摘要:

Increasing evidence suggests that substance P (SP) and its receptor (neurokinin [NK]-1 receptor [NK1R]) might play an important role in the modulation of stress-related, affective and/or anxious behaviour. First, SP and NK1R are expressed in brain regions that are involved in stress, fear and affective response (e.g. amygdala, hippocampus, hypothalamus and frontal cortex). Second, the SP content in these areas changes upon application of stressful stimuli. Third, the central administration of SP produces a range of fear-related behaviours. In addition, the SP/NK1R system shows significant spatial overlap with neurotransmitters such as serotonin and noradrenaline (norepinephrine), which are known to be involved in the regulation of stress, mood and anxiety. Therefore, it was hypothesised that blockade of the NK1R might have anxiolytic as well as antidepressant effects.Preclinical studies investigating the effects of genetic or pharmacological NK1R inactivation on animal behaviour in assays relevant to depression and anxiety revealed that the behavioural changes resemble those seen with reference antidepressant or anxiolytic drugs. Furthermore, antagonism or genetic inactivation of the NK1R causes alterations in serotonin and norepinephrine neuronal transmission that are likely to contribute to the antidepressant/anxiolytic activity of NK1R antagonists but that are – at least partially – distinct from those produced by established antidepressant drugs. This underlines the conceivable unique mechanism of action of this new class of compounds. In three independent clinical trials with three different compounds (aprepitant [MK-869], L-759274 and CP-122721), an antidepressant effect of NK1R antagonists could be demonstrated. These results, however, have been challenged by recent failed studies with aprepitant.There are numerous indications from preclinical studies that, in addition to SP and NK1R, other neurokinins and/or neurokinin receptors might also be involved in the modulation of stress-related behaviour and that exclusive blockade of the NK1R might not be sufficient to produce consistent anxiolytic and antidepressant effects. One such candidate is the neurokinin-2 receptor (NK2R), and clinical trials to assess the antidepressant effects of NK2R antagonists are currently underway. Of special interest might also be substances that block more than one receptor type such as NK1/2R antagonists or NK1/2/3R antagonists. These compounds may be more efficacious in antagonising the effects of SP than compounds that only block the NK1R.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Stroke is a common and important medical problem. Intravenous thrombolysis with alteplase (recombinant tissue plasminogen activator; rtPA) is the only available direct treatment that reduces neurological injury following ischaemic stroke. Strong efficacy data from randomised, controlled trials support the use of intravenous thrombolysis to improve outcomes for patients with acute ischaemic stroke. Numerous studies have provided effectiveness data that demonstrate that intravenous thrombolytic therapy can be given safely outside clinical trial settings. However, effectiveness studies have demonstrated that intravenous thrombolytic therapy is often given despite protocol violations when it is prescribed in routine clinical practice. Protocol violations must be avoided because they are associated with adverse events including higher mortality and increased haemorrhagic complications. Although thrombolytic therapy with alteplase is currently being used in only <10% of patients with acute ischaemic stroke, recent studies demonstrate that quality management efforts can improve both the absolute rate of use as well as the proficiency with which alteplase is administered. Given the complexities inherent in prescribing thrombolysis for patients with acute ischaemic stroke, alteplase should be used by clinicians who are experienced in the diagnosis and management of stroke, working in medical centres that have systems in place to ensure that alteplase is given without protocol violations.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Genital herpes is a common, chronic, recurrent, viral sexually transmitted infection (STI) occurring worldwide. The first episode may be severe and prolonged, but most recurrences are usually short lived and minor. Although most individuals with this infection have no symptoms, STIs, including genital herpes, often cause psychological and psychosexual morbidity. Unfortunately, the existing data on the psychological symptoms associated with genital herpes have many limitations, including anecdotal reporting, evaluation of small and selected populations, use of varied and sometimes unevaluated questionnaires, and lack of controls. Some individuals with recurrent genital herpes display a range of emotional responses, including depression, anguish, distress, anger, diminution of self-esteem and hostility towards the person believed to be the source of infection. However, it is always important to consider the possibility of pre-existing psychopathology. Several retrospective studies have suggested that stress could lead to recurrences of genital herpes infection. However, prospective studies have been unable to demonstrate any relationship between pre-existing stress and recurrences. What these studies were able to demonstrate was that stress and recurrences occurred simultaneously, suggesting that perhaps it was the recurrences that were causing stress, rather than the reverse.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

DSM-IV has recommended use of the Social and Occupational Functioning Scale (SOFAS) as a clinician-rated global assessment scale for measuring social functioning; this scale is analogous to the Clinical Global Impression (CGI) scale traditionally used as a secondary outcome measure in patients with depressive symptoms. However, we believe that health-related quality of life is the most appropriate indicator of social functioning when considering this dimension as an endpoint in clinical trials of antidepressants. As health-related quality of life is a purely subjective measure, patient-rated questionnaires have been found to be most important in this context. In this respect, the Sheehan Disability Scale has been recommended as the most relevant global self-reported assessment of social functioning in trials of antidepressants.A review of questionnaires found that the three most frequently used scales selectively directed at obtaining information about social functioning in trials of antidepressants are the Social Adjustment Scale – Self Report (SAS-SR), the Social Adaptation Self-Evaluation Scale (SASS) and the Short-Form Health Survey (SF-36). However, the number of placebo-controlled trials of antidepressants that have used these scales is still too limited to allow comparisons in terms of responsiveness.Health-related quality of life includes dimensions other than social functioning, e.g. physical health and mental health (including both cognitive and affective problems). The SF-36 includes subscales relating to physical and mental health, which, like the social functioning subscales, are measured in terms of degrees of well being. Another quality-of-life questionnaire, the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), covers social, mental and physical problems, in this case measured in terms of degrees of satisfaction. Recently, the Q-LES-Q has been reduced from a comprehensive scale including 60–92 items to a brief version including 15 items. An additional item measures overall life satisfaction. As most of the items in the brief Q-LES-Q include social functioning, the scale can be considered as an alternative to SF-36 or the Sheehan Disability Scale when the focus is on satisfaction with treatment. However, there are insufficient numbers of trials of antidepressants using these questionnaires to allow comparisons.The examples of trials of antidepressants with the SF-36 subscales discussed in this review have mostly involved SSRIs. These trials have demonstrated that although antidepressants improve social functioning compared with placebo over a 6-week treatment period, the endpoint scores are still significantly below the national norms at this point. Only after 12 weeks of therapy are the endpoint scores of the social functioning scales within the limits of the national norms. In relapse prevention trials or in maintenance trials to prevent recurrence of depression, comparisons of social functioning scores with national norms can be important supplementary indicators of the need for treatment.In conclusion, social functioning as part of the health-related concept of the patient-reported quality-of-life measure should constitute an endpoint in trials of antidepressants to help clarify the goals of treatment in patients with major depression. In medium- and long-term trials, SF-36 subscales should be used as a supplement to symptom-orientated scales. In trials of shorter (6–8 weeks) duration, use of other scales such as the SAS-SR, the Q-LES-Q or the Sheehan Disability Scale should be considered. These scales should be considered as supplementary to each other rather than alternatives; it may be necessary to use more than one of these scales in a trial.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Peripheral neuropathy is associated with numerous systemic illnesses including HIV infection. Neuropathic pain constitutes approximately 25–50% of all pain clinic visits. Distal symmetrical polyneuropathy (DSP) is the most common form of peripheral neuropathy in individuals with HIV infection. DSP is distinguished from other forms of neuropathy on the basis of history and neurological examination. The pain associated with DSP can be debilitating. Therefore, it is important to diagnose HIV-associated DSP properly and treat the neuropathic pain in order to improve quality of life. We review the clinical manifestations, epidemiology, pathophysiology and management strategies for HIV-associated DSP.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

▴ Sumatriptan, a serotonin 5-HT1B/1Dagonist, constricts cranial blood vessels and inhibits neuroinflammatory processes.▴ A single dose of sumatriptan 10mg (approved European dosage) was significantly more effective than placebo in achieving headache relief at 1 hour post-dose in a well designed study. Headache relief occurred in significantly more adolescents administered a single dose of intranasal sumatriptan 20mg (at 1 and 2 hours) and 5mg (at 2 hours) than placebo (pooled data from two studies).▴ Sustained headache relief (1–24 and 2–24 hours) occurred in significantly more recipients of a single dose of intranasal sumatriptan 20mg and 5mg than placebo (pooled data from two studies).▴ Intranasal sumatriptan was generally well tolerated in adolescent migraineurs (in single-episode studies or long term in multiple-episode studies). Taste disturbance occurred more often with intranasal sumatriptan than with placebo.Table. Features and properties of intranasal sumatriptan (Imitrex®/Imigran®Nasal Spray) in adolescent migraineurs

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Zonisamide (Zonegran®, Excegran®) is a new-generation, broad-spectrum antiepileptic drug (AED) currently approved as adjunctive therapy for the treatment of medically refractory partial seizures in adults in the US and as adjunctive therapy or monotherapy in the control of partial and generalised seizures in adults and children in Japan and Korea.Either as adjunctive therapy or monotherapy, zonisamide effectively reduces the frequency of partial seizures, with or without secondary generalisation to tonic-clonic seizures, in adults and children with epilepsy. The drug is generally well tolerated and, additionally, has a favourable pharmacokinetic profile permitting once- or twice-daily administration. Direct head-to-head comparisons with other AEDs would be beneficial in fully defining the place of zonisamide in therapy. In the meantime, adjunctive therapy or monotherapy with zonisamide is a convenient, useful option for the management of partial seizures, including those refractory to other AEDs.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS