General practitioners' perceptions of the tolerability of antidepressant drugs: a comparison of selective serotonin reuptake inhibitors and tricyclic antidepressants.

OBJECTIVE: To examine inceptions and discontinuations of antidepressants in general practice. DESIGN: An observational study analysing data from an ongoing cross sectional postal survey. Every three months a representative sample of 250 doctors recorded prescribing activity for four weeks. This provided 4000 general practitioner weeks of recording per year. SETTING: A representative panel of general practitioners in England, Wales, and Scotland. SUBJECTS: Patients who began a new course of an antidepressant or had their treatment stopped or changed by the general practitioner between 1 July 1990 and 30 June 1995. MAIN OUTCOME MEASURES: Numbers of patients prescribed a new course of antidepressant; numbers discontinuing treatment; the ratio of antidepressant discontinuations to antidepressant inceptions; reasons for discontinuation; proportion of switches to another antidepressant. RESULTS: There were 13,619 inceptions and 3934 discontinuations of selective serotonin reuptake inhibitors and tricyclic antidepressants during the study. The number of newly prescribed courses of antidepressants increased by 116%, mostly due to an increase in prescribing of serotonin reuptake inhibitors. The ratio of total discontinuations to inceptions was significantly lower for serotonin reuptake inhibitors (22%) than for tricyclic antidepressants (33%). Differences persisted when controlled for age and sex of patients and severity of depression. However, there was more switching away from selective serotonin reuptake inhibitors when they failed (72%) than from tricyclic antidepressants (58%). CONCLUSIONS: Selective serotonin reuptake inhibitors are less likely than tricyclic antidepressants to be discontinued. A prospective study is needed in general practice to assess the implications of differences in discontinuation rates and switches on clinical and economic outcomes.     

DDT (dicophane) and postmenopausal breast cancer in Europe: case-control study.

OBJECTIVE: To examine any possible links between exposure to DDE (1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene), the persistent metabolite of the pesticide dicophane (DDT), and breast cancer. DESIGN: Multicentre study of exposure to DDE by measurement of adipose tissue aspirated from the buttocks. Laboratory measurements were conducted in a single laboratory. Additional data on risk factors for breast cancer were obtained by standard questionnaires. SETTING: Centres in Germany, the Netherlands, Northern Ireland, Switzerland, and Spain. SUBJECTS: 265 postmenopausal women with breast cancer and 341 controls matched for age and centre. MAIN OUTCOME MEASURE: Adipose DDE concentrations. RESULTS: Women with breast cancer had adipose DDE concentrations 9.2% lower than control women. No increased risk of breast cancer was found at higher concentrations. The odds ratio of breast cancer, adjusted for age and centre, for the highest versus the lowest fourth of DDE distribution was 0.73 (95% confidence interval 0.44 to 1.21) and decreased to 0.48 (0.25 to 0.95; P for trend = 0.02) after adjustment for body mass index, age at first birth, and current alcohol drinking. Adjustment for other risk factors did not materially affect these estimates. CONCLUSIONS: The lower DDE concentrations observed among the women with breast cancer may be secondary to disease inception. This study does not support the hypothesis that DDE increases risk of breast cancer in postmenopausal women in Europe.     

Stages of regulated exocytosis

Despite its unique features of spatial organization, Ca;2;+ regulation and speed, neurotransmitter secretion is a paradigm for studies of membrane fusion because it shares homologous proteins and common mechanisms with constitutive exocytosis in all eukaryotic cells.Recent advances have expanded knowledge of the number of gene products required for neurosecretion, and a current major challenge is to determine their mechanisms of action and the stages at which they function in the multistep exocytic pathway.This review discusses progress in this direction from in vivo and in vitro studies that have characterized roles for specific proteins in post-docking steps proximal to membrane fusion.