Article Abstract:
Research has demonstrated low levels of serotonin (5-HT) in patients with Alzheimer's disease (AD), vascular dementia (VD), and senile dementia of Alzheimer type (SDAT). Citalopram is an antidepressant medication which blocks the reuptake of 5-HT into serotonin receptors, leaving more active serotonin free in the body system. To assess the effects of citalopram in dementia disorders, 98 patients diagnosed with moderate AD, SDAT or VD were evaluated in Norway in a double-blind study of citalopram versus placebo (neither the patients nor the experimenters knew who received citalopram and who received placebo). All patients took placebo for one week (baseline period), and were then randomly assigned to either citalopram or placebo treatment for four weeks. After this, all patients knowingly took citalopram for eight weeks, and then were again randomly assigned to either placebo or citalopram treatment for a few weeks, when withdrawal effects were evaluated. Various scales, physical exams and laboratory tests assessed treatment efficacy and side effects at the end of the baseline period and over the course of the experiment. Baseline ratings indicated emotional disturbances in 85 patients. The most common disturbances were mild depression, low motivation, emotional blunting, anxiety and confusion. After four weeks of double-blind treatment, the AD and SDAT patients treated with citalopram showed significant improvements in emotional blunting, confusion, irritability, anxiety, panic, depressed mood and restlessness. Citalopram was not found to have any significant effects on the VD population, and no effects were found in placebo-treated patients. Citalopram led to very few and very mild side-effects. No withdrawal symptoms were found when administration of citalopram was stopped. (Consumer Summary produced by Reliance Medical Information, Inc.)
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Article Abstract:
Studies of treatment regimens in dementia are difficult to interpret, in part, because most demented patients are elderly, have additional medical disorders (e.g., hypertension), and age-related reactions (e.g., low toxicity thresholds) to the drugs being tested. Two theories have emerged from studies examining the neurobiological aspects of senile dementia: the specificity theory suggests that each type of dementia is characterized by particular patterns of abnormalities of the substances that facilitate nerve signal transmission (neurotransmitters); the selectivity theory suggests that neurotransmitter abnormalities in each type of dementia are related to specific patterns of neuron loss. Cognitive (information acquisition and processing) deficits are central to most concepts of dementia, while behavioral and mood changes are viewed as secondary complications. Alzheimer's disease (AD) is the most studied of all dementias. In the late 1970s, it was discovered that alterations in cholinergic (involving the release of the neurotransmitter acetylcholine) activity are related to cognitive deficits in AD patients. Due to their side effects and the fact that they cannot selectively target central neurons, cholinergic activators have not been widely investigated in humans. Other treatment regimens involve vitamin therapy and drugs which modify the synthesis of various hormones, or modify serotonin, dopamine, gamma-aminobutyric acid and peptide neurotransmission. Although there are no known consistently effective drugs to prevent or relieve dementia, there is a great deal of ongoing research. An understanding of the molecular pathology of degenerative neurological disorders will likely provide the best approach for future treatment and prevention strategies. (Consumer Summary produced by Reliance Medical Information, Inc.)
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Article Abstract:
Donepezil has joined tacrine hydrochloride as the only approved drugs for the treatment of dementia in Alzheimer's patients. Alzheimer's dementia is thought to be caused by a depletion of acetylcholine, which is a neurotransmitter. Donepezil, whose trade name is Aricept, blocks the enzyme that breaks down acetylcholine. In three controlled trials, donepezil was more effective than a placebo in improving cognitive function, but the effects were modest. Adverse effects include nausea, vomiting and diarrhea.
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