摘要:

Treating dementia has become a major challenge in clinical practice. Presently, acetylcholinesterase inhibitors are the first-line drugs in the treatment of Alzheimer’s disease (AD). These options are now complemented by memantine, which is approved for the treatment of moderate-to-severe AD. Altogether, a minimum of six agent classes already exist, all of which are approved for clinical use and are either already being tested or ready for phase III clinical trials for the treatment of AD. These include cholinesterase inhibitors, blockers of the NMDA receptor, antioxidants or blockers of oxidative deamination (includingGingko biloba), anti-inflammatory agents, neurotrophic factors (including hormone replacement therapy and drugs acting on insulin signal transduction) and antiamyloid agents (including cholesterol-lowering therapy). These approaches hold promise for disease modification and have a potential to be used as combination therapy for cognitive enhancement.Presently, only nine clinical studies have been published that have investigated the effects of a combination regimen on cognitive performance or AD. Among those, one study was conducted in elderly cognitively intact persons; the others involved patients with AD. Only five of the treatment studies followed a randomised, controlled design. Not all studies favoured the superior efficacy of combination therapy over monotherapy. Some studies, however, showed some evidence for synergistic combination effects of symptomatic therapy, including delay or prevention of disease progression in AD patients. In addition, six studies investigated the effects of AChE inhibitor in combination with antipsychotic or antidepressant therapy on behavioural aspects of AD symptomatology. In four of those studies there were indications that combination therapy had greater efficacy over monotherapy.The treatment of AD patients requires optimised options for all stages of illness based on the available drugs. There is a great need for further well designed studies on combination therapy in AD.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Clozapine is the most effective antipsychotic available for the treatment of schizophrenia that has proved resistant to other medications and the only antipsychotic licensed for this indication. Although the drug is increasingly being used more widely in patients with schizophrenia and with other psychiatric and neurological disorders, it is still underused. The main reasons for this are that it can cause adverse effects such as weight gain and sedation, and the need for regular blood test monitoring because of the risk of agranulocytosis. While these hurdles are unavoidable, another problem in the UK has been the historical practice of admitting patients to hospital to initiate treatment with clozapine. However, protocols have now been developed for both home and day-hospital initiation. The experience of one assertive community treatment team of starting clozapine in patients’ own homes has been positive, with no major adverse events reported. This approach is, however, extremely demanding of staff resources and for many services the use of day-hospitals to initiate treatment with clozapine is more appropriate. Research into staff and patients’ views about community initiation of clozapine, and its economic costs, would be welcome.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Disability, characterised by the loss of ability to perform activities of daily living (ADL), is a defining feature of dementia that results in growing caregiver burden and the eventual need for alternative care or nursing home placement. Functional decline in patients with dementia can also result from causes other than dementia, such as comorbid medical and psychiatric illnesses and sensory impairment. ADL consists of instrumental ADL (IADL) [complex higher order skills, such as managing finances] and basic ADL (BADL) [self-maintenance skills, such as bathing]. Assessment of IADL and BADL is recommended to establish a diagnosis of dementia. Functional assessment also helps the healthcare provider to offer appropriate counselling regarding safety concerns and need for custodial care. Functional capacity measures have been used increasingly in pharmacological trials of patients with Alzheimer’s disease (AD) and related dementias, although at the present time these measures are generally not primary outcome measures. Functional impairment is not a uniform construct; rather, it is multifaceted and can be measured with various clinical instruments. Many scales have been validated for use in patients with AD for characterising functional impairment and evaluating the efficacy of treatment. Research to date indicates that cholinesterase inhibitors have the potential for modest but meaningful beneficial effects on ADL in patients with mild-to-moderate AD. Memantine also has promising beneficial effects on functional abilities in persons with moderate-to-severe AD. Assessment of ADL as a primary efficacy measure using a validated scale that is non-gender biased and cross-nationally relevant is recommended in new treatment trials of patients with AD and related dementias.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Schizophrenia is a long-term disabling illness that affects approximately 1% of the population. Its course is generally chronic with acute psychotic exacerbations that may require frequent hospitalisations. The clinical picture includes a range of symptoms such as delusions, hallucinations, agitation, suspiciousness, hostility, conceptual disorganisation, blunted affect, emotional and social withdrawal, lack of spontaneity, poverty of speech and a wide range of neurocognitive deficits. Over the past 50 years, antipsychotic medications have emerged as the cornerstone of management in concert with other important interventions, such as psychosocial and economic support and rehabilitation efforts. However, the unrivalled role of conventional antipsychotic medications has been continuously challenged by the wide range of adverse effects of these medications and their lack of usefulness in the treatment of neurocognitive deficits as well as deficit and negative symptoms. In addition, the lack of subjective tolerability of these agents and their negative impact on quality of life have complicated management for a large number of patients. Over the last 15 years, several new atypical antipsychotic medications have been introduced, including amisulpride, remoxipride, risperidone, sertindole, olanzapine, zotepine, quetiapine, ziprasidone and aripiprazole. In general, the new antipsychotics have shown themselves to be at least comparable in efficacy to conventional antipsychotics but with superior subjective tolerability and a more favourable adverse effect profile.The majority of quality of life studies involving new antipsychotic agents have evaluated the benefits of risperidone, olanzapine and clozapine; only a few studies have examined the effects of other new antipsychotics. While most of these studies have methodological and design limitations, the weight of evidence from them nevertheless points to a trend towards a more positive impact on quality of life with atypical agents.A number of recommendations can be made. First, more independent well designed and controlled studies are urgently needed to evaluate the effects of antipsychotic therapy on quality of life in patients with schizophrenia. New comparative studies should explore not only the differences between new and old antipsychotics but also identify any potential differences between individual new agents. The role of cost-effectiveness studies such as cost utility approaches in schizophrenia needs to be revisited, notwithstanding the fact that these types of studies have been reported to be feasible in schizophrenia. Finally, quality-of-life-based pharmacoeconomic studies of antipsychotic agents should not concentrate solely on cost reduction or containment, as it is likely that in order to maximise the benefits of new antipsychotic medications, greater expenditure on rehabilitation programmes and other support services will be necessary in the short-term at least.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Cannabis has been used for recreational, medicinal and religious purposes in different cultures since ancient times. There have been various reports of adverse effects due to or associated with cannabis consumption, including psychotic episodes. Historically, our understanding of these clinical observations has been significantly hindered by a lack of knowledge regarding their underlying neurobiological and pharmacological processes. However, the discovery of the endogenous cannabinoid system has allowed a greater understanding of these adverse effects to develop.From a clinical perspective, toxic or transient psychotic reactions to the administration of herbal cannabis preparations or specific cannabinoid compounds have to be differentiated from longer-lasting, persistent schizophrenia-like disorders associated with the use of cannabis/cannabinoids. The latter are most likely to be associated with a predisposition or vulnerability to schizophrenia. Interestingly, the recently suggested role of the endogenous cannabinoid system in schizophrenia not related to previous cannabinoid consumption introduces an additional perspective on the mechanism underlying cannabis-associated schizophrenia-like disorders, as well as on the effects of cannabis consumption in schizophrenia.At present, acute psychopharmacological treatment options for cannabis-associated transient and persistent schizophrenia-like psychotic episodes are similar and are based on the use of benzodiazepines and antipsychotics. However, new pharmacological strategies using the endogenous cannabinoid system as a primary target are under development. Long-term psychotherapeutic treatment options involve case management strategies and are mainly based on specialised psychotherapeutic programmes to encourage cannabis users to stop their use of the drug.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

BackgroundThe economic burden of depression is known to be high and was estimated to be $US83.1 billion in 2000. Serotonin reuptake inhibitors (SRIs), including both selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs), have a superior adverse effect and safety profile relative to traditional agents (e.g. TCAs), and as a result have demonstrated superior cost effectiveness. Although efficacy across the SRIs is similar, the incidence of adverse drug reactions (ADRs) within SRIs remains significant and varies by agent. Patients who experience ADRs from SRIs may seek medical care, require additional treatment, and even discontinue treatment altogether, leading to increased utilisation and cost of therapy.ObjectiveThis study estimates the direct cost and cost effectiveness, taking into account the impact of treatment-related ADRs, of eight currently marketed SRIs (citalopram, escitalopram, generic fluoxetine, paroxetine, paroxetine controlled release [CR], sertraline, venlafaxine and venlafaxine extended release [XR]) used as initial treatment for depression.MethodsA decision analytic model with a 6-month treatment goal was used to estimate the direct cost and cost effectiveness of treatment from the managed care/payer perspective. Estimates of SRI-related ADRs, associated treatments and costs were derived from the US FDA-approved prescribing information and published literature. Efficacy was assumed to be similar across all SRIs. Effectiveness was measured using quality-adjusted life years (QALY) based on EuroQol EQ-5D scores derived from the 2000 Medical Expenditure Panel Survey (MEPS). Censored least absolute deviations (CLAD) regression analysis was used to derive age-adjusted estimates of utility for all health states. Univariate and Bayesian second-order multivariate probabilistic sensitivity analyses were conducted to examine the impact of uncertainty in the parameter estimates.ResultsThe expected direct cost and cost effectiveness of treatment from least to most expensive were: escitalopram ($US3891; 0.341), citalopram ($US3938; 0.340), generic fluoxetine ($US4034; 0.335), venlafaxine XR ($US4226; 0.336), sertraline ($US4250; 0.335), generic paroxetine ($US4385; 0.332), paroxetine CR ($US4440; 0.332) and venlafaxine ($US4613; 0.326). Monte Carlo simulation results suggested that escitalopram was the most likely (77%) to be cost effective for a willingness to pay ≤$US50 000 per QALY, followed by citalopram (22%), generic fluoxetine (0.3%) and all other SRIs (0%). Sensitivity analyses indicated that the results of the study were robust to the assumptions underpinning the model.ConclusionsSRI-related ADRs have a significant impact on the direct cost and cost effectiveness of treatment. Escitalopram, with the lowest ADR rate of the SRIs, had the lowest expected treatment cost and greatest effectiveness when compared with citalopram, generic fluoxetine, generic paroxetine, paroxetine CR, sertraline, venlafaxine and venlafaxine XR.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Amisulpride (Solian®), a substituted benzamide derivative, is a second-generation antipsychotic that preferentially binds to dopamine D2/D3receptors in limbic rather than striatal structures. High dosages preferentially antagonise postsynaptic D2/D3receptors, resulting in reduced dopamine transmission, and low dosages preferentially block presynaptic D2/D3receptors, resulting in enhanced dopamine transmission.Amisulpride (200–1200 mg/day) was at least as effective as haloperidol and as effective as risperidone or olanzapine, in studies of up to 1 year in patients with schizophrenia manifesting predominantly positive symptoms. Amisulpride (50–300 mg/day) was significantly more effective than placebo in studies of up to 6 months in patients manifesting predominantly negative symptoms. Quality of life was also improved significantly more in patients receiving amisulpride than in those receiving haloperidol in 4- and 12-month studies in patients with predominantly mixed symptoms.Amisulpride was generally well tolerated in clinical trials. In patients with predominantly positive symptoms, amisulpride appeared to be better tolerated than haloperidol and was tolerated as well as risperidone and olanzapine. The incidence of extrapyramidal adverse effects with amisulpride was lower than with haloperidol but was generally similar to risperidone or olanzapine. Weight gain with amisulpride was less than that with risperidone or olanzapine and, unlike these agents, amisulpride does not seem to be associated with diabetogenic effects. Plasma prolactin levels are increased during amisulpride therapy and amenorrhoea occurs in about 4% of women. The incidence of adverse events with low dosages of amisulpride (≤300 mg/day) in patients with predominantly negative symptoms was similar to that observed with placebo.In conclusion, oral amisulpride (200–1200 mg/day) is at least as effective as haloperidol, and as effective as risperidone or olanzapine, in the treatment of patients with schizophrenia manifesting predominantly positive symptoms. In the treatment of patients manifesting predominantly negative symptoms, low dosages of amisulpride (50–300 mg/day) are significantly more effective than placebo. Amisulpride appears to be better tolerated than haloperidol, causing a lower incidence of extrapyramidal adverse effects and an improved quality of life. Compared with risperidone or olanzapine, amisulpride is more likely to cause hyperprolactinaemia, but has a lower propensity to cause weight gain and does not seem to be associated with diabetogenic effects. Thus, amisulpride is an effective and well tolerated option for the first-line treatment of patients with acute schizophrenia as well as for those requiring long-term maintenance therapy.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS