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.

Measurable outcomes in psychiatric disorders: remission as a marker of wellness.

BACKGROUND: Mental disorders are highly prevalent, heterogeneous, and of multifactorial etiology. Collectively, they are associated with significant morbidity, mortality, and economic cost. Wellness is the optimal outcome in the management of chronic medical and psychiatric disorders. OBJECTIVES: This review provides a synopsis of definitions and operational criteria for remission in major depressive disorder, bipolar disorder, schizophrenia, anxiety disorders, and attention-deficit/hyperactivity disorder (ADHD). The overall goals were to propose a treatment framework that gives primacy to therapeutic outcomes and to provide a rationale for psychiatry to quantify and measure patient outcome. METHODS: Articles proposing definitions for remission were identified using a MEDLINE search (1966-April 2005) of the English-language literature (key terms: remission, anxiety disorders, bipolar disorder, major depressive disorder, attention-deficit/hyperactivity disorder, and schizophrenia). RESULTS: Operationalizing and quantifying critical end points in psychiatric disorders may help sharpen the focus of therapeutic activity and benefit patient outcome. In the absence of a validated biomarker of psychiatric illness activity, symptomatic remission and functional restoration are the only available markers of wellness in psychiatry. There is an emerging consensus regarding a definition for remission in major depressive disorder; several working definitions for bipolar disorder, schizophrenia, and anxiety disorders have been proposed. Developments in adult mood disorders-albeit incomplete-have been informative; managing psychiatric disorders that first appear in childhood (eg, ADHD) may also benefit by objectifying patient outcome. CONCLUSIONS: Research is needed to determine the impact of applying a remission-focused model of illness management--emphasizing quantifiable, objective, and measurable end points--on overall patient outcomes.

A randomized, double-blind, cross-over, phase IV trial of oros-methylphenidate (CONCERTA(®)) and generic novo-methylphenidate ER-C (NOVO-generic).

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder with onset during childhood. Multiple aspects of a child's development are hindered, in both home and school settings, with negative impacts on social, emotional, and cognitive functioning. If left untreated, ADHD is commonly associated with poor academic achievement and low occupational status, as well as increased risk of substance abuse and delinquency. The objective of this study was to evaluate adult ADHD subject reported outcomes when switched from a stable dose of CONCERTA(®) to the same dose of generic Novo-methylphenidate ER-C(®). METHODS: Randomized, double-blind, cross-over, phase IV trial consisted of two phases in which participants with a primary diagnosis of ADHD were randomized in a 1:1 ratio to 3 weeks of treatment with CONCERTA or generic Novo-Methylphenidate ER-C. Following 3 weeks of treatment, participants were crossed-over to receive the other treatment for an additional 3 weeks. Primary efficacy was assessed through the use of the Treatment Satisfaction Questionnaire for Medication, Version II (TSQM-II). RESULTS: Participants with ADHD treated with CONCERTA were more satisfied in terms of efficacy and side effects compared to those receiving an equivalent dose of generic Novo-Methylphenidate ER-C. All participants chose to continue with CONCERTA treatment at the conclusion of the study. CONCLUSION: Although CONCERTA and generic Novo-Methylphenidate ER-C have been deemed bioequivalent, however the present findings demonstrate clinically and statistically significant differences between generic and branded CONCERTA. Further investigation of these differences is warranted.

Adult ADHD and comorbid depression: A consensus-derived diagnostic algorithm for ADHD.

OBJECTIVE: Many patients present to their physician with depression as their primary symptom. However, depression may mask other comorbid disorders. This article presents diagnostic criteria and treatment recommendations (and monitoring) pertaining to the diagnosis of adult attention deficit hyperactivity disorder (ADHD), which may be missed in patients who present with depressive symptoms, or major depressive disorder (MDD). Other co-occurring conditions such as anxiety, substance use, and bipolar disorder are briefly discussed. METHODS: A panel of psychiatrist-clinicians with expertise in the area of child and adolescent ADHD and mood disorders, adult mood disorders, and adult ADHD was convened. A literature search for recommendations on the diagnosis and treatment of co-occurring conditions (MDD, anxiety symptoms, and substance use) with adult ADHD was performed. Based on this, and the panel's clinical expertise, the authors developed a diagnostic algorithm and recommendations for the treatment of adult ADHD with co-occurring MDD. RESULTS: Little information exists to assist clinicians in diagnosing ADHD co-occurring with other disorders such as MDD. A three-step process was developed by the panel to aid in the screening and diagnosis of adult ADHD. In addition, comorbid MDD, bipolar disorder, anxiety symptoms, substance use and cardiovascular concerns regarding stimulant use are discussed. CONCLUSION: This article provides clinicians with a clinically relevant overview of the literature on comorbid ADHD and depression and offers a clinically useful diagnostic algorithm and treatment suggestions.

Osmotic-release oral system methylphenidate augmentation of antidepressant monotherapy in major depressive disorder: results of a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy, safety, and tolerability of adjunctive osmotic-release oral system (OROS) methylphenidate in outpatients with major depressive disorder (MDD) receiving a stable oral antidepressant regimen. METHOD: This multicenter, double-blind, randomized, placebo-controlled, parallel-group, 5-week trial enrolled 145 subjects who met DSM-IV-TR criteria for MDD and who had failed 1 to 3 previous antidepressant monotherapies (including current antidepressant) of adequate dose and duration. Augmentation therapy was initiated with 18 mg of OROS methylphenidate and increased to a maximum dose of 54 mg of OROS methylphenidate until an optimal dose was achieved. Efficacy scales included the Montgomery-Asberg Depression Rating Scale (MADRS), 7 atypical items from the 31-item Hamilton Rating Scale for Depression, the Clinical Global Impressions-Severity of Illness (CGI-S) scale, the CGI-Improvement scale (CGI-I), the Sex Effects scale, the Multidimensional Assessment of Fatigue (MAF) scale, and the Apathy Evaluation Scale (AES). Subjects were recruited at 17 community and academic centers across Canada. The study was conducted from June 8, 2005, to April 18, 2006. RESULTS: There was no statistically significant difference between the groups at endpoint on the MADRS. OROS methylphenidate was superior to placebo in improving apathy and fatigue as measured by the AES and the MAF. Statistically significant differences using mixed-model analysis were observed on the AES at all visits and at endpoint (p = .01) and on the MAF (p < .01). No differences were observed on other secondary measures, including the CGI-I and CGI-S. There were no clinically significant findings on electrocardiogram. CONCLUSIONS: OROS methylphenidate did not demonstrate statistical significance on the MADRS at endpoint. Apathy and fatigue were significantly improved with OROS methylphenidate treatment, which was well tolerated with minimal side effects. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00246233.

Does OROS-methylphenidate improve core symptoms and deficits in executive function? Results of an open-label trial in adults with attention deficit hyperactivity disorder.

OBJECTIVE: This pilot, uncontrolled, open-label study evaluated the safety/tolerability and potential effectiveness of OROS-methylphenidate (OROS-MPH) in adult attention deficit hyperactivity disorder (ADHD). METHODS: Adults with DSM-IV-defined ADHD were enrolled in this 38-day study. Retrospective childhood diagnosis was made using the Wender Utah Rating Scale. Eligible patients required a baseline Conners Adult ADHD Rating Scale (CAARS) score > or = 24, Clinical Global Impression of Severity (CGI-S) score > or = 4 (at least moderate illness), and Montgomery-Asberg Depression Rating Scale (MADRS) score < or = 16. Safety/tolerability measurements included adverse event reporting, vital signs, electrocardiograms (ECGs), weight, physical examination. Primary effectiveness evaluated changes in CAARS scores. Secondary effectiveness parameters included executive function. RESULTS: Thirty-two patients formed the safety analysis; however, 30 comprised the effectiveness analysis since two patients did not meet diagnostic inclusion criteria. No serious adverse events were reported and there were no early withdrawals due to adverse events. There were no clinically significant changes in endpoint ECGs, physical examination, or blood pressure. Mean pulse rate increased by 5.9 beats/min (p = 0.003) and mean body weight decreased by 2.2 kg at endpoint (p < 0.0001). Total CAARS scores decreased significantly at endpoint as well as the inattention (p < 0.0001) and hyperactivity/impulsivity symptom subscales (p < 0.0001) separately. Statistically significant improvements were observed in executive function and all other secondary measures, including the CAARS self report, CGI-S/CGI-I, Subject Satisfaction with treatment and the Sheehan Disability Scale (SDS). Mean dose of OROS-MPH = 52.3 +/- 14.0 mg. Modal dose = 54 mg. Study limitations include: the lack of placebo control in the study design leading to potential observer bias, the exclusion of adults with unstable psychiatric and other medical conditions which is less reflective of clinical practice, and the short study duration. CONCLUSIONS: This uncontrolled, open-label trial suggests that OROS-MPH is well tolerated, providing core symptom control with the added benefit of improving executive function. However, future larger, randomized, controlled trials are required.

Pharmacotherapy to sustain the fully remitted state.

Full remission should be the goal of antidepressant therapy; anything less leaves the patient with residual symptoms and an increased risk of relapse and recurrence. Most antidepressant agents offer similar rates of response, but there are some differences in the ability of different agents to promote a full remission. The greatest chance of achieving full remission occurs early in the course of treatment; thus, initial antidepressant strategies should be those that have the greatest therapeutic potential. Other strategies that may help improve the chances of achieving full remission include optimizing drug dosages and using combination and augmentation strategies. Failure to achieve full remission and early discontinuation of antidepressant therapy have been associated with a greater incidence of relapse and recurrence. Continued antidepressant therapy has clearly been shown to effectively reduce the probability of relapse and recurrence by about half compared with placebo. Therefore, once a patient achieves remission, it is important to continue the same antidepressant therapy for at least 6-12 months and, for many patients, considerably longer. Medication should continue at the dose that was initially effective because using low-dose maintenance therapy appears to decrease the protective benefits.