Prevalence and extent of distress of adverse effects of antipsychotics among callers to a United Kingdom National Mental Health Helpline

The aims of this cross-sectional survey were to assess psychotic sufferers' perception of the effectiveness of their medication, the distress caused by adverse effects and the impact these might have on overall patient satisfaction with treatment. Three hundred and forty-one people diagnosed with psychosis who called a national mental health helpline (SANELINE) in the UK, between July 1998 and February 1999, were asked to take part in the survey. They were given a choice of either a postal questionnaire or a telephone interview in which the same questionnaire was used. One hundred and nineteen were interviewed on the telephone and 83 (out of 222) returned completed questionnaires. In total, information was available from 202 callers. Almost one-half of the respondents were dissatisfied with their medication, and almost all of them reported experiencing at least one adverse effect. Depression (or low mood), sedation and difficulty thinking and concentrating were the most prevalent adverse effects. Weight gain was the most distressing, particularly to women. Those taking atypical antipsychotics were significantly more likely than those on typical antipsychotics to experience insomnia and dry mouth, but were less likely to perceive depression and difficulty thinking/concentrating as quite or extremely distressing. Low satisfaction, as opposed to high satisfaction, was significantly associated with reporting weight gain, difficulty thinking/concentrating, insomnia and sexual dysfunction. It was also significantly associated with reporting weight gain, difficulty thinking/concentrating, muscle/joint stiffness and depression as quite or extremely distressing. Attention should be given to the management of cognitive impairment and weight gain as adverse effects of antipsychotics. Doctors should be more open to discussing the risks and nature of adverse effects with patients who should also be encouraged to do so.     

Should TPMT genotype and activity be used to monitor 6‐mercaptopurine treatment in children with acute lymphoblastic leukaemia?

BACKGROUND AND OBJECTIVE: The activity of thiopurine S-methyltransferase (TPMT), a key enzyme in the metabolism of purine analogues, displays wide inter-subject variability partly due to a genetic polymorphism. Previous studies have suggested adjusting purine analogues dosing according to TPMT activity but measurements are costly and time-consuming. It is still unclear, especially under treatment, whether the simpler TPMT genotyping reliably predicts enzyme activity. Our aim was to study the possible correlation of TPMT genotype with phenotype. METHODS: We determined the genotypic status and TMPT activity, at diagnosis and after 6 months of maintenance therapy, of 118 children with acute lymphoblastic leukaemia (ALL). RESULTS AND DISCUSSION: Eighty-nine per cent of the children had a homozygous wild-type genotype (group 1), 11% had one or two mutant allele(s) (group 2). At both time points, TPMT activity (U/mL peripheral red blood cell) was significantly higher in group 1 than in group 2 (P < 0.001) but inter-group levels overlapped considerably. There was considerable heterogeneity in the percentage increase in TPMT activity after therapy, and little correlation between metabolites ratio [6-methylmercaptopurine derivative/6-thioguanine nucleotides (6-TGN)] and TPMT activity at the end of 6 months' maintenance treatment. These results show that TPMT activity cannot be used as an accurate tool for 6-mercaptopurine monitoring. CONCLUSION: Genotyping at diagnosis identifies patients with a homozygous mutant TPMT and may prevent severe and life-threatening toxicity. ALL treatment monitoring should preferentially be based on repeated determinations of intracellular active metabolites (6-TGN) and methylated metabolites.     

Lamotrigine in patients with epilepsy and comorbid depressive symptoms

PurposeThis open-label study evaluated the antidepressant qualities of lamotrigine (LTG) in people with epilepsy.MethodsEligible patients exhibited low to moderate depressive symptoms and required a change in antiepileptic drug (AED) therapy, but were excluded if they had a major depressive disorder (MDD). Lamotrigine was added onto a stable AED regimen, and self-report instruments were administered to evaluate changes in mood states. Evaluations were conducted at baseline, at the end of 19 weeks of adjunctive treatment, and 36 weeks following conversion to monotherapy.ResultsOne hundred and fifty-eight patients with epilepsy participated; 96 patients completed adjunctive treatment, and 66 patients completed monotherapy. Intent-to-treat analyses for all instruments showed improvement in depression scores after adjunctive LTG treatment. Improvement was maintained for those converted to monotherapy.ConclusionsThese data suggest that LTG may have antidepressant activity for patients with epilepsy and comorbid low to moderate depressive symptoms, and warrant a randomized controlled trial for validation.     

Exploring the oral bacterial flora: current status and future directions

Oral Diseases (2010) 16 , 136–145 Objective: The oral cavity forms an indispensable part of the human microbiome, for its unique and diverse microflora distributed within various niches. While majority of these organisms exhibit commensalism, shifts in bacterial community dynamics cause pathological changes within oral cavity and distant sites. The aim of this review was to appraise the current and emerging methods of detecting bacteria of the oral cavity paying particular attention to the cultivation independent methods. Design: Literature pertaining to cultivation based and cultivation independent methods of oral bacterial identification was reviewed. Methods: The specific advantages and disadvantages of cultivation based, microscopic, immunological and metagenomic identification methods were appraised. Results: Because of their fastidious and exacting growth requirements, cultivation based studies grossly underestimate the extent of bacterial diversity in these polymicrobial infections. Culture independent methods deemed more sensitive in identifying difficult to culture and novel bacterial species. Conclusion: Apart from characterizing potentially novel bacterial species, the nucleic acid sequence data analyzed using various bioinformatics protocols have revealed that there are in excess of 700 bacterial species inhabiting the mouth. Moreover, the latest pyrosequencing based methods have further broadened the extent of bacterial diversity in oral niches.     

Topiramate Overdose: Clinical and Laboratory Features

Limited data exist on overdose with new antiepileptic drugs. We reviewed the medical records of two patients who took a topiramate overdose as a suicide attempt. We recorded their medical and seizure histories, concomitant antiepileptic medications, neurologic examination, and laboratory findings at the time of presentation following the overdose. We also recorded their progress and the evolution of laboratory abnormalities. Both patients progressed to coma and had generalized convulsive status epilepticus, requiring intubation and treatment with benzodiazepines. Both patients recovered within 2 days but had a non-anion-gap metabolic acidosis that persisted for 5-6 days. Physicians should carefully monitor patients treated with topiramate who develop signs of clinical depression. The non-anion-gap metabolic acidosis observed may be due to inhibition of renal cortical carbonic anhydrase.