Adult adhd treatment

adult adhd treatment

Abstract

Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in young adults and causes significant psychosocial impairment and economic burden to society. Because of the paucity of long-term evidence and lack of national guidelines for diagnosis and management of adult ADHD, most of the data are based on experience derived from management of childhood ADHD. This article reviews the current evidence for the diagnosis and management of adult ADHD with special emphasis on the role of methylphenidate hydrochloride preparations in its treatment. Methylphenidate hydrochloride, a stimulant that acts through the dopaminergic and adrenergic pathways, has shown more than 75% efficacy in controlling the symptoms of adult ADHD. Although concern for diversion of the drug exists, recent data have shown benefits in preventing substance use disorders in patients with adult ADHD.

Introduction

Attention-deficit hyperactivity disorder (ADHD), characterized by inattention, hyperactivity and/or impulsivity, causes significant impairment in psychological, occupational and social functioning in adults.1 –3 It is estimated that 1% to 36% of children diagnosed with ADHD will continue to manifest symptoms into adulthood depending on the diagnostic criteria used.4 Estimates increase to between 40% and 60% when considering persistence rates in adults experiencing partial remission.4 Recent data suggest an adult ADHD prevalence rate of 4.4% with increased incidence in males.5 A retrospective analysis of National Ambulatory Medical Care survey over an 8-year period from 1996 to 2003 estimated a total of 10.5 million ambulatory adult ADHD visits accounting for 3.5% of 301 million adult mental health disorder visits.6 Adult ADHD diagnosis and management pose unique challenges to physicians because of an increased incidence of comorbid psychiatric and substance use disorders in this population. These comorbidities may result in substantial undertreatment in patients with adult ADHD because of providers attributing symptoms to the comorbid psychiatric disorder rather than adult ADHD.7 As a result, patients’ ADHD may remain untreated, which has been shown to result in impairment in patients’ self-care, mobility, cognition, and role functioning.3 ,5 Stimulants including methylphenidate, amphetamine and dextroamphetamine salts were the mainstay of treatment until atomoxetine, a nonstimulant, selective noradrenaline reuptake inhibitor, was approved for adult ADHD treatment. In this paper, we will briefly review the diagnosis and management of adult ADHD and detail the role of methylphenidate hydrochloride in the treatment of ADHD and comorbid disorders in adults.

Diagnosis

The diagnosis of adult ADHD poses challenges to clinicians as symptoms in adulthood may differ from those in childhood.8 –10 For example, the DSM criteria require behaviors such as running or climbing excessively, which are unlikely to be symptoms present in adults.1 Further, many ADHD adults learn over time to compensate for their symptoms and thus may not manifest symptoms seen in childhood.9 ,10 Diagnosis can be further complicated when adults present without a childhood diagnosis of ADHD and have comorbid psychiatric and substance use disorders.3 ,8 In a study by Faroane et al, most patients with adult ADHD were self-reported and self-referred, and there was significant delay in time to first diagnosis and initiation of treatment, especially in the primary care setting.3

Diagnostic criteria

The Diagnostic and Statistical Manual for Mental disorders, Fourth Edition Text Revision (DSM-IV-TR) requires 6 out of 9 symptoms of inattention (ie, failure to attend to detail, difficulty sustaining attention, not listening when spoken to, failure to follow through on tasks, organizational deficits, difficulty concentrating, losing items, distractibility, forgetfulness) or hyperactivity/impulsivity (ie, fidgeting, difficulty staying seated, excessive running/climbing, difficulty playing quietly, acts as though “driven by a motor”, excessive talking, difficulty awaiting one’s turn, interrupting frequently, prematurely responding to questions) be present for a diagnosis of ADHD.1 In addition, the symptoms must be present before age 7 and result in significant impairment observable in at least two settings. The three ADHD subtypes according to DSM criteria are: predominantly hyperactive-impulsive type, inattentive type and combined type.1 However, it is important to note that the DSM criteria were developed based on childhood presentation and may not adequately represent symptoms in adults.9 –14

The Utah criteria, developed for identification of adult ADHD, may be utilized as an alternative to DSM criteria. According to these criteria, an adult must have a childhood history of ADHD and current motor hyperactivity, attention deficits and 2 of the following: labile affect, temper outbursts, excessive emotional reactivity, disorganization, impulsivity and associated features of ADHD.15 One disadvantage of these criteria is the focus on affective symptoms and requirement for hyperactivity, particularly given that these symptoms may decline more quickly over time than symptoms of inattention.11 Further, according to Utah criteria, ADHD may be diagnosed only in the absence of other psychiatric disorders, posing a diagnostic challenge given the increased incidence of comorbid psychiatric disorders.2 ,16

Assessment

Unfortunately, there are currently no assessments diagnostic of adult ADHD. Therefore, a multi-pronged approach including interviews, rating scales and checklists may be helpful in establishing a diagnosis.2 ,17 The first step is to be aware of common clinical presentations of adult ADHD. Adults with ADHD may present with cognitive (eg, difficulty concentrating, poor memory) or affective complaints (eg, anxiety, irritability, depressed mood) and/or behavioral difficulties (eg, disorganization, failure to complete projects, poor school/work performance).2 ,3 ,8 Further, adults with ADHD experience higher rates of disruption in their interpersonal relationships, driving-related problems (eg, accidents, citations) and substance abuse.18 –21 Employing a screening measure, such as the World Health Organization’s Adult ADHD Self-Report Scale Screener, may be helpful in identifying patients for further evaluation.22

Upon suspicion of an ADHD diagnosis, it is important to first conduct a thorough interview. Patients should be queried about past and present ADHD symptoms, with information gathered from family members and previous school records if possible to establish a childhood diagnosis.3 ,23 Functional impairment can be assessed by querying patients about their performance in a variety of situations during the prior week, the level of effort required to function and coping strategies utilized.23 –25 Assessing family history of ADHD may also be helpful given that ADHD has approximately 70% heritability.2 ,26 Diagnostic interviews are available to assist with the interview process, including the Brown ADD Scale, Connor’s Adult ADHD Diagnostic Interview for DSM-IV and the Diagnostic Interview Schedule.24 Rating scales, many of which require no special training and take less than 5 minutes to administer (eg, Brown ADD Scale for Adults, Connor’s Adult ADHD Rating Scale, Adult ADHD Self Report Scale, ADHD Rating Scale-IV), are available for administration to patients and their family members and can serve as useful adjuncts in the diagnostic process.22 ,27 Providers should take care to determine that symptoms are not due to other psychiatric diagnoses, such as mood disorders, anxiety disorders and personality disorders, many of which share symptoms with ADHD.2 ,3 ,17 ,25 Routine laboratory and radiological tests are useful for differentiating ADHD from common medical conditions that can mimic symptoms of ADHD, including thyroid disorder, seizure disorders, drug interactions, hepatic diseases, lead toxicity, post-head injury, sleep disorders and hearing deficits.2 ,17 A complete blood count, metabolic profile and thyroid function studies can identify anemia, thyroid disorders or liver disorders. Routine radiological evaluation including computed tomography is not required for the initial diagnosis of ADHD and should be reserved for patients with a recent history of head trauma.2 ,17

Treatment

Similar to the diagnostic challenges mentioned above, most recommendations for the management of adult ADHD are derived from clinical experiences in childhood ADHD treatment. Currently, there is no practice guideline available in the United States for adult ADHD management. However, the British Association for Psychopharmacology

(BAP) published a guideline in 2007 for ADHD management in adults and adolescents in transition to adult services.28

Adult ADHD results in significant functional and psychosocial impairment; treatment therefore consists of pharmacological, behavioral or combination interventions. As mentioned previously, comorbid psychiatric disorders and substance use disorders are not uncommon, posing unique challenges to the physician utilizing pharmacological management.3 Physicians’ concerns about prescribing medications with the potential for abuse further complicate and may delay initiation of appropriate treatment.29 In addition to physician bias, insurance reimbursement sources other than private or self-pay significantly reduce the likelihood of ADHD treatment, including ADHD-specific pharmacotherapy.6

Nonpharmacological treatment

Several behavioral strategies for assisting adults with managing their ADHD symptoms have been suggested, including organizational and time management strategies.17 ,30 Though the research is still in its relative infancy, cognitive behavioral strategies are the most commonly investigated of the nonpharmacologic strategies. Cognitive-behavioral therapy includes identification and modification of patients’ maladaptive thought patterns and behaviors and has shown statistically significant improvements in ADHD symptoms, functional impairment, depression, anxiety, hopelessness, health status and self-esteem.30 ,31 Skills typically taught during cognitive-behavioral therapy include education about symptoms and medications, emotional regulation, self-esteem building, problem-solving skills, mindfulness and strategies for improving motivation, concentration, listening, impulsivity, organization and time management.3 ,30 ,31 It is important to note that cognitive behavioral therapy alone may be insufficient, and thus combining it with pharmacological interventions is recommended.31 ,32 Family therapy and support groups may also prove a useful adjunct in adult ADHD management.2 ,17

Pharmacologic treatment

Stimulants and atomoxetine are the mainstay of pharmacological adult ADHD treatment and have been shown to improve symptoms of ADHD and comorbid psychiatric disorders. They have also been shown to improve associated symptoms of adult ADHD, including self-esteem, social and family functioning, driving skills and substance use risk.32 –35

The most commonly used stimulants in the treatment of adult ADHD include methylphenidate hydrochloride preparations (MPH), dextroamphetamines (DEX) and mixed amphetamine salts levo amphetamine and dextroampheatmine (AMP). Pemoline, a weak stimulant medication, has been withdrawn from the market because of hepatotoxicity.36 Stimulants have shown a response rate of 25% to 78% depending on the diagnostic criteria, dose of medication administered and the presence of comorbid psychiatric disorders. Response rates of greater than 75% have been demonstrated with higher doses of both methylphenidate and mixed amphetamine salts.37 –40 Lisdexamphetamine (Vyvanse ® ; Shire Pharmaceuticals), the once daily prodrug stimulant, was approved by the United States Food and Drug Administration (FDA) for treatment of adult ADHD in 2007. In a study of 420 adults with moderate to severe ADHD by DSM-IV criteria, lisdexamphetamine was superior to placebo in all 3 doses, and patients tolerated it well with minimal side effects.41

Despite their benefit, it is important to note that one barrier to appropriate treatment with stimulant medications is physician discomfort with prescribing controlled substances with the potential for abuse. In one study, 38% of physicians surveyed preferred prescribing a nonstimulant medication, and 58% preferred prescribing a noncontrolled medication with no evidence of abuse potential in patients with ADHD.29

Atomoxetine, a selective noradrenergic reuptake inhibitor, is the only nonstimulant medication approved by the FDA for ADHD treatment and has the benefit of not being a controlled substance. It has demonstrated efficacy in reducing inattentiveness, hyperactivity and impulsivity with minimal side effects in children and adolescents with ADHD. Among adults with DSM-IV criteria for ADHD, administration of atomoxetine in 2 randomized controlled trials of 10-week duration (study I, n = 280; study II, n = 256) resulted in significant improvements in both inattentive and hyperactive/impulsive symptoms on the Connor’s Adult ADHD Rating Scales. The discontinuation rate was less than 10% in both the studies.42 The most common side effects were dry mouth, decreased appetite, insomnia, erectile dysfunction and nausea with no significant cardiovascular side effects. A recent 4-year open label study of 384 adult patients demonstrated statistically significant improvement in ADHD symptom scores with minimal side effects, demonstrating the long-term efficacy and safety of atomoxetine.43 Despite being recommended as a first-line treatment for pediatric patients with ADHD because of its comparable efficacy with stimulant medications and low abuse potential, among adult patients its use has primarily been limited to patients with comorbid substance use, psychiatric and tic disorders.32 ,44

Antidepressants have demonstrated less comparable efficacy than stimulants in the treatment of adult ADHD. The response is dose-related and delayed in comparison to stimulant preparations.45 –47 Bupropion has been the most extensively studied of the antidepressants. In a meta-analysis of 5 clinical trials comparing the efficacy of bupropion to placebo, bupropion was 2.4 times more likely to result in improved clinical outcomes.47 The alpha-agonist clonidine has also been used in the treatment of ADHD, primarily as an adjunct to stimulants in cases of comorbid aggression, insomnia or tics.32 ,48

Modafinil, a novel cognitive enhancer approved for the treatment of narcolepsy, has been found to improve neuropsychological task performance in children and adults with ADHD with minimal side effects and low abuse potential. An analysis of 4 randomized control trials showed significant improvement in primary outcomes and cognitive function in ADHD patients. Insomnia and headache were the more common side effects, seen in 20% of the patients. There are no data on modafinil’s long-term efficacy, and hence it may be considered in patients with ADHD who do not respond to standard treatment.17 ,49

Nonstimulants can also be combined with stimulants for patients with inadequate response and for treatment of comorbid psychiatric disorders.28 ,32 ,44 Patients who fail to respond to appropriate doses of stimulants may have comorbid psychiatric or developmental disorders; hence a careful re-evaluation of the patient’s diagnosis is warranted. A trial of behavioral therapy may be initiated prior to adding nonstimulants in such situations. Clonidine may alleviate symptoms of impulsivity or hyperactivity and sleep disturbance or tics from use of stimulants. Bupropion may be combined with stimulants for treatment of comorbid mood disorders, bipolar or substance use disorders.28 ,32 ,44

Methylphenidate in the management of adult ADHD

Psychostimulants, especially amphetamines, were the most effective treatment for hyperactivity syndromes in children from the 1930s until methylphenidate (Ritalin ® ) received FDA approval in 1968.45 Since its introduction, methylphenidate has become the most prescribed medication for ADHD treatment in children and adults.33

Mechanism of action

Methylphenidate hydrochloride (MPH) is a piperidine derivative, structurally related to amphetamines. The exact mechanism of action of stimulants in ADHD is not completely understood, but they are presumed to act through the dopaminergic and adrenergic pathways of the frontostriatal areas in the brain.50 ,51 Unlike amphetamines which can cause a direct release of dopamine and norepinephrine into the presynaptic cleft, MPH is a mild central nervous system stimulant which acts by blocking the reuptake of dopamine and norepinephrine into the presynaptic cleft by blocking the dopamine transporter protein (DAT). MPH has also been shown to reduce the availability of striatal dopamine transporter proteins in adults with ADHD. In 10 patients treated with MPH, single photon emission computed tomography (SPECT) imaging demonstrated that MPH lowered striatal DAT availability in adults with ADHD.52

MPH oral preparations are readily absorbed after oral administration with a peak plasma concentration in 2 hours. It crosses the blood–brain barrier, and 80% of the dose is excreted through urine as ritalinic acid, the main urinary metabolite.17

Preparations and dosage

MPH is available in short-, intermediate- and long-acting preparations and through a transdermal delivery system.

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