摘要:

Approximately 10% of patients with multiple sclerosis (MS) run a primary progressive course characterised by an accumulation of neurological deficits without relapse or remission. Designing therapeutic trials in primary progressive MS (PPMS) has presented several problems. Patient recruitment may be difficult because of the relative rarity of PPMS and historically has been hindered by the lack of specific diagnostic criteria. There has been a limited choice of validated outcome measures, although, in recent studies, the MS functional composite measure and magnetic resonance imaging measures of lesion load and atrophy have been widely used.Despite these problems, several trials have been designed specifically for PPMS, including exploratory randomised controlled trials of interferon-β-1a and interferon-β-1b and mitoxantrone, a phase III trial of glatiramer acetate, and an open-label study of riluzole. Patients with PPMS have also been included in randomised controlled trials of azathioprine, methotrexate, cladribine, intravenous immunoglobulin and cyclophosphamide, and open-label studies of haematopoietic stem cell transplantation and pirfenidone in progressive MS. However, no treatment has been proven definitively to modify the course of the disease. Looking to the future, therapeutic agents should aim to target the underlying pathogenic mechanisms in PPMS. As a result of the relative lack of inflammation in PPMS, neuroprotective agents that target neuronal loss directly, rather than inflammation, may be more worthwhile. However, further investigation into the pathogenic mechanisms in PPMS is required to guide the development of future therapeutic agents.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Social anxiety disorder (SAD) is a prevalent and disabling disorder associated with significant co-morbidity. An increased awareness of SAD over the past two decades has given impetus to advances in the pharmacotherapeutic and psychotherapeutic treatment options for this disorder. On the basis of consistent data from randomised controlled trials, present consensus supports the use of SSRIs as the first-line treatment in generalised SAD, partly because of established short- and long-term efficacy in this disorder, evidence for safety and tolerability, and ability to treat co-morbid conditions. There is more recent evidence that venlafaxine XR (extended release) may also be considered a first-line treatment in SAD. Second-line treatments include MAOIs (e.g. phenelzine) and reversible inhibitors of monoamine oxidase A (e.g. moclobemide), while some benzodiazepines and antiepileptics (e.g. clonazepam and pregabalin) may also be useful. Over the past two decades, cognitive behavioural therapies for SAD have gained increasing empirical support. The optimal approach to the management of treatment-refractory SAD patients requires additional study.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Risperidone and olanzapine are novel antipsychotic medications that compete as first-line agents in treating patients with schizophrenia. The objective of this paper is to review the available evidence regarding the effectiveness and cost of risperidone versus olanzapine. We reviewed both randomised and peer-reviewed non-randomised head-to-head (olanzapine versus risperidone) studies in populations with schizophrenia. The studies were selected through a MEDLINE search.Risperidone and olanzapine provide control of positive, negative and global symptoms of schizophrenia. Each drug has a distinct adverse effect profile. Five randomised trials comparing risperidone with olanzapine suggested grossly similar efficacy in the first 2 months of treatment, with some results indicating advantages for olanzapine over the longer term. Only two of the trials included measures of service utilisation. One had 28-week follow-up, and the other followed patients for 12 months but had small sample sizes. Both experimental and naturalistic studies indicated that the acquisition cost of olanzapine is about 50% greater than for risperidone at dose levels commonly used for the treatment of schizophrenia. The only experiment with 12-month total treatment cost data found essentially equivalent costs for patients assigned to olanzapine or risperidone, showing that there are circumstances where total cost is similar in spite of the higher drug acquisition cost of olanzapine. Most retrospective studies also reported comparable total cost. Few studies gave enough information to evaluate cost effectiveness. The clear difference in acquisition cost of these two medications was rarely reflected in overall treatment cost in the studies we reviewed.Overall, our review of the literature highlights that there is inadequate evidence to distinguish the relative total cost of care associated with risperidone versus olanzapine, although accumulating evidence suggests the difference is small. This population-based conclusion does not indicate which medication is more costly or more cost effective for a particular patient; this depends on each patient’s response to each medication.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Although women are exposed to proportionately fewer traumatic events in their lifetime than men, they have a higher lifetime risk of post-traumatic stress disorder (PTSD). In addition to gender-differential rates of rape and sexual assault, including greater exposure to intimate partner violence, the preponderance of PTSD in women may be attributable to factors other than trauma type, such as sensitisation of stress hormone systems in response to early adverse experiences, inherent neuroendocrine factors, subjective interpretation of the event, and peritraumatic dissociation. Women with PTSD arguably experience a greater symptom burden, longer course of illness and have worse quality-of-life outcomes than men. An expanding knowledge base of the psychobiological alterations in PTSD is providing stimulus for the development of improved pharmacological and psychosocial treatment options. Recent randomised controlled studies conducted in large samples of women with chronic PTSD indicate that: (i) SSRIs have efficacy on all three symptom clusters of PTSD and should be used as first-line pharmacotherapy; and (ii) cognitive behavioural strategies (e.g. prolonged exposure treatment and cognitive processing) are effective in sexually and non-sexually assaulted women. Studies also suggest that female gender may be associated with better response rates to pharmacotherapy. Emerging empirical data on the potential usefulness of antiadrenergic agents and preventive cognitive behavioural treatments in managing acute trauma reactions and stemming the emergence of PTSD are paving the way for further work in this area. However, additional innovative treatments are needed for traumatised women and for female children/adolescents presenting with acute stress reactions and PTSD.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Risperidone (Risperdal®) is an atypical antipsychotic with high affinity for 5-hydroxytryptamine (5-HT)2A, dopamine D2and α1- and α2-adrenergic receptors. Risperidone is now approved in the UK and the US for use in bipolar mania.Risperidone ≤6 mg/day, as monotherapy or adjunctive therapy with first-line mood stabilisers, significantly improves moderate and severe bipolar mania and improves global functioning over 3 weeks. Improvements in Young Mania Rating Scale (YMRS) scores in double-blind trials were greater with risperidone than with placebo over 3 weeks, and similar to those with haloperidol over 3 and 12 weeks. Risperidone was reasonably well tolerated. Limited data are available on the combination of risperidone and carbamazepine. Risperidone, as monotherapy or combined therapy with lithium or valproate semisodium, is an effective treatment option in bipolar mania.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Acamprosate (Campral®delayed-release tablet), a synthetic compound with a similar structure to that of the neurotransmitter GABA and the neuromodulator taurine, facilitates the maintenance of abstinence in detoxified alcohol-dependent patients. Although the precise mechanism(s) of action of the drug remains to be fully elucidated, it appears that it most likely involves beneficial modulation of the glutamatergic neurotransmitter system, including antagonism of the mGLu5 metabotropic glutamate receptor, to counteract the imbalance between the glutamatergic and GABAergic systems associated with chronic alcohol exposure and alcohol withdrawal.In several double-blind, placebo-controlled trials of up to 12 months' duration, acamprosate effectively maintained complete abstinence in detoxified alcohol-dependent patients, irrespective of disease severity or the type of psychosocial support. The drug showed better efficacy than placebo and was very well tolerated. Limited data from a relatively well designed trial indicate that the drug has similar efficacy to that of naltrexone and that combination therapy with these two agents provides better efficacy than acamprosate monotherapy, although multicentre direct head-to-head investigations are required to fully establish the potential of this combination. The drug may be particularly useful in those with hepatic impairment and/or liver disease. Thus, in combination with psychosocial and behavioural management programmes, acamprosate is a promising option for the maintenance of abstinence in alcohol-dependent patients after alcohol withdrawal.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS