摘要:

The high prevalence of migraine in women during their reproductive years means that new drug treatments for migraine, such as the serotonin 5-HT1B/1Dreceptor agonists (the ‘triptans’), are likely to be widely used by women of childbearing potential. Scrutiny of these agents in an effort to detect any signal of teratogenicity is thus important.A systematic review of the medical literature was conducted to identify information regarding the safety of sumatriptan during pregnancy. This agent was chosen to be investigated because it has been available for the longest and is the most widely used of the triptan class. Information was obtained regarding the impact of migraine on pregnancy outcome, and data on sumatriptan use in pregnancy were obtained from animal studies, preclinical drug trials, postmarketing surveillance efforts, prospective pregnancy registries, national birth registries and teratogen information services.Synthesis of information from these sources is sufficient to rule out a large increase in birth defects from sumatriptan use during pregnancy and is reassuring for cases where inadvertent exposure to sumatriptan during pregnancy has occurred. However, current information is not sufficient to rule out small increases in the risk for birth defects. For this reason, caution should be exercised in making a positive recommendation for the use of sumatriptan during pregnancy.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Bipolar depression is the predominant abnormal mood state in bipolar disorder. However, despite the key pertinence of this phase of the condition, the focus of research and indeed of clinical interest in the management of bipolar disorder has been mainly on mania. Bipolar depression has been largely neglected, and early studies often failed to distinguish depression due to major unipolar depression from that due to bipolar disorder. Consequently, many treatments used in the management of major depression have been adopted for use in bipolar depression without any robust evidence of efficacy.The selective serotonin reuptake inhibitors (SSRIs), bupropion, tricyclic antidepressants and monoamine oxidase inhibitors are all effective antidepressants in the management of bipolar depression. They are all associated with a small risk of antidepressant-induced mood instability.The mood stabilisers lithium, carbamazepine and valproate semisodium (divalproex sodium) all appear to have modest acute antidepressant properties. Among these, lithium is supported by the strongest data, but the use of lithium in the treatment of bipolar depression as a monotherapeutic agent is limited by its slow onset of action. Recently, there has been a growing body of evidence suggesting that lamotrigine may have particular effectiveness in both the acute and prophylactic management of bipolar depression.Clinical management of bipolar depression involves various combinations of antidepressants and mood stabilisers and is partly determined by the context in which the depressive episode occurs. In general, ‘de novo’ and ‘breakthrough’ (where the patient is already receiving medication) bipolar depression may be successfully managed by initiating mood stabiliser monotherapy, to which an antidepressant or second mood stabiliser may be added at a later date, if necessary. Breakthrough episodes of bipolar depression occurring in patients receiving combination therapy (two mood stabilisers or a mood stabiliser plus an antidepressant) require either switching of ongoing medications or further augmentation. If this fails, then novel strategies or ECT should be considered.Bipolar depression is a disabling illness and the predominant mood state for the vast majority of those with bipolar disorder. It therefore warrants prompt management once suitably diagnosed, especially as it is associated with a considerable risk of suicide and in the majority of instances is eminently treatable.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

An emerging body of evidence suggests that an increased prevalence of insulin abnormalities and insulin resistance in Alzheimer's disease may contribute to the disease pathophysiology and clinical symptoms. It has long been known that insulin is essential for energy metabolism in the periphery. In the past 2 decades, convergent findings have begun to demonstrate that insulin also plays a role in energy metabolism and other aspects of CNS function. Investigators reported 20 years ago that insulin and insulin receptors were densely but selectively expressed in the brain, including the medial temporal regions that support the formation of memory. It has recently been demonstrated that insulin-sensitive glucose transporters are localised to the same regions supporting memory and that insulin plays a role in memory functions. Collectively, these findings suggest that insulin may contribute to normal cognitive functioning and that insulin abnormalities may exacerbate cognitive impairments, such as those associated with Alzheimer's disease.Insulin may also play a role in regulating the amyloid precursor protein and its derivative β-amyloid (Aβ), which is associated with senile plaques, a neuropathological hallmark of Alzheimer's disease. It has been proposed that insulin can accelerate the intracellular trafficking of Aβ and interfere with its degradation. These findings are consistent with the notion that insulin abnormalities may potentially influence levels of Aβ in the brains of patients with Alzheimer's disease.The increased occurrence of insulin resistance in Alzheimer's disease and the numerous mechanisms through which insulin may affect clinical and pathological aspects of the disease suggest that improving insulin effectiveness may have therapeutic benefit for patients with Alzheimer's disease. The thiazolidinedione rosiglitazone has been shown to have a potent insulin-sensitising action that appears to be mediated through the peroxisome proliferator-activated receptor-γ (PPAR-γ). PPAR-γ agonists, such as rosiglitazone, also have anti-inflammatory effects that may be of therapeutic benefit in patients with Alzheimer's disease.This review presents evidence suggesting that insulin resistance plays a role in the pathophysiology and clinical symptoms of Alzheimer's disease. Based on this evidence, we propose that treatment of insulin resistance may reduce the risk or retard the development of Alzheimer's disease.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Tardive dyskinesia has been and continues to be a significant problem associated with long-term antipsychotic use, but its pathophysiology remains unclear. In the last 10 years, preclinical studies of the administration of antipsychotics to animals, as well as clinical studies of oxidative processes in patients given antipsychotic medications, with and without tardive dyskinesia, have continued to support the possibility that neurotoxic free radical production may be an important consequence of antipsychotic treatment, and that such production may relate to the development of dyskinetic phenomena.In line with this hypothesis, evidence has accumulated for the efficacy of antioxidants, primarily vitamin E (α-tocopherol), in the treatment and prevention of tardive dyskinesia. Early studies suggested a modest effect of vitamin E treatment on existing tardive dyskinesia, but later studies did not demonstrate a significant effect. Because evidence has continued to accumulate for increased oxidative damage from antipsychotic medications, but less so for the effectiveness of vitamin E, especially in cases of long-standing tardive dyskinesia, alternative antioxidant approaches to the condition may be warranted. These approaches may include the use of antioxidants as a preventive measure for tardive dyskinesia or the use of other antioxidants or neuroprotective drugs, such as melatonin, for established tardive dyskinesia.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS