Let's Talk about Sex and ADHD: Findings from an Anonymous Online Survey.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity and impulsivity. A dearth of studies have investigated psychosexuality in this population, often with few (predominantly male) participants. We recruited individuals with and without ADHD via an anonymous online survey distributed electronically by ADHD support organizations and social media. We investigated sexual history; interests and practices; and relationships. Of 1392 respondents, we classified an 'ADHD' group (n = 541; 30.5% male) and compared them to individuals of similar ages without ADHD, ('Other' group; n = 851; 37.6% male). The ADHD group (both males and females) had a significantly higher preference for same-sex or either-sex partners; and higher rates of electronic sexual exchanges, masturbation, and sexually transmitted diseases. They were more adventurous in sexual interests and practices and substantially less satisfied with their partners, both sexually and generally. Within the ADHD group, significant sex differences emerged: females had younger onset of sexual activities, used contraception less frequently, had more sexual partners and practiced more infidelity. Sexual interests differed between the sexes, but females more commonly acted on them, whereas males did not. Findings suggest both sexes engage in risky sexual behaviors, perhaps driven by impulsivity, but risk is substantially greater for females with ADHD.

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. However, the psychiatric literature has repeatedly cautioned on the addictive potential of ketamine and raised caution for both less supervised and longer-term use of ketamine. To date, these concerns have not been discussed in view of available evidence, nor have they been discussed within a broader clinical context. This paper examines the available relevant literature and suggests that ketamine misuse risks appear not dissimilar to those of other well-established and commonly prescribed agents with abuse potential, such as stimulants or benzodiazepines. As such, ketamine prescribing should be considered in a similar risk/benefit context to balance patient access and need for treatment with concern for potential substance misuse. Our consortium of mood disorder specialists with significant ketamine prescribing experience considers prescribing of non-parenteral ketamine a reasonable clinical treatment option in select cases of treatment-resistant depression. This paper outlines where this may be appropriate and makes practical recommendations for clinicians in judicious prescribing of non-parenteral ketamine.

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 pharmacokinetics of PRC-063 administered as capsule contents sprinkled on apple sauce, yoghurt, or ice cream were also investigated. FINDINGS/RESULTS: PRC-063 demonstrated biphasic absorption, with 2 distinct peak plasma concentrations. Intake of a high-fat, high-calorie meal did not increase the peak plasma methylphenidate concentration (Cmax) or extent of absorption (area under the curve), however; it resulted in slower uptake versus a fasted state. During repeated dosing, steady state was reached with no further accumulation of methylphenidate from day 3. At steady state, PRC-063 gave higher evening and trough plasma methylphenidate levels than immediate-release methylphenidate (3 times daily). The pharmacokinetics of PRC-063 sprinkled on food were comparable to that of intact capsules. Reported adverse events (AEs) were consistent with the established safety profile of methylphenidate. There were no serious AEs, but 3 subjects discontinued the repeat-dosing study because of AEs assessed as possibly related to study treatment. IMPLICATIONS/CONCLUSIONS: Our data indicate that PRC-063 can be taken with or without food or by sprinkling capsule contents on food.

Esketamine for treatment resistant depression.

Introduction: Treatment Resistant Depression (TRD) is a common and burdensome condition with poor outcomes and few treatment options. Esketamine is the S-enantiomer of ketamine and has recently been FDA approved in the United States for treating depression that has failed to respond to trials of two or more antidepressants. Areas covered: This review will briefly discuss current treatment options for TRD, then review esketamine. Relevant literature was identified through online database searches, and clinical trial data were provided by Janssen Pharmaceuticals. Pharmacology, including kinetics and dynamics, is discussed, then clinical data regarding efficacy and safety for esketamine from Phase 2-3 trials are reviewed. Expert opinion: In the expert opinion, the authors discuss multiple factors including patient, physician, and social factors that will influence the use of esketamine. While the efficacy of esketamine compared to off-label use of racemic ketamine remains unclear, both esketamine's approval for use in TRD and longer-term safety data may position it preferentially above racemic ketamine, although factors such as cost and monitoring requirements may limit its use. While questions remain regarding duration and frequency of treatment, as well as addictive potential, esketamine is a novel treatment option offering new hope for TRD.

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. A small number of pilot studies have been undertaken but lack rigorous methodology required to draw conclusions about a clinical role for this nutrient in treatment resistant depression. METHODS: This study was designed as a randomized, double-blind, placebo controlled intervention study administering a weekly (bolus) dose of 28 000IU of Vitamin D3 or placebo to 125 patients with non-remitted depression adjunct to current antidepressant medication. Patients were followed weekly for eight weeks plus a one month follow up. Outcomes measured included depression severity, serum vitamin D levels and safety. Due to slow recruitment during the first season, amendments were made. These included extending the age range to 18-75 and removing the requirement for failing to respond to one pharmacologic antidepressant agent. The protocol was amended to reduce the burden on participants by changing the in-office visits to bi-weekly. Three additional tertiary psychiatric clinics were also added as trial sites. RESULTS: Over three recruitment period years (fall/winter), a total of 148 participants completed screening, 24 (16.2%) of whom qualified to participate in the study. Use of too many or no psychiatric medications, comorbid exclusionary psychiatric conditions, current use of a vitamin D supplement, and lack of participant compensation were the predominant reasons for ineligibility or unwillingness to participate. 9 participants were successfully enrolled in the study, 7 (77.8%) of whom completed the trial as per the protocol. After the third season, futility was declared based on inability to enroll participants. The sample size of enrolled participants (7/125, 5.6%) lacks power to conduct a full assessment of findings. DISCUSSION: High accessibility of vitamin D, as well as a growing lack of equipoise in patients and clinicians about the potential ubiquitous benefits of vitamin D for Canadians, not just for mood disorders, resulted in a large proportion of ineligible potential participants. Limited funding provided to studies on natural health products hampered recruitment. The labile and fluctuating nature of non-remitted depression as well as frequent co-morbid conditions creates additional challenges for conducting trials in this population. Future studies assessing vitamin D in depression should consider our experiences in design and conduct of research. Innovations in clinical trial design such as preference trials or accepting patients already using vitamin D but not achieving an optimal target value are potential solutions to some of these challenges.

A survey of adult referrals to specialist attention-deficit/hyperactivity disorder clinics in Canada.

BACKGROUND: Canadian guidelines encourage family physicians to diagnose/manage adults with uncomplicated attention-deficit/hyperactivity disorder (ADHD); specialist referral is recommended only for complex cases. This retrospective case review investigated adults referred to Canadian ADHD clinics. METHODS: Adult ADHD specialists reviewed referral letters/charts of patients (aged ≥18 years and no family history/known/expressed childhood ADHD) from family physicians/psychiatrists over 2 years. RESULTS: Data on 515 referrals (mean age 33 years, 60% males) were collected (December 2014 to September 2015); 472/515 (92%) were made by family physicians. No psychiatric comorbid symptoms were noted in 344/515 (67%) referrals. ADHD was confirmed by a specialist in 483/515 (94%) cases, whether comorbid symptoms were noted at referral (155/171 [91%]) or not (328/344 [95%]). ADHD was reported to impact "work" (251/317 [79%]), "school" (121/166 [73%]), "social/friends" (260/483 [54%]), and "spouse/family" (231/483 [48%]). Overall, 335/483 (69%) patients had more than or equal to one comorbid symptom (diagnosed by referring physician or specialist). Stimulant monotherapy was recommended for 383/483 (79%) patients, non-stimulant monotherapy for 41/483 (8%) patients, and stimulant plus non-stimulant monotherapy for 39/483 (8%) patients. Almost half of patients were returned for referring physician's follow-up, either before treatment initiation (102/483 [21%]) or after treatment stabilization (99/483 [20%]). Follow-up was by a specialist for 282/483 (58%) patients. CONCLUSION: ADHD diagnosis was specialist confirmed in most cases. Although most referrals (67%) noted no psychiatric comorbid symptoms, 69% of patients had ≥1 such symptom (diagnosed by a referring physician or specialist), so comorbid symptoms although not always noted at referral, may have contributed to the decision to refer. ADHD has a wide-ranging impact on patients' daily lives. It is possible that greater confidence of family physicians to diagnose and treat adult ADHD could help to meet patients' needs.

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. The most frequent comorbid psychopathologies include mood and anxiety disorders, substance use disorders, and personality disorders. There are strong familial links and neurobiological similarities between ADHD and the various associated psychiatric comorbidities. The overlapping symptoms between ADHD and comorbid psychopathologies represent challenges for diagnosis and treatment. Guidelines recommend that when ADHD coexists with other psychopathologies in adults, the most impairing condition should generally be treated first.Early recognition and treatment of ADHD and its comorbidities has the potential to change the trajectory of psychiatric morbidity later in life. The use of validated assessment scales and high-yield clinical questions can help identify adults with ADHD who could potentially benefit from evidence-based management strategies.

Understanding the role of adjunctive nonpharmacological therapies in management of the multiple pathways to depression.

Major depressive disorder (MDD) is a common disorder with a lifetime prevalence of 16.2% and the fourth highest cause of disability globally. It is hypothesized to be a syndromatic manifestation of multiple pathological processes leading to similar clinical manifestation. MDD is associated with at least three categories of peripheral hormone-type factors including neurotrophic factors, proinflammatory cytokines, and processes that impair regulation of the hypothalamic-pituitary-adrenocortical axis. Neuroimaging studies have identified functional abnormalities including subcortical systems associated with reward and emotion processing, medial prefrontal and anterior cingulate cortical regions and the lateral prefrontal cortical systems involved in cognitive control and voluntary emotion regulation. Studies investigating the effects of psychotherapy and pharmacotherapy on functional brain measures show normalization of brain function with return to euthymia. Nevertheless, approximately 50% of patients with MDD will not respond sufficiently and 60 to 70% will not achieve full remission with first-line pharmacotherapy, therefore clinicians strive to improve patient responses through the use of adjunct therapies. This review discusses recent research in the various biological processes associated with MDD as well as recent data in support of the use of adjunctive non-pharmacological therapies including psychotherapy, bibliotherapy, Internet therapy, "natural" or herbal approaches, exercise therapy, and somatic therapies.

Comorbid attention deficit/hyperactivity disorder and substance use disorder: treatment considerations.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is predominantly a diagnosis of childhood and adolescence but has also been recognized in adults. It is associated with high rates of comorbid psychiatric conditions, particularly substance use disorders (SUD). METHODS: A review of the literature was conducted with a focus on ADHD, SUD, their comorbidity, and treatment considerations. RESULTS: Literature suggests that the use of methylphenidate (MPH) in children does not increase SUD later in life, and may in fact reduce substance use and abuse in adolescence and adulthood. Concurrent treatment of ADHD-SUD, which may be supported theoretically, has yielded inconsistent data on clinical trials. While MPH use in adults with ADHDSUD may be effective in alleviating ADHD symptoms, the benefits on SUD are not clear and remain controversial. Studies suggest that adults with comorbid ADHD-SUD do not misuse or divert their medication, but MPH does not consistently improve substance use. However, data are lacking for substances other than cocaine and stimulants other than MPH. While the risk of stimulant abuse should not be ignored, it may be minimized by selecting medications that are not readily crushed and solubilized for parenteral administration, or by utilizing non-stimulant medications and/or psychotherapy. CONCLUSION: While there are a lack of evidence-based guidelines for the concurrent treatment of ADHD and SUD, evidence to date suggests that stimulant medications should not necessarily be avoided for patients with comorbid ADHDSUD and that concurrent treatment may be a successful approach to improve ADHD outcomes without worsening SUD symptoms.

Adult ADHD and its comorbidities, with a focus on bipolar disorder.

Attention deficit hyperactivity disorder (ADHD) is a syndrome that most often presents in childhood. However, the condition is also relatively common in adults, with prevalence rates reaching 5% in the general population, with more than half the children affected by ADHD retaining the condition during their adult years. While the disorder in children is most often described as a disorder involving hyperactivity and impulsiveness, ADHD presents with very different characteristics in adulthood, notably with less externalizing symptoms and with a higher rate of psychiatric comorbidities, including major depressive disorder, bipolar disorder (BD), anxiety disorders and substance abuse. This review will focus on the evidence relating to bipolar disorder BD and its potential link with ADHD, looking at epidemiological, familial and neuroimaging studies. The comorbid presentation of people suffering with ADHD and BD (ADHD/BD) is associated with a more severe disease course, more severe mood disorder symptoms, and lower functional scores. Importantly, the co-segregation of these two conditions makes ADHD diagnosis challenging because its symptoms are often mistakenly assumed to be part of BD. As a result, patients with comorbid ADHD/BD are under-diagnosed and under-treated. Optimal diagnosis, understanding and treatment of the comorbid condition are important, as ADHD/BD has been associated with significant functional impairment and suboptimal treatment responses when compared to ADHD or BD populations alone.