摘要:

The UK National Institute for Clinical Excellence (NICE) was set up in 1999 to advise the National Health Service (NHS) on the use of new technologies largely, but not exclusively, on the basis of their clinical and cost effectiveness. There have been problems with this, as with any developing system, most of which have arisen from issues not directly under the control of NICE. Despite this, NICE has already achieved a pivotal role in determining the uptake of new therapies into the NHS.In the area of neuropsychiatric therapies, NICE has examined a number of topics and has generally facilitated the increased use of the agents examined, approving the use, within limitations, of such drugs as riluzole, atypical antipsychotics and cholinesterase inhibitors. Although the use of some of these therapies had been growing, it had previously been restricted by funding in the NHS. As a result of NICE guidance, these funding restrictions have generally been lifted.NICE has rejected one area of neurological therapy so far – that of interferon-β products and glatiramer acetate for multiple sclerosis – on the grounds of clinical uncertainty about long-term benefits and poor cost effectiveness. However, the UK Government has created a novel risk-sharing scheme in collaboration with the sponsoring companies to make these drugs available at a level of cost effectiveness acceptable to the NHS. The feasibility of this scheme is as yet unclear. This might be seen as either a triumph for NICE or as an undermining of it for political ends.One interesting aspect that is more prominent in neuropsychiatric disorders than in other areas of NICE activity has been the power of patient advocacy in encouraging acceptance of therapies where the evidence base was weak or the incremental cost-effectiveness ratio was unfavourable.The principles behind the activities of NICE attract wide support within the NHS, but the details of its decisions have often not been popular within NHS management who have to deliver them. Some of this relates more to the context and political environment within which NICE operates than to a failing within NICE itself. NICE will continue to become increasingly important in determining the use of new drugs within the UK NHS.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

A range of aberrant drug-taking behaviours can occur in patients who are undergoing treatment for chronic pain, especially if opioid therapy is involved. Assessing and understanding these behaviours, and their relationship to addiction (or substance use disorder), can be difficult but it is necessary for assuring quality pain management. Aberrant drug-taking behaviour may be evident, for example, when a patient with pain is unilaterally escalating doses of opioids or using the medications to treat other symptoms or when prescriptions are being mishandled. In patients with a history of substance abuse, these are often serious developments to which a clinician must know how to react. These complex behaviours may be indicative of addiction or may be simply a reaction to under-medicated pain. The clinician therefore is challenged to understand such behaviours and plan interventions accordingly.Although it is becoming increasingly common to avoid opioid therapy in patients demonstrating such challenging behaviours for fear of regulatory scrutiny, clinical management can be tailored to address the many possibilities that might be giving rise to such behaviours. In addition, control over prescriptions can be accomplished without necessarily terminating the prescribing of controlled substances entirely. Optimal medical management of chronic pain in those patients with addiction problems or engaging in problematic behaviours involves careful, ongoing assessment by the clinician as well as a tailored management approach. This approach should use multiple structures including strict contracts, prudent drug selection and frequent follow-ups to pain and addiction treatments, including the use of urine toxicology screening, to maximise the likelihood of a good outcome.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

The restless legs syndrome (RLS) is defined by four essential criteria obligatory for clinical diagnosis which were established, and recently revised, by the International RLS Study Group. These arethe urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs, which areworse during rest/inactivity,partially or totally relieved by movement andworse at night/in the evening.Treatment with levodopa leads to symptom relief, but augmentation (occurrence of symptoms before levodopa administration in the evening) may occur, limiting the long-term use of this drug. This article gives an overview of the treatment in general and the role of dopamine receptor agonists in the therapy of RLS and periodic limb movements (PLMs). Dopamine receptor agonists are widely used as an effective treatment for RLS and PLMs, presumably because of their longer half-lives, lower likelihood of augmentation and good tolerability compared with levodopa. It was shown that, for example, pergolide, ropinirole, pramipexole and cabergoline alleviated RLS symptoms in 70–90% of patients. A new non-oral (transdermal) formulation of one dopamine receptor agonist, rotigotine, has recently been developed and shown to be efficacious in RLS. Further research should focus on long-term observations and comparisons of different dopamine receptor agonists in RLS.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

IntroductionWhile benzodiazepines are the most widely used psychotropic drugs, there are relatively few studies that have examined deficits in cognitive functioning after long-term use. The literature that is available is difficult to interpret due to conflicting results as well as a variety of methodological flaws.ObjectiveTo systematically evaluate and integrate the available research findings to determine the effect of long-term benzodiazepine use on cognitive functioning using meta-analytical techniques.MethodsThirteen research studies that employed neuropsychological tests to evaluate cognitive performance after long-term use of benzodiazepine medication met inclusion criteria. The neuropsychological tests employed in these 13 studies were each categorised as measuring one of 12 cognitive domains. Separate effect sizes were calculated for each of the 12 cognitive categories. Each study was only allowed to contribute one effect size to each cognitive category by averaging together the effect sizes from the same study if more than one type of test was used to measure a particular category. This strategy resulted in equal weight being given to each study per category, regardless of the number of tests in that category.ResultsThe overall mean number of patients who were benzodiazepine users was 33.5 (SD ± 28.9) and the mean number of controls was 27.9 (SD ± 19.6). The duration of benzodiazepine use ranged from 1 to 34 (mean 9.9) years. Long-term benzodiazepine users were consistently more impaired than controls across all cognitive categories examined, with effect sizes ranging in magnitude from −1.30 to −0.42. The mean weighted effect size was −0.74 (SD ± 0.25). None of the effect sizes had 95% CIs that spanned zero and, therefore, all of these effects were significant and different to zero.ConclusionModerate-to-large weighted effect sizes were found for all cognitive domains suggesting that long-term benzodiazepine users were significantly impaired, compared with controls, in all of the areas that were assessed. However, this study has several limitations, one being that it includes a relatively small number of studies. Further studies need to be conducted; ideally, well designed, controlled studies that thoroughly investigate certain areas of cognitive functioning and present data in such a way so as to be amenable to inclusion in a meta-analysis. Incorporating the information from these studies into a larger meta-analysis would allow for a more thorough and statistically sound investigation of the effects of moderator variables. The observation that long-term benzodiazepine use leads to a generalised effect on cognition has numerous implications for the informed and responsible prescription of these drugs.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

ObjectiveTo provide initial information on the safety and efficacy of the atypical antipsychotic zotepine in the treatment of behavioural and psychological symptoms of dementia (BPSD).No significant differences in treatment response or adverse effect profile were noted between the 12 patients with Alzheimer’s disease and the 12 patients with other types of dementia.Zotepine was well tolerated, with tiredness and sedation (five and four cases, respectively) being the most frequent complaints. No clinically significant emergence of extrapyramidal symptoms was seen.MethodsThis was an open-label, single-centre field study. Twenty-four patients with BPSD associated with Alzheimer’s disease (n = 12) or other forms of dementia (n = 12) were included. During the 8-week observation period, the patients received zotepine (Nipolept®) [12.5–150 mg/day] for the psychotic components of BPSD; no other treatment interventions for BPSD were allowed. At baseline, day 28 and day 56, patients were evaluated using the Clinical Global Impressions (CGI) scale; the Mini-Mental State Examination (MMSE), the Syndrome Brief Test (SKT) and the Age Concentration Test (AKT) to assess cognition; and the Neuropsychiatric Inventory (NPI) and the Cohen-Mansfield Agitation Inventory (CMAI) to assess BPSD. General adverse effects and, more specifically, the emergence of extrapyramidal symptoms were also assessed.No significant differences in treatment response or adverse effect profile were noted between the 12 patients with Alzheimer’s disease and the 12 patients with other types of dementia.Zotepine was well tolerated, with tiredness and sedation (five and four cases, respectively) being the most frequent complaints. No clinically significant emergence of extrapyramidal symptoms was seen.ResultsThere was no change from baseline to day 56 in the CGI score and the caregiver burden (as indicated by the caregiver-related section of the NPI). There was also no change in cognition (as assessed by the MMSE, SKT and AKT). The neuropsychiatric symptom score according to part 1 of the NPI (especially key psychotic symptoms, aggression and disinhibition) and the CMAI scores improved by 36% and 15%, respectively, between baseline and the end of the study in a highly statistically significant fashion.No significant differences in treatment response or adverse effect profile were noted between the 12 patients with Alzheimer’s disease and the 12 patients with other types of dementia.Zotepine was well tolerated, with tiredness and sedation (five and four cases, respectively) being the most frequent complaints. No clinically significant emergence of extrapyramidal symptoms was seen.ConclusionsZotepine appears to be well tolerated and effective in treating BPSD, consistent with the performance of other atypical antipsychotic drugs in this condition. Larger, controlled studies are warranted.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Oxcarbazepine (Trileptal®, Timox®) is structurally related to carbamazepine and has anticonvulsant activity. Studies suggest that the anticonvulsant activity of oxcarbazepine is mediated via the blocking of neuronal ion channels.In patients aged <18 years, the efficacy of oxcarbazepine monotherapy was similar to that of phenytoin in children with partial onset or generalised tonic-clonic seizures in a 48-week trial. Additional supporting findings demonstrated that 43–71% of patients with partial onset, generalised or undetermined epilepsy were seizure free after oxcarbazepine monotherapy (mean dosage 27.7–50 mg/kg/day; duration 1–5 years). In contrast, one small nonblind trial showed more patients treated with oxcarbazepine monotherapy than with carbamazepine monotherapy had recurrent seizures during 16 months of therapy (although the conclusions that can be drawn from this trial are limited).As adjunctive therapy, oxcarbazepine was significantly better than placebo at reducing seizure frequency in children and adolescents with refractory partial onset seizures with or without secondary generalisation: the median percentage change in partial onset seizure frequency was 35% versus 9%, respectively, during 16 weeks of therapy. In noncomparative trials of adjunctive oxcarbazepine (mean dosage of 34.5–56.7 mg/kg/day), 7–11% of patients with partial onset or generalised seizures were seizure free during treatment, and 20–54% had seizure reductions of ≥50%.Oxcarbazepine was generally well tolerated during monotherapy and adjunctive therapy; 2.5% and 10% of patients withdrew from well controlled trials of oxcarbazepine monotherapy and adjunctive therapy. Oxcarbazepine monotherapy was better tolerated than phenytoin and events observed in oxcarbazepine-treated patients were transient.Oxcarbazepine metabolism is largely unaffected by induction of the cytochrome (CYP) P450 system. However, oxcarbazepine can inhibit CYP2C19 and induce CYP3A4 and CYP3A5, thereby interfering with the metabolism of other drugs (e.g. phenytoin). In addition, oxcarbazepine decreases plasma levels of oral contraceptives and alternative contraceptive methods should be used.In conclusion, oxcarbazepine (as both monotherapy and adjunctive therapy) has shown efficacy in the treatment of partial onset seizures in children with epilepsy. Nevertheless, the generally favorable tolerability profile and relatively low potential for drug interactions of oxcarbazepine make it a valuable option in the treatment of childhood epilepsy.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Lamotrigine (Lamictal®), a phenyltriazine derivative, is a well established anticonvulsant agent that has shown efficacy in the prevention of mood episodes in adult patients with bipolar I disorder. The mechanism of action of the drug in patients with bipolar disorder may be related to the inhibition of sodium and calcium channels in presynaptic neurons and subsequent stabilisation of the neuronal membrane.Lamotrigine monotherapy significantly delayed time to intervention with additional pharmacotherapy or electroconvulsive therapy for any new mood episode (mania, hypomania, depression and mixed episodes), compared with placebo, in two large, randomised, double-blind trials of 18 months' duration. Additionally, lamotrigine was significantly superior to placebo at prolonging time to intervention for depression. These effects of lamotrigine were demonstrated in both recently manic/hypomanic and recently depressed patients. Lamotrigine showed efficacy in delaying manic/hypomanic episodes in pooled data only, although lithium was superior to lamotrigine on this measure.Two of four double-blind, short-term studies have shown lamotrigine to be more effective than placebo in the treatment of patients with treatment-refractory bipolar disorder or those with bipolar depression. Lamotrigine has not demonstrated efficacy in the treatment of acute mania.Lamotrigine was generally well tolerated in maintenance studies with the most common adverse events being headache, nausea, infection and insomnia. Incidences of diarrhoea and tremor were significantly lower in lamotrigine- than in lithium-treated patients. The incidence of serious rash with lamotrigine treatment was 0.1% in all studies of bipolar disorder and included one case of mild Stevens-Johnson syndrome. Lamotrigine did not appear to cause bodyweight gain.The dosage of lamotrigine is titrated over a 6-week period to 200 mg/day to minimise the incidence of serious rash. Adjustments to the initial and target dosages are required if coadministered with valproate semisodium or carbamazepine.ConclusionLamotrigine has been shown to be an effective maintenance therapy for patients with bipolar I disorder, significantly delaying time to intervention for any mood episode. Additionally, lamotrigine significantly delayed time to intervention for a depressive episode and showed limited efficacy in delaying time to intervention for a manic/hypomanic episode, compared with placebo. Although not approved for the short-term treatment of mood episodes, lamotrigine has shown efficacy in the acute treatment of patients with bipolar depression but has not demonstrated efficacy in the treatment of acute mania. Lamotrigine is generally well tolerated, does not appear to cause bodyweight gain and, unlike lithium, generally does not require monitoring of serum levels.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS