摘要:

Dysthymic disorder is a chronic depressive condition occurring in 0.6–4.6% of children and 1.6–8.0% of adolescents. Although symptoms are less severe than those observed in major depression, childhood-onset dysthymic disorder is characterised by a persistent and long-term depressed or irritable mood (mean episode duration 3–4 years), a worse outcome than major depression and, frequently, comorbid disorders (in around 50% of patients). Long-lasting depressive symptoms seem responsible for long-term disabling consequences on social skill learning, psychosocial functioning and consequent professional life, probably contributing to a higher risk of relapse or development of major depression. Consistently, the first episode of major depression occurs 2–3 years after the onset of dysthymic disorder, suggesting that the latter is one of the gateways to recurrent mood disorders.The primary aims of treatment for dysthymic disorder should be to resolve depressive symptoms, reduce the risk of developing other mood disorders over time and strengthen psychosocial functioning, especially in children and adolescents, in order to prevent the potentially serious sequelae of this disorder. As children with dysthymia often have multiple problems, interventions should involve multiple levels and measures: individual psychotherapy, family therapy/education and pharmacological treatment.Psychotherapeutic techniques, such as cognitive-behaviour therapy and interpersonal therapy, have been found to be efficacious interventions in treating children and adolescents with mild to moderate depression in studies including patients with either dysthmia or double depression.SSRIs are the first-line drug treatment for children and adolescents because of their safety, adverse effect profile and ease of use (the safety of paroxetine is currently under investigation). Several nonblind studies have shown the efficacy and good tolerability of SSRIs in children and adolescents with dysthymic disorder, but further research is needed to confirm their efficacy and that of newer antidepressants in the treatment of this disorder.Regardless of whether psychotherapeutic or medical treatments are planned, according to clinical experience, psychoeducational interventions and psychosocial support should be provided to parents and other caregivers during the acute treatment phase to help manage the child’s irritable mood and foster a therapeutic alliance and better compliance with treatment.Unfortunately, no studies have focused on continuation treatment of paediatric dysthymic disorder. Given the chronicity, recurrence, psychosocial consequences and peculiar response pattern to treatment of dysthymic disorder, establishing effective ‘acute’ and ‘continuation’ interventions in this group of patients should be a priority in mental health management.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Cholinesterase inhibitors are the only pharmacological class indicated for the treatment of mild to moderate Alzheimer's disease. These drugs are also being used off label to treat severe cases of Alzheimer’s disease or vascular dementia and other disorders. The widespread use of cholinesterase inhibitors raises the possibility of their use in combination regimens, with the subsequent risk of deleterious drug-drug interactions in high-risk populations. The purpose of this review is to present the possible sources of pharmacokinetic or pharmacodynamic drug-drug interactions involving cholinesterase inhibitors.The four cholinesterase inhibitors (tacrine, donepezil, rivastigmine and galantamine) that are currently available have different pharmacological properties that expose patients to the risk of several types of drug interactions of nonequivalent clinical relevance. The principal proven clinically relevant drug interactions involve tacrine and drugs metabolised by the cytochrome P450 (CYP) 1A2 enzyme, as well as tacrine or donepezil and antipsychotics (which results in the appearance of parkinsonian symptoms). The bioavailability of galantamine is increased by coadministration with paroxetine, ketoconazole and erythromycin. It is of interest to note that because rivastigmine is metabolised by esterases rather than CYP enzymes, unlike the other cholinesterase inhibitors, it is unlikely to be involved in pharmacokinetic drug-drug interactions. Care must be taken to reduce the risk of inducing central (excitation, agitation) or peripheral (e.g. bradycardia, loss of consciousness, digestive disorders) hypercholinergic effects via drug interactions with cholinesterase inhibitors.A review of the literature does not reveal any alarming data but does highlight the need for prudent prescription, particularly when cholinesterase inhibitors are given in combination with psychotropics or antiarrhythmics. Possible interactions involving other often coprescribed antidementia agents (e.g. memantine, antioxidants, cognitive enhancers) remain an open area requiring particularly prudent use.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

ObjectiveThe mixed dopamine D2/D3 receptor agonist pramipexole is effective as monotherapy in early Parkinson's disease and as adjunctive therapy in advanced disease. Clinical trials suggest that the benefits of pramipexole may extend beyond the relief of motor symptoms (akinesia, rigidity and tremor at rest) to amelioration of depressive symptoms in Parkinson’s disease. The aim of this study was to confirm the beneficial effects of pramipexole on the core symptoms of Parkinson’s disease (with a focus on tremor), as well as to assess its antidepressant activity, during routine clinical practice. The study also aimed to demonstrate the practicability of the Snaith-Hamilton Pleasure Scale (SHAPS-D), the Tremor Impact Scale (TIS) and the Short Parkinson's Evaluation Scale (SPES) under conditions of routine clinical practice.Pramipexole was well tolerated and accepted by the vast majority of physicians and patients.Study designThis was a prospective observational study.Pramipexole was well tolerated and accepted by the vast majority of physicians and patients.PatientsData for 657 outpatients with Parkinson’s disease were collected from German hospitals and specialist practices. The majority of patients were in Hoehn & Yahr stage II or III and were receiving levodopa.Pramipexole was well tolerated and accepted by the vast majority of physicians and patients.MethodsPramipexole (Sifrol®) was initiated at a dosage of 0.375 mg/day (using a three-times-daily schedule) and titrated upwards, as required, at weekly intervals over a 4-week period to a maximum dosage of 4.5 mg/day (three times daily). Clinical evaluation was performed at baseline, at the end of the titration phase and at the end of maintenance therapy. Patients were assessed via the German questionnaire versions of the physician-assessed SPES, the self-evaluated TIS and the SHAPS-D. Changes in scale scores were evaluated nonparametrically, using the Wilcoxon-matched pairs test. Crombach's α was used as a measure for item consistency.Pramipexole was well tolerated and accepted by the vast majority of physicians and patients.ResultsPramipexole significantly improved SPES subscores for motor symptoms, complications of therapy, psychological status and activities of daily living. Pramipexole also reduced the detrimental effect of tremor on activities of daily living and social interactions, as assessed by patients via the TIS. As indicated by the results of the SHAPS-D questionnaire, pramipexole significantly reduced anhedonia in patients who had associated depression. Internal consistency of SPES subscales was found to be unaltered between the initial evaluation and follow-up. Likewise, internal consistency for TIS and SHAPS-D was demonstrated.Pramipexole was well tolerated and accepted by the vast majority of physicians and patients.ConclusionIn addition to ameliorating the core symptoms of akinesia and rigidity in Parkinson's disease, pramipexole improves tremor and depressive symptoms in routine clinical practice. The SPES, TIS and SHAPS-D were found to be useful instruments with validity in this study.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

▴ Gabapentin is a structural analogue of the neurotransmitter γ-aminobutyric acid (GABA) approved for use in adults with postherpetic neuralgia.▴ Gabapentin does not bind to GABAAor GABABreceptors. Its mechanism of action in humans is unclear, but may involve binding to α2δ calcium channel subunits in animal models.▴ Reductions in the mean daily pain score from baseline to week 7 or 8 of treatment (primary endpoint) were significantly greater with gabapentin 1800–3600 mg/day than placebo therapy in two well designed trials in patients with postherpetic neuralgia. The proportion of responders (patients showing a ≥50% reduction in mean daily pain score at endpoint versus baseline) was significantly greater with gabapentin than placebo.▴ Daily sleep rating scores, the Short Form McGill Pain Questionnaire (total pain scores), Patient and Clinician Global Impression of Change and measures on the Short Form-36 Health Survey (including physical functioning, role-physical, bodily pain, vitality or mental health) improved to a significantly greater extent with gabapentin than placebo.▴ Adverse events associated with gabapentin in patients with postherpetic neuralgia were usually mild to moderate in intensity, with dizziness, somnolence and peripheral oedema being commonly reported.Table. Features and properties of gabapentin (Neurontin®)

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

摘要:

▴ Topiramate is an antiepileptic drug that has a broad spectrum of antiseizure effects, which appear to be the result of several neurostabilising pharmacological mechanisms. These include blockade of ion channels, potentiation of GABA neuroinhibition and glutamate receptor antagonism at non-NMDA receptors, as well as mild inhibition of carbonic anhydrase.▴ Topiramate monotherapy dose dependently reduced the number of patients who met seizure related exit criteria in children (aged ≥6 years) and adults with epilepsy.▴ This effect was also observed in patients who had previously experienced partial onset seizures and for those who had experienced generalised tonic clonic seizures. Six-month and 1-year seizure-free rates were dose-dependently reduced.▴ In epilepsy, topiramate monotherapy 100 or 200 mg/day was as effective as carbamazepine 600 mg/day or valproate 1250 mg/day as measured by time to study exit for any reason, time to first seizure and percentage of patients seizure-free in the final 6 months of treatment (mean treatment duration 244 days).▴ Adverse events associated with topiramate monotherapy that were dosage related included paraesthesia, weight loss and diarrhoea. Renal calculi were also reported in both fully published trials.Table. Features and properties of topiramate (Topamax®)

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