摘要:

SSRIs are the most commonly prescribed antidepressant drugs, in part because of their favourable safety profile compared with older antidepressants. However, the widespread use of SSRIs leads to an increased occurrence of rare adverse effects. This review, based on data from published experimental research, clinical studies and case reports, describes the role of serotonin in the control of intraocular pressure (IOP) and the evidence for IOP modifications in patients receiving SSRIs.In a small percentage of patients with depression, the cause of SSRI withdrawal has been the occurrence of ill-defined visual disturbances. It can be speculated that in some of these patients, the iatrogenic ocular alterations could have been due to changes in IOP. There have also been a limited number of case reports of acute attacks of glaucoma occurring during treatment with SSRIs. Although causality is not exactly specified, the relationship between SSRIs and this ocular adverse event is strongly implied. Nevertheless, in a small clinical study assessing the effect of a single dose of fluoxetine on IOP, the drug was shown to increase this parameter, although the effect was asymptomatic. The clinical signs of unexpected adverse drug effects are often disregarded, with the exception of those characterised by serious symptoms (such as acute angle-closure glaucoma in the case of IOP modifications). Also, the distribution of iridocorneal angle configurations in the general population implies that an adverse effect on IOP will be pauci- or asymptomatic in most patients (intermittent, sub-acute or progressive angle-closure glaucoma). As a result, it is likely that the incidence of SSRI-related IOP modifications is underestimated.Until the involvement of SSRIs in IOP modifications is better understood, ophthalmological consultations should be considered before starting and during treatment with any SSRI in patients with glaucomatous risk factors, especially those who are elderly.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Over the last 20 years, the role of adjuvant pharmacotherapy in optimising outcome in rehabilitation programmes for alcohol-dependent patients has become increasingly evident. New avenues for rational drug treatment have arisen from better understanding of the neurobiological substrates of alcohol dependence, including adaptive changes in amino acid neurotransmitter systems, stimulation of dopamine and opioid peptide systems, and, possibly, changes in serotonergic activity.Disulfiram, naltrexone and acamprosate are currently the only treatments approved for the management of alcohol dependence. However, there is still no unequivocal evidence from randomised controlled clinical trials that disulfiram improves abstinence rates over the long term. Aversive therapy with disulfiram is not without risk for certain patients, and should be closely supervised. Both naltrexone and acamprosate improve outcome in rehabilitation of alcohol-dependent patients, but seem to act on different aspects of drinking pathology. Naltrexone is thought to decrease relapse to heavy drinking by attenuating the rewarding effects of alcohol. However, data from the naltrexone clinical trial programme are somewhat inconsistent, with several large studies being negative. Acamprosate is believed to maintain abstinence by blocking the negative craving that alcohol-dependent patients experience in the absence of alcohol. The clinical development programme has involved a large number of patients and studies, of which the vast majority have shown a beneficial effect of acamprosate on increasing abstinence rates. Both drugs are generally well tolerated; nausea is reported by around 10% of patients treated with naltrexone, while the most frequent adverse effect reported with acamprosate is diarrhoea.Another opioid receptor antagonist, nalmefene, has shown promising activity in pilot studies, and may have a similar profile to naltrexone. Data from studies of SSRIs in alcohol dependence are somewhat heterogeneous, but it appears that these drugs may indirectly improve outcome by treating underlying depression rather than affecting drinking behaviourper se. Similarly, the anxiolytic buspirone may act by ameliorating underlying psychiatric pathology. Dopaminergic neuroleptics, benzodiazepines and antimanic drugs have not yet demonstrated evidence of activity in large controlled clinical trials. Trials with drugs acting at serotonin receptors have yielded disappointing results, with the possible exception of ondansetron.Because the biological basis of alcohol dependence appears to be multifactorial, the future of management of alcoholism may be combination therapy, using drugs acting on different neuronal pathways, such as acamprosate and naltrexone. Pharmacotherapy should be used in association with appropriate psychosocial support and specific treatment provided for any underlying psychiatric comorbidities.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

For nearly 50 years, antidepressant drugs have been the first-line treatment for various forms of depression. Despite their widespread use, these medications have significant shortcomings, in particular problems of patient compliance due to adverse effects. The introduction of new formulations of existing antidepressant medications may provide patients with benefits in terms of convenience of use. As a consequence, improvements in compliance may lead to better antidepressant efficiency.An orally disintegrating formulation of mirtazapine (mirtazapine SolTab®), a once-weekly formulation of fluoxetine, an enantiomer-specific formulation of citalopram (escitalopram), an extended-release formulation of venlafaxine (venlafaxine XR), a controlled-release formulation of paroxetine (paroxetine CR) and intravenous formulations of some of the newer antidepressants have all been evaluated in limited clinical trials. In this article, a review of the pharmacokinetics and clinical evaluations of these formulations is presented.While there do not appear to be major clinical advantages for the new formulations in terms of antidepressant efficacy, none of them is less efficacious than their older counterpart. Indeed, some of the new formulations are more acceptable to patients (fluoxetine once-weekly, paroxetine CR), others have pharmacokinetic advantages (venlafaxine XR, paroxetine CR), while others may have a faster onset of effect (mirtazapine SolTab®, intravenous formulations). Further evaluation of some formulations is still required (mirtazapine SolTab®, fluoxetine once-weekly), while others (venlafaxine XR, escitalopram) are finding widespread acceptance in clinical practice.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Interferon-β-1b (Betaseron®, Betaferon®) is a non-glycosylated recombinant human interferon-β approved for high-frequency, subcutaneous (SC) administration in the treatment of multiple sclerosis (MS). Its mechanism of action is unknown, but may involve modulation of the autoimmune pathogenic processes of MS.In a randomised, double-blind trial in patients with relapsing-remitting MS (RRMS), SC interferon-β-1b 250µg (8 million International Units [MIU]) every other day reduced the annual relapse rate and increased the proportion of relapse-free patients compared with placebo. It also reduced relapse severity, hospitalisations, and disease activity assessed by magnetic resonance imaging (MRI), and increased the time to first relapse. Progression of disability showed a trend towards reduction relative to placebo and baseline, but did not reach statistical significance.SC interferon-β-1b 250µg every other day was shown in a randomised trial to be superior to intramuscular (IM) interferon-β-1a 30µg (6 MIU) once weekly with respect to reductions in relapse-related parameters, disability progression and MRI-assessed disease activity.In patients with secondary progressive MS (SPMS), SC interferon-β-1b 250µg every other day slowed progression of the disease relative to placebo in one randomised, double-blind trial, but not in another. In both studies, interferon-β-1b 250µg recipients had fewer relapses and less MRI-assessed disease activity than placebo recipients. The difference in primary outcome may reflect differences in patient entry criteria.Interferon-β-1b is generally well tolerated and the common adverse events (e.g. injection site reactions, asthenia and an influenza-like symptom complex) are clinically manageable. In a randomised trial, the tolerability of SC interferon-β-1b 250µg every other day was generally similar to that of IM interferon-β-1a 30µg once weekly, except for higher incidences of injection site reactions and neutralising anti-interferon-β antibodies with SC interferon-β-1b.In conclusion, SC interferon-β-1b 250µg every other day reduces the frequency and severity of relapses and MRI measures of disease activity and may delay the progression of disability in RRMS. The drug appeared to be more effective than, and as well tolerated as, IM interferon-β-1a 30µg once weekly. Interferon-β-1b also has positive effects on relapse rates and disease activity in patients with SPMS, although its effects on disease progression remain uncertain. The drug is generally well tolerated, and the common adverse events are clinically manageable. Thus, interferon-β-1b is a valuable first-line therapy for patients with RRMS and a potentially useful option in those with SPMS.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS