral disturbances than patients not receiving this agent (P< or =0.011). Specifically, donepezil patients were described as significantly (P< or =0.05) less likely to be threatening, destroy property, and talk loudly. Also, significantly fewer patients receiving donepezil were treated with sedatives (P< or =0.005). These findings support the growing body of evidence that cholinesterase inhibitors have psychotropic properties and reduce behavioral disturbances in patients with AD.     

Fluoxetine decreases stereotypic behavior in primates

BACKGROUND: Primates reared in captivity may display stereotypic behaviors. These behaviors are arguably reminiscent of human obsessive-compulsive or posttraumatic symptoms, which respond to selective serotonin reuptake inhibitors (SSRIs). Captive primates with marked stereotypic behaviors were entered into a randomized controlled study of the SSRI, fluoxetine. METHODS: A sample of 10 vervet monkeys with behaviors such as marked saluting, somersaulting, weaving, or head tossing was selected. Subjects were randomized to receive fluoxetine 1 mg/kg for 6 weeks (n=5) or no treatment (n=5). A rater blind to the medication status of subjects noted the frequency of the stereotypic behaviors. RESULTS: Repeated-measures analysis of variance (RM-ANOVA) demonstrated a significant GroupxTime difference with significantly fewer stereotypic symptoms in the fluoxetine group by endpoint. At this time, three of the five fluoxetine-treated subjects (but none of the no-treatment subjects) were responders on the Clinical Global Impressions (CGI) change item (CGI < or =2). CONCLUSIONS: Stereotypic behaviors in captive vervets gradually and partially decrease in response to administration of an SSRI, paralleling research on human anxiety symptoms. Further research on animal stereotypies may be useful in providing appropriate veterinary care, and in exploring the underlying neurobiology of certain psychiatric disorders.