Several psychotropic drugs, including clozapine, are known to cause agranulocytosis and this may lead to a fatal condition. Lamotrigine is an anticonvulsant that the Food and Drug Administration (FDA) has approved for the depression of bipolar disorder. A few cases of lamotrigine-induced agranulocytosis have been previously reported on, but the pathophysiology and clinical manifestations are not yet known. This case series reports on 3 patients with different medical conditions who experienced agranulocytosis during treatment with lamotrigine. In these cases, the agranulocytosis occurred a few weeks after initiation of lamotrigine and it rapidly disappeared after discontinuation. We also discuss several characteristics of lamotrigine-induced agranulocytosis.
Agranulocytosis* ; Bipolar Disorder ; Clozapine ; Depression ; Humans ; Psychotropic Drugs ; United States Food and Drug Administration

INTRODUCTIONA bibliometric study was carried out to ascertain the volume and impact of scientific literature published on second-generation antipsychotic drugs (SGAs) in Singapore from 1997 to 2011.

METHODSA search of the EMBASE and MEDLINE databases was performed to identify articles originating from Singapore that included the descriptors 'atypic* antipsychotic*', 'second-generation antipsychotic*', 'clozapine', 'risperidone', 'olanzapine', 'ziprasidone', 'quetiapine', 'sertindole', 'aripiprazole', 'paliperidone', 'amisulpride', 'zotepine', 'asenapine', 'iloperidone', 'lurasidone', 'perospirone' and 'blonanserin' in the article titles. Certain bibliometric indicators of production and dispersion (e.g. Price's Law on the increase of scientific literature, and Bradford's Law) were applied, and the participation index of various countries was calculated. The bibliometric data was also correlated with some social and health data from Singapore, such as the total per capita expenditure on health and gross domestic expenditure on research and development.

RESULTSFrom 1997 to 2011, a total of 51 articles on SGAs in Singapore were published. Our results suggested non-fulfilment of Price's Law (r = 0.0648 after exponential adjustment vs. r = 0.2140 after linear adjustment). The most widely studied drugs were clozapine (21 articles), risperidone (16 articles) and olanzapine (8 articles). Division into Bradford zones yielded a nucleus occupied by the Journal of Clinical Psychopharmacology (6 articles) and the Singapore Medical Journal(4 articles). The analysed material was published in a total of 30 journals, with the majority from six journals. Four of these six journals have an impact factor greater than 2.

CONCLUSIONPublications on SGAs in Singapore are still too few to confirm an exponential growth of scientific literature.

Antipsychotic Agents ; therapeutic use ; Benzodiazepines ; administration & dosage ; Bibliometrics ; Biomedical Research ; methods ; Clozapine ; administration & dosage ; Humans ; Journal Impact Factor ; Publications ; Risperidone ; administration & dosage ; Singapore

OBJECTIVE: Although antipsychotic treatments are effective for schizophrenia, at least 25% of schizophrenic patients have little response to conventional neuroleptics. Although patients respond well to antipsychotics initially, they often result in heavy loss of costs and social burden due to the frequent relapse which often require intensive institutional care while the patients experience significant social and functional disabilities. Many studies have come out recently concerning the cost of schizophrenia and its cost-effectiveness in treatment. Clozapine has the risk of agranulocytosis and greater initial cost, however, it has been reported to be cost-effective for the treatment of refractory schizophrenia because of its highly effectiveness, in addition, it has reduced rehospitalization rates and hospital stays. The purpose of this retrospective study was to ascertain the cost-effectiveness of clozapine treatment for patients with refractory schizophrenia in Korea. METHOD: We studied 17 patients with refractory schizophrenia treated by clozapine over a two year period. The numbers of hospitalization, hospital stays two years before clozapine treatment, and two years after clozapine treatment were investigated. Direct costs of psychiatric hospitalization, outpatient treatment, and other costs were estimated. Data on patients' clinical characteristics, use of mental health services and information about the cost of treatments were collected from psychiatric hospitalization records, outpatient records and hospital administration records. Some of the patient data information before the introduction of clozapine treatment were gathered through direct interviews of their families. Therapeutic outcome measures included the Clinical Global Impression (CGI) scale and Global Assessment of Functioning (GAF) score. RESULT: At the initial clozapine treatment, the mean age of subjects was 29 (+/- 7.9) years old. The mean duration of previous psychiatric treatment was 8 (+/- 3.0) years. Average total direct costs were reduced from \4,106,480 in the second pretreatment year to \2,338,427 in the second posttreatment year while the mean hospitalization costs, a percentage of total direct costs, were reduced from 82.9% to 27.4%. Also, the mean hospital stays per year were decreased from 83.4 days to 15.7 days, the mean numbers of hospitalization from 0.59 to 0.18. CGI scale scores and GAF scores showed a statistically significant clinical improvement between before and after clozapine treatment. CONCLUSION: These results suggest that a long-term treatment of clozapine for patients with refractory schizophrenia is indeed more cost-effective than conventional neuroleptic treatment. We suggest more comprehensive and prospective study due to the limitations of this retrospective study.
Agranulocytosis ; Antipsychotic Agents ; Clozapine* ; Hospital Administration ; Hospitalization ; Humans ; Korea ; Length of Stay ; Mental Health Services ; Outcome Assessment (Health Care) ; Outpatients ; Recurrence ; Retrospective Studies ; Schizophrenia*

Brown adipose tissue is specialized to burn lipids for thermogenesis and energy expenditure. Second-generation antipsychotics (SGA) are the most commonly used drugs for schizophrenia with several advantages over first-line drugs, however, it can cause clinically-significant weight gain. To reveal the involvement of brown adipocytes in SGA-induced weight gain, we compared the effect of clozapine, quetiapine, and ziprasidone, SGA with different propensities to induce weight gain, on the differentiation and the expression of brown fat-specific markers, lipogenic genes and adipokines in a mouse brown preadipocyte cell line. On Oil Red-O staining, the differentiation was inhibited almost completely by clozapine (40 microM) and partially by quetiapine (30 microM). Clozapine significantly down-regulated the brown adipogenesis markers PRDM16, C/EBPbeta, PPARgamma2, UCP-1, PGC-1alpha, and Cidea in dose- and time-dependent manners, whereas quetiapine suppressed PRDM16, PPARgamma2, and UCP-1 much weakly than clozapine. Clozapine also significantly inhibited the mRNA expressions of lipogenic genes ACC, SCD1, GLUT4, aP2, and CD36 as well as adipokines such as resistin, leptin, and adiponectin. In contrast, quetiapine suppressed only resistin and leptin but not those of lipogenic genes and adiponectin. Ziprasidone (10 microM) did not alter the differentiation as well as the gene expression patterns. Our results suggest for the first time that the inhibition of brown adipogenesis may be a possible mechanism to explain weight gain induced by clozapine and quetiapine.
Adipocytes, Brown/drug effects ; Adipogenesis/drug effects ; Adipokines/metabolism ; Animals ; *Antipsychotic Agents/administration & dosage/adverse effects ; Cell Differentiation/drug effects ; Cell Line ; Cell Survival/drug effects ; *Clozapine/administration & dosage/adverse effects ; *Dibenzothiazepines/administration & dosage/adverse effects ; Gene Expression Regulation/drug effects ; Humans ; Mice ; *Piperazines/administration & dosage/adverse effects ; Schizophrenia/drug therapy ; *Thiazoles/administration & dosage/adverse effects ; Weight Gain/*drug effects