A review of the efficacy and tolerability of agomelatine in the treatment of major depression.

Agomelatine is a novel agent that is under late-stage development as a potential antidepressant. Compared with available antidepressant agents, the drug may have a distinct mechanism of action, with significant interactions with melatonin receptors, in addition to serotonergic brain systems. Agomelatine has been shown to be active in preclinical models indicative of antidepressant activity and the results of a large-scale clinical trial programme, conducted in major depressive disorder, indicate both antidepressant activity and a favourable tolerability profile. As agomelatine may have a pharmacological profile and mechanism of action distinct from available agents, it may come to represent a valuable additional treatment option in those patients who do not respond fully or who prove unable to tolerate the side effects of existing antidepressants.

Quetiapine demonstrates good tolerability and is associated with improvements in extrapyramidal symptoms in patients with schizophrenia switched from other antipsychotics: results of a naturalistic study.

Objectives. Compared with conventional agents, atypical antipsychotics such as quetiapine (Seroquel®; AstraZeneca) show improved tolerability and a lower liability to cause extrapyramidal symptoms (EPS). In the routine treatment of schizophrenia, it is usual practice to consider a change of medication when the current treatment is ineffective or poorly tolerated, although few studies are available to guide clinicians. This paper reports the results from the Seroquel Method. Patient Evaluation on Changing Treatment Relative to Usual Medication (SPECTRUM) trial, a 12-week, open-label, noncomparative study that evaluated clinical benefit and tolerability of switching patients with schizophrenia from their existing antipsychotic to quetiapine. Patients were switched because of intolerance to, or lack of efficacy with, their previous antipsychotic. Quetiapine was titrated to 400 mg/day over 7 days, then dosed flexibly up to 750 mg/day over the remaining weeks (mean modal dose 505 mg/day). Results. In the overall population of 506 evaluable patients, quetiapine was well tolerated, with a low incidence of adverse events and minimal requirement for anticholinergic medication. Significant improvements in EPS, including parkinsonism and akathisia, were observed, irrespective of reason for switching, although greatest improvements were observed in patients switching because of EPS. Conclusions. This study provides further evidence for the utility and tolerability of quetiapine, in patients with schizophrenia who had been switched from a previous antipsychotic, following problems with efficacy or tolerability.

A review of the evidence for the use of antipsychotics in the maintenance treatment of bipolar disorders.

Antipsychotic agents have long had a place in the clinical treatment of bipolar disorder, in both acute and maintenance phases. Recent clinical research conducted with the new generation of antipsychotic agents has contributed enormously to the data available on antipsychotic agents in bipolar disorder. Even now, however, the clinical trial data relates principally to the short-term treatment of acute mania. With the exception of recent data generated during the clinical trial programme for olanzapine, studies of maintenance treatment, conducted with antipsychotic agents, both established and newly-introduced, have generally been small and prone to methodological weakness. As a result, many important clinical questions, concerning the utility of antipsychotic agents in bipolar maintenance, can not be answered by reference to the data. Taken together, the findings of the clinical trials in bipolar maintenance, conducted with antipsychotic agents other than olanzapine, can be regarded only as tentative. As was conducted with olanzapine, larger, more rigorously designed studies are required to provide definitive evidence of efficacy in longer-term treatment. Due to the logistical complexity and expense of these sorts of study, it is likely that, for many antipsychotic agents with a potential role in long-term treatment in bipolar disorder, the definitive studies will never be undertaken.

Evaluation of the Two-Way Communication Checklist as a clinical intervention. Results of a multinational, randomised controlled trial.

BACKGROUND: Patients and doctors often have divergent views on care needs. AIMS: To examine whether providing patients with an opportunity to identify and discuss their needs would improve communication and induce changes in care. METHOD: Patients with schizophrenia (n=134) were randomly allocated to either standard care or use of the Two-Way Communication Checklist (2-COM). Before seeing their clinician for a routine follow-up, participants in the active intervention group were given 2-COM, a list of 20 common needs, and told to indicate those areas they wanted to discuss with their doctor. Outcomes were assessed immediately and again after 6 weeks. RESULTS: Using 2-COM induced a stable improvement of patient-reported quality of patient-doctor communication (B=0.33, P=0.031), and induced changes in management immediately after the intervention (OR=3.7, P=0.009; number needed to treat, 6). Treatment change was more likely inpatients with more reported needs, and needs most likely to induce treatment change displayed stronger associations with non-medication than with medication changes. CONCLUSIONS: A simple intervention to aid people in discussion of their needs results in improved communication and changes in management.

Quetiapine: a well-tolerated and effective atypical antipsychotic.

Quetiapine is an atypical antipsychotic, licensed in the UK for the treatment of schizophrenia. This review of published literature identifies the evidence that quetiapine is both effective and well-tolerated and highlights the particular indications in which quetiapine will be of most value to clinicians and patients.

Patients' subjective experiences of antipsychotics: clinical relevance.

The subjective experience of patients with schizophrenia who are receiving antipsychotic medication has been a neglected research area, as has the satisfaction of patients with their drug treatments. This is unfortunate, as satisfaction with treatment appears to be related strongly to the readiness of patients to take their medication as prescribed, and thereby to outcome. Patients' perceptions of their treatment do not appear to be related strongly to severity of illness or symptom ratings, although there are associations between perceptions of treatment and adverse effects. Surveys of patient experience with typical antipsychotics have tended to indicate high levels of dissatisfaction and perceived adverse effects. There have been a number of surveys of patients' perceptions of treatment with the atypical antipsychotics. These tend to accord with the expectation that a relative freedom from adverse effects with the atypical antipsychotics will be reflected in enhanced levels of satisfaction and perceived well-being. In general, these studies share a number of weaknesses, including small sample sizes, bias in selection of respondents, open treatment and lack of suitable comparator groups. In addition, many have adopted a cross-sectional, rather than longitudinal, approach and have relied on nonvalidated and perhaps idiosyncratic rating measures. Recently, there have been studies of better methodological quality. These, too, have indicated that patients regard the newer treatments more positively than the older regimens. In addition, there is now evidence that the various new-generation antipsychotics may be evaluated differently by patients.

Oxcarbazepine (Trileptal) in the treatment of bipolar disorders: a review of efficacy and tolerability.

Oxcarbazepine, although structurally similar to carbamazepine, is metabolised very differently. As a consequence, oxcarbazepine's pharmacokinetic profile is comparatively less complex, and a more predictable, linear relationship between oxcarbazepine and blood levels is apparent. Furthermore, hepatic enzyme induction is considerably less with oxcarbazepine. Unlike carbamazepine, oxcarbazepine does not appear to induce its own metabolism, nor is it highly protein bound. These pharmacokinetic and metabolic characteristics raise the expectation that potential for drug interactions and side effects with oxycarbazepine will be less than that reported for carbamazepine. This review compares the pharmacokinetic and metabolic profiles of the two drugs and the available efficacy and safety data of carbamazepine and oxcarbazepine, in the treatment of bipolar disorder.