Juliana Lima Quintas

Use of psychotropic medications by caregivers of elderly patients with dementia: is this a sign of caregiver burden?

This study evaluated the consumption of psychotropic medications by caregivers of elderly patients with or without dementia. This was a cross-sectional study conducted at all geriatric units in Brasília, Brazil, during a two-month period. Structured interviews were performed with 311 caregivers of people with or without dementia and they completed questionnaires. Among the caregivers, 196 (63%) were caregivers of patients with dementia and 115 (37%) were caregivers of patients without dementia. Forty-four caregivers (14.1%) were taking psychotropic drugs (benzodiazepines or antidepressants), and this usage was more frequent among caregivers of patients with dementia (p<0.01). Twenty-two caregivers of patients with dementia (11.4%) had used sleeping pills after beginning care, compared with only five (4.3%) caregivers of patients without dementia (p<0.01). In conclusion, this study found that caregivers of patients with dementia took psychotropic drugs (benzodiazepines and antidepressants) more frequently than the ones of patients without dementia.

Circadian rhythm in Alzheimer disease after trazodone use.

A circadian rhythm is a cycle of approximately 24 h, responsible for many physiological adjustments, and ageing of the circadian clock contributes to cognitive decline. Rhythmicity is severely impaired in Alzheimer disease (AD) and few therapeutic attempts succeeded in improving sleep disorders in such context. This study evaluated sleep parameters by actigraphy in 30 AD patients before and after trazodone use for 2 weeks, and we show a significant improvement in relative rhythm amplitude (RRA), compatible with a more stable daytime behavioral pattern. So, trazodone appears to produce a stabilization of the circadian rhythms in individuals with AD.

Mirtazapine does not improve sleep disorders in Alzheimer's disease: results from a double-blind, placebo-controlled pilot study

The aim of this study was to test the efficacy and safety of mirtazapine in the treatment of sleep disorders in patients with Alzheimers disease by means of a randomized, double‐blind, placebo‐controlled trial. Measurements were obtained for 7 days before intervention (baseline) and for 2 weeks after the onset of treatment.

Trazodone and cognitive performance in Alzheimer disease.

To the Editors: Cognitive impairment is well recognized as a common adverse effect of sleeping pills, such as benzodiazepines and ‘‘z-drugs.’’ There are few studies about the effect of antidepressants (including trazodone) on cognition. Despite its approval by the Food and Drug Administration to treat depression, insomnia is the most frequent reason for trazodone prescription. It exerts hypnotic actions at low doses (25 to 150 mg of dose range) due to blockade of 5-HT2A receptors as well as of H1 histaminic and >1 adrenergic receptors. In a recent study, Roth et al evaluated the cognitive and psychomotor effects of 50 mg of trazodone for 7 days in 16 primary insomniacs (mean age, 44 years) in a randomized, double-blind, placebo-controlled trial, resulting in small but significant impairment of short-term memory, verbal learning, balance, and arm muscle endurance among users. On the other hand, a double-blind, crossover trial from Rush et al compared the acute, subject-rated performance-impairing effects of trazodone (50, 100, 200 mg) and of triazolam (0.125, 0.25, 0.50 mg) with placebo in healthy subjects, which produced significant impairment in learning, recall, and performance skills with triazolam, but not with trazodone. Recently, our group published the results of a randomized, double-blind, placebo-controlled trial to examine possible improvements in sleep parameters in Alzheimer disease (AD) patients admitted with sleep disorders (SDs) after use of trazodone 50 mg. Briefly, patients were assessed by wrist actigraphy for a period of 7 to 9 days at baseline (to establish a sleep profile) and for 2 weeks during intervention when receiving 50 mg once daily at 10:00 P.M. (or placebo, in a 1:1 ratio). This trial was registered at clinicaltrials.gov, accession #NCT01142258. The results concerning the primary aim (trazodone effect on SD of AD patients) are presented therein along with detailed aspects of our methods and procedures. As secondary aim, our hypothesis was that trazodone 50 mg can be used in AD patients with no worsening of cognitive skills, and the scope of the present letter relies on discussing this important finding. With approval of the protocol by the institutional Research Ethics Committee, written informed consent was obtained from all (participants and/or caregiver), including for this complementary investigation. In brief, a neuropsychological inventory was put together to comprise a cast of cognitive assessments based on the criteria of being easy-to-handle and producing useful information by covering a range of cognitive abilities usually impaired in AD patients, so to justify their frequent usage in clinical and research scenarios in view of the author’s experience. These instruments were as follows: Mini Mental State Examination (MMSE); Paired Associate Learning Test-Form I (short-term memory) and Paired Associate Learning Test-Form II (long-term memory) of the Wechsler Memory Scale; and Digit Span Test, Arithmetic, Letter-Number Sequencing, Digit Symbol-Coding and Symbol Search of the Wechsler Adult Intelligence Scale (third edition, WAIS-III). Prior and after intervention, all tests were performed by one single trained neuropsychologist, blinded, with assessment and reassessment done in the same interviews in which the actigraphic device was placed or returned, respectively. Tests were applied in the morning (10Y12 hours) after the most recent dose. This routine of trazodone use and reassessments probably reduced biases related to major intersubject variance in bloodstream concentration of the drug, whose elimination half-life in the male and female elderly ranges from 8.2 and 7.1 hours, respectively. Thirty-six participants were randomized to either the active treatment (n = 19) or the placebo group (n = 17). One subject of the trazodone group was excluded for not complying with regular use of the prescribed antihypertensive and antiarrhythmic drugs, evolving into heart failure. One patient of the placebo group was also excluded because of an episode of agitation and consequent arm fracture. Complete analyses comprised 34 patients: 18 in active treatment and 16 in placebo. Comparing baseline measures of the 2 groups using the W test for categorical variables or the Student t test for continuous variables (Mann-Whitney U test for non-Gaussian distributed traits), no differences could be devised. The mean age of the whole group was 81.0 T 7.5 years, with women comprising 66.7% of the sample. The mean MMSE score was 11.2 T 6.2 and the most frequent clinical dementia rating scores were 2 and 3. Demographic and descriptive variables (age, sex, marital status, educational level, clinical dementia rating, Cornell depression scale) were the same (P Q 0.05) across intervention groups. None of these variables were reexamined at the end point stage. On what concerns medication use, it is probably worth mentioning that the frequency of users of the most common drugs to treat AD (donepezil, galantamine, rivastigmine, and memantine) as well as of users of antipsychotic drugs was no different across treatment arms. Patients were not allowed to change medications during the study period. Posttreatment scores were herein expressed as the value of absolute, net change in each test, compared using analysis of covariance between treatment arms taking baseline scores as covariables. Our main finding was no differential cognitive performance of trazodone-treated subjects compared to placebo-treated equals, with results shown here (in parenthesis) as the observed net difference followed (in brackets) by the range of its 95% confidence interval and by (after semicolon) the significance level achieved: MMSE (0.1 [j0.9 to 1.1]; P = 0.866), forward/backward digit span task (0.9 [j0.3 to 2.3]; P = 0.150), letter-number sequencing (0.0 [j0.9 to 0.9]; P = 0.958), arithmetic (0.2 [j0.4 to 0.9]; P = 0.453), digit-symbol coding (0.6 [j1.3 to 2.4]; P = 0.528), and symbol search (j0.9 [j2.4 to 0.5]; P = 0.191). The Paired Associate Learning Tests of the Wechsler Memory Scale could not be performed due to the severity of the dementia, and the authors advise other research groups to rule out the instrument whether investigating moderate to severe statuses. All in all, on top of improving sleep of AD patients (as described in our primary report), trazodone demonstrates the property of not impairing (nor improving) cognitive functions. A body of evidence helps advocating in favor of our conclusion. A double-blind, crossover study evaluated the use of trazodone 100 mg in healthy adults aged 60 years or older in comparison with amitriptyline and placebo and did not observe effects on either information processing, attention or visual-motor skills. Another study evaluating continuous nocturnal doses of mirtazapine 15 mg, trazodone 25mg, or placebo for 8 days in healthymen showed that trazodone did not impair driving or cognitive skills. In the largest prospective cohort so far (4414 cognitively preserved participants; aged 50 years or older), trazodone was not implicated in decline of psychometric performance. Some reasons might explain the disparities between these former (including our) Letters to the Editors Journal of Clinical Psychopharmacology & Volume 35, Number 1, February 2015

Lack of association between apolipoprotein E genotypes and cognitive performance in the non-demented elderly

The ε4 alelle of the apolipoprotein E gene is known to be a key genetic risk factor for Alzheimers disease and possibly for other neurological disorders. Some evidence in the literature indicates that the ε4 allele interferes with human cognition independently of chronological age and diagnosis of Alzheimers disease. The present study investigated the correlation of allelic variants of apolipoprotein E with the cognitive performance of elderly individuals without apparent cognitive impairment.

Apathy syndrome treated successfully with modafinil

The treatment of apathy is often complicated and difficult. The authors present a case of apathy syndrome that was treated successfully with modafinil. An 87-year-old widowed Brazilian woman presented with loss of interest and pleasure in activities. Her level of apathy, as evaluated by the Brazilian care giver version of the apathy scale, was 25 (a score higher than 18 points is associated with an apathy syndrome). No diagnosis of depression or sleep disorder was noted. After 2 years with many different antidepressants, modafinil treatment was started at 100 mg/day. One month after the initiation of modafinil therapy, the patient reported feeling more motivation, and she also returned to her favorite physical activity, which was swimming (400 m/day). Apathy scale revealed an improvement (18 points). Actigraphic analysis was performed, and no sleep disturbances were noted before or after treatment. Modafinil may be a promising option in the treatment of apathy.

Incidência de distúrbios do sono em pacientes com doença de Alzheimer

OBJECTIVE To determine the incidence of sleep disorder at a follow-up examination from 1 to 4 years, in demented patients diagnosed at first visit, besides analyzing associated demographic and comorbidities characteristics. METHODS A total of 122 elderly patients aged 60 years or older and diagnosed with dementia (Alzheimer and other) were followed in a reference geriatric center for dementia. The clinical protocols included interviews with patient and caregiver, complete physical examination, laboratory and imaging tests. Criteria for the diagnosis of sleep disorder included complain of insomnia from the patient or caregiver using the Neuropsychiatric Inventory nighttime. RESULTS The incidence density of sleep disorder among dements was 18.7/100 person/years. The risk of developing sleep disorder within the frst and fourth years of follow-up was 9.8% and 50.9%, respectively. Multivariate Coxregression analysis revealed that educational level less than 8 years and report of aggressiveness at baseline were an independent predictor of sleep disorder, increased risk in 3.1 (95%CI: 1.30-9.22) and 2.1 times (95%CI: 1.16-4.17), respectively. CONCLUSION The incidence of sleep disorder in demented patients was elevated, and was particularly associated to low educational level and aggressiveness at admission.

A 95-year-old woman with leucocytosis and eosinophilia: anaplastic carcinoma in an ectopic thyroid

A 95-year-old woman had been treated over the past 8 years for progressive dysphagia. When her condition worsened, blood tests revealed the presence of leucocytosis and eosinophilia in the absence of anaemia or thrombocytopenia. Within 11 days of diagnosis, the patient died of respiratory failure. Necropsy showed normal thyroid tissue and an absence of infectious disease. However, an upper mediastinal tumour was found and was histopathologically diagnosed as a neoplastic transformation of the ectopic thyroid. Only 1% of endothoracic goitres present as ectopic or autonomous goitre with no parenchymal or vascular connection to the thyroid gland. This case represents a very rare situation in which a leukemoid reaction and peripheral hypereosinophilia were observed as a manifestation of an anaplastic thyroid carcinoma in an ectopic mass.