Medicamentos utilizados para trastornos cognitivos: Análisis de un millón y medio de prescripciones en la Argentina / Drugs used for cognitive impairment: Analysis of 1.5 million prescriptions in Argentina

Los costos originados por trastornos cognitivos y demencias son significativos para los sistemas de salud. Según guías nacionales e internacionales, los fármacos recomendados para su tratamiento son inhibidores de colinesterasa (donepecilo, galantamina y rivastigmina) y memantina. En la Argentina también son utilizados otros nootrópicos, galantamina, rivastigmina, vasodilatadores, vitaminas y antioxidantes. El objetivo del presente estudio es describir y comparar el patrón de prescripción de drogas para el tratamiento de trastornos cognitivos y demencias en las distintas regiones del país. Se realizó un estudio observacional retrospectivo a partir de las prescripciones (1 814 108 envases) realizadas en la práctica clínica habitual durante el segundo semestre del 2008 y el primer y segundo semestre del 2009. El trabajo fue realizado sobre la población total del Instituto Nacional de Servicios Sociales para Jubilados y Pensionados. Se analizaron variables demográficas, cantidad y tasa de prescripciones, presentaciones y dosis utilizadas por regiones. Considerando todo el país, memantina fue la droga más prescripta en esos períodos, con un total de 570 893 envases. Memantina, donepecilo, rivastigmina e idebenona presentaron un incremento en las tasas de prescripción 2008-2009. Analizando los cambios regionales en tasas de prescripción, la memantina aumentó en el Noroeste y Noreste argentino, la idebenona en el Noroeste y la Patagonia y el donepecilo en el Noreste. Grupos de fármacos no recomendados fueron altamente prescriptos en todas las regiones del país. Algunos fueron indicados en adultos jóvenes o de mediana edad.

Cognitive impairment and dementia treatment costs are significant for health systems. According to national and international guidelines, recommended drugs for treatment of dementias are cholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine. Despite these guidelines recommendations, other nootropics, vasodilators and antioxidants are often used in Argentina. The purpose of this study was to describe and compare the prescription pattern of commonly used drugs for the treatment of cognitive disorders and dementia in different regions of Argentina. An observational, retrospective study of 1 814 108 recipes prescribed to National Institute of Social Services for Retired and Pensioners outpatients during the during the second half of 2008 and the first and second half of 2009 was performed, taking in count the whole country and also different Argentina´s regions. Demographic variables, quantity and rate of prescriptions, dosage forms and strengths were analyzed. Considering the entire country, memantine was the most prescribed drug in these periods (570 893 packages). An increase in the memantine, donepezil, rivastigmine and idebenone rates of prescription was observed. Prescription rate of memantine increased in the North-West and North-East regions, that of idebenone in the North-East region and Patagonia and donepezil in the North-East region. Non recommended drugs were highly prescribed in all the analyzed regions. Some of them were indicated to young and middle-aged patients.

Disfunção cognitiva após cirurgia cardíaca / Postoperative cognitive dysfunction after cardiac surgery

Disfunção cognitiva pós-operatória é situação freqüente em cirurgias cardíacas, o que pode levar a conseqüências imensuráveis para os indivíduos acometidos. Os processos fisiopatológicos envolvidos nessa condição ainda não se encontram totalmente elucidados, apresentando um caráter multifatorial. Além de fatores pré-operatórios, como idade e escolaridade, alguns fatores intra-operatórios também são de extrema importância. Entretanto, conforme ampla literatura sobre o tema, esses fatores não são capazes de esclarecer etiologicamente a totalidade dos casos, remetendo a uma base genética para essa seqüela neurológica. Nessa revisão, avaliamos fatores envolvidos na disfunção cognitiva e a terapia farmacoprotetora empregada em sua prevenção.

Postoperative cognitive dysfunction is frequent in cardiac surgeries leading to major consequences. The physiopathological processes involved in this condition are still not completely elucidated, despite the multifactor character. Besides pre-operative factors such as age and education, some intra-operative factors are also of extreme importance. However, according to a vast literature on the subject, these factors are not capable to clarify the totality of the cases, taking us to a genetic base for this neurological sequel. In this revision, we briefly assess the factors involved in this cognitive dysfunction as well as discuss the pharmacotherapy in the prevention of this event.

Cognitive improvement after treatment of depressive symptoms in the acute phase of stroke

Os resultados do tratamento com antidepressivo para os sintomas depressivos e comprometimento cognitivo da fase aguda do acidente vascular cerebral não estão estabelecidos. Investigamos 93 pacientes, 36 com sintomas depressivos graves (HAM-D: Escala de Depressão de Hamilton >18) foram tratados com citalopram, enquanto 19 pacientes com sintomas depressivos leves e 38 não-deprimidos não foram tratados. Ao início do tratamento (duas semanas depois do icto), pacientes com sintomas depressivos graves tinham escores mais baixos na Escala de Avaliação de Demência (DRS) total e nas subescalas de atenção e de memória da DRS do que os pacientes não-deprimidos (p<0,001). Ao fim de três meses de acompanhamento essas diferenças tinham desaparecido, mas pacientes que inicialmente tinham sintomas depressivos leves passaram a ter escores mais altos no HAM-D do que os não-deprimidos (p=0,015), e escores mais baixos nas subescalas de atenção e memória da DRS (p<0,01) do que os pacientes tratados com citalopram. O tratamento associou-se a melhora de humor, memória e atenção, e demonstra que é necessário um estudo controlado com placebo para o tratamento de sintomas depressivos leves.

Emprego de metilfenidato para o tratamento de déficit cognitivo em paciente com seqüela de traumatismo cranioencefálico / Methylphenidate for the treatment of cognitive deficit in traumatic brain injury

O traumatismo cranioencefálico (TCE) é a principal causa de morte e deficiência em jovens. Déficits da atenção e das funções executivas são freqüentes relatos após comprometimentos do córtex pré-frontal. Os autores relatam um caso de emprego de metilfenidato para o tratamento de alterações cognitivas em paciente com cerca de dois anos de evolução pós-TCE. Com dois meses de tratamento, o paciente relatou melhora significativa de suas dificuldades cognitivas, com maior poder de concentração na leitura, melhor capacidade de manter a atenção em conversas e filmes, além de redução do número de vezes em que perdia objetos. Como efeito colateral, houve um pequeno aumento da irritabilidade nas primeiras duas semanas de tratamento. Ao exame neuropsicológico, constatou-se melhora substancial nas medidas de velocidade de processamento, nos erros por omissão e nos erros por comissão.

Traumatic brain injury is the main cause of death and disability among young people. Attention deficits and executive dysfunction occur frequently after prefrontal cortex damage. The authors report a case of methylphenidate use for the treatment of cognitive deficits in a patient with a two-year evolution of traumatic brain injury. After two months, the patient reported significant improvement in his cognitive deficits, with increased ability to pay attention to reading, talking, watching films and reduction in the frequency of losing objects. As a side effect, he complained of a small increase in irritability in the first two weeks. The neuropsychological assessment showed a substantial improvement in the mental processing speed, in the omission errors and in the commission errors.

Clinical and laboratory features and response to treatment in patients presenting with vitamin B12 deficiency-related neurological syndromes.

AIMS AND OBJECTIVES: To study the clinical and laboratory features of patients admitted with vitamin B12 deficiency-related (B12def) neurological syndromes. SETTINGS AND DESIGN: A hospital-based retrospective and prospective study conducted at a referral teaching hospital. MATERIALS AND METHODS: Consecutive patients admitted with vitamin B12 deficiency-related neurological disorders during a three-year period from June 2000 to May 2003 were included. Data regarding clinical and laboratory features were obtained. Follow-up was done at least six months following treatment with parenteral vitamin B12. Chi-square test was used for statistical analysis. RESULTS: A total of 63 patients (52 males) with a mean age of 46.2 years were studied. The mean duration of symptoms at presentation was 10.3 months. Myeloneuropathy (54%) was the commonest neurological manifestation, followed by myeloneuropathy with cognitive dysfunction (34%), and peripheral neuropathy (9%). Neuropsychiatric manifestations and dementia were observed in 38% and 19% of patients respectively. All the patients had megaloblastic changes in the bone marrow smear. Eleven (17.5%) patients had both hemoglobin and the mean corpuscular volume (MCV) within the normal range. Follow-up after at least six months of therapy with parenteral B12 showed improvement in 54% patients. CONCLUSIONS: A high index of suspicion of B12def is required in patients presenting with myelopathy, cognitive decline, or neuropathy. A normal hemoglobin or MCV does not exclude B12def; therefore, other tests such as bone marrow smear and serum vitamin B12 assay are essential, as the condition is often reversible with treatment.

Vitamin B12 and folate depletion in cognition: a review.

In cross-sectional studies, low levels of folate and B12 have been shown to be associated with cognitive decline and dementia Evidence for the putative role of folate, vitamin B12 in neurocognitive and other neurological functions comes from reported cases of severe vitamin deficiencies, particularly pernicious anemia, and homozygous defects in genes that encode for enzymes of one-carbon metabolism. The neurological alterations seen in these cases allow for a biological role of vitamins in neurophysiology. Results are quite controversial and there is an open debate in literature, considering that the potential and differential role of folate and B12 vitamin in memory acquisition and cognitive development is not completely understood or accepted. What is not clear is the fact that vitamin B12 and folate deficiency deteriorate a pre-existing not overt pathological situation or can be dangerous even in normal subjects. Even more intriguing is the interaction between B12 and folate, and their role in developing hyperhomocysteinemia. The approach to the rehabilitation of the deficiency with adequate vitamin supplementation is very confusing. Some authors suggest it, even in chronic situations, others deny any possible role. Starting from these quite confusing perspectives, the aim of this review is to report and categorize the data obtained from the literature. Despite the plausible biochemical mechanism, further studies, based on clinical, neuropsychological, laboratory and (lastly) pathological features will be necessary to better understand this fascinating biochemical riddle.

Evaluation of cognitive function of fluoxetine, sertraline and tianeptine in isolation and chronic unpredictable mild stress-induced depressive Wistar rats.

Depressive illness is generally associated with cognitive impairment. Serotonergic selective antidepressant drugs, fluoxetine (FLX), sertraline (SER) and tianeptine (TIA), are claimed to have less or no effect on cholinergic system, the key system involved in memory. In the present study, these drugs were evaluated for their influence on cognitive behavior in both depressive and non-depressive animals. Depression was induced by two models, (i) 60 days social isolation of litter; and ii) by applying chronic unpredictable mild stress for 21 days. Depression in the rats was confirmed by behavioral despair test. Transfer latency on elevated plus maze and inflexion ratio in passive avoidance step through behavior were employed to assess learning and memory. The results indicated that administration of fluoxetine; sertraline and tianeptine attenuated the cognitive deficits observed in depressive rats. In non-depressive rats these drugs produced retention deficit, which was found to be parameter and model dependent. Data suggested that, FLX and SER (SSRI's) effectively attenuated the isolation-induced depression and cognitive deficit, whereas TIA (SSRE) produced better effect in stress-induced depressive conditions. It was concluded that behavioral profiles of fluoxetine, sertraline and tianeptine on cognition were model and parameter dependent.

Demencia por déficit de vitamina B12. Caso clínico / Dementia caused by vitamin B12 deficiency. Clinical case

Cyanocobalamin (vitamin B12) deficiency can cause polyneuropathy, myelopathy, blindness, confusion, psychosis and dementia. Nonetheless, its deficiency as the sole cause of dementia is infrequent. We report a 59 years old man with a 6 months history of progressive loss of memory, disorientation, apathy, paranoid delusions, gait difficulties with falls, and urinary incontinence. He had suffered a similar episode 3 years before, with a complete remission. On examination there was frontal type dementia with Korsakoff syndrome, a decrease in propioception and ataxic gait. Cerebrospinal fluid examination showed a protein of 0.42 g/L. Brain computed tomography showed sequelae of a frontal left trauma. Brain single photon computed tomography (SPECT) was normal. Complete blood count showed a macrocytic anemia with a hematocrit 29 per cent and a mean corpuscular volume of 117 micron3. Plasma vitamin B12 levels were undetectable, erythrocyte folate levels were 3.9 ng/ml and plasma folate was normal. The myelogram showed megaloblastosis and the gastric biopsy showed atrophic gastritis. Treatment with parenteral B12 vitamin and folic acid reverted the symptoms, with normalization of the neuropsychological tests and reintegration to work.

The use of naltrexone to treat ambulatory patients with alcohol dependence

The purpose of this study is to evaluate the efficacy of Naltrexone in decreasing craving symptoms among Puerto Rican male veterans with alcohol dependence. METHOD: This is a double blind placebo control study with a convenience sample of eleven patients divided in two groups (placebo and Naltrexone). Scales consisting of Zung Depression, Zung Anxiety, MMSE, OCD Screener, Craving, and Somatization were administered at baseline, and weekly for four weeks as follow up. RESULTS: There were no statistically significant differences between the two groups on any of the outcome variables at baseline or follow up measurements. A statistical trend was noted toward a decrease in somatization. A decrease in craving symptoms was observed in the experimental group. CONCLUSIONS: Even though our results did not show evidence of the efficacy of Naltrexone in decreasing craving symptoms, a small number of patients did benefit from the medication. The results could have been affected by the small sample size

Neurossífilis atípica: relato de caso / Atypical neurosyphilis: report of a case

O presente estudo é baseado na observaçäo de um caso de neurossífilis no serviço de internaçäo da Clínica Olivé Leite em agosto-1992. A paciente, do sexo feminino e com 31 anos de idade, foi admitida por apresentar quadro de psicose orgânica no qual predominavam sintomas de tipo deterioraçäo cognitiva (síndrome demencial), associados a elementos paranóides (alucinaçöes e delírios). A investigaçäo diagnóstica evidenciou testes imunológicos positivos para sífilis no sangue e no LCR. Destaca-se este caso pelos seguintes aspectos peculiares: forma da apresentaçäo clínica, gravidade dos sintomas (amaurose e severo déficit cognitivo), sexo, idade e por ser este o primeiro caso diagnosticado no serviço desde 1968 (data do último registro de caso de neurossífilis no seu Banco de Dados). Após penicilinoterapia e seguimento de 9 meses, a paciente apresenta algumas melhoras, caracterizadas por: diminuiçäo da sintomatologia produtiva de tipo alucinatória e delirante, diminuiçäo do déficit cognitivo em termos de orientaçäo e maior produtividade nas atividades sociais e comportamentais

Panorama atual do tratamento farmacológico do déficit cognitivo da doença de Alzheimer: um estudo de revisäo / Actual view of the pharmacological treatment of cognitive deficit of Alzheimer disease: a review

Neste artigo o autor faz uma revisäo das estratégias farmacoterápicas mais recentes, usadas no cenário internacional, para o tratamento do declínio cognitivo progressivo que caracteriza a Doença de Alzheimer. Para tanto, baseia-se no conhecimento atual acerca da etiopatogenia e neuropatologia desta demência. Apesar dos progressos obtidos pela investigaçäo científica, a etiologia desta doença é ainda obscura e os resultados dos tratamento ainda duvidosos, priorizando-se no momento medidas terapêuticas que impliquem na lentificaçäo do processo degenerativo.

Nootropic effect of BR-16A (Mentat), a psychotropic herbal formulation, on cognitive deficits induced by prenatal undernutrition, postnatal environmental impoverishment and hypoxia in rats.

Subchronic administration of BR-16A (Mentat), a compound herbal formulation, and the nootropic agent, piracetam, augmented learning acquisition and retention of learning in normal rats, as well as in states of cognitive deficits induced by prenatal undernutrition, postnatal environmental impoverishment and sodium nitrite hypoxia. The test paradigms used were step-down latency in a passive avoidance test and transfer latency in elevated plus maze. The drugs were administered orally once daily for 7 days, behavioural testing being done 1 hr after the last administration on day 7. Post-trial performances of the rats at 24 hr and after another 7 days was assessed as indices of learning acquisition and retention of learning (memory), respectively. Mentat (100 mg/kg) and piracetam (100 mg/kg) induced statistically significant nootropic effect in all the test parameters. However, the lower dose (50 mg/kg) of Mentat did not significantly augment learning acquisition in normal rats and in induced states of cognitive deficits, but significantly improved retention of learning in normal rats and in animals with cognitive deficits. Acute single administration of either Mentat (100 mg/kg, orally) and piracetam (100 mg/kg, orally) did not exhibit any discernible nootropic effect in any of the paradigms or parameters investigated. The results indicate that Mentat, like piracetam, can facilitate learning and memory, and can be categorized as a nootropic agent. They also corroborate clinical reports on the memory-facilitative effect of Mentat and earlier experimental evidence of its nootropic activity in mice.

Evaluation of BR-16 A (Mentat) in cognitive and behavioural dysfunction of mentally retarded children--a placebo-controlled study.

It is important to control abnormal behaviour and hyperactivity, and improve cognition in mentally retarded children (MRC), which would help in their education, training and subsequent rehabilitation. Recently it has become known that amongst other side-effects, protracted use of anti-convulsant medication induces cognitive and behavioural dysfunction, which is a major problem in mentally retarded epileptics. In a placebo-controlled study, we confirmed the efficacy of a herbal preparation, BR-16A (Mentat) in controlling such behavioural and cognitive deficits in 40 mentally retarded children. The efficacy of this remedy was further evaluated in 19 MRCs with epilepsy. Twelve patients had generalised seizure, 4 with partial and 3 with mixed seizure pattern was continued. Inspite of the usual antiepileptic treatment, the frequency of seizures ranged from 1 to 7 attacks in periods from 1 week to 1 year. With active drug Br-16A, it was possible to note a reduction in seizure frequency. Patients with higher frequency responded better. There was no further increase in the dosage of antiepileptic drugs. There was significant control of other abnormal behaviour as shown by reduction in rating score on the Children's Behavioural Inventory test. BR-16A was effective in controlling abnormal behaviour, especially hyperactivity and incongruous behaviour in mentally retarded children with and without epilepsy.

Effect of dihydroergotoxine, a cerebral vasodilator, on cognitive deficits induced by prenatal undernutrition and environmental impoverishment in young rats.

The study was conducted on 64 Charles Foster strain albino rats, which were equally distributed into 8 evenly matched groups, following a 2 x 2 x 2 factorial design, by varying three independent factors at two levels: nutrition--normal and undernutrition; environment--enrichment and impoverishment, and drug treatment--vehicle and dihydroergotoxine (3 mg/kg, i.p.). Prenatal undernutrition was induced by restricting the mother's food intake. The environmental enrichment/impoverishment and the vehicle/dihydroergotoxine treatments were given during the postweaning period of the pups. The rats were subjected to original and subsequent reversal brightness discrimination learning tests in a single unit T-maze at 8-9 weeks of age. Thereafter, the animals were tested for passive avoidance learning. The results indicate that undernutrition caused significant original and reversal discrimination learning, deficits whereas environmental deprivation attenuated only the original discrimination learning performance. Dihydroergotoxine treatment facilitated the learning performance of rats in both the original and reversal learning tests. Nutritional, environmental and dihydroergotoxine treatments had no effect on the retention of the passive avoidance learning, both at 24 hr and 1 week intervals. Dihydroergotoxine treatment attenuated the learning deficits induced by prenatal undernutrition. The results indicate that dihydroergotoxine is not likely to be useful in cognitive deficits, induced by malnutrition, though it facilitated learning acquisition, since it had no effect on retention.