Clinical Trials Of Pharmacotherapy Research Articles

Considerations for the design and conduct of pediatric obesity pharmacotherapy clinical trials: Proceedings of expert roundtable meetings.

Anti-obesity medications (AOMs) have emerged as one element of comprehensive obesity clinical care intended to improve long-term health outcomes for children and adolescents. The number of pediatric AOM clinical trials has burgeoned in recent years as new pharmacotherapeutics have been developed. Factors related to growth and development in children and adolescents can present unique challenges in terms of designing and conducting clinical trials investigating the safety and efficacy of AOMs. These barriers can delay the AOM development and evaluation process, increase the cost of performing trials, create challenges in the interpretation of results, influence the generalizability of the findings and present ethical dilemmas. In an effort to address these issues and provide guidance to streamline the process of designing and conducting pediatric AOM clinical trials, relevant key stakeholders convened a series of roundtable meetings to discuss, debate and achieve harmonization on design features. Stakeholder participants included a multidisciplinary group of international pediatric obesity experts, patient (parent) representatives and representatives from academic medicine, key regulatory agencies and industry. Topics of discussion included primary efficacy end-points, secondary end-points, eligibility criteria, trial run-in and follow-up phases, use of active comparators and guidelines for down-titration and/or stopping rules for excessive weight reduction. Consensus recommendations were agreed upon. Regarding end-points, emphasis was placed on moving away from BMI z-score as a primary outcome, incorporating multiple alternative BMI-related outcomes and measuring adiposity/body fat as a prominent secondary end-point. Trial eligibility criteria were carefully considered to maximize generalizability while maintaining safety. The limited value of trial run-in phases was discussed. It was also underscored that designing trials with extended follow-up periods after AOM withdrawal should be avoided owing to ethical issues (including possible psychological harm) related to weight regain without providing the opportunity to access other treatments. The panel emphasized the value of the randomized, placebo-controlled trial but recommended the thoughtful consideration of the use of active comparators in addition to, or instead of, placebo to achieve clinical equipoise when appropriate. Finally, the panel recommended that clinical trial protocols should include clear guidance regarding AOM down-titration to avoid excessive weight reduction when applicable.

Ongoing and Future Clinical Trials of Pharmacotherapy for Heart Failure.

Increasing knowledge of the processes leading to heart failure (HF) has allowed significant developments in therapies for HF over the past few decades. Despite the evolution of HF treatment, it still places a large burden on patients and health care systems across the world.We used clinicaltrials.gov to gather information about clinical trials as of August 2023 studying pharmacotherapy for HF. We included interventional trials that were "active, not recruiting", "recruiting", or looking for participants but "not yet recruiting". In total, 119 studies met our criteria of ongoing clinical trials studying novel as well as currently approved HF pharmacotherapies. The major interventions were novel medications/already approved medications for other diseases 29 % (34 trials), sodium-glucose co-transporter inhibitors 21 % (25 trials), angiotensin receptor blocker-neprilysin inhibitors 10 % (12 trials), diuretics 14 % (17 trials) and mineralocorticoid receptor antagonists 5 % (6 trials). Ongoing research will aid in reducing the impact of HF and we summarize clinical trials leading the way to better HF treatment in this review.

Patient Priorities, Decisional Comfort, and Satisfaction with Metformin versus Insulin for the Treatment of Gestational Diabetes Mellitus.

We compared patient priorities, decisional comfort, and satisfaction with treating gestational diabetes mellitus (GDM) with metformin versus insulin among pregnant individuals with GDM requiring pharmacotherapy. We conducted a cross-sectional study of patients' perspectives about GDM pharmacotherapy in an integrated prenatal and diabetes care program from October 19, 2022, to August 24, 2023. The exposure was metformin versus insulin as the initial medication decision. Outcomes included standardized measures of patient priorities, decisional comfort, and satisfaction about their medication decision. Among 144 assessed individuals, 60.4% were prescribed metformin and 39.6% were prescribed insulin. Minoritized individuals were more likely to receive metformin compared with non-Hispanic White individuals (34.9 vs. 17.5%; p = 0.03). Individuals who were willing to participate in a GDM pharmacotherapy clinical trial were more likely to receive insulin than those who were unwilling (30.4 vs. 19.5%; p = 0.02). Individuals receiving metformin were more likely to report prioritizing avoiding injections (62.4 vs. 19.3%; adjusted odds ratio [aOR]: 2.83; 95% confidence interval [CI]: 1.10-7.31), wanting to take a medication no more than twice daily (56.0 vs. 30.4%; aOR: 3.67; 95% CI: 1.56-8.67), and believing that both medications can equally prevent adverse pregnancy outcomes (70.9 vs. 52.6%; aOR: 2.67; 95% CI: 1.19-6.03). Conversely, they were less likely to report prioritizing a medication that crosses the placenta (39.1 vs. 82.5%; aOR: 0.09; 95% CI: 0.03-0.25) and needing supplemental insulin to achieve glycemic control (21.2 vs. 47.4%; aOR: 0.36; 95% CI: 0.15-0.90). Individuals reported similarly high (mean score > 80%) levels of decisional comfort, personal satisfaction with medication decision-making, and satisfaction about their conversation with their provider about their medication decision with metformin and insulin (p ≥ 0.05 for all). Individuals with GDM requiring pharmacotherapy reported high levels of decision comfort and satisfaction with both metformin and insulin, although they expressed different priorities in medication decision-making. These results can inform future patient-centered GDM treatment strategies. · Pregnant individuals with GDM requiring pharmacotherapy expressed a high level of decisional comfort and satisfaction with medication decision making.. · Individuals placed different priorities on deciding to take metformin versus insulin.. · These results can inform interventions aimed at delivering person-centered diabetes care in pregnancy that integrates patient autonomy and knowledge about treatment options..

Characteristics of United States Counties in Which Heart Failure Clinical Trials of Pharmacotherapy Were Conducted.

HomeCirculation: Heart FailureAhead of PrintCharacteristics of United States Counties in Which Heart Failure Clinical Trials of Pharmacotherapy Were Conducted No AccessResearch ArticleRequest AccessAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessResearch ArticleRequest AccessCharacteristics of United States Counties in Which Heart Failure Clinical Trials of Pharmacotherapy Were Conducted Elisabeth Cox, Muath A. Alsalloum, Marin Vander Schaaf, Abdulaziz S. Alfehaid, Marwah E. Alnewais and Erin R. Weeda Elisabeth CoxElisabeth Cox Medical University of South Carolina College of Pharmacy, Charleston (E.C., M.A.A., M.V.S., A.S.A., M.E.A., E.R.W.). Search for more papers by this author , Muath A. AlsalloumMuath A. Alsalloum Medical University of South Carolina College of Pharmacy, Charleston (E.C., M.A.A., M.V.S., A.S.A., M.E.A., E.R.W.). Department of Pharmacy Practice, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia (M.A.A.). Search for more papers by this author , Marin Vander SchaafMarin Vander Schaaf Medical University of South Carolina College of Pharmacy, Charleston (E.C., M.A.A., M.V.S., A.S.A., M.E.A., E.R.W.). Search for more papers by this author , Abdulaziz S. AlfehaidAbdulaziz S. Alfehaid Medical University of South Carolina College of Pharmacy, Charleston (E.C., M.A.A., M.V.S., A.S.A., M.E.A., E.R.W.). Pharmaceutical Care Services, King Faisal General Hospital, Alahsa Health Cluster, Ministry of Health, Saudi Arabia (A.S.A.). Search for more papers by this author , Marwah E. AlnewaisMarwah E. Alnewais Medical University of South Carolina College of Pharmacy, Charleston (E.C., M.A.A., M.V.S., A.S.A., M.E.A., E.R.W.). College of Clinical Pharmacy, King Faisal University, Alahsa, Saudi Arabia (M.E.A.). Search for more papers by this author and Erin R. WeedaErin R. Weeda Correspondence to: Erin R. Weeda, PharmD, Medical University of South Carolina, Department of Clinical Pharmacy and Outcomes Sciences, 280 Calhoun St, QE213C MSC140, Charleston, SC 29425. Email E-mail Address: [email protected] https://orcid.org/0000-0001-7876-5802 Medical University of South Carolina College of Pharmacy, Charleston (E.C., M.A.A., M.V.S., A.S.A., M.E.A., E.R.W.). Search for more papers by this author Originally published16 May 2023Circulation: Heart Failure. 2023;0:e010449FootnotesThis work was conducted at the Medical University of South Carolina.For Sources of Funding and Disclosures, see page XXX.Correspondence to: Erin R. Weeda, PharmD, Medical University of South Carolina, Department of Clinical Pharmacy and Outcomes Sciences, 280 Calhoun St, QE213C MSC140, Charleston, SC 29425. Email [email protected]edu Previous Back to top Next FiguresReferencesRelatedDetails Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.PMID: 37191025 Originally publishedMay 16, 2023 Keywordsapplicabilitysocial determinants of healthdiversitygeneralizableruralclinical trialsexternal validityPDF download Advertisement SubjectsHeart Failure

Future Pharmacotherapy for Sensorineural Hearing Loss by Protection and Regeneration of Auditory Hair Cells.

Sensorineural hearing loss has been a global burden of diseases for decades. However, according to recent progress in experimental studies on hair cell regeneration and protection, clinical trials of pharmacotherapy for sensorineural hearing loss have rapidly progressed. In this review, we focus on recent clinical trials for hair cell protection and regeneration and outline mechanisms based on associated experimental studies. Outcomes of recent clinical trials provided valuable data regarding the safety and tolerability of intra-cochlear and intra-tympanic applications as drug delivery methods. Recent findings in molecular mechanisms of hair cell regeneration suggested the realization of regenerative medicine for sensorineural hearing loss in the near future.

Cannabidiol pharmacotherapy for delta-9-tetrahidrocannabinol dependence

Addictions are one of the most important health problems worldwide. Within these disorders, cannabis is one of the psychoactive substances with more burden of morbidity and mortality worldwide. The actual knowledge about the effectiveness of treatments for cannabis use disorders is unsatisfactory. This review aims to explore the evidence on cannabidiol for the treatment of cannabis use disorder. There are several clinical pharmacotherapy trials researching cannabis use disorders with limited evidence. A smaller number of trials in animal models and humans on the use of cannabinoids, especially Cannabidiol and Tetrahydrocannabinol to treat cannabis dependence show evidence of reduction in days of use, withdrawal symptoms and craving. New trials are under development, and there is an urgent need for trials with larger numbers of patients and longer treatment periods to support possible indications in the near future.

1.107 Examining Demographics and Modes of Cannabis Use Among Youth Enrolling in a Cannabis Use Disorder Treatment Trial

Youth cannabis use is common and may be associated with short- and long-term adverse consequences. Adolescent-onset cannabis users are more likely than adult-onset users to develop a maladaptive pattern of use characterized as cannabis use disorder. While epidemiological surveys provide information on characteristics of youth who use cannabis, less is known about these characteristics among those presenting for cannabis use disorder treatment. Within an ongoing cannabis use disorder pharmacotherapy clinical trial for youth aged 15 to 21 years, we sought to examine participant demographics and preferred modes of cannabis use.

Pharmacotherapy for mild traumatic brain injury: an overview of the current treatment options

Introduction Accounting for 90% of all traumatic brain injuries (TBIs), mild traumatic brain injury (mTBI) is currently the most frequently seen type of TBI. Although most patients can recover from mTBI, some may suffer from prolonged symptoms for months to years after injury. Growing evidence indicates that mTBI is associated with neurodegenerative diseases including dementias and Parkinson’s disease (PD). Pharmacological interventions are necessary to address the symptoms and avoid the adverse consequences of mTBI. Areas covered To provide an overview of the current treatment options, the authors herein review the potential drugs to reduce the secondary damage and symptom-targeted therapy as well as the ongoing clinical trials about pharmacotherapy for mTBI. Expert opinion There has been no consensus on the pharmacotherapy for mTBI. Several candidates including n-3 PUFAs, melatonin, NAC and statins show potential benefits in lessening the secondary injury and improving neurological deficits in pre-clinic studies, which, however, still need further investigation in clinical trials. The current pharmacotherapy for mTBI is empirical in nature and mainly targets to mitigate the symptoms. Well-designed clinical trials are now warranted to provide high level evidence.

The relationship of frequency of cocaine use to substance and psychiatric disorders in the U.S. general population

BackgroundIn clinical trials of pharmacotherapy for substance use, abstinence is the primary endpoint accepted by regulatory agencies. However, this endpoint could be overly restrictive, impeding efforts to identify effective medications for cocaine use disorder. To examine non-abstinent gradations in cocaine use as potential indicators of improvement, we investigated the relationship of frequency of cocaine use to clinical correlates in national survey data. MethodsLifetime cocaine users (n = 2501) were interviewed in the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) in 2001−2002 and re-interviewed in 2004–2005. Adjusted odds ratios (aORs) indicated associations between heaviest frequency of cocaine use and use of other substances, DSM-IV substance use disorders, psychiatric disorders, and change between 2001−2002 and 2004–2005. The reference category for all aORs was non-users. ResultsGreater lifetime cocaine use frequency was associated with lifetime cocaine, alcohol, and cannabis dependence (aOR for a linear trend = 2.80, 1.22, 1.22, respectively) and past-year cocaine, alcohol, and cannabis dependence (aOR = 1.78, 1.13, 1.16, respectively). Greater lifetime cocaine use frequency was associated with past-year depressive, panic, and generalized anxiety disorders (aOR = 1.07, 1.09, 1.12, respectively). Among cocaine users in 2001−2002, compared to the reference group using less than monthly, use ≥1x/week and use 1−3 times a month was associated with cocaine use disorder in 2004–2005 (aOR = 2.13 and aOR = 1.67, respectively). ConclusionGradations in risk for dependence on cocaine, other substances and psychiatric disorders by frequency of cocaine use indicates a promising direction for more sensitive outcome measures of treatment effects on cocaine outcomes than binary indicators (e.g., any use vs. none). Study results add to findings suggesting that non-abstinent measures might be useful indicators of treatment efficacy in clinical trials.

Neurodevelopmental disorders in children and the possibilities of their pharmacotherapy

Neurodevelopmental disorders (NDD) are characterized by disturbances of the formation of cognitive functions, communication skills, behavior characteristics and/or motor skills, which are caused by abnormalities in the course of the processes of neuroontogenesis. In the clinical practice of a pediatric neurologist and pediatrician, a significant part consists of patients with NDD without a general decrease in intelligence, primarily with speech development disorders, attention deficit hyperactivity disorder (ADHD), specific learning disorders (dyslexia, dysgraphia, dyscalculia). NDD represent a heterogeneous group of diseases, having multifactorial origin and a neurobiological nature, which are caused by genetic mechanisms and early (perinatal) brain damage. Among children with NDD, there is a higher occurrence of anxiety disorders compared to their peers. With NDD, early intervention is indicated, and its positive effect is possible during the period when the brain is most plastic and capable of changes. The published results of multicenter, double-blind, placebo-controlled, randomized clinical trials of pharmacotherapy with the medication "Tenoten for children" for ADHD, specific learning disorders, anxiety disorders and the consequences of perinatal damage to the central nervous system are reviewed.

Diagnostic and interventional circulating biomarkers in nonalcoholic steatohepatitis.

IntroductionIn the setting of the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent forms of chronic liver disease worldwide. Approximately 25% of adults globally have NAFLD which includes those with NAFL, or simple steatosis, and individuals with nonalcoholic steatohepatitis (NASH) where inflammation, hepatocyte injury and potentially hepatic fibrosis are found in conjunction with steatosis. Individuals with NASH, particularly those with hepatic fibrosis, have higher rates of liver‐related and overall mortality, making this distinction of significant clinical importance. One of the core challenges in current clinical practice is identifying this subset of individuals with NASH without the use of liver biopsy, the gold standard for both diagnostics and staging disease severity. Identifying noninvasive biomarkers, an accurately measured and reproducible parameter, would aide in identifying patients eligible for NASH pharmacotherapy clinical trials and to help tailor intensity of monitoring required.Methods, Results and ConclusionsIn this review, we highlight both the currently available and novel diagnostic and interventional circulating biomarkers under investigation for NASH, underscoring their accuracy and limitations relevant to our patient population and current clinical practice.

The inadequacy of cardiovascular safety reporting in breast cancer clinical trials.

e24100 Background: Although some cardiovascular (CV) toxicity is detected in early phase trials of therapeutic agents, most CV toxicities are not appreciated until later phase clinical trials or general clinical practice. The high prevalence of cardiovascular disease (CVD) in the general population warrants study of how later phase oncologic pharmacotherapy clinical trials address eligibility and assess for treatment-related cardiotoxicity. We focused our study on phase 2 and 3 breast cancer trials to limit disease-specific variations. Methods: A methodical Embase search was performed for phase 2 and 3 trials administering breast cancer pharmacotherapy and including > 50 participants. Firstly, we examined CVD as an exclusion criterion. Secondly, we identified what CV safety assessments were reported such as troponin, brain natriuretic peptide (BNP), lipid profile, electrocardiogram (ECG), or CV imaging. Thirdly, we examined whether trials reported adverse CV events. Fischer’s exact test was applied to compare reporting amongst trial characteristics (trial funding source and type of agent administered), and a 2 sided p-value of < 0.05 was considered significant. Results: 50 published articles from 46 separate clinical trials were included. Patients with prevalent CVD were excluded in 67.4% of trials, the most frequently excluded CVD was heart failure/NYHA class > 1 (65.2% of trials). At least one pre or post-treatment CV safety assessment was reported in only 58.7% of trials, most commonly an ECG (52.2% of trials). BNP or troponin assessments were not reported in any trial. Adverse CV events were reported in 82.6% of trials, the most frequently reported event was hypertension (43.5% of trials). CV Safety assessments were more frequently reported in pharmaceutically funded trials compared to non-pharmaceutically funded trials (86.4 vs 10.0%, p < 0.001), and in trials administering targeted/immunotherapy agents compared to those administering only traditional chemotherapy/hormonal therapy (85.2 vs 21.1%, p < 0.001). Conclusions: Later stage breast cancer clinical trials are conducted in populations under-representative of patients with prevalent CVD, a common comorbidity. Trial funding source and type of agent administered impact whether or not CV toxicity is monitored. Despite the frequent exclusion of patients with CVD and poor safety assessment reporting, adverse CV events are frequently encountered and reported. Thus, these trials may underestimate CV toxicity risks for the greater population receiving such agents in clinical practice.

Blunts versus joints: Cannabis use characteristics and consequences among treatment-seeking adults

BackgroundDespite the high prevalence of blunt smoking among cannabis users, very few studies examine the clinical profile of blunt smokers relative to those using more common methods of cannabis use, such as joints. MethodsThe current study uses baseline data from the ACCENT (Achieving Cannabis Cessation-Evaluating N-acetylcysteine Treatment) study, a multi-site randomized pharmacotherapy clinical trial within the National Drug Abuse Treatment Clinical Trials Network, to predict the association between blunt and joint use frequency and cannabis use characteristics (e.g., grams of cannabis used) and consequences (e.g., withdrawal) among past-month cannabis users (N = 377) who were screened for study participation. ResultsAfter controlling for race, age, gender, other forms of cannabis use (including joint use) and nicotine dependence, multivariable linear regression models indicated that the number of days of blunt use in the past month was a significant predictor of the average amount of cannabis per using day (t = 3.04, p < .01), the estimated average cost of cannabis (t = 2.28, p < .05) and Cannabis Withdrawal Scale scores (t = 1.94, p < .05). Frequency of joint use did not significantly predict any of the cannabis use characteristics or consequences. ConclusionsBlunt smokers may present to treatment with greater amounts of cannabis smoked and more intense withdrawal symptoms, which may adversely impact their likelihood of successful abstinence. Cannabis-dependent blunt smokers may be more likely to benefit from treatment that targets physiological and mood-related withdrawal symptoms.

Effects of Initiating Abstinence from Alcohol on Daily Craving and Negative Affect: Results from a Pharmacotherapy Clinical Trial.

Craving and negative affect are distressing and commonly experienced during alcohol use disorder (AUD) treatment. Patients may assume that initiating abstinence will intensify their cravings and negative affect despite limited empirical data to support this assumption. This study extends and replicates, under improved methodological conditions, previous work that found reductions in daily craving associated with initiating abstinence. Seventy-eight adults (80.8% male, 57.1% Caucasian) in a clinical trial testing prazosin for AUD provided daily reports of drinking, craving, and negative affect for up to 12weeks (mean=64.77 daily reports). Participants were classified into 3 subgroups based on whether and when they initiated 14days of continuous abstinence, including (i) "abstinence initiators" who quit drinking during treatment (n=17), (ii) "already abstainers" who were abstinent at the start of treatment (n=20), and (iii) "continued drinkers" who never initiated abstinence (n=41). The timing and degree of change in craving and negative affect were compared across these groups using multivariate growth curve modeling. All participant subgroups reported gradual reductions in craving over the course of treatment, with "abstinence initiators" reporting additional sudden reductions in craving upon initiating abstinence from alcohol. "Continued drinkers" reported higher levels of craving than "already abstainers" throughout the full course of treatment. Negative affect followed a different pattern of change, with "abstinence initiators" experiencing gradual reductions in negative affect after initiating abstinence but no changes prior to or immediately upon initiating abstinence, and with "already abstainers" and "continued drinkers" experiencing no changes in negative affect over time. Initiating abstinence is associated with immediate reductions in craving, followed by gradual reductions in both craving and negative affect. Results provide insight into the timing and magnitude of changes in theoretically and clinically important variables and may help patients anticipate when to expect improvement in craving and negative effect.

Spirometric Criteria for Chronic Obstructive Pulmonary Disease in Clinical Trials of Pharmacotherapy

ABSTRACTClinical trials of pharmacotherapy in chronic obstructive pulmonary disease (COPD) often include older persons with moderate-to-severe airflow-obstruction, as defined by the Global Initiative for chronic Obstructive Lung Disease (GOLD). In this context, spirometric airflow-obstruction establishes COPD. Because GOLD misidentifies COPD and its severity in older persons, we set out to apply more age-appropriate spirometric criteria from the Global Lung function Initiative (GLI) in a prior clinical trial of COPD pharmacotherapy, specifically the Towards a Revolution in COPD Health (TORCH) trial — N = 6,112, mean age 65 years. In the TORCH trial, which enrolled GOLD-defined moderate COPD (26.2%, n = 1,200) and GOLD-defined severe COPD (73.8%, n = 4,511), the GLI reclassification yielded a higher frequency of severe COPD (89.6%, n = 5,474), the inclusion of restrictive-pattern (6.9%, n = 420) and, in turn, a very low frequency of moderate COPD (3.5%, n = 212). These GLI reclassification results suggest that GOLD-based enrollment criteria for the TORCH trial may have assembled a cohort that was: 1) less likely to respond to COPD pharmacotherapy, given the greater representation of severe COPD, very minor representation of moderate COPD, and inclusion of a non-obstructive spirometric impairment (restrictive-pattern); and 2) more likely to have medication-related adverse events, given the inappropriate use of COPD pharmacotherapy in misidentified COPD (restrictive-pattern). We therefore propose that future clinical trials of COPD pharmacotherapy should consider GLI criteria for defining COPD, including a greater representation of GLI-defined moderate COPD.

Effects of venlafaxine versus lithium monotherapy on quality of life in bipolar II major depressive disorder: Findings from a double-blind randomized controlled trial

Bipolar disorder is associated with decreased quality of life, especially during depressive episodes. There are few studies that have examined whether quality of life improves following pharmacological treatments of bipolar depression. In this exploratory study, we examined the effects of antidepressant versus mood stabilizer monotherapy on quality of life ratings in bipolar II subjects during acute (12 week) treatment. Data were derived from a randomized double-blind comparison of venlafaxine (n = 65) versus lithium (n = 64) monotherapy. The Quality of Life Index (QLI) was administered at baseline (n = 126; 98%) and again at the end of treatment. We explored treatment differences in continuous changes on the QLI using last-observation carried forward. Additionally, we explored the likelihood of experiencing clinically-significant improvements as well as baseline correlates of QLI and changes in QLIe. Venlafaxine was superior to lithium in reducing symptoms of depression during acute treatment. However, there were no significant differences between treatments in QLI ratings. Changes in symptoms of depression were correlated to, but not redundant, with improvements in QLI ratings. These findings suggest that quality of life may be an important secondary outcome to target and measure as a part of comparative clinical trials of pharmacotherapy for bipolar II depression.

Management of mood and anxiety disorders in patients receiving opioid agonist therapy: Review and meta-analysis.

Patients with opioid use disorders and mood and anxiety symptoms have a variable prognosis. Few randomized controlled trials (RCTs) have evaluated treatment of depression or anxiety in patients receiving opioid agonist therapies (OAT). This review evaluates studies of pharmacotherapy/psychotherapy for treating symptoms of depression or anxiety in patients receiving OAT. Public databases were searched for clinical trials of pharmacotherapy or psychotherapy for managing depression or anxiety symptoms in adults receiving OAT. Subsequently, we conducted a random effects meta-analysis model of RCTs by antidepressants subclasses. In our literature search, we identified 22 RCTs, eight of which were eligible for meta-analysis. Seven studies evaluated antidepressants in patients already maintained on OAT; two studies reported significant results for antidepressant effects versus placebo. Similarly, two of the seven studies that initiated antidepressants with OAT had advantages over placebo. Meta-analysis of grouped data revealed that tricyclic antidepressants (TCAs) (n = 235) significantly improved mean depression scores (SMD = -2.35, 95%CI: [-4.35, -0.34], z = -2.29, p = .022) while Selective Serotonin Reuptake Inhibitors (SSRIs) (n = 311) were not significantly different than placebo (SMD = 0.47, 95%CI: [-0.35, 1.30], z = 1.12, p = .263). Four out of five studies that implemented psychotherapeutic approaches reported a greater reduction of depressive symptoms than the comparison group. To date, psychotherapy has the most documented evidence for efficacy. TCAs appears effective but with more adverse effects than SSRIs. Further studies of OAT and adjunct antidepressant treatments for dual diagnosis patients are warranted. (Am J Addict 2017;26:551-563).

Pediatric obesity pharmacotherapy: current state of the field, review of the literature and clinical trial considerations.

Despite the increasing number of medications recently approved to treat obesity among adults, few agents have been formally evaluated in children or adolescents for this indication. Moreover, there is a paucity of guidance in the literature addressing best practices with regard to pediatric obesity pharmacotherapy clinical trial design, and only general recommendations have been offered by regulatory agencies on this topic. The purposes of this article are to (1) offer a background of the current state of the field of pediatric obesity medicine, (2) provide a brief review of the literature summarizing pediatric obesity pharmacotherapy clinical trials, and (3) highlight and discuss some of the unique aspects that should be considered when designing and conducting high-quality clinical trials evaluating the safety and efficacy of obesity medications in children and adolescents. Suggestions are offered in the areas of target population and eligibility criteria, clinical trial end-point selection, trial duration, implementation of lifestyle modification therapy and recruitment and retention of participants. Efforts should be made to design and conduct trials appropriately to ensure that high-quality evidence is generated on the safety and efficacy of various medications used to treat pediatric obesity.

Impact of Pharmacotherapy on Cognitive Dysfunction in Patients with Multiple Sclerosis.

Cognitive impairment is a common symptom of multiple sclerosis (MS), adversely impacting many spheres of daily functioning. Yet the effectiveness of pharmacological interventions for cognitive impairment in MS is unclear. Clinicians and patients alike would benefit from formal guidelines regarding effective management of cognitive symptoms. We reviewed the background on the measurement, pathophysiology and risk factors for cognitive dysfunction in MS, and then examined the published clinical trials of pharmacotherapy, including both disease-modifying treatments (DMTs) and symptom-management therapies (SMTs). Our review of DMTs revealed only a single well-designed, randomized, controlled trial where intramuscular interferon (IFN)-β1a, administered once weekly, was compared with placebo. The results showed significant benefits in terms of cognitive processing speed and memory. Less convincing but promising data have shown the potential benefits of IFN-β1b and natalizumab. The literature on SMTs is replete with placebo-controlled, single-centre studies, with a failure to replicate initially promising results. The results for SMTs such as acetylcholinesterase inhibitors and psychostimulants are mixed. Some encouraging data show promise but not to a threshold of indication for standard clinical use. Numerous methodological factors hamper research in this area. Acknowledging the lack of firm conclusions, we argue that all DMTs are likely to benefit cognition and that, if otherwise safe, SMTs with some empirical support may be attempted at the discretion of the treating clinician. We offer some guidance on the assessment and monitoring of cognitive function to inform off-license treatment of cognitive impairment in MS patients.

Recruitment Techniques for Alcohol Pharmacotherapy Clinical Trials

Alcohol use disorders (AUDs) represent a large public health burden with relatively few efficacious pharmacotherapies. Randomized controlled trials (RCTs) for new AUD therapies can be hampered by ineffective recruitment, leading to increased trial costs. The current analyses examined the effectiveness of recruitment efforts during two consecutive outpatient RCTs of novel AUD pharmacotherapies conducted between 2009 and 2012. During an initial phone screen, participants identified an ad source for learning about the study. Qualified persons were then scheduled for in-person screens. The present analyses examined demographic differences amongst the eight ad sources utilized. Recruitment effectiveness was determined by dividing the number of persons meeting criteria for an in-person screen by the total number of callers from each ad source. Cost-effectiveness was determined by dividing total ad source cost by number of screens, participants randomized, and completers. 1,813 calls resulted in 1,005 completed phone screens. The most common ad source was TV (34%), followed by print (29%), word-of-mouth (11%), flyer (8%), internet (5%), radio (5%), bus ad (2%), and billboard (1%). Participants reporting bus ads (46%), billboard (44%), or print ads (34%) were significantly more likely than the other sources to meet criteria to be scheduled for in-person screens. The most cost-effective ad source was print ($2,506 per completer), while bus ad was the least cost-effective ($13,376 per completer). Recruitment in AUD RCTs can be successful using diverse advertising methods. The present analyses favored use of print ads as most cost-effective.