Because of certain side effects of cimetidine therapy which may be hormonally mediated (e.g. gynecomastia), there has been recent interest in the possible endocrine effects of this H2 histamine receptor-blocking agent used in the treatment of peptic ulcer disease. Accordingly, the effect of chronic cimetidine therapy on anterior pituitary function was examined in 12 adult men with mild peptic ulcer disease. TRH and insulin-hypolycemic stimulation tests were performed by standard methods. Serum for TSH and PRL RIA was obtained after TRH; serum for GH, cortisol, and PRL RIA was obtained after insulin-induced hypoglycemia. In addition, serum for LH, FSH, testosterone, and PRL was obtained every 4 h for 24 h. After these baseline studies, 300 mg cimetidine were administered orally 4 times a day for 4--8 weeks and the studies were repeated as before. Chronic treatment with cimetidine caused a significant increase in the peak TSH response to TRH at 30 min (mean peak TSH value before cimetidine, 7.0 microU/ml; after cimetidine, 10.2 microU/ml; P less than 0.05) as well as a significant increase in the TSH area under the curve. There was no statistically significant effect of cimetidine on basal TSH or basal or stimulated PRL secretion. Cimetidine had no effect on the GH, PRL, or cortisol response to insulin-induced hypolycemia or the 24-h secretion of LH, FSH, testosterone, or PRL.

AimsThis review and meta-analysis aim to estimate the cumulative incidence of clozapine induced agranulocytosis and leukopenia the impact of the associated factors such as dose of clozapine, duration of follow-up, gender and race on the cumulative incidence.BackgroundClozapine is the only medication licensed for treatment-resistant schizophrenia. There has been a renewed interest in the role of Clozapine in the treatment of Schizophrenia based on strong evidence that favours its efficacy and safety. Despite the evidence that Clozapine has superior efficacy and has been recommended for treatment-resistant cases by the national guidelines, the drug is underutilised.MethodWe included all studies in which clozapine was used for a psychotic illness. We included studies which provided data on two primary indices; Leucopenia or agranulocytosis and neutropenia; defined according to the cut off used by CPMS for total WBC and neutrophil count. Additionally we included studies reporting another blood dyscrasia or death due to agranulocytosis. Studies were identified by searching AMED, BIOSIS, CINAHL, EMBASE, MEDLINE, PsycINFO, PubMed, and registries of Clinical Trials and their monthly updates, hand searches, gray literature, and conference proceedings from the first available date until 2nd February, 2015. The search was updated on 15th March, 2017. The Protocol was initiated and then registered with PROSPERO International prospective register of systematic reviews University of York, Centre for Reviews and Dissemination.ResultThe cumulative incidence of the agranulocytosis in all studies was 00.32 % (CI 00.1-0.63). The cumulative incidence in all studies for different types of blood dyscrasia were following: leucopenia 00.96 % (CI 0.39-1.70), neutropenia 2.93 % (CI 1.49-4.72), other blood dyscrasias 4.64% (CI 2.34-7.52) and any blood dyscrasia was 2.23 (CI 1.46-3.12).ConclusionThe limitations of this review are mainly due to the nature of evidence from the included studies. We adopted a broad inclusion criteria to include all the available evidence. Number of patients started on Clozapine may be withdrawn from the Clozapine on the earliest signs of blood dyscrasias since the introduction of Clozapine monitoring services. This means that the true incidence of agranulocytosis and neutropenia may be higher and this may be a major bias in finding the true incidence of Clozapine induced neutropenia.