Adjunctive Pharmacotherapy Research Articles

Advances in Type 1 Diabetes Mellitus Management in Children.

Recent advancements in the management of type 1 diabetes mellitus (T1DM) have significantly improved outcomes and quality of life for patients, particularly children. Technological innovations, such as continuous glucose monitoring (CGM) systems and insulin pump therapy, including hybrid closed-loop systems, have enhanced glycemic control by providing real-time data and automated insulin delivery. Ultrarapid-acting insulins and adjunctive pharmacotherapies, like sodium-glucose transport protein 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists, offer improved postprandial glucose management and reduced insulin requirements. Immunotherapy and beta-cell replacement therapies, including stem cell research and encapsulation devices, aim to preserve or restore endogenous insulin production. Digital health platforms and telemedicine have expanded access to education and support, fostering better self-management. Future directions in precision medicine, artificial intelligence, and microbiome research hold promise for personalized and potentially curative treatments. Collectively, these advances are transforming T1DM management, reducing disease burden, and enhancing the prospects for children with T1DM.

Antiplatelet De-Escalation Strategies in Patients Undergoing Percutaneous Coronary Intervention.

Dual antiplatelet therapy-the combination of aspirin and a P2Y12 inhibitor-remains the standard antiplatelet regimen recommended to prevent ischemic complications immediately after percutaneous coronary intervention. Nonetheless, recent advances in stent technologies, percutaneous coronary intervention techniques, adjunctive pharmacotherapy for secondary prevention, and the rising awareness of the prognostic impact of bleeding, which are inevitably associated with dual antiplatelet therapy, led to the investigation of alternative antiplatelet regimens related to fewer bleeding and a preserved ischemic protection. Thrombotic complications occur mostly in the first months after percutaneous coronary intervention, while the risk of bleeding remains stable over time; this observation laid the foundation of the concept of antiplatelet de-escalation, consisting of a more intense antiplatelet regimen early after percutaneous coronary intervention, followed by a less potent antiplatelet therapy thereafter. According to new definitions proposed by the Academic Research Consortium, de-escalation can be achieved by discontinuation of 1 antiplatelet agent, switching from a potent P2Y12 inhibitor to clopidogrel, or by reducing the dose of antiplatelet agents. This review discusses the rationale and the evidence supporting antiplatelet de-escalation, provides practical guidance to use these new regimens, and gives insights into future developments in the field.

Prescribing and deprescribing guidance for benzodiazepine and benzodiazepine receptor agonist use in adults with depression, anxiety, and insomnia: an international scoping review

Clinical practice guidelines and guidance documents routinely offer prescribing clinicians' recommendations and instruction on the use of psychotropic drugs for mental illness. We sought to characterise parameters relevant to prescribing and deprescribing of benzodiazepine (BZD) and benzodiazepine receptor agonist (BZRA), in clinical practice guidelines and guidance documents internationally, for adult patients with unipolar depression, anxiety disorders and insomnia to understand similarities and discrepancies between evidence-based expert opinion. A Scoping Review was conducted to characterize documents that offered evidence-based and/or consensus pharmacologic guidance on the management of unipolar depression, anxiety disorders, obsessive-compulsive disorders, post-traumatic stress disorders and insomnia. A systematic search was conducted of PubMed, SCOPUS, PsycINFO and CINAHL from inception to October 13, 2023 and supplemented by a gray literature search. Documents were screened in Covidence for eligibility. Subsequent data-charting on eligible documents collected information on aspects of both prescribing and deprescribing. 113 documents offering guidance on BZD/BZRA use were data-charted. Overall, documents gathered were from Asia (n=11), Europe (n=34), North America (n=37), Oceania (n=7), and South America (n=4) with the remainder being "International" (n=20) and not representative to any particular region or country. By condition the documents reviewed covered unipolar depressive disorders (n=28), anxiety disorders, obsessive-compulsive disorder and post-traumatic stress disorder (n=42) and Insomnia (n=25). Few documents (n=18) were sufficiently specific and complete to consider as de-prescribing focused documents. Documents were in concordance in terms of BZD and BZRA not being used routinely as first-line pharmacologic agents. When used, it is advisable to restrict their duration to "short-term" use with the most commonly recommended duration being less than four weeks. Documents were less consistent in terms of prescriptive recommendations for specific drug, dosing and administration pattern (i.e regular or 'as needed') selection for each condition. Deprescribing documents were unanimously in favor of gradual dose reduction and patient shared decision-making. However, approaches towards dose-tapering differed substantially. Finally, there were inconsistencies and/or insufficiency of detail, among deprescribing documents, in terms of switching to a long-acting BZD, use of adjunctive pharmacotherapies and micro-tapering. The authors received no funding for this work.

Recent Advances in the Treatment of Treatment-Resistant Depression: A Narrative Review of Literature Published from 2018 to 2023.

We review recent advances in the treatment of treatment-resistant depression (TRD), a disorder with very limited treatment options until recently. We examine advances in psychotherapeutic, psychopharmacologic, and interventional psychiatry approaches to treatment of TRD. We also highlight various definitions of TRD in recent scientific literature. Recent evidence suggests some forms of psychotherapy can be effective as adjunctive treatments for TRD, but not as monotherapies alone. Little recent evidence supports the use of adjunctive non-antidepressant pharmacotherapies such as buprenorphine and antipsychotics for the treatment of TRD; side effects and increased medication discontinuation rates may outweigh the benefits of these adjunctive pharmacotherapies. Finally, a wealth of recent evidence supports the use of interventional approaches such as electroconvulsive therapy, ketamine/esketamine, and transcranial magnetic stimulation for TRD. Recent advances in our understanding of how to treat TRD have largely expanded our knowledge of best practices in, and efficacy of, interventional psychiatric approaches. Recent research has used a variety of TRD definitions for study inclusion criteria; research on TRD should adhere to inclusion criteria based on internationally defined guidelines for more meaningfully generalizable results.

Phenobarbital Versus Benzodiazepines for the Treatment of Severe Alcohol Withdrawal.

Phenobarbital may offer advantages over benzodiazepines for severe alcohol withdrawal syndrome (SAWS), but its impact on clinical outcomes has not been fully elucidated. The purpose of this study was to determine the clinical impact of phenobarbital versus benzodiazepines for SAWS. This retrospective cohort study compared phenobarbital to benzodiazepines for the management of SAWS for patients admitted to progressive or intensive care units (ICUs) between July 2018 and July 2022. Patients included had a history of delirium tremens (DT) or seizures, Clinical Institute Withdrawal Assessment of Alcohol-Revised (CIWA-Ar) >15, or Prediction of Alcohol Withdrawal Severity Scale (PAWSS) score ≥4. The primary outcome was hospital length of stay (LOS). Secondary outcomes included progressive or ICU LOS, incidence of adjunctive pharmacotherapy, and incidence/duration of mechanical ventilation. The final analysis included 126 phenobarbital and 98 benzodiazepine encounters. Patients treated with phenobarbital had shorter median hospital LOS versus those treated with benzodiazepines (2.8 vs 4.7 days; P < 0.0001); a finding corroborated by multivariable analysis. The phenobarbital group also had shorter median progressive/ICU LOS (0.7 vs 1.3 days; P < 0.0001), and lower incidence of dexmedetomidine (P < 0.0001) and antipsychotic initiation (P < 0.0001). Fewer patients in the phenobarbital group compared to the benzodiazepine group received new mechanical ventilation (P = 0.045), but median duration was similar (1.2 vs 1.6 days; P = 1.00). Scheduled phenobarbital was associated with decreased hospital LOS compared to benzodiazepines for SAWS. This was the first study to compare outcomes of fixed-dose, nonoverlapping phenobarbital to benzodiazepines in patients with clearly defined SAWS and details a readily implementable protocol.

Mobile phone intervention to reduce dropout from treatment at an outpatient mental health service for older people in Nigeria.

Half of older Africans drop out of treatment after a single contact with biomedical mental health services. This study examined the effect of introducing a mobile phone reminder intervention delivered by volunteering health staff to reduce dropout from an outpatient mental health service for older people in Nigeria. 405 patients were studied using a quasi-experimental design: 169 who attended clinic pre-intervention (2016-2017) and 236 who attended during intervention (2018-2019). We estimated annual dropout rates, reasons for dropout and predictors of drop-out. We found a trend for decreasing dropout rates during intervention (p<0.001). The most common reasons for dropout were distance to the clinic (19.5%) and unavailability of a caregiver (47.6%). Current single status (O.R =2.02, 95% C. I=1.02-3.99) and treatment without adjunctive pharmacotherapy (O. R=2.14, 95% CI; 1.07-4.26) predicted dropout. Mobile phone call reminders improved treatment engagement in this population. Findings are important for policy to improve access to mental healthcare in Africa.

Nurse practitioner educational preparation and confidence related to managing antipsychotic medications and associated drug-induced movement disorders.

Antipsychotic medications (APMs) have been used to treat multiple psychiatric disorders for decades. The conditions to use these medications have expanded from primarily psychotic disorders to Food and Drug Administration-approved uses as first-line mood stabilizers in bipolar disorder and adjunctive pharmacotherapy in unipolar depression. Antipsychotic medications can have serious side effects, including drug-induced movement disorders (DIMDs). Nurse practitioners (NPs) in non-psychiatric-mental health specialties are increasingly managing psychotropic medication regimes. There is a void in peer-reviewed literature capturing the scope of NPs managing APMs, such as whether they received training to prescribe and manage risks of APM, and if so, what type (e.g., continuing education, attending conferences, consulting), and their confidence assessing and managing DIMDs. To describe the scope of NP management, knowledge, and confidence related to APMs and associated risks of DIMDs. Nonexperimental, descriptive, cross-sectional survey. Participants ( n = 400) recruited through a professional association membership portal. Nearly two-thirds of participants reported managing APMs (64%) and receiving training to prescribe and manage risks of APMs (63%). More than half (54%) reported they received training to do so in their NP education program. Thirty-five percent of participants indicated they were either completely (6%) or fairly (29%) confident, whereas most (65%) endorsed being somewhat (26%), slightly (20%), or not (19%) confident in assessing and managing DIMDs. Opportunities exist to broaden NP education in managing APMs and associated risks of DIMDs.

Early Family Intervention for Youth at Risk for Bipolar Disorder: Psychosocial and Neural Mediators of Outcome.

The impairing neurodevelopmental course of bipolar disorder (BD) suggests the importance of early intervention for youth in the beginning phases of the illness. We report the results of a 3-site randomized trial of family-focused therapy for youth at high-risk (FFT-HR) for BD, and explore psychosocial and neuroimaging variables as mediators of treatment effects. High-risk youth (<18 years) with major depressive disorder or other specified BD, active mood symptoms, and a family history of BD were randomly assigned to 4 months of FFT-HR (psychoeducation, communication and problem-solving skills training) or 4 months of enhanced care psychoeducation. Adjunctive pharmacotherapy was provided by study psychiatrists. Neuroimaging scans were conducted before and after psychosocial treatments in eligible participants. Independent evaluators interviewed participants every 4-6 months over 1-4 years regarding symptomatic outcomes. Among 127 youth (mean 13.2 ± 2.6 years) over a median of 98 weeks, FFT-HR was associated with longer intervals prior to new mood episodes and lower levels of suicidal ideation than enhanced care. Reductions in perceived family conflict mediated the effects of psychosocial interventions on the course of mood symptoms. Among 34 participants with pre-/post-treatment fMRI scans, youth in FFT-HR had (a) stronger resting state connectivity between ventrolateral PFC and anterior default mode network, and (b) increased activity of dorsolateral and medial PFC in emotion processing and problem-solving tasks, compared to youth in enhanced care. FFT-HR may delay new mood episodes in symptomatic youth with familial liability to BD. Putative treatment mechanisms include neural adaptations suggestive of improved emotion regulation.

Bail-Out Techniques in Percutaneous Intervention for Ellis Grade III Coronary Perforation in Left Main Distal Bifurcation Lesions.

The left main (LM) coronary artery stenosis is associated with high morbidity and mortality and has traditionally been treated with coronary artery bypass grafting. However, in recent years, advancements in device technology and adjunctive pharmacotherapy have led to the widespread use of percutaneous coronary intervention (PCI) as a treatment for unprotected LM lesions. Despite this, LM lesions are often complex, involving distal bifurcation and heavy calcification, which increases the risk of coronary perforation (CP) during PCI. In addition, the use of rotational or orbital atherectomy in severely calcified LM bifurcation lesions carries a higher risk of complications and in-hospital mortality than that in non-LM lesions. CP is a rare but potentially fatal complication of PCI, particularly in cases of Ellis grade III (CP-G3), with a high rate of cardiac tamponade and mortality. The management of CP-G3 in LM distal bifurcation lesions is challenging and requires specialized techniques. This article presents a flowchart of bail-out strategies for CP-G3 in LM distal bifurcation lesions and provides detailed procedures for each technique. Furthermore, we highlight the challenges and limitations of each technique, requiring careful management when CP-G3 occurs in LM distal bifurcation lesions.

Effect of mTOR Inhibitors in Epilepsy Treatment in Children with Tuberous Sclerosis Complex Under 2 Years of Age

Mechanistic target of rapamycin (mTOR) inhibitors sirolimus and everolimus are an effective therapy for subependymal giant cell astrocytomas, cardiac rhabdomyomas, renal angiomyolipomas, and lymphangioleiomyomatosis associated with tuberous sclerosis complex (TSC). Everolimus was recently approved in the EU and the USA for the treatment of refractory focal-onset seizures. Despite frequent use of mTOR inhibitors, there are only a few studies on their effect on epilepsy control in children under 2years of age. This study aims to assess the effect of adjunctive mTOR inhibitor treatment on seizure frequency in this age group. We performed retrospective data analysis of medical records of patients with TSC who initiated sirolimus or everolimus under the age of 2years. Participants' antiseizure medication was adjusted according to their epilepsy control independently from mTOR inhibitor administration. The data was assessed separately for patients treated with mTOR inhibitors before and after the onset of seizures. We also compared the treatment group with a matched control group. The follow-up duration was up to 24months. Twenty-one patients with TSC from two clinical centers were included in the study. Nine participants had no history of seizures before mTOR inhibitor initiation. Twelve reported active epilepsy in the month prior to treatment initiation. Most patients treated preventively with mTOR inhibitors did not report active epilepsy at the end of their follow-up. In the second group, the mean frequency of seizures decreased with time. According to the comparative analysis, seizure control was better in the groups treated with mTOR inhibitors. Patients with TSC treated with mTOR inhibitors demonstrated better seizure control than individuals without this treatment. Adjunctive pharmacotherapy with mTOR inhibitors appears to have a beneficial effect on epilepsy outcome in young children. Further prospective clinical trials should be conducted to determine the efficacy of mTOR inhibitors on epilepsy in patients with TSC under the age of 2years.

Modern approaches to the management of patients with obesity (according to the materials of the Consensus of the American Gastroenterological Association in 2022)

Over the past few decades, the prevalence of obesity has increased dramatically worldwide. Obesity‑related complications such as cardiovascular disease, stroke, type 2 diabetes mellitus, nonalcoholic steatohepatitis, obstructive sleep apnea, osteoarthritis, and certain cancers (eg, colorectal cancer) have also increased, contributing to the high incidence and mortality. Lifestyle modification is the mainstay of long‑term treatment for obesity, but it has limited effectiveness and durability for most people. Pharmacotherapies developed and approved for the long‑term management of obesity are more effective in achieving weight loss, although the daily use of anti‑obesity medications is limited for many reasons. Prioritizing the development of clinical guidelines to inform the use of pharmacologic therapy for the long‑term treatment of obesity in adults, the American Gastroenterological Association published its consensus in 2022 that addresses the important desired (benefits) and undesired (harms) pharmacotherapy outcomes for patients. Outcomes of critical decision‑making included percent of total body weight loss (TBWL), proportion of patients achieving &gt;5%, &gt;10%, and &gt;15% TBWL, discontinuations due to side effects, and serious adverse events. The mean difference of 3% of TBWL between adjunctive pharmacotherapy and lifestyle modification alone, or an absolute 5% of TBWL above the baseline, was considered as a minimal clinically important difference in the effectiveness of pharmacotherapy in the treatment of obesity that corresponded to important benefits for patients. The strength of evidence for all outcomes was assessed using the GRADE system, in which evidence from randomized clinical trials was interpreted as high‑certainty, and confidence in the evidence conveyed confidence in the effect estimates. For each outcome, the evidence was divided into 4 categories (high, moderate, low or very low). According to the GRADE approach, recommendations were marked as «strong» when the phrase «we recommend» was used, or «conditional» when the phrase «we suggest» was used. The guideline panel made 9 recommendations and strongly recommended the use of pharmacotherapy in addition to lifestyle intervention in adults with overweight and obesity who have an inadequate response to the lifestyle interventions. Four drugs have been approved by FDA for long‑term use in obesity: liraglutide 3.0 mg/day, semaglutide 2.4 mg/week, phentermine‑topiramate ER, and naltrexone‑bupropion ER. They are considered to have moderate to significant effects on weight loss and little or no harm, so these drugs have a positive balance in favor of their long‑term use. Unfortunately, the last three drugs are not registered in Ukraine.

Tirzepatide for Weight Loss: Can Medical Therapy "Outweigh" Bariatric Surgery?

The worldwide prevalence of obesity has been increasing progressively over the past few decades and is predicted to continue to rise in coming years. Unfortunately, this epidemic is also affecting increasing rates of children and adolescents, posing a serious global health concern. Increased adiposity is associated with various comorbidities and increased mortality risk. Conversely, weight loss and chronic weight management are associated with improvements in overall morbidity and mortality. The pathophysiology of obesity is multifactorial with complex interactions between genetic and environmental factors. The foundation of most weight loss plans is lifestyle modification including dietary change and exercise. However, lifestyle modification alone is often insufficient to achieve clinically meaningful weight loss due to physiological mechanisms that limit weight reduction and promote weight regain. Therefore, research has focused on adjunctive pharmacotherapy to enable patients to achieve greater weight loss and improved chronic weight maintenance compared to lifestyle modification alone. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin hormone analogs that have proven effective for the management of type 2 diabetes mellitus as well as obesity and overweight. Tirzepatide is a novel "twincretin" that functions as a dual glucose-dependent insulinotropic polypeptide and GLP-1 RA. Tirzepatide was recently approved by the Food and Drug Administration for the management of type 2 diabetes. Similar to previously approved GLP-1RAs, weight loss is a common side effect of tirzepatide which prompted research focused on its use as a primary weight loss therapy. Although this drug has not yet been approved as an antiobesity medication, there are several phase 3 clinical trials that have demonstrated superior weight loss efficacy compared with previously approved medications. This review article will discuss the discovery and mechanism of tirzepatide, as well as the completed and ongoing trials that may lead to its approval as an adjunctive pharmacotherapy for weight loss.

Adherence to augmentation therapy for the treatment of major depressive disorder

ABSTRACT Background Inadequate response to antidepressant medication is common. Often, adjunctive pharmacotherapy or psychotherapy is recommended. Objective To measure adherence to adjunctive pharmacotherapy and psychotherapy among individuals with major depressive disorder (MDD). Methods Retrospective cohort study of individuals with MDD on antidepressant monotherapy who added adjunctive pharmacotherapy and/or psychotherapy. Medication adherence was measured by proportion of days covered (PDC) with optimal adherence defined as PDC≥0.80 and psychotherapy adherence defined by count of visits (optimal 8+ visits). Factors associated with optimal adherence were assessed by logistic regression. Results Among 218,192 individuals with adjunctive therapy, 185,349 added pharmacotherapy and 32,843 added psychotherapy. In the subsequent 12 months, 36.2% and 54.9% achieved optimal adherence to adjunctive pharmacotherapy and psychotherapy, respectively. Adherence to adjunctive pharmacotherapy was associated with adding psychotherapy, index antidepressant adherence, medical comorbidities, and MDD severity codes. Adherence to adjunctive psychotherapy was associated with adding another medication, previous psychiatry visit and psychiatric comorbidities. Conclusion Adjunctive psychotherapy appears under-utilized and adherence to adjunctive therapy was low. Low adherence to adjunctive therapy reinforces challenges in managing MDD. That a second adjunctive therapy enhanced adherence to the initial adjunctive therapy indicates an opportunity to explore alternative adjunctive therapies.

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting for Revascularization of Left Main Coronary Artery Disease.

Owing to a large-jeopardized myocardium, left main coronary artery disease (LMCAD) represents the substantial high-risk anatomical subset of obstructive coronary artery disease. For several decades, coronary artery bypass grafting (CABG) has been the "gold standard" treatment for LMCAD. Along with advances in CABG, percutaneous coronary intervention (PCI) has also dramatically evolved over time in conjunction with advances in the stent or device technology, adjunct pharmacotherapy, accumulated experiences, and practice changes, establishing its position as a safe, reasonable treatment option for such a complex disease. Until recently, several randomized clinical trials, meta-analyses, and observational registries comparing PCI and CABG for LMCAD have shown comparable long-term survival with tradeoffs between early and late risk-benefit of each treatment. Despite this, there are still several unmet issues for revascularization strategy and management for LMCAD. This review article summarized updated knowledge on evolution and clinical evidence on the treatment of LMCAD, with a focus on the comparison of state-of-the-art PCI with CABG.

Advances in endobariatrics: past, present, and future.

The obesity epidemic in the USA and worldwide is well documented and continues to grow. Endoscopic metabolic and bariatric therapies may offer a less invasive approach than surgical intervention. This article will review advances in endobariatrics over the last several decades, addressing the past and current state of bariatric and metabolic endoscopy. Food and Drug Administration-cleared devices and interventions currently under investigation are described including gastric devices, gastric remodeling procedures, small-bowel devices, duodenal ablation, as well as procedures to address weight regain after bariatric surgery. Future studies evaluating gastric and duodenal combination therapy, adjunctive pharmacotherapy, as well as individualized precision-health algorithms are underway.

1105: PHENOBARBITAL VERSUS LORAZEPAM FOR THE MANAGEMENT OF ALCOHOL WITHDRAWAL IN HOSPITALIZED PATIENTS

Introduction: Alcohol withdrawal syndrome (AWS) is a potentially life-threatening medical condition and even though benzodiazepines (BZDs) are the standard of care in the treatment of AWS, therapy-associated complications like respiratory depression requiring ventilatory support and the use of adjunctive pharmacotherapy persist. Studies have shown promising results with phenobarbital (PB), but have been limited to use in the emergency department or as an agent of choice for refractory AWS in the intensive care unit (ICU). Our study aims to compare the ICU admissions rate between lorazepam versus PB in treating AWS in hospitalized patients. Methods: We conducted a retrospective cohort study on patients hospitalized for AWS from 2019 to 2022. Patients were categorized into those who received lorazepam using the revised Clinical Institute Withdrawal Assessment of alcohol scale (CIWA-Ar) and those who received PB based on the Richmond Agitation- Sedation scale (RASS). The primary outcome was the rate of admission to the ICU. Secondary outcomes included total length of hospital and ICU stay, mechanical ventilation rate, use of adjunctive medications and mortality. Results: 300 patients met the inclusion criteria, of whom 148 received lorazepam and 152 received PB. The mean patient age was 56 years and 51 years in the PB and lorazepam groups, respectively (p=0.001). There were significant differences between lorazepam and PB in terms of ICU admission (13.5% vs 5.3%, p=0.014), mechanical ventilation rate (9.5% vs 0.7%, p=0.0004), need for adjunctive dexmedetomidine (9.5% vs 1.3%, p=0.0016) and mean length of hospital days (6.16 vs 4.89 days, p value =0.004), and ICU days (1.07 vs 0.21 days, respectively, p value=0.003). Conclusions: AWS patients treated with PB per protocol were found to have a significantly decreased rate of ICU admission, need for invasive ventilation and adjunctive dexmedetomidine treatment, along with reduced ICU and total length of hospital stay as compared to those treated with lorazepam. We conclude that our results support the growing evidence of efficacy of PB over lorazepam as the primary treatment for AWS patients, due to its mechanism of action that better targets AWS pathophysiology. Prospective, randomized controlled studies that compare PB vs BDZs for AWS are needed.

Antipsychotics in the Management of Disruptive Behavior Disorders in Children and Adolescents: An Update and Critical Review.

Disruptive behaviour disorders (DBDs) in childhood include conduct disorder (CD) and oppositional defiant disorder (ODD). Though psychological therapies are considered to be the first-line treatment for DBDs, many patients require adjunctive pharmacotherapy for the control of specific symptoms, such as aggression. Three prior systematic reviews have examined the evidence for the use of antipsychotics in DBDs and have concluded that their efficacy is marginal and limited by adverse effects. This paper has two objectives: (i) to summarize the findings of existing systematic reviews of antipsychotics for the management of DBDs in children and adolescents (2012-2017), and (ii) to provide an update to these reviews by examining recent clinical trials of antipsychotics in this population, published in the period from 2 January 2017 to 10 October 2022. The PubMed, Scopus and ScienceDirect databases were searched for relevant citations using the search terms "disruptive behaviour disorder", "oppositional defiant disorder", "conduct disorder" and their variants, along with "antipsychotic", "atypical antipsychotic" and the generic names of all currently approved atypical antipsychotics. Six relevant trials were identified during this period, including five randomized controlled trials and one naturalistic open-label trial. These trials were critically evaluated in terms of outcome measures, efficacy and safety. Overall, the data from these trials suggests that of all available antipsychotics, risperidone appears to be effective in the short-term management of DBDs. All available antipsychotics are associated with significant metabolic adverse effects in this population. These results are discussed in the light of global trends towards increasing off-label prescription of antipsychotic medication in children and adolescents and of recent literature on the neuropharmacology of aggression in this patient population. The need for rational, short-term use of these drugs is highlighted, as well as the importance of post-marketing surveillance for long-term or severe adverse events.

Measuring Response to Adjunctive Therapy Among Individuals with Major Depressive Disorder.

Incomplete or inadequate response to first-line antidepressant therapy (ADT) for major depressive disorder (MDD) is common. Response to adjunctive therapy is less understood. To estimate response to adjunctive pharmacotherapy or psychotherapy among individuals with MDD on an antidepressant using the PHQ-9 questionnaire. This was a retrospective cohort analysis using medical and pharmacy insurance claims among individuals with MDD or ADT who initiated adjunctive pharmacotherapy, psychotherapy, or both (dual). Eligible individuals initiated adjunctive therapy between 7/1/2014-12/31/2018. Symptom severity was measured by PHQ-9 score in the 6-month baseline and 12-month follow up. Multivariate logistic regression identified factors associated with improved symptom severity. Most (81.8%) of the 2389 participants initiated adjunctive pharmacotherapy, followed by psychotherapy (12.7%) and dual adjunctive (5.5%). Only 30.2% had both a baseline and follow-up PHQ-9 score. Among those with mild or more severe PHQ-9 baseline scores, 36.7% had the same or worse MDD severity during follow-up. Among those with moderate or more severe baseline scores, 28.1% had the same or worse MDD severity during follow-up. Most individuals with moderate-to-severe MDD did not receive a follow-up questionnaire, suggesting incomplete monitoring of treatment response. Among those with a PHQ-9 following initiation of adjunctive therapy, many continued to report impactful symptoms. Future studies should explore alternate treatment approaches and methods to support the utilization of the PHQ-9 for monitoring treatment response.

Relationship between baseline cognition and 18-month treatment response in bipolar disorder

BackgroundTo date, few studies have examined baseline cognitive function as a predictor of clinical outcome following treatment in bipolar disorder (BD). The aim of this analysis was therefore to examine the relationship between baseline cognitive function and treatment outcome in a sample of young adults with BD receiving Interpersonal Social Rhythm Therapy (IPSRT) or Specialist Supportive Care (SSC) with adjunctive pharmacotherapy. MethodsEighty-six BD patients underwent baseline cognitive testing and completed 18 months of IPSRT or SCC. Univariate analyses examined the relationship between baseline cognitive function (global and individual cognitive domains) and change in mood symptom burden, and psychosocial functioning, from baseline to treatment-end. ResultsBaseline global cognition was not predictive of change in mood symptom burden over 18 months of treatment. However, poorer baseline psychomotor speed performance was associated with less improvement in mood symptom burden at treatment-end. Neither baseline global cognition nor individual cognitive domain scores were associated with change in psychosocial functioning. LimitationsDue to the exploratory nature of the study, correction was not made for multiple comparisons. Data was obtained from a relatively small sample and has been the subject of prior analysis, thereby increasing the likelihood of chance findings. ConclusionAlthough global cognition was not associated with outcome, when examining individual domains, poorer baseline psychomotor speed predicted less change in mood symptom burden following 18-months of psychotherapy and pharmacotherapy. This suggests that pre-treatment measures of psychomotor speed may help to identify those who require additional, and more targeted, intervention. Further large-scale research is required.

Comparing the Benefit of Duplex Ultrasound Surveillance Following Both Infrainguinal Bypass Surgery and Stenting for Femoro-Popliteal Disease

Duplex ultrasound surveillance (DUS) is commonly used following infrainguinal vein bypass. The role of DUS following endovascular revascularisation is as yet unclear. This study focuses on the role of DUS in a contemporary group of patients undergoing infrainguinal bypass or stent insertion. All patients undergoing either an infrainguinal vein graft bypass or stent insertion into the femoro-popliteal segment (November 2014 - January 2017) were identified. Patients were followed up for 2years. Data on entry into DUS, pre-operative characteristics, adjunctive pharmacotherapy and reintervention were collated. The primary outcomes were major lower limb amputation and mortality at 2years post revascularisation. One hundred and thirty-five patients underwent infrainguinal vein bypass and 100 patients underwent stent insertion. 107 patients in the bypass cohort and 58 patients in the stent cohort entered DUS. For the bypass cohort, entering DUS was associated with a lower mortality rate (P = .003) but was not associated with an improvement in amputation rates. The odds ratio of major amputation or mortality was greater in the no surveillance group (4.58, 95% CI: 1.855 - 11.364). In the stent cohort, DUS was not associated with a significant improvement in either major amputation or death (odds ratio 2.13 (95% CI 0.903 - 5.051; P = .081). DUS was associated with improved survival rates in patients undergoing lower limb bypass but had no benefit in those patients undergoing stent insertion. The role of DUS following stent insertion in the femoropopliteal segment needs to be better defined.