Risks Of Drug Treatment Research Articles

Successful secukinumab therapy in plaque psoriasis is associated with altered gut microbiota and related functional changes.

The role of gut microbiome dysbiosis in the pathogenesis of psoriasis has gained increasing attention in recent years. Secukinumab, targeting interleukin (IL)-17, has a promising efficacy in psoriasis treatment. However, it remains unclear the gut microbiota alteration and related functional changes caused by successful secukinumab therapy in psoriatic patients. In our study, we compared the fecal microbiome profile between psoriatic patients after secukinumab successful treatment (AT) and the other two groups, psoriatic patients without therapy (BT) and healthy people (H), respectively, by using next-generation sequencing targeting 16S ribosomal RNA. Then, shotgun metagenomic sequencing was first used to characterize bacterial gut microbial communities and related functional changes in the AT group. We found that the diversity and structure of the microbial community in the AT group were significantly changed compared to those in the BT group and the H group. The AT group showed a microbiota profile characterized by increased proportions of the phylum Firmicute, families Ruminococcaceae, and a reduction in the phylum Bacteroidota (elevated F/B ratio). To detect functional alteration, we discovered that secukinumab treatment may construct a more stable homeostasis of the gut microbiome with functional alteration. There were different KEGG pathways, such as the downregulated cardiovascular diseases pathway and the upregulated infectious diseases in the AT group. By metagenomic analysis, the metabolic functional pathway was changed after secukinumab therapy. It seems that gut microbiota investigation during biologic drug treatment is useful for predicting the efficacy and risks of drug treatment in disease.

Current Clinical Psychopharmacology in Borderline Personality Disorder.

Background Patients with Borderline Personality Disorder (BPD) manifest affective and behavioral symptoms causing personal distress, relationship difficulties, and reduced quality of life with global functioning impairment, mainly when the disease takes an unfavorable course. A substantial amount of healthcare costs is dedicated to addressing these issues. Many BPD patients receive medications, mostly those who do not respond to psychological interventions.Objective Our aim was to assess the efficacy of the most used strategies of pharmacological interventions in BPD with a comprehensive overview of the field.Methods We searched the PubMed database for papers focused on the most used psychotropic drugs for BPD. We included randomized controlled trials and open studies in adult patients with BPD, focusing on the efficacy and tolerability of single classes of drugs with respect to specific clinical presentations that may occur during the course of BPD.Results Specific second-generation antipsychotics (SGAs) or serotonergic antidepressants can be effective for different core symptoms of BPD, mainly including mood symptoms, anxiety, and impulse dyscontrol. Some atypical antipsychotics can also be effective for psychotic and dissociative symptoms. Specific antiepileptics can be useful in some cases in treating different BPD symptoms, mainly including mood instability, impulsiveness, and anger.Conclusion No medication is currently approved for BPD, and clinicians should carefully assess the benefits and risks of drug treatment. Further studies are needed to identify specific personalized treatment strategies, also considering the clinical heterogeneity and possible comorbidities of BPD.

¿Hay lugar para el consentimiento informado en los tratamientos de las personas con psicosis?: una reflexión sobre el tratamiento de las psicosis

Informed consent (IC) in Mental Health care is unusual, especially for psychotic patients. However, current legislation, statements of professional associations, patient organizations and deontological codes advocate informed consent and patients' autonomy, also for people with psychosis. Patients and their relatives usually are unaware of the scope, limits and risks of drug treatment and the existence of other approaches. The reasons for the IC’s lack can be found in the peculiarities of these patients, but also on the assumption that psychosis impacts the core of the person, and therefore they are unfit of understanding and consent. Today there are two different ways to receive the patient with psychosis problems: first, the mainstream whose objective is to block the process and reverse psychotic symptoms principally using antipsychotics drugs, and another one, that includes various clinic models, that receive psychotic person with their difficulties, proposing to build a framework of understanding for their experiences. The outcomes don’t reveal superiority for the mainstream model, rather the opposite. When listening to the users, they clearly opt for their autonomy and right to choose, rejecting coercive models. Informed consent is a right that empowers the patients and also a recovery factor for many of them. Its implementation will require significant changes in the training of professionals and in the current Mental Health Care networks.

Adverse Effects and Tolerability of Medications for the Treatment of Tobacco Use and Dependence

Tobacco use is the leading cause of preventable death and disability in the world. Although gradually declining in most developed countries, the prevalence of tobacco use has increased among developing countries. Treatment for tobacco use and dependence is effective, although long-term abstinence rates remain disappointingly low. In response, new treatments continue to be developed. In addition, many of the pharmacotherapies that have been available for years have found new applications with the use of medication combinations, higher doses and a longer duration of therapy for approved medications. There are now seven medications (nicotine patch, nicotine gum, nicotine lozenge, nicotine inhaler, nicotine nasal spray, bupropion sustained release and varenicline) approved for tobacco dependence treatment in most countries, and many national and professional society practice guidelines recommend their use. Although each of the medications used for tobacco dependence treatment has been rigorously tested for efficacy and safety, broader experience in clinical trials and in observational population-based studies suggests that adverse events associated with these medications are relatively common. Since 2008, two of the medications (varenicline and bupropion) have come under increasing scrutiny because of reports of unexplained serious adverse events (SAEs), including behaviour change, depression, self-injurious thoughts and suicidal behaviour. To date, this association has not been shown to be caused by these medications, but concerns about medication safety continue. Prescribers require a working knowledge of the common adverse effects for all of these medications as well as a more detailed knowledge of the SAE potential. Nicotine replacement therapy (NRT) has been rigorously tested in clinical trials for over 30 years. A number of adverse effects are commonly associated with NRT use, although SAEs are rare. The adverse effects associated with NRT are due to the pharmacological action of nicotine as well as the mode and site of the NRT application. Bupropion has been tested in over 40 controlled clinical trials and has been associated with higher rates of treatment discontinuation due to adverse events than NRTs. A number of SAEs are associated with bupropion and new warnings were recently added to bupropion prescribing information because of observed neuropsychiatric symptoms including suicidal thoughts and behaviours. Varenicline is the most recently approved medication for tobacco dependence treatment and, although proven safe in clinical testing, new safety concerns have arisen based on post-marketing reports. Warnings have been added to the prescribing information for varenicline because of neuropsychiatric symptoms also including suicidal thoughts and behaviours. Informed decision making regarding the use of pharmacotherapy for the treatment of tobacco dependence requires knowledge about the risks of drug treatment that is weighed against the risks of continued tobacco use and the benefits of treatment. Over half of all long-term smokers will die of a tobacco-related disease and the risk of a serious or life-threatening adverse event with tobacco cessation pharmacotherapy is vanishingly small. Pharmacotherapy for tobacco dependence is also among the most cost-effective preventive health interventions. Given these factors, the benefit : risk ratio is strongly in favour of pharmacotherapy for tobacco dependence treatment in virtually all smokers who are motivated to quit.

Estimation of Cefuroxime Dosage Using Pharmacodynamic Targets, MIC Distributions, and Minimization of a Risk Function

An approach for estimation of dosing strategies based on data-derived models and assessment of the risk associated with deviation from the treatment target is presented. The work is illustrated by establishing a dosing strategy to be used for a priori individualization on the basis of renal function for the antibiotic cefuroxime. Treatment involved exposing patients to concentrations above the minimum inhibitory concentration (MIC) for 50% of the dosing interval. The risk (penalty) function incorporated both deviations from the target and the use of excess amount of drug. Dosing strategies were estimated for a target population by minimizing the risk function. The population was characterized by a population pharmacokinetic model, and distributions of CLcr and body weight were reflective of the target group. The estimated dosing strategies were assessed by evaluating population distributions of (1) percentage of dosing interval with concentrations above MIC, (2) time of drug exposure below MIC, and (3) drug administered in excess to reach the target. These distributions were generated using wild-type MIC distributions for Escherichia coli and Streptococcus pneumoniae. The authors illustrate how benefits and risks of drug treatment can be weighed quantitatively in decision-based risk functions and subsequently used in the estimation of drug dosing.

Individual case safety reports in children in commonly used drug groups – signal detection

BackgroundDue to few paediatric drug safety studies, knowledge on risks of drug treatment in children is limited. The knowledge needs to be increased to make proper risk-benefit analyses possible when treating paediatric patients with drugs. The aim of the present study was to investigate drug groups commonly used in children concerning type and frequency of individual case safety reports in children.MethodsNumber and type of individual case safety reports in the 30 groups of drugs (5th level ATC-code) most sold (number of defined daily doses) in outpatient treatment to children (<15 years old) during 2005 were obtained. Descriptive analyses of the adverse drug reactions reported in children were performed.ResultsThe number of individual case safety reports per million defined daily doses in children varied in the groups of drug between 0 and 24. The largest number was found in the drug group R03DC, the leukotriene receptor antagonist montelukast; the majority of the children being <5 years old and experiencing psychiatric adverse drug reactions.ConclusionThe number of individual case safety reports per million defined daily doses varies in different groups of drugs. A possible signal for montelukast and psychiatric adverse drug reactions was found, which should be further explored.

Balancing the Benefits and Risks of Drug Treatment

To examine the extent to which the attributes of a treatment affect patients' choice of treatment for psoriasis and the magnitude and nature of trade-offs between risks and benefits of treatment. A questionnaire, including a stated-preference, discrete choice experiment, was used to elicit patients' preferences for the treatment of psoriasis. Dermatology clinics in England. A total of 126 patients with psoriasis. Preferences of patients for, and trade-offs between, the 6 attributes of time to moderate (50%) improvement, relapse, and risks of experiencing skin irritation, high blood pressure, liver damage, and skin cancer. The mean age of respondents was 47.6 years, and the mean duration of psoriasis was 23 years. All 6 attributes were important factors affecting choice of treatment. The results indicated that patients with psoriasis prioritized low risk of skin cancer (beta = -0.054; P < .01) and liver damage (beta = -0.054; P < .01) and preferred treatment that resulted in a shorter time to achieve a moderate improvement (beta = -0.034; P < .01) over a longer time to relapse (beta = 0.028; P < .01). Patients were most willing to wait longer for a treatment to work if the likelihood of skin cancer or liver damage was reduced. This study shows that treatment attributes influence patients with psoriasis in their choice of treatment. The results of the discrete choice experiment presented herein indicate that most respondents would be willing to trade between different aspects of treatment to achieve improvements in their psoriasis and minimize the risks of adverse events.

Combining pharmacotherapy with psychotherapy in the treatment of anxiety disorder.

Anxiety disorders are more prevalent than any other mental health problem in the USA, but afflicted patients are often untreated or treated only by a primary care physician. Anxiety disorders can be understood in the context of the interplay of biological, psychosocial, and behavioral factors. Psychiatry has defined effective treatment that integrates education, psychotherapy and psychopharmacology. A combination of treatment approaches may be beneficial. Anxiety related symptoms, other than a true anxiety disorder, may be precipitated by normal stresses of daily life. These patients may also benefit from treatments used in anxiety disorders. Anxiety can also occur secondary to medical disorders and medications, as well as being present as part of other psychiatric syndromes. Diagnosis requires a history, physical examination and laboratory tests. Anxiety disorders, although common, are easily overlooked because patients may present with somatic complaints rather than admit to having emotional problems. Anxiety disorders are divided into seven categories in DSM IV, with each allowing for a differential treatment approach. Non-pharmacological treatments are the first line of treatment, and may include behavior therapy and cognitive therapy. The physician-patient relationship is itself a powerful treatment tool. Key areas in which the psychiatrist can help the patient cope are outlined. Benefits and risks of drug treatment for anxiety disorders are discussed.

Is it best to obtain informed consent from schizophrenic patients about the possible risk of drug treatment, for example, tardive dyskinesia, before initiating treatment or at a later date?

Professor of Psychiatry, University of Pittsburgh Director, Law and Psychiatry Program, WPIC Director, Adult Psychiatric Services, WPIC