Do anti-TNF-α drugs increase cancer risk in rheumatoid arthritis patients?

Concern has been raised about an increased risk of lymphoma and skin cancers in patients with rheumatoid arthritis due to administration of anti-TNF-α drugs. Meta-analysis of observational data from registries as well as from randomized controlled trials has failed to show a significant increase in the risk of lymphoma when the sample size has been sufficiently large; skin cancer risk may represent a valid concern. Issues relating to interpretation of these data are discussed.     

Type 2 diabetes in children and adolescents--the next epidemic?

OBJECTIVE: To provide an overview of the incidence of type 2 diabetes in children and adolescents and provide direction for clinicians who care for children and adolescents. RESEARCH DESIGN AND METHOD: The data presented in this review were obtained from published literature and abstracts presented at scientific meetings. Clinical trials and review articles were identified using the search terms 'metabolic syndrome', 'type 2 diabetes mellitus', 'children', and 'adolescents' in a MEDLINE search from 1995-2005. Additionally, the bibliographies of the identified articles were reviewed. RESULTS: Type 2 diabetes is rising rapidly in children and adolescents worldwide. Changing a child's living environment to include physical activity, and a well balanced, low fat, high fiber diet, are important for the maintenance of a desirable body weight and improving insulin sensitivity. Maintaining euglycemia with metformin, sulfonylureas, thiazolinediones, and insulin is recommended. Effective treatment of co-morbid problems such as hypertension and dyslipidemia can decrease the risk of cardiovascular complications. CONCLUSIONS: The prevalence of type 2 diabetes in children will continue to rise until effective measures are taken to prevent obesity in this age group. Ensuring that children have a well-balanced low fat, high fiber, diet, combined with physical activity, will promote weight loss or maintenance, improve insulin sensitivity, and decrease the risk of diabetes and cardiovascular disease. Pharmacologic therapy is recommended for children who are unable to achieve satisfactory glycemic control through physical activity and diet.     

Treating depression in children and adolescents: what options now?

There have been significant developments in the understanding of depression in children and adolescents in the past few years, including an increased recognition that significant depressive illness occurs in this patient group. Pharmacological and psychotherapeutic treatments are used to manage depression in children and adolescents, and there is evidence from randomised, double-blind, placebo-controlled trials of benefit for both approaches. However, not all medication trials have been positive. In addition, there have been increasing concerns about specific safety issues related to the use of medications to treat depression, with an overall finding of mood-related adverse effects, including suicide attempts, in 4% of active drug versus 2% of placebo recipients in controlled trials involving children and adolescents. This has resulted in regulatory actions in a number of countries that have ranged from the declaration of contraindication for most antidepressants (in Great Britain), to relegation of antidepressants to a second-line intervention (in New Zealand) to a Black Box warning (in the US). It can be concluded that best practice combines treatment with both medication and psychotherapy, and that important safety issues must be monitored carefully when children and adolescents are treated for depression. On balance, there appears to be evidence of the benefit for antidepressant medications in children and adolescents, which outweigh safety concerns.     

Do atypical antipsychotics cause stroke?

Post hoc analyses of pooled results from 11 randomised controlled trials of risperidone and olanzapine in elderly dementia subjects revealed an increased incidence of cerebrovascular adverse events compared with placebo. Reanalysis of the risperidone trials suggests that some of the increased incidence may be accounted for by nonspecific events that were not strokes. Large observational administrative health database studies appear to confirm that risperidone and olanzapine are not associated with an increased risk of stroke in elderly patients compared with typical antipsychotics or untreated dementia patients. A larger number of subjects with vascular and mixed dementias were included in the risperidone studies compared with the olanzapine studies, which likely accounts for the increased incidence of cerebrovascular adverse events in the risperidone trials compared with the olanzapine studies. Potential mechanisms proposed to explain an association between atypical antipsychotics and cerebrovascular adverse events include thromboembolic effects, cardiovascular effects (e.g. orthostatic hypotension, arrhythmias), excessive sedation resulting in dehydration and haemoconcentration, and hyperprolactinaemia. However, there is little evidence to support these hypothesised mechanisms at present. The association between atypical antipsychotics and cerebrovascular adverse events requires further clarification. At the present time, this association is another factor that clinicians should consider when weighing the risks and benefits of treating behavioural and psychological disturbances in elderly dementia patients.     

Do differences in atypical antipsychotics matter in routine practice? Medication switch from olanzapine and risperidone to amisulpride

Atypical antipsychotics are often addressed as one class of drugs, although there are marked differences in their pharmacological profiles. It is unknown how this is seen by practitioners and to what extent they differentiate between the various atypical compounds. In a drug utilization study, 472 schizophrenic outpatients who were switched for individual reasons from either olanzapine or risperidone to amisulpride were monitored. Data on patients, illness and treatment as well as on reasons to switch were collected. The reasons to switch from olanzapine to amisulpride were preferably 'weight gain' (72.6% of the physicians), or the 'expectancy of less weight gain with amisulpride' (84.1%) and 'patient request' (60.2%). Specific reasons to switch from risperidone were 'extrapyramidal symptoms' (58.5%), or the 'expectancy of few extrapyramidal symptoms with amisulpride' (82.5%). In conclusion, this study confirms that physicians do not consider 'atypical antipsychotics' as one homogeneous class of drugs but make differences that reflect the specific pharmacological profiles of the respective drugs.     

Do antipsychotic drugs increase seizure frequency in epilepsy patients?

To investigate whether addition of antipsychotic drugs (APD) would increase seizure frequency in epilepsy patients who were already treated with anti-epileptic drugs (AED), we compared a one-year seizure control outcome in 150 epilepsy patients with APD treatment for psychiatric conditions and 309 epilepsy patients without APD treatment matched for ages at epilepsy onset and the baseline evaluation and types of epilepsy. The seizure frequency was recorded at the baseline (immediately before the start of APD) and after the 1st, 3rd, 6th and 12th months. The seizure outcome at each of the four follow-up points was compared with the baseline. The seizure outcome was compared between the two groups as a whole and according to the types of epilepsy (idiopathic generalized and partial epilepsies). In the APD group, the seizure outcome was also analyzed according to the types of APD (first and second generation APD and combination of first and second generation APD) and the types of psychiatric conditions (psychosis and non-psychosis). The seizure outcome was significantly better in the APD group than control group at all the four follow-up points. According to the epilepsy types, the improvement in the seizure outcome was only observed in the patients with partial epilepsy. Of the APD group, there was no significant difference in the seizure outcome according to the types of APD or the psychiatric conditions. In epilepsy patients who are already treated with AED, APD treatment seems safe in seizure control outcome for treatment of psychiatric conditions.     

Suicide and epilepsy: do antiepileptic drugs increase the risk?

Introduction: Years after the US FDA issued an alert on an increased risk of suicide ideation and behavior in people with epilepsy treated with antiepileptic drugs (AEDs), this issue still remains controversial. The FDA alert was based on a meta-analysis of clinical trials of AEDs in all indications.

Areas covered: We discuss major methodological problems of this meta-analysis. Available evidence coming from the published studies is also discussed highlighting that the majority of them are also affected by major methodological limitations, which do not allow an absolute conclusion.

Expert opinion: Suicide in epilepsy is a complex phenomenon but most agree that suicide rates are higher in people with epilepsy when compared to the general population. Screening for suicide seems to be appropriate and well-designed prospective studies are urgently needed in order to clarify fully a possible role of AEDs.     

How does stress increase risk of drug abuse and relapse?

RATIONALE: The notion that stress leads to drug abuse in vulnerable individuals and relapse in addicts is not new. Most major theories of addiction postulate that stress plays an important role in increasing drug use and relapse. Several animal studies and some human laboratory studies have shown that stress exposure enhances drug self-administration. Although clinical observations suggest that exposure to stress increases drug use, and are associated with craving and relapse in addicts, human research in this area is largely correlational and at times contradictory. OBJECTIVE: Given the growing preclinical evidence that supports the key role of stress in substance abuse, careful examination of this research area in humans is warranted. This paper examines empirical evidence on how stress may increase the vulnerability to drug abuse, and explores whether chronic drug abuse alters the stress response and coping in addicts, thereby increasing the likelihood of drug seeking and relapse. Unanswered questions on the association between stress and substance abuse in humans are identified. CONCLUSION: Preclinical research has shown that stress, in addition to drug itself, plays a key role in perpetuating drug abuse and relapse. However, the mechanisms underlying this association in humans remain unclear. A greater understanding of how stress may perpetuate drug abuse will likely have a significant impact on both prevention and treatment development in the field of addiction.     

Olmesartan medoxomil in children and adolescents with hypertension†: profile report

?Adapted and reproduced from the original article published in Drugs 2010; 70 (18): 2439-47.     

Do noncontingent vouchers increase drug use?

Data from 2 contingency management trials, targeting opiate or cocaine use, were used to investigate whether noncontingent vouchers inadvertently reinforce drug use. The control group in each trial received noncontingent vouchers matched in value and frequency to those received by experimental groups, but independent of urinalysis. Vouchers were offered thrice weekly for 8 weeks (opiates) or 12 weeks (cocaine). Both dose-response and temporal associations of noncontingent voucher receipt with drug-positive urines were assessed. Drug use was unrelated to frequency of noncontingent voucher delivery and noncontingent voucher receipt when being drug positive was unassociated with risk of subsequent drug use, with one exception: cocaine use in the cocaine study (relative risk = 1.05, 95% confidence interval: 1.01-1.09). Overall, results do not indicate a causal relationship between noncontingent voucher receipt and increased drug use.     

How safe are antipsychotics in dementia?

Around 800,000 people in the UK have dementia, about 80% of whom will have behavioural changes or psychological symptoms in the course of the illness. Such features lower quality of life for both patients and carers, and often result in transfer to residential care and higher costs. Currently, no drugs are licensed in the UK specifically for behavioural changes and psychological symptoms in patients with dementia. Nevertheless, antipsychotic medications have been used in people with dementia, both for psychotic symptoms and also for less specific problems such as agitation and aggression. There have been long-standing concerns about the inappropriate use of these drugs in such settings. In 2004, following worries over an increased likelihood of stroke with risperidone and olanzapine, the former UK Committee on Safety of Medicines (CSM) advised that these drugs "should not be used for the treatment of behavioural symptoms of dementia". However, this led to reports of unsuitable interpretation of the guidance, with groups of patients having their medication withdrawn inappropriately or being switched to other, potentially more harmful, drugs. Here we assess the safety of antipsychotic medication in people with dementia.     

Bullying and fighting among adolescents - Do drinking motives and alcohol use matter?

The present study investigates the direct and indirect links (through alcohol use) between adolescents' drinking motives and violent behaviors (i.e. bullying and fighting). Structural equation models were estimated based on a national representative sample of 5419 8th to 10th graders in Switzerland (mean age 15.0, SD=.86). Results demonstrate that enhancement motives were only indirectly linked (through alcohol use) to violent behaviors, whereas coping motives were both directly and indirectly linked, particularly among girls. No consistent link was found for social motives. Despite the negative indirect link (through alcohol use), conformity motives were the strongest predictor of bullying and fighting among boys, and even stronger than alcohol use itself. To conclude, drinking motives have a bearing on other problem behaviors besides excessive drinking, and may be useful for early identification and intervention for students who are likely to experience a variety of problems.     

Impulsive sensation seeking,binge drinking,and alcohol-related consequences: Do protective behavioral strategies help high risk adolescents?

This study examined protective behavioral strategies (PBS) as a moderator of the relationship between impulsive sensation seeking and binge drinking and alcohol-related consequences in a sample of high school seniors (N = 346). Hierarchical regression analyses indicated that impulsive sensation seeking was a significant predictor of binge drinking and alcohol-related consequences and that PBS moderated these relationships. Specifically, manner of drinking moderated the relationships such that among students with high impulsive sensation seeking, those using strategies related to how they drink (e.g. avoiding rapid and excessive drinking) reported lower levels of binge drinking and alcohol-related consequences than those using fewer of these strategies. Clinical implications are discussed including using personality-targeted interventions that equip high impulsive sensation seeking adolescents with specific strategies to reduce binge drinking and alcohol-related consequences.