摘要:

Estrogen replacement therapy (ERT) is widely used in postmenopausal women for the prevention of cardiovascular disorders and decreased bone mineral density (osteoporosis). A possible role of ERT in reducing depression and cognitive impairment has been suggested. However, an increased incidence of depression after menopause is still controversial and, similarly, the cognitive changes associated with menopause need further study and clarification. While the response of these conditions to ERT is still controversial, the findings of several studies indicate that ERT reduces the deterioration of well-being and cognition in otherwise healthy postmenopausal women.

ISSN:1172-7047    

出版商:ADIS    

年代:1995

数据来源: ADIS

摘要:

Tacrine, a centrally acting, reversible acetylcholinesterase inhibitor, is effective in the treatment of Alzheimer's disease. However, a major adverse effect of the drug is hepatotoxicity, which affects about one-half of patients treated.The pathogenic mechanisms of this hepatotoxicity are poorly understood, but probably involve reactive metabolites. The liver injury is predominantly that of hepatocellular necrosis, and manifests as an increase in serum alanine aminotransferase (ALT) levels; 25 and 2% of patients will experience ALT levels greater than 3 times and 20 times the upper limit of the normal range, respectively.Although hepatotoxicity is generally asymptomatic and has not led to death, severe reactions have been reported, and careful monitoring of ALT levels is mandatory in all patients, especially during initiation of therapy and following dose escalation. An ALT level exceeding 3 times the upper limit of the normal range should prompt withdrawal of the drug.Following cessation of tacrine, ALT levels generally decrease rapidly and usually normalise within 6 weeks. Rechallenge can be safely attempted once ALT levels are near normal, except in patients whose ALT levels were markedly increased or in whom a moderate increase of ALT levels was associated with features of hypersensitivity (e.g. rash, fever, eosinophilia). Approximately 90% of those patients rechallenged with tacrine will tolerate the drug and continue with therapy on a long term basis. Minimisation of morbidity and maximisation of the number of patients treated in the long term can be achieved by following sensible guidelines and by the early recognition of danger signs.

ISSN:1172-7047    

出版商:ADIS    

年代:1995

数据来源: ADIS

摘要:

Insomnia is defined as the inability to get the amount or quality of sleep necessary for optimal functioning and well being. Long term or chronic insomnia has been conventionally considered to be that lasting for at least 21 to 30 nights; however, it usually persists for months or years. It is more frequent in women than in men, and becomes more pronounced with age.Chronic insomnia is associated with mental disorders, psychophysiological conditions, inadequate sleep hygiene, neurological disorders and drug dependency. The most prevalent diagnosis is chronic insomnia associated with psychiatric disorders, followed in precedence by psychophysiological conditions.In chronic psychophysiological insomnia, idiopathic insomnia and insomnia associated with generalised anxiety, nonpharmacological strategies and sleeppromoting medication (e.g. hypnotics) are indicated. In patients with chronic insomnia associated with major depressive disorders, antidepressants that induce acute sedation (e.g. amitriptyline, doxepin, trazodone) represent the primary drug treatments of choice. When necessary, hypnotics can be added.Currently used hypnotics include benzodiazepine derivatives, the cyclopyrrolone zopiclone and the imidazopyridine zolpidem. Hypnotics with a short half-life show the best profile of efficacy versus adverse effects with regard to morning awakening and daytime functioning. In patients with chronic insomnia, hypnotics reduce sleep-onset latency, decrease the number of nocturnal awakenings and reduce the time spent awake. The increase in total sleep time is related to greater amounts of non-rapid eye movement (NREM) sleep.Few differences exist between benzodiazepines, zopiclone and zolpidem in terms of effectiveness in inducing and maintaining sleep. However, in contrast to the benzodiazepines and zopiclone, zolpidem does not suppress slow-wave sleep. Sleep laboratory and clinical studies tend to indicate that benzodiazepines are only effective when administered for relatively short periods of time in patients with chronic insomnia. Furthermore, a rebound insomnia has been described for short- and intermediate-acting benzodiazepines and zopiclone, and a withdrawal syndrome, denoting the presence of psychological and physical dependence, follows the abrupt cessation of benzodiazepine administration. In contrast, no evidence of tolerance or rebound insomnia has been observed in relation to zolpidem administration.

ISSN:1172-7047    

出版商:ADIS    

年代:1995

数据来源: ADIS

摘要:

HIV infection is associated with considerable psychiatric, as well as medical, morbidity. Epidemiological studies indicate that patients who are infected with HIV are at an increased risk of having a psychiatric disorder compared with uninfected individuals. Knowledge of infection with HIV is associated with considerable psychological stress. Moreover, HIV infection produces direct and indirect brain injury leading to the development of psychiatric conditions. Conversely, the vulnerabilities and behaviours necessary for contracting HIV are associated with some psychiatric disorders, so that increasingly large numbers of patients with these disorders are becoming infected with the virus. Patients with psychiatric disorders are at higher risk than others in the general population of continuing high-risk HIV-related behaviour, and are less responsive to education.The psychiatric disorders that are most common among individuals who have HIV infection are substance abuse, mood, anxiety and cognitive disorders. Psychiatric disorders are an aspect of HIV infection that responds to appropriate treatment. Such treatment is based on careful evaluation and differential diagnosis of psychiatric symptoms. A variety of psychotherapeutic agents are available to the clinician to treat these disorders. These are best administered after the establishment of good doctor-patient rapport, and in tandem with ongoing education and supportive psychotherapy.

ISSN:1172-7047    

出版商:ADIS    

年代:1995

数据来源: ADIS

摘要:

The abuse of prescription and over-the-counter psychoactive medications, tobacco, caffeine or alcohol (ethanol) by elderly adults is a clinical situation that many physicians encounter. The issues of diagnosis and clinical presentation of drug abuse may differ in the elderly compared with younger individuals, and physicians need to be aware of these issues to ensure the most appropriate management of elderly patients.Cognitive (e.g. memory loss), physical (e.g. falls) and behavioural (e.g. depression, insomnia) changes may be signs of substance abuse in elderly individuals. However, these signs may be misdiagnosed as being due to aging. The quantity of the substance(s) used by elderly persons may underestimate the frequency and severity of problems as, due to altered pharmacokinetics and pharmacodynamics, the elderly are more sensitive to the effects of many drugs.Hypnosedatives are among the most commonly used psychotropic medications in the elderly and they have a high potential for abuse. The elderly are very sensitive to the CNS depressant effects of these drugs and, as a result, misuse (e.g. unintentional overuse) can lead to dependence and abuse. There is limited information on the abuse of opioid analgesics, but their misuse can result in physical dependence.Although the prevalence of tobacco smoking is relatively low among the elderly, older smokers tend to smoke more and be more dependent on nicotine than their younger counterparts. Quitting smoking in old age has significant health benefits, and increased age has been found to be associated with an increased success in achieving abstinence.Caffeine, consumed mainly in the form of tea, may contribute to insomnia and complaints about sleep quality, especially among the institutionalised elderly. Ulcers, pancreatic cancer and osteoporosis have been related to caffeine intake in some, but not all, studies.Alcohol abuse, dependence and associated problems are less likely to be detected in the elderly because many of the diagnostic criteria (e.g. work-related problems) do not apply. Elderly patients in acute alcohol withdrawal may require more careful management than younger ones.Prevention strategies for substance abuse range from the education of patients, physicians and other healthcare workers to monitoring, regulations and legislations by governments. Future research should aim to improve the diagnosis and detection of substance abuse, and to develop treatment and prevention programmes.

ISSN:1172-7047    

出版商:ADIS    

年代:1995

数据来源: ADIS

摘要:

Recurrent brief depression (RBD) fulfils DSM-IV criteria for major depression, with the exception of the duration of the depressive episodes. Recent epidemiological studies have confirmed the existence of RBD and estimated that it has a high prevalence in the general population and in general practice (approximately 10%). These studies also indicate a high comorbidity of RBD with attempted suicide, other forms of depression, anxiety disorders and substance abuse.At present, data on the treatment of this disorder are sparse. Results from the few preliminary treatment studies that have been performed to date do not indicate that antidepressants are the treatment of choice. However, the mechanism of action and appropriate dosage of antidepressants in this disorder and the influence of comorbid disorders on treatment response have not yet been addressed sufficiently. Studies in carefully selected patient samples with RBD using various pharmacological approaches are required to further clarify which drugs might be specifically effective in this disorder.

ISSN:1172-7047    

出版商:ADIS    

年代:1995

数据来源: ADIS

摘要:

SynopsisSelegiline (deprenyl) increases nigrostriatal dopamine levels by several mechanisms, including selective and irreversible inhibition of cerebral monoamine oxidase type-B. Through this mechanism it may also protect neurons against damage by free radicals and possibly exogenous neurotoxins.When used alone in patients with early Parkinson's disease, oral selegiline 5mg twice daily initially reduces symptom severity compared with placebo. During prolonged therapy, selegiline slows the rate of symptom progression and delays the need for levodopa therapy by 6 to 9 months.The benefits of coadministration of selegiline with levodopa as de novo therapy in early Parkinson's disease compared with levodopa monotherapy remain unclear. Studies have shown either similar disease progression in both treatment groups after 3 years or significantly slowed disease progression and reduced levodopa requirement after 14 to 54 months in patients treated with both drugs compared with levodopa monotherapy.In patients with more advanced disease who have mild levodopa response fluctuations, concomitant selegiline allows a reduction in levodopa dosage. Improvements in overall disability and ‘end-of-dose’ fluctuations are observed, although benefits are rarely maintained for longer than a year.Improvements in cognitive function, behaviour and activities of daily living have been observed in patients with Alzheimer's disease following administration of selegiline 10 mg/day for up to 15 months, and the drug appeared to be more effective in this regard than l-acetylcarnitine, oxiracetam and phosphatidylserine in single-blind studies. In addition, preliminary findings suggest that selegiline may have an additive effect when coadministered with cholinergic therapy.At the dosage recommended for Parkinson's disease and Alzheimer's disease, selegiline is not associated with the tyramine (‘cheese’) reaction.Thus, selegiline is a valuable treatment option for de novo therapy of patients with early Parkinson's disease, improving symptoms and postponing the need for levodopa therapy. Whether it also offers clinically significant neuroprotection remains unclear. Selegiline is a useful adjunct to long term levodopa therapy in patients with more advanced disease experiencing response fluctuations, and recent findings suggest that it may offer some clinical benefit to patients with Alzheimer's disease.Overview of Pharmacological PropertiesSelegiline increases cerebral dopamine levels through selective irreversible inhibition of monoamine oxidase type-B (MAO-B), an enzyme involved in central dopamine metabolism.The drug has proven to be an effective treatment for the symptoms of Parkinson's disease, a disorder that results from a progressive loss of dopaminergic cells in the substantia nigra and consequent depletion of the neurotransmitter dopamine. While opinion remains divided as to whether selegiline is also neuroprotective in patients with early Parkinson's disease, several mechanisms of action have been identified which may account for a neuroprotective effect of the drug. Inhibition of MAO-B by selegiline may reduce the free radical formation and oxidative stress associated with dopamine metabolism, which can cause neuronal damage and cell death. In addition, selegiline-mediated inhibition of MAO-B may prevent the conversion of environmental agents [such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)] to their active toxic forms which are capable of inducing Parkinson-like symptoms in humans. In animal studies, selegiline inhibited neurotoxin uptake into neurons and protected dopaminergic neurons against damage from neurotoxins by inhibiting MAO-B activity. Selegiline also rescued damaged neurons through a trophic-like effect independent of MAO-B inhibition. Other activities of selegiline supporting a neuroprotective effect have also been identified inin vitroand animal studies; however, no direct pathological evidence supporting a neuroprotective effect of selegiline in humans is available.While prolonged selegiline administration increased the lifespan of aged rodents, data on such an effect in humans with Parkinson's disease are conflicting.Findings that patients with Alzheimer's disease have reduced brain dopamine levels and increased MAO-B activity indicate that selegiline may be of some clinical benefit in the treatment of this disease.The bioavailability, mean peak plasma concentration (Cmax) and time to reach Cmaxfollowing an oral 10mg dose of selegiline are, respectively, about 10%, 2 μg/L and 0.6 hours. Selegiline is subjected to extensive and rapid hepatic metabolism, the main metabolites beingl-methamphetamine,l-amphetamine and demethyl-selegiline. While demethyl-selegiline has some MAO-B inhibitory activity,l-methamphetamine andl-amphetamine may contribute to neuroprotective effects of the drug. The apparent volume of distribution of selegiline is 500L, although the drug is 94% bound to plasma proteins. Renal elimination is the predominant route of excretion, with 86% of an oral dose recovered in the urine, principally asl-methamphetamine (59%) andl-amphetamine (26%).Clinical EfficacyImprovements in symptom severity have been observed in previously untreated patients with early Parkinson's disease during the first 3 months of monotherapy with oral selegiline 5mg twice daily. In particular, initial improvements in the Unified Parkinson's Disease Rating Scale (UPDRS) scores for motor function and mental state were observed. During prolonged therapy (1 to 3 years), selegiline monotherapy significantly slowed symptom progression compared with placebo. Scores for overall disability were lower in selegiline recipients after 1 to 3 years of therapy, and the need for levodopa to control symptoms was delayed by 6 to 9 months. Subsequent coadministration of selegiline with levodopa reduced the dosage of levodopa required to maintain an adequate response by up to 80% after 5 years' combined treatment.A single comparative study found that while levodopa monotherapy was associated with a higher incidence of motor fluctuations than selegiline, lisuride or bromocriptine monotherapy in patients with early Parkinson's disease, fewer patients treated with levodopa required add-on therapy compared with the other treatment groups after a mean follow-up of 20 months.Coadministration of selegiline with levodopa asde novotherapy in patients with early Parkinson's disease significantly improved disability scores compared with levodopa monotherapy over treatment periods of 14 to 54 months in 3 recent double-blind studies. In addition, the need to increase the levodopa dose to compensate for disease progression was less common in patients who received selegiline. In contrast to these findings, a large nonblind randomised study found no clinical benefit of adding selegiline to levodopa therapy over a 3-year period.Concomitant administration of selegiline to patients experiencing response fluctuations during long term levodopa therapy generally improved motor function, reduced disability rating scores, improved ‘end-of-dose’ fluctuations and reduced levodopa dosage requirements (by 10 to 30%). However, long term studies indicate that the benefits of adding selegiline to long term levodopa therapy are maintained in the majority of patients for only 7 to 8 months.Double-blind placebo-controlled trials indicate that selegiline is of some clinical benefit in patients with Alzheimer's disease. In the majority of studies, selegiline therapy was associated with greater improvements in rating scores for cognitive function, behaviour and activities of daily living compared with placebo, or the neuropsychotherapeutic agentsl-acetylcarnitine (ST-200), oxiracetam and phosphatidylserine. Preliminary findings suggest that selegiline may have an additive effect when coadministered with cholinesterase inhibitors (such as tacrine or physostigmine salicylate), although this requires further investigation.Pharmacoeconomic ConsiderationsStudies evaluating the pharmacoeconomic value of selegiline in the treatment of Parkinson's disease are unavailable at present. However, clinical studies indicate that the drug is likely to improve patient quality of life and have a favourable cost-effectiveness ratio as monotherapy in patients with early disease and when used as adjunctive therapy in patients with response fluctuations receiving long term levodopa therapy. Selegiline therapy has the potential to reduce direct costs including hospitalisation, medical care and physician fees, and indirect costs associated with the significant impairment in quality of life in patients with Parkinson's disease. The greatest economic benefit of selegiline is anticipated to result from a delay in the onset of disability in patients with early Parkinson's disease. It has been estimated that an agent which slowed progression of disability by around 10% would realise savings (through reduction in both direct and indirect costs) in the order of $US330 million per annum in the US. While the available evidence indicates that selegiline delays symptom progression by up to 9 months, further study is required to determine the true pharmacoeconomic value of the drug to society.TolerabilitySelegiline, at the dosage used for treatment of Parkinson's and Alzheimer's diseases, is a selective and irreversible MAO-B inhibitor which is not associated with the tyramine (‘cheese’) reaction. Peak concentration dyskinesias may be exacerbated when selegiline is added to the levodopa treatment regimen, and mood elevation, insomnia, hallucinations and confusion have been reported during coadministration of both drugs. Insomnia and euphoria may occur during selegiline monotherapy, as well as gastrointestinal symptoms (mainly nausea) and orthostatic hypotension.Dosage and AdministrationSelegiline 5mg twice daily (with breakfast and at midday), administered orally either as monotherapy or in combination with levodopa, is recommended for the treatment of patients with Parkinson's disease. Clinical trials to date indicate that the same dosage of selegiline may be of clinical benefit in patients with Alzheimer's disease.The concurrent use of selegiline with pethidine (meperidine) is contraindicated, and administration of selegiline with selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors or tricyclic antidepressants should be avoided.

ISSN:1172-7047    

出版商:ADIS    

年代:1995

数据来源: ADIS