Adverse Events During Dosing of Delayed-release/Extended-release Methylphenidate: Learnings From the Open-label Phase of a Registration Trial and a Real-world Postmarketing Surveillance Program.

Purpose: Delayed-release/extended-release methylphenidate (DR/ER-MPH) (formerly HLD200) is an evening-dosed agent used for the treatment of attention-deficit/hyperactivity disorder. Postmarketing surveillance data from approximately 74,000 patients exposed to DR/ER-MPH (up to June 17, 2022) were reported and compared with the open-label, treatment-optimization phase of a Phase III clinical trial to derive possible learnings on how to approach adverse events (AEs) that emerge during dose titration.

Methods: An analysis of AEs spontaneously reported to Ironshore in postmarketing surveillance included, where available, age, dose, timing, and discontinuations.

Practical pathway for the management of depression in the workplace: a Canadian perspective.

Major depressive disorder (MDD) and other mental health issues pose a substantial burden on the workforce. Approximately half a million Canadians will not be at work in any week because of a mental health disorder, and more than twice that number will work at a reduced level of productivity (presenteeism). Although it is important to determine whether work plays a role in a mental health condition, at initial presentation, patients should be diagnosed and treated per appropriate clinical guidelines.

Efficacy of adjunctive brexpiprazole on symptom clusters of major depressive disorder: A post hoc analysis of four clinical studies.

Background: Major depressive disorder (MDD) is a clinically heterogenous condition and its treatment should be individualized according to the presence of particular symptom clusters. The aim of this pooled analysis was to investigate the effects of adjunctive brexpiprazole on different symptom clusters in MDD.

Methods: Data were included from four similarly designed, short-term, randomized, double-blind, placebo-controlled studies of adjunctive brexpiprazole in adults with MDD and inadequate response to 2-4 antidepressant treatments (ADTs), including 1 administered by investigators.

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders - Version 3. Part II: OCD and PTSD.

Aim: This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders which was published in 2002 and revised in 2008.

Method: A consensus panel of 34 international experts representing 22 countries developed recommendations based on efficacy and acceptability of the treatments. In this version, not only medications but also psychotherapies and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medication treatments.

Effectiveness of Vortioxetine in Patients With Major Depressive Disorder in Real-World Clinical Practice: Results of the RELIEVE Study.

Background: Randomized controlled clinical trials have shown vortioxetine to be efficacious and well tolerated for the treatment of major depressive disorder (MDD). The Real-Life Effectiveness of Vortioxetine in Depression (RELIEVE) study was undertaken to demonstrate the effectiveness and safety of vortioxetine for the treatment of MDD in routine clinical practice.

Methods: RELIEVE was a 24-week, observational, prospective cohort study in outpatients with MDD initiating treatment with vortioxetine at their physician's discretion in routine care settings in Canada, France, Italy, and the USA (NCT03555136).

Neurobiology of the Orexin System and Its Potential Role in the Regulation of Hedonic Tone.

Orexin peptides comprise two neuropeptides, orexin A and orexin B, that bind two G-protein coupled receptors (GPCRs), orexin receptor 1 (OXR1) and orexin receptor 2 (OXR2). Although cell bodies that produce orexin peptides are localized in a small area comprising the lateral hypothalamus and adjacent regions, orexin-containing fibres project throughout the neuraxis. Although orexins were initially described as peptides that regulate feeding behaviour, research has shown that orexins are involved in diverse functions that range from the modulation of autonomic functions to higher cognitive functions, including reward-seeking, behaviour, attention, cognition, and mood.

Non-parenteral Ketamine for Depression: A Practical Discussion on Addiction Potential and Recommendations for Judicious Prescribing.

Intravenous (IV) ketamine is increasingly used off-label at subanesthetic doses for its rapid antidepressant effect, and intranasal (IN) esketamine has been recently approved in several countries for treating depression. The clinical utility of these treatments is limited by a paucity of publicly funded IV ketamine and IN esketamine programs and cost barriers to private treatment programs, as well as the drug cost for IN esketamine itself, which makes generic ketamine alternatives an attractive option. Though evidence is limited, use of non-parenteral racemic ketamine formulations (oral, sublingual, and IN) may offer more realistic access in less rigidly supervised settings, both for acute and maintenance treatment in select cases.

Automated Screening for Social Anxiety, Generalized Anxiety, and Depression From Objective Smartphone-Collected Data: Cross-sectional Study.

Background: The lack of access to mental health care could be addressed, in part, through the development of automated screening technologies for detecting the most common mental health disorders without the direct involvement of clinicians. Objective smartphone-collected data may contain sufficient information about individuals' behaviors to infer their mental states and therefore screen for anxiety disorders and depression.

Objective: The objective of this study is to compare how a single set of recognized and novel features, extracted from smartphone-collected data, can be used for predicting generalized anxiety disorder (GAD), social anxiety disorder (SAD), and depression.

Smartphone-Detected Ambient Speech and Self-Reported Measures of Anxiety and Depression: Exploratory Observational Study.

Background: The ability to objectively measure the severity of depression and anxiety disorders in a passive manner could have a profound impact on the way in which these disorders are diagnosed, assessed, and treated. Existing studies have demonstrated links between both depression and anxiety and the linguistic properties of words that people use to communicate. Smartphones offer the ability to passively and continuously detect spoken words to monitor and analyze the linguistic properties of speech produced by the speaker and other sources of ambient speech in their environment.

Randomized Controlled Crossover Trials of the Pharmacokinetics of PRC-063, a Novel Multilayer Extended-Release Formulation of Methylphenidate, in Healthy Adults.

Purpose/background: PRC-063 is a once-daily, extended-release oral formulation of methylphenidate hydrochloride developed to provide early and prolonged symptom improvement in patients with attention-deficit/hyperactivity disorder.

Methods/procedures: We conducted 3 randomized, open-label crossover studies of the pharmacokinetics of PRC-063 in healthy, nonobese men and women aged 18 to 45 years. PRC-063 (100 mg/d) was compared with immediate-release methylphenidate (20 mg, 3 times daily) when administered on a single day under fasted and fed conditions and at steady state (day 5 of repeat dosing under fasted conditions).

The Relationship Between Smartphone-Recorded Environmental Audio and Symptomatology of Anxiety and Depression: Exploratory Study.

Background: Objective and continuous severity measures of anxiety and depression are highly valuable and would have many applications in psychiatry and psychology. A collective source of data for objective measures are the sensors in a person's smartphone, and a particularly rich source is the microphone that can be used to sample the audio environment. This may give broad insight into activity, sleep, and social interaction, which may be associated with quality of life and severity of anxiety and depression.

Effect of Osteopathic Manipulative Therapy on Generalized Anxiety Disorder.

Context: Traditional management options for generalized anxiety disorder (GAD) have produced low remission rates. As a result, the medical community has turned to complementary and alternative medicine for adjunctive treatment.

Objective: To investigate the efficacy of adjunctive osteopathic manipulative therapy (OMTh; manipulative care provided by foreign-trained osteopaths) in individuals with GAD.

Effects of desvenlafaxine versus placebo on MDD symptom clusters: A pooled analysis.

Background: Major depressive disorder is characterized by the presence of at least five of nine specific symptoms that contribute to clinically significant functional impairment. This analysis examined the effect of desvenlafaxine (50 or 100 mg) versus placebo on symptom cluster scores and the association between early improvement in symptom clusters and symptomatic or functional remission at week 8.

Methods: Using data from nine double-blind, placebo-controlled studies of desvenlafaxine for the treatment of major depressive disorder (=4317), the effect of desvenlafaxine 50 or 100 mg versus placebo on scores for symptom clusters based on 17-item Hamilton Rating Scale for Depression items was assessed using analysis of covariance.

Need for Bioequivalence Standards that Reflect the Clinical Importance of the Complex Pharmacokinetics of Paliperidone Palmitate Long-Acting Injectable Suspension.

Paliperidone palmitate is a second generation antipsychotic, approved for the treatment of schizophrenia in the form of the long-acting injectable (LAI) products INVEGA SUSTENNA® (once monthly injection) and INVEGA TRINZA® (once every 3 months injection). Paliperidone palmitate dissolves slowly after deep intramuscular injection before being hydrolyzed to paliperidone and absorbed into the systemic circulation. The pharmacokinetic (PK) profile of the INVEGA SUSTENNA® formulation is biphasic, comprised of an initial relatively fast zero-order input, which allows rapid attainment of therapeutic concentrations without oral supplementation; and a subsequent maintained second-stage, first-order input, allowing for once monthly administration.

The Bell Tolls for Homeopathy: Time for Change in the Training and Practice of North American Naturopathic Physicians.

North American naturopathic medicine is a distinct form of practice that is woven into the larger fabric of integrative medicine; in a number of US states and Canadian provinces, naturopathic doctors enjoy a wide scope of practice, including the ability to make diagnoses, order tests, use medical technology, write prescription drugs, and perform minor surgeries. However, the basic premise of naturopathic medicine and its guiding principles-considering the whole person and supporting healthy lifestyle behaviors-is the unifying approach in clinical practice. In the 1970s, homeopathy-considered in many circles to be a hypothesis-driven, fringe form of alternative medicine-became embedded into the training and practice of North American naturopathic doctors.

Low hedonic tone and attention-deficit hyperactivity disorder: risk factors for treatment resistance in depressed adults.

Background: The burdens imposed by treatment-resistant depression (TRD) necessitate the identification of predictive factors that may improve patient treatment and outcomes. Because depression and attention-deficit hyperactivity disorder (ADHD) are frequently comorbid and share a complex relationship, we hypothesized that ADHD may be a predictive factor for the diagnosis of TRD. This exploratory study aimed to determine the percentage of undetected ADHD in those with TRD and evaluate factors associated with treatment resistance and undetected ADHD in depressed patients.

Adjunctive Vitamin D in the treatment of non-remitted depression: Lessons from a failed clinical trial.

Background: Many patients with depression fail to achieve remission after several consecutive treatments. Vitamin D deficiency is prevalent and new research suggests that it may have an impact on mood, primarily through an effect on neurotransmitters. Numerous observational studies suggest a relationship between low levels of vitamin D and increased incidence and severity of mood disorders.

Functional Recovery in Major Depressive Disorder: Providing Early Optimal Treatment for the Individual Patient.

Major depressive disorder is an often chronic and recurring illness. Left untreated, major depressive disorder may result in progressive alterations in brain morphometry and circuit function. Recent findings, however, suggest that pharmacotherapy may halt and possibly reverse those effects.

Adult ADHD and comorbid disorders: clinical implications of a dimensional approach.

Attention-deficit/hyperactivity disorder (ADHD) in the adult population is frequently associated with comorbid psychiatric diseases that complicate its recognition, diagnosis and management.The prevalence of ADHD in the general adult population is 2.5% and it is associated with substantial personal and individual burden.

Speed of Improvement in Symptoms of Depression With Desvenlafaxine 50 mg and 100 mg Compared With Placebo in Patients With Major Depressive Disorder.

Purpose/background: This post hoc analysis examined the time point at which clinically significant improvement in major depressive disorder (MDD) symptoms occurs with desvenlafaxine versus placebo.

Methods: Data were pooled from 9 short-term, double-blind, placebo-controlled studies in adults with MDD randomly assigned to desvenlafaxine 50 mg/d, 100 mg/d, or placebo. A mixed-effects model for repeated-measures analysis of change from baseline score was used to determine the time point at which desvenlafaxine treatment groups separated from placebo on the 17-item Hamilton Rating Scale for Depression and psychosocial outcomes.

Intolerance of uncertainty, social anxiety, and generalized anxiety: Differences by diagnosis and symptoms.

Research suggests that Intolerance of Uncertainty (IU) is related to the severity of suffering in Generalized Anxiety Disorder (GAD). However, its role in Social Anxiety Disorder (SAD) has not been extensively studied. This study examines IU in a clinical sample of 248 individuals referred to a tertiary care clinic.