Kathleen N. Franco, MD

Autism spectrum disorder (ASD) has increased significantly over the past 40 years. Even in the past 2 decades, the prevalence increased from 6.7 per 1,000 in 2000¹ to 14.6 per 1,000 in 2012—1 in 59 people.² Of those with ASD, 46% have an intelligence quotient (IQ) greater than 85, meaning they are of average or above-average intelligence.¹

See related editorial

As more children with autism become adults, understanding this condition across the life span grows paramount. While many studies have focused on understanding how diagnosis and treatment can help young children, few have focused on adults with autism and how primary care teams can better assist these individuals. However, this is changing, with studies of the benefits of employment programs and pharmacologic treatment, and reproductive health needs of adults with ASD. Here we provide an updated review of ASD in adult patients.

NO MORE ASPERGER SYNDROME— IT’S ON THE SPECTRUM NOW

As the scientific understanding of autism has expanded, revisions in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5),³ published in 2013, have paralleled these advances. For many adult patients with autism who were evaluated as children, these revisions have led to changes in diagnosis and available services.

In the previous edition (DSM-IV-TR, published in 2000),⁴ autistic disorder and Asperger syndrome were separate (Table 1). However, DSM-5 lumped autistic disorder and Asperger disorder together under the diagnosis of ASD; this leaves it to the clinician to specify whether the patient with ASD has accompanying intellectual or language impairment and to assign a level of severity based on communication deficits and restrictive behaviors.

The shift in diagnosis was worrisome for some, particularly for clinicians treating patients with DSM-IV Asperger syndrome, who lost this diagnostic label. Concerns that patients with Asperger syndrome may not meet the DSM-5 criteria for ASD were validated by a systematic review showing that only 50% to 75% of patients with DSM-IV autistic disorder, Asperger syndrome, or pervasive developmental disorder not otherwise specified (PDD-NOS) met the DSM-5 criteria for ASD.⁵ Most of those who no longer met the criteria for ASD carried a DSM-IV diagnosis of Asperger syndrome or PDD-NOS or had an IQ over 70.⁵ Nevertheless, these individuals may struggle with impairing symptoms related to repetitive behaviors or communication or may be affected by learning or social-emotional disabilities. Additionally, even if they meet the criteria for ASD, some may identify with the Asperger syndrome label and fear they will be stigmatized should they be classified as having the more general ASD.^6,7

Although future revisions to the DSM may include further changes in classification, grouping adults with ASD according to their functional and cognitive ability may allow for pragmatic characterization of their needs. At least 3 informal groupings of autistic adults have been described that integrate cognitive ability and independence⁸:

• Those with low cognitive and social abilities, who need lifelong support
• Those with midrange cognitive and social limitations but who can complete their work in special education classes; they often find employment in supervised workshops or other work with repetitive tasks
• Those who have greater cognitive ability and some social skills; they may proceed to college and employment and live independently.

UNCERTAIN PROGNOSIS

Prognostication for people with ASD remains an area of research. Some adults experience a reduction in symptoms as they age, with significant improvements in speech and, sometimes, modest improvements in restrictive and repetitive behaviors.^9,10

Nevertheless, autism remains a lifelong disorder for many. Adults may still require significant support and may experience impairment, particularly in social interaction.¹⁰ In longitudinal studies, only 15% to 27% of patients with ASD are characterized as having a positive outcome (often defined as variables related to independent function, near-normal relationships, employment, or a quantified reduction in core symptoms), and many experience significant dependency into adulthood.^10–13

IQ has been cited as a possible prognostic factor,^10,13 with an IQ below 70 associated with poorer outcome, although an IQ above 70 does not necessarily confer a positive outcome. Less-severe impairment in speech at baseline in early childhood also suggests better outcomes in adulthood.¹⁰

As we see more adults with autism, studies that include both children and adults, such as the Longitudinal European Autism Cohort, will be important to characterize the natural history, comorbidities, and genetics of ASD and may help provide more specific predictors of disease course into adulthood.¹⁴

While many patients are recognized as having autism in early to mid-childhood, some adults may not receive a formal diagnosis until much later in life. Those with fluent language and normal-range IQ are likely to be overlooked.¹⁵ People with ASD may have had mild symptoms during childhood that did not impair their functioning until demands of daily life exceeded their capacities in adulthood. Alternatively, parents of a child with newly diagnosed ASD may realize that they themselves or another adult family member also show signs of it.

The UK National Institute of Health and Care Excellence suggests that assessment should be considered if the patient meets psychiatric diagnostic criteria and one of the following:

• Difficulty obtaining or sustaining employment or education
• Difficulty initiating or sustaining social relationships
• Past or current contact with mental health or learning disability services
• History of a neurodevelopmental or mental health disorder.^15,16

Currently, diagnosis typically involves a multidisciplinary approach, with psychiatric assessment, neuropsychological testing, and speech and language evaluation.¹⁷ Providers may need to refer patients for these services, sometimes at the patient’s request, if previous mental health misdiagnoses are suspected, if patients report symptoms or impairment consistent with ASD, or if benefits, services, or accommodations, such as a coach in the workplace, are needed.

Diagnosing ASD in adults can be difficult, given that the gold-standard diagnostic tests such as the Autism Diagnostic Observation Schedule-2 (ADOS-2)¹⁸ and the Autism Diagnostic Interview-Revised (ADI-R)¹⁹ are typically used to diagnose autism in children. However, Module 4 in the ADOS-2 was developed for adolescents and older patients with fluent language and has shown at least moderate power to distinguish adults with ASD from those without ASD.^18,20

An initial psychiatric assessment should include a thorough history taken from the patient and, if applicable, the patient’s caregiver, as well as a psychiatric interview of the patient. Neuropsychological testing should include evaluation of cognitive function, social functioning (using the ADOS-2 for adults without intellectual disability, the ADI-R, or both), and adaptive functioning (using the Vineland Adaptive Behavior Scales, second edition²¹).

Evaluation of speech and language is particularly important in patients with limited language ability and should include both expressive and receptive language abilities. Serial testing every few years, as is often recommended in childhood, may help establish the pattern of impairment over time.

Comorbid psychiatric disorders are common

Many people with ASD also have other psychiatric disorders,^17,22 which clinicians should keep in mind when seeing an adult seeking evaluation for ASD.

Attention-deficit/hyperactivity disorder is present at higher rates in patients of average intellectual function with ASD than in the general population.²³

Anxiety disorders, including obsessive-compulsive disorder, were found to often coexist with autism in a sample of adults with autism without intellectual disability,^24,25 and approximately 40% of youths with ASD have at least 1 comorbid anxiety disorder.²⁶

Mood disorders are also prevalent in adults with ASD, with a small study showing that 70% of adults with DSM-IV Asperger syndrome had at least 1 depressive episode in their lifetime.²⁷

BEHAVIORAL AND PHARMACOLOGIC THERAPIES FOR THE ADULT PATIENT

Services and medications for adults with ASD are discussed below. These will vary by individual, and services available may vary by region.

Historically, vocational and social outcomes have been poor for adults with ASD. It is estimated that most larger universities may be home to 100 to 300 students with ASD. To combat isolation, the University of California, Los Angeles, the University of Alabama, and others provide special support services, including group social activities such as board games and individual coaching.⁸ Nevertheless, half of the students with autism who attend institutions of higher learning leave without completing their intended degree.²⁹ Many still struggle to establish meaningful friendships or romantic relationships.²⁹

Planning for a transition of care

Healthcare transition planning is important  but is strikingly underused.³⁰ Individual providers, including adult psychiatrists, vary in their level of training and comfort in diagnosing, treating, and monitoring adults with autism. Youths with ASD are half as likely to receive healthcare transition services as other youths with special healthcare needs.³¹

Pediatric providers, including pediatric psychiatrists, developmental behavioral specialists, and pediatric neurologists, may be best equipped to treat young adult patients or to refer patients to appropriate generalists and specialists comfortable with autism-specific transition of care. The question of eligibility for services is important to patients and families during the transition period, with many parents and professionals unaware of services available to them.³² Receiving adequate transition services is enabled by having a medical home during childhood—that is, a comprehensive, centralized medical record, culturally competent care, interaction with schools, and patient access to clear, unbiased information.³¹

Ideally, in our experience, transitioning should be discussed well before the child ages out of the pediatric provider’s practice. If necessary, healthcare transition services should include 4 components:

• Discussing the switch to a new physician who treats adults
• Discussing changing healthcare needs as an adult
• Planning insurance coverage as an adult
• Encouragement by the physician for the child to take age-appropriate responsibility for his or her healthcare.^31,33

Tools such as the Got Transition checklist from the National Health Care Transition Center can provide support during this process.³⁴

Other services

Other services provided as an extension or adjunct to the medical home in early adulthood may include customized vocational or employment training, specialized mentorship or support in a college setting, housing support, and psychological services.³⁵

Community-based programs that emphasize leisure have been shown to improve participants’ independence and quality of life.³⁶ Similarly, participants in programs that emphasized supported employment, with a job coach, on-the-job support, collaboration with the participant’s larger social support network, and selection of tasks to match an individual’s abilities and strengths, demonstrated improved cognitive performance, particularly executive functioning,³⁷ and employment.^38,39 These programs work best for patients who have mild to moderate symptoms.^37,39

Patients with symptoms that are more severe may do better in a residential program. Many of these programs maintain an emphasis on vocational and social skills development. One such long-standing program is Bittersweet Farms, a rural farming community in Ohio for adults with ASD, where individuals with moderate to low function live in a group setting, with emphasis on scheduled, meaningful work including horticulture, animal care, carpentry; and activities of daily living.⁴⁰

Studies of patients across the autism spectrum have generally found better outcomes when vocational support is given, but larger and randomized studies are needed to characterize how to best support these individuals after they leave high school.⁴¹

Psychological services such as applied behavioral therapy, social cognition training, cognitive behavioral therapy, and mindfulness training may be particularly useful in adults.^42–44

Some versions of applied behavioral therapy, such as the Early Start Denver Model,⁴⁵ have been found to be cost-effective and offset some expenses in the care of children with autism, using play-based and relationship-based interventions to promote development across domains while reducing symptoms.

In randomized controlled trials, modified cognitive behavioral therapy⁴³ and mindfulness⁴⁴ were shown to reduce symptoms of anxiety, obsessive-compulsive disorder, and depression.

Dialectical behavior therapy, used to find a balance between accepting oneself and desiring to change, may help in some circumstances to regulate emotions and reduce reactivity and lability, although large randomized clinical trials have not been conducted in the ASD population.⁴⁶

Drug therapy

Medications may be appropriate to manage symptoms or comorbid conditions in adults with ASD. Over 75% adults with ASD have been found to use psychotropic medications.⁴⁷ However, although these drugs have been approved for treating behaviors commonly associated with ASD, none of them provide definitive treatment for this disorder, and they have not been rigorously tested or approved for use in adults with ASD.⁴⁸

Irritability and aggression associated with ASD can be treated with risperidone (approved for children over age 5), aripiprazole (approved for children ages 6–17), clozapine, or haloperidol.⁴⁹

Aberrant social behavior can be treated with risperidone.⁵⁰ Treatments under investigation include oxytocin and secretin.⁴⁹

While no approved drug has been shown to improve social communication,⁵¹ balovaptan, a vasopressin V1a agonist, has shown potential and has been granted breakthrough status by the US Food and Drug Administration for treating challenging behaviors in adults, with additional studies ongoing in children.^52,53

Repetitive behaviors, if the patient finds them impairing, can be managed with selective serotonin reuptake inhibitors.⁴⁹

Much more study of drug therapy in adults with ASD is needed to fully understand the best approaches to psychotropic medication use, including appropriate classes and effective dosage, in this population.

SEX: UNEXPLORED TERRITORY

The reproductive health needs of people with autism remain largely underexplored.⁵⁴ Historically, individuals with ASD were thought to have little interest in sexual activity or parenthood, owing to the nature of the core symptoms of the disorder. This has been shown to be untrue, particularly as studies on this topic began to engage in direct interviews with people with ASD, rather than solely gathering information from caregivers or parents. The findings reinforce the importance of broaching this component of health in this population, for the following reasons:

Adults with ASD are at increased risk of sexual victimization, with nearly 4 out of 5 reporting unwanted sexual advances, coercion, or rape.⁵⁵

They have a smaller pool of knowledge with respect to sexual health. They report⁵⁶ that they learned about sex from television and from “making mistakes.” They use fewer sources. They are less likely to speak to peers and figures of authority to gain knowledge about sexually transmitted infections, sexual behaviors, and contraception. And they are more likely to use forms of nonsocial media, such as television, for information.⁵⁵

They report more concerns about the future with respect to sexual behavior, suggesting the need for targeted sexual education programs.⁵⁶

College-age young adults with ASD who misread communication may be particularly affected by Title IX, which requires schools to promptly investigate reports of sexual harassment and sexual assault, should they struggle to comport themselves appropriately.⁵⁷ Early and frank conversations about issues of consent and appropriate displays of interest and affection may better equip youth to navigate new social scenarios as they plan to leave a supervised home environment for college or the workforce.

Gender identification: Male, female, other

In one study, 77.8% of birth-sex males with ASD said they identified as men, and 67.1% of birth-sex females identified as women,  compared with 93.1% of birth-sex males and 87.3% of birth-sex females without ASD. Many of the remaining individuals with ASD reported a transgender, genderqueer, or other gender identity.⁵⁸ Some studies have found females with ASD report a gay or bisexual orientation more often than males with ASD.^59–61

Adolescents and young adults may be exploring their changing bodies, sexual preferences, and gender roles, and as for all people at this age, these roles emerge against a backdrop of familial and societal expectations that may or may not be concordant with their own projected path regarding sexuality and reproductive health.⁶²

Having the conversation

As with non-ASD patients, a thorough sexual history should be collected via open-ended questions when possible to determine types of sexual activity and partners.

Education of the patient, alongside caregivers and parents, about healthy and safe sexual practices, screening for sexual violence, and hormonal and nonhormonal contraception options are important components of care for this population.

CAREGIVER STRESS MAY PERSIST INTO PATIENT’S ADULTHOOD

Caregiver burden is a monumental concern for parents or others who may have lifelong primary responsibility for these neurodiverse adults.⁶³ Family members may feel isolated and may feel they have encountered many barriers to services.⁶⁴ Remaining sensitive, knowledgeable, and inquisitive about the types of support that are needed may help forge a trusting relationship between the provider and the family.

Parents of children with ASD have been reported to experience worse physical and emotional health than parents whose children do not have developmental disabilities.^63,65 These disparities have been found to persist  as their children enter adolescence and young adulthood.^66,67 Parents of children with ASD report more anxiety, depression, and distress compared with parents of children without ASD,⁶³ and parents themselves may be affected by ASD symptoms, which has been linked to increased parenting stress.⁶⁸ Some studies have found blunted cortisol responses,^63,69,70 and some,⁷¹ but not all,⁶³ have found elevated blood pressure in caregivers of children with developmental disabilities. Headache, backache, muscle soreness, and fatigue may also be commonly reported.⁶⁷

In our experience, caregivers are tremendously appreciative when provided connections to adult ASD services and support systems as their child ages. The school system and other formal support systems often assist until the time of transition into adulthood. This transition can be stressful for the adolescent and family alike, and informal support systems such as friends and family may become increasingly crucial, particularly if the adolescent still lives at home.^72,73

The affected young adult’s unmet needs, as perceived by the caregiver, have been found to be significantly associated with caregiver burden, whereas the severity of the adult patient’s ASD symptoms has not.⁶⁶ Therefore, it may be helpful to ask caregivers whether they perceive any unmet needs, regardless of the clinician’s perception of the severity of the patient’s ASD symptoms. Providing support to address these needs, particularly those relating to the child’s mood disorders, communication, social needs, safety, and daytime activities, may be the domains of support that most effectively reduce the caregiver burden in this population.⁶⁶

Caregiver positivity, lower stress levels, and increased social support, particularly in the form of friends and family members providing no-cost assistance to caregivers whose children do not live independently,⁷⁴ have been linked to better outcomes for caregivers.^70,74,75 Rigorous studies that examine caregiver burden as individuals with ASD enter mid- and late-adulthood are limited.

THE ROLE OF THE INTERNIST IN CARING FOR ADULTS WITH AUTISM

A major challenge for many adults with ASD is the transition from services provided during childhood to those provided in adulthood. While children with autism have subspecialty providers who diagnose and manage their condition, including developmental-behavioral pediatricians, pediatric neurologists, and child psychiatrists, adults with autism may have fewer options.

Autism centers are becoming more available across the nation, and many provide care across the life span. However, depending on a patient’s needs, the primary care provider may need to manage residual symptoms as the patient transitions from pediatric to adult care, ultimately deciding when and where to refer the patient.

The patient’s family should pay close attention to function and mood around the time the patient leaves the structure of high school, and they should build rapport with a primary care provider they can turn to if problems persist or arise. Referrals for behavioral therapy and for social work, job training, and vocational support can greatly benefit patients as they transition to young adulthood. Referrals and suggestions for social support can also help caregivers.

Medical care

Deciding when and how to medicate the patient for symptoms of autism and related behaviors necessitates consideration of the patient’s impairment, side effects of the medication, and the impact medications may have on the patient’s other conditions. Disordered eating, mood problems, anxiety, and attention-deficit/hyperactivity disorder should be considered, and, as in all patients, regular screenings of mental health status should be conducted.^76,77

Comorbid medical conditions may cause worsening of a patient’s known behavioral symptoms or may precipitate new behaviors or aggression as a result of pain or discomfort, particularly in patients with limited speech. A change in stereotypes or increased irritability warrants a thoughtful investigation for a cause other than ASD before adding or increasing behavioral medications. Common comorbid conditions include gastrointestinal distress, most commonly constipation and diarrhea in an idiopathic ASD population, with increasing ASD symptom severity correlating with increased odds of a gastrointestinal problem.⁷⁸ Allergies, sleep disorders, seizures, and other psychiatric conditions are also frequent.⁷⁹

Preventive care, including vaccinations, should be given as scheduled. Caregivers and patients can be reminded if needed that vaccines do not cause or worsen autism, and vaccination is intended to improve the safety of the patient and those around them, protecting against potentially life-threatening disease. Regular dental care visits, particularly for patients who are using medications that may affect tooth or gingival health,⁸⁰ and regular visits to an optometrist or ophthalmologist for screening of vision are also advised.

Adverse effects. Weight gain and metabolic syndrome are common adverse effects of medications used for behavioral management, and the primary care physician may uncover diabetes, cardiac disorders, and hyperlipidemia. Patients with ASD may be particularly sensitive to the effects of medications and therefore may require a lower dose or a slower titration than other patients. Working with a behavioral team, careful weaning of psychiatric medications to the minimum needed is strongly recommended whenever possible.⁸¹

TAKE-HOME POINTS

As more adults with autism enter society, they may require varying levels of support from the healthcare community to ensure that therapeutic gains from childhood persist, allowing them to achieve maximal functional potential.

Adults with ASD may have a high, normal, or low IQ and intellectual capability. Knowledge of this and of the patient’s symptom severity and presence of comorbid psychiatric and other health conditions can help the clinician guide the patient to appropriate social services and pharmacologic treatments.

Individualized support in the workplace, as well as education regarding sexual health, can help improve outcomes for affected individuals.

Caregiver burden for individuals with autism can be high, but it can be mitigated by social support.

Further research regarding appropriate diagnostic instruments in adulthood and appropriate treatments for impairing autism-related symptoms across the life span may be particularly helpful in supporting this patient population.

Autism spectrum disorder (ASD) has increased significantly over the past 40 years. Even in the past 2 decades, the prevalence increased from 6.7 per 1,000 in 2000¹ to 14.6 per 1,000 in 2012—1 in 59 people.² Of those with ASD, 46% have an intelligence quotient (IQ) greater than 85, meaning they are of average or above-average intelligence.¹

See related editorial

As more children with autism become adults, understanding this condition across the life span grows paramount. While many studies have focused on understanding how diagnosis and treatment can help young children, few have focused on adults with autism and how primary care teams can better assist these individuals. However, this is changing, with studies of the benefits of employment programs and pharmacologic treatment, and reproductive health needs of adults with ASD. Here we provide an updated review of ASD in adult patients.

NO MORE ASPERGER SYNDROME— IT’S ON THE SPECTRUM NOW

As the scientific understanding of autism has expanded, revisions in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5),³ published in 2013, have paralleled these advances. For many adult patients with autism who were evaluated as children, these revisions have led to changes in diagnosis and available services.

In the previous edition (DSM-IV-TR, published in 2000),⁴ autistic disorder and Asperger syndrome were separate (Table 1). However, DSM-5 lumped autistic disorder and Asperger disorder together under the diagnosis of ASD; this leaves it to the clinician to specify whether the patient with ASD has accompanying intellectual or language impairment and to assign a level of severity based on communication deficits and restrictive behaviors.

The shift in diagnosis was worrisome for some, particularly for clinicians treating patients with DSM-IV Asperger syndrome, who lost this diagnostic label. Concerns that patients with Asperger syndrome may not meet the DSM-5 criteria for ASD were validated by a systematic review showing that only 50% to 75% of patients with DSM-IV autistic disorder, Asperger syndrome, or pervasive developmental disorder not otherwise specified (PDD-NOS) met the DSM-5 criteria for ASD.⁵ Most of those who no longer met the criteria for ASD carried a DSM-IV diagnosis of Asperger syndrome or PDD-NOS or had an IQ over 70.⁵ Nevertheless, these individuals may struggle with impairing symptoms related to repetitive behaviors or communication or may be affected by learning or social-emotional disabilities. Additionally, even if they meet the criteria for ASD, some may identify with the Asperger syndrome label and fear they will be stigmatized should they be classified as having the more general ASD.^6,7

Although future revisions to the DSM may include further changes in classification, grouping adults with ASD according to their functional and cognitive ability may allow for pragmatic characterization of their needs. At least 3 informal groupings of autistic adults have been described that integrate cognitive ability and independence⁸:

• Those with low cognitive and social abilities, who need lifelong support
• Those with midrange cognitive and social limitations but who can complete their work in special education classes; they often find employment in supervised workshops or other work with repetitive tasks
• Those who have greater cognitive ability and some social skills; they may proceed to college and employment and live independently.

UNCERTAIN PROGNOSIS

Prognostication for people with ASD remains an area of research. Some adults experience a reduction in symptoms as they age, with significant improvements in speech and, sometimes, modest improvements in restrictive and repetitive behaviors.^9,10

Nevertheless, autism remains a lifelong disorder for many. Adults may still require significant support and may experience impairment, particularly in social interaction.¹⁰ In longitudinal studies, only 15% to 27% of patients with ASD are characterized as having a positive outcome (often defined as variables related to independent function, near-normal relationships, employment, or a quantified reduction in core symptoms), and many experience significant dependency into adulthood.^10–13

IQ has been cited as a possible prognostic factor,^10,13 with an IQ below 70 associated with poorer outcome, although an IQ above 70 does not necessarily confer a positive outcome. Less-severe impairment in speech at baseline in early childhood also suggests better outcomes in adulthood.¹⁰

As we see more adults with autism, studies that include both children and adults, such as the Longitudinal European Autism Cohort, will be important to characterize the natural history, comorbidities, and genetics of ASD and may help provide more specific predictors of disease course into adulthood.¹⁴

While many patients are recognized as having autism in early to mid-childhood, some adults may not receive a formal diagnosis until much later in life. Those with fluent language and normal-range IQ are likely to be overlooked.¹⁵ People with ASD may have had mild symptoms during childhood that did not impair their functioning until demands of daily life exceeded their capacities in adulthood. Alternatively, parents of a child with newly diagnosed ASD may realize that they themselves or another adult family member also show signs of it.

The UK National Institute of Health and Care Excellence suggests that assessment should be considered if the patient meets psychiatric diagnostic criteria and one of the following:

• Difficulty obtaining or sustaining employment or education
• Difficulty initiating or sustaining social relationships
• Past or current contact with mental health or learning disability services
• History of a neurodevelopmental or mental health disorder.^15,16

Currently, diagnosis typically involves a multidisciplinary approach, with psychiatric assessment, neuropsychological testing, and speech and language evaluation.¹⁷ Providers may need to refer patients for these services, sometimes at the patient’s request, if previous mental health misdiagnoses are suspected, if patients report symptoms or impairment consistent with ASD, or if benefits, services, or accommodations, such as a coach in the workplace, are needed.

Diagnosing ASD in adults can be difficult, given that the gold-standard diagnostic tests such as the Autism Diagnostic Observation Schedule-2 (ADOS-2)¹⁸ and the Autism Diagnostic Interview-Revised (ADI-R)¹⁹ are typically used to diagnose autism in children. However, Module 4 in the ADOS-2 was developed for adolescents and older patients with fluent language and has shown at least moderate power to distinguish adults with ASD from those without ASD.^18,20

An initial psychiatric assessment should include a thorough history taken from the patient and, if applicable, the patient’s caregiver, as well as a psychiatric interview of the patient. Neuropsychological testing should include evaluation of cognitive function, social functioning (using the ADOS-2 for adults without intellectual disability, the ADI-R, or both), and adaptive functioning (using the Vineland Adaptive Behavior Scales, second edition²¹).

Evaluation of speech and language is particularly important in patients with limited language ability and should include both expressive and receptive language abilities. Serial testing every few years, as is often recommended in childhood, may help establish the pattern of impairment over time.

Comorbid psychiatric disorders are common

Many people with ASD also have other psychiatric disorders,^17,22 which clinicians should keep in mind when seeing an adult seeking evaluation for ASD.

Attention-deficit/hyperactivity disorder is present at higher rates in patients of average intellectual function with ASD than in the general population.²³

Anxiety disorders, including obsessive-compulsive disorder, were found to often coexist with autism in a sample of adults with autism without intellectual disability,^24,25 and approximately 40% of youths with ASD have at least 1 comorbid anxiety disorder.²⁶

Mood disorders are also prevalent in adults with ASD, with a small study showing that 70% of adults with DSM-IV Asperger syndrome had at least 1 depressive episode in their lifetime.²⁷

BEHAVIORAL AND PHARMACOLOGIC THERAPIES FOR THE ADULT PATIENT

Services and medications for adults with ASD are discussed below. These will vary by individual, and services available may vary by region.

Historically, vocational and social outcomes have been poor for adults with ASD. It is estimated that most larger universities may be home to 100 to 300 students with ASD. To combat isolation, the University of California, Los Angeles, the University of Alabama, and others provide special support services, including group social activities such as board games and individual coaching.⁸ Nevertheless, half of the students with autism who attend institutions of higher learning leave without completing their intended degree.²⁹ Many still struggle to establish meaningful friendships or romantic relationships.²⁹

Planning for a transition of care

Healthcare transition planning is important  but is strikingly underused.³⁰ Individual providers, including adult psychiatrists, vary in their level of training and comfort in diagnosing, treating, and monitoring adults with autism. Youths with ASD are half as likely to receive healthcare transition services as other youths with special healthcare needs.³¹

Pediatric providers, including pediatric psychiatrists, developmental behavioral specialists, and pediatric neurologists, may be best equipped to treat young adult patients or to refer patients to appropriate generalists and specialists comfortable with autism-specific transition of care. The question of eligibility for services is important to patients and families during the transition period, with many parents and professionals unaware of services available to them.³² Receiving adequate transition services is enabled by having a medical home during childhood—that is, a comprehensive, centralized medical record, culturally competent care, interaction with schools, and patient access to clear, unbiased information.³¹

Ideally, in our experience, transitioning should be discussed well before the child ages out of the pediatric provider’s practice. If necessary, healthcare transition services should include 4 components:

• Discussing the switch to a new physician who treats adults
• Discussing changing healthcare needs as an adult
• Planning insurance coverage as an adult
• Encouragement by the physician for the child to take age-appropriate responsibility for his or her healthcare.^31,33

Tools such as the Got Transition checklist from the National Health Care Transition Center can provide support during this process.³⁴

Other services

Other services provided as an extension or adjunct to the medical home in early adulthood may include customized vocational or employment training, specialized mentorship or support in a college setting, housing support, and psychological services.³⁵

Community-based programs that emphasize leisure have been shown to improve participants’ independence and quality of life.³⁶ Similarly, participants in programs that emphasized supported employment, with a job coach, on-the-job support, collaboration with the participant’s larger social support network, and selection of tasks to match an individual’s abilities and strengths, demonstrated improved cognitive performance, particularly executive functioning,³⁷ and employment.^38,39 These programs work best for patients who have mild to moderate symptoms.^37,39

Patients with symptoms that are more severe may do better in a residential program. Many of these programs maintain an emphasis on vocational and social skills development. One such long-standing program is Bittersweet Farms, a rural farming community in Ohio for adults with ASD, where individuals with moderate to low function live in a group setting, with emphasis on scheduled, meaningful work including horticulture, animal care, carpentry; and activities of daily living.⁴⁰

Studies of patients across the autism spectrum have generally found better outcomes when vocational support is given, but larger and randomized studies are needed to characterize how to best support these individuals after they leave high school.⁴¹

Psychological services such as applied behavioral therapy, social cognition training, cognitive behavioral therapy, and mindfulness training may be particularly useful in adults.^42–44

Some versions of applied behavioral therapy, such as the Early Start Denver Model,⁴⁵ have been found to be cost-effective and offset some expenses in the care of children with autism, using play-based and relationship-based interventions to promote development across domains while reducing symptoms.

In randomized controlled trials, modified cognitive behavioral therapy⁴³ and mindfulness⁴⁴ were shown to reduce symptoms of anxiety, obsessive-compulsive disorder, and depression.

Dialectical behavior therapy, used to find a balance between accepting oneself and desiring to change, may help in some circumstances to regulate emotions and reduce reactivity and lability, although large randomized clinical trials have not been conducted in the ASD population.⁴⁶

Drug therapy

Medications may be appropriate to manage symptoms or comorbid conditions in adults with ASD. Over 75% adults with ASD have been found to use psychotropic medications.⁴⁷ However, although these drugs have been approved for treating behaviors commonly associated with ASD, none of them provide definitive treatment for this disorder, and they have not been rigorously tested or approved for use in adults with ASD.⁴⁸

Irritability and aggression associated with ASD can be treated with risperidone (approved for children over age 5), aripiprazole (approved for children ages 6–17), clozapine, or haloperidol.⁴⁹

Aberrant social behavior can be treated with risperidone.⁵⁰ Treatments under investigation include oxytocin and secretin.⁴⁹

While no approved drug has been shown to improve social communication,⁵¹ balovaptan, a vasopressin V1a agonist, has shown potential and has been granted breakthrough status by the US Food and Drug Administration for treating challenging behaviors in adults, with additional studies ongoing in children.^52,53

Repetitive behaviors, if the patient finds them impairing, can be managed with selective serotonin reuptake inhibitors.⁴⁹

Much more study of drug therapy in adults with ASD is needed to fully understand the best approaches to psychotropic medication use, including appropriate classes and effective dosage, in this population.

SEX: UNEXPLORED TERRITORY

The reproductive health needs of people with autism remain largely underexplored.⁵⁴ Historically, individuals with ASD were thought to have little interest in sexual activity or parenthood, owing to the nature of the core symptoms of the disorder. This has been shown to be untrue, particularly as studies on this topic began to engage in direct interviews with people with ASD, rather than solely gathering information from caregivers or parents. The findings reinforce the importance of broaching this component of health in this population, for the following reasons:

Adults with ASD are at increased risk of sexual victimization, with nearly 4 out of 5 reporting unwanted sexual advances, coercion, or rape.⁵⁵

They have a smaller pool of knowledge with respect to sexual health. They report⁵⁶ that they learned about sex from television and from “making mistakes.” They use fewer sources. They are less likely to speak to peers and figures of authority to gain knowledge about sexually transmitted infections, sexual behaviors, and contraception. And they are more likely to use forms of nonsocial media, such as television, for information.⁵⁵

They report more concerns about the future with respect to sexual behavior, suggesting the need for targeted sexual education programs.⁵⁶

College-age young adults with ASD who misread communication may be particularly affected by Title IX, which requires schools to promptly investigate reports of sexual harassment and sexual assault, should they struggle to comport themselves appropriately.⁵⁷ Early and frank conversations about issues of consent and appropriate displays of interest and affection may better equip youth to navigate new social scenarios as they plan to leave a supervised home environment for college or the workforce.

Gender identification: Male, female, other

In one study, 77.8% of birth-sex males with ASD said they identified as men, and 67.1% of birth-sex females identified as women,  compared with 93.1% of birth-sex males and 87.3% of birth-sex females without ASD. Many of the remaining individuals with ASD reported a transgender, genderqueer, or other gender identity.⁵⁸ Some studies have found females with ASD report a gay or bisexual orientation more often than males with ASD.^59–61

Adolescents and young adults may be exploring their changing bodies, sexual preferences, and gender roles, and as for all people at this age, these roles emerge against a backdrop of familial and societal expectations that may or may not be concordant with their own projected path regarding sexuality and reproductive health.⁶²

Having the conversation

As with non-ASD patients, a thorough sexual history should be collected via open-ended questions when possible to determine types of sexual activity and partners.

Education of the patient, alongside caregivers and parents, about healthy and safe sexual practices, screening for sexual violence, and hormonal and nonhormonal contraception options are important components of care for this population.

CAREGIVER STRESS MAY PERSIST INTO PATIENT’S ADULTHOOD

Caregiver burden is a monumental concern for parents or others who may have lifelong primary responsibility for these neurodiverse adults.⁶³ Family members may feel isolated and may feel they have encountered many barriers to services.⁶⁴ Remaining sensitive, knowledgeable, and inquisitive about the types of support that are needed may help forge a trusting relationship between the provider and the family.

Parents of children with ASD have been reported to experience worse physical and emotional health than parents whose children do not have developmental disabilities.^63,65 These disparities have been found to persist  as their children enter adolescence and young adulthood.^66,67 Parents of children with ASD report more anxiety, depression, and distress compared with parents of children without ASD,⁶³ and parents themselves may be affected by ASD symptoms, which has been linked to increased parenting stress.⁶⁸ Some studies have found blunted cortisol responses,^63,69,70 and some,⁷¹ but not all,⁶³ have found elevated blood pressure in caregivers of children with developmental disabilities. Headache, backache, muscle soreness, and fatigue may also be commonly reported.⁶⁷

In our experience, caregivers are tremendously appreciative when provided connections to adult ASD services and support systems as their child ages. The school system and other formal support systems often assist until the time of transition into adulthood. This transition can be stressful for the adolescent and family alike, and informal support systems such as friends and family may become increasingly crucial, particularly if the adolescent still lives at home.^72,73

The affected young adult’s unmet needs, as perceived by the caregiver, have been found to be significantly associated with caregiver burden, whereas the severity of the adult patient’s ASD symptoms has not.⁶⁶ Therefore, it may be helpful to ask caregivers whether they perceive any unmet needs, regardless of the clinician’s perception of the severity of the patient’s ASD symptoms. Providing support to address these needs, particularly those relating to the child’s mood disorders, communication, social needs, safety, and daytime activities, may be the domains of support that most effectively reduce the caregiver burden in this population.⁶⁶

Caregiver positivity, lower stress levels, and increased social support, particularly in the form of friends and family members providing no-cost assistance to caregivers whose children do not live independently,⁷⁴ have been linked to better outcomes for caregivers.^70,74,75 Rigorous studies that examine caregiver burden as individuals with ASD enter mid- and late-adulthood are limited.

THE ROLE OF THE INTERNIST IN CARING FOR ADULTS WITH AUTISM

A major challenge for many adults with ASD is the transition from services provided during childhood to those provided in adulthood. While children with autism have subspecialty providers who diagnose and manage their condition, including developmental-behavioral pediatricians, pediatric neurologists, and child psychiatrists, adults with autism may have fewer options.

Autism centers are becoming more available across the nation, and many provide care across the life span. However, depending on a patient’s needs, the primary care provider may need to manage residual symptoms as the patient transitions from pediatric to adult care, ultimately deciding when and where to refer the patient.

The patient’s family should pay close attention to function and mood around the time the patient leaves the structure of high school, and they should build rapport with a primary care provider they can turn to if problems persist or arise. Referrals for behavioral therapy and for social work, job training, and vocational support can greatly benefit patients as they transition to young adulthood. Referrals and suggestions for social support can also help caregivers.

Medical care

Deciding when and how to medicate the patient for symptoms of autism and related behaviors necessitates consideration of the patient’s impairment, side effects of the medication, and the impact medications may have on the patient’s other conditions. Disordered eating, mood problems, anxiety, and attention-deficit/hyperactivity disorder should be considered, and, as in all patients, regular screenings of mental health status should be conducted.^76,77

Comorbid medical conditions may cause worsening of a patient’s known behavioral symptoms or may precipitate new behaviors or aggression as a result of pain or discomfort, particularly in patients with limited speech. A change in stereotypes or increased irritability warrants a thoughtful investigation for a cause other than ASD before adding or increasing behavioral medications. Common comorbid conditions include gastrointestinal distress, most commonly constipation and diarrhea in an idiopathic ASD population, with increasing ASD symptom severity correlating with increased odds of a gastrointestinal problem.⁷⁸ Allergies, sleep disorders, seizures, and other psychiatric conditions are also frequent.⁷⁹

Preventive care, including vaccinations, should be given as scheduled. Caregivers and patients can be reminded if needed that vaccines do not cause or worsen autism, and vaccination is intended to improve the safety of the patient and those around them, protecting against potentially life-threatening disease. Regular dental care visits, particularly for patients who are using medications that may affect tooth or gingival health,⁸⁰ and regular visits to an optometrist or ophthalmologist for screening of vision are also advised.

Adverse effects. Weight gain and metabolic syndrome are common adverse effects of medications used for behavioral management, and the primary care physician may uncover diabetes, cardiac disorders, and hyperlipidemia. Patients with ASD may be particularly sensitive to the effects of medications and therefore may require a lower dose or a slower titration than other patients. Working with a behavioral team, careful weaning of psychiatric medications to the minimum needed is strongly recommended whenever possible.⁸¹

TAKE-HOME POINTS

As more adults with autism enter society, they may require varying levels of support from the healthcare community to ensure that therapeutic gains from childhood persist, allowing them to achieve maximal functional potential.

Adults with ASD may have a high, normal, or low IQ and intellectual capability. Knowledge of this and of the patient’s symptom severity and presence of comorbid psychiatric and other health conditions can help the clinician guide the patient to appropriate social services and pharmacologic treatments.

Individualized support in the workplace, as well as education regarding sexual health, can help improve outcomes for affected individuals.

Caregiver burden for individuals with autism can be high, but it can be mitigated by social support.

Further research regarding appropriate diagnostic instruments in adulthood and appropriate treatments for impairing autism-related symptoms across the life span may be particularly helpful in supporting this patient population.

Autism spectrum disorder (ASD) has increased significantly over the past 40 years. Even in the past 2 decades, the prevalence increased from 6.7 per 1,000 in 2000¹ to 14.6 per 1,000 in 2012—1 in 59 people.² Of those with ASD, 46% have an intelligence quotient (IQ) greater than 85, meaning they are of average or above-average intelligence.¹

See related editorial

As more children with autism become adults, understanding this condition across the life span grows paramount. While many studies have focused on understanding how diagnosis and treatment can help young children, few have focused on adults with autism and how primary care teams can better assist these individuals. However, this is changing, with studies of the benefits of employment programs and pharmacologic treatment, and reproductive health needs of adults with ASD. Here we provide an updated review of ASD in adult patients.

NO MORE ASPERGER SYNDROME— IT’S ON THE SPECTRUM NOW

As the scientific understanding of autism has expanded, revisions in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5),³ published in 2013, have paralleled these advances. For many adult patients with autism who were evaluated as children, these revisions have led to changes in diagnosis and available services.

In the previous edition (DSM-IV-TR, published in 2000),⁴ autistic disorder and Asperger syndrome were separate (Table 1). However, DSM-5 lumped autistic disorder and Asperger disorder together under the diagnosis of ASD; this leaves it to the clinician to specify whether the patient with ASD has accompanying intellectual or language impairment and to assign a level of severity based on communication deficits and restrictive behaviors.

The shift in diagnosis was worrisome for some, particularly for clinicians treating patients with DSM-IV Asperger syndrome, who lost this diagnostic label. Concerns that patients with Asperger syndrome may not meet the DSM-5 criteria for ASD were validated by a systematic review showing that only 50% to 75% of patients with DSM-IV autistic disorder, Asperger syndrome, or pervasive developmental disorder not otherwise specified (PDD-NOS) met the DSM-5 criteria for ASD.⁵ Most of those who no longer met the criteria for ASD carried a DSM-IV diagnosis of Asperger syndrome or PDD-NOS or had an IQ over 70.⁵ Nevertheless, these individuals may struggle with impairing symptoms related to repetitive behaviors or communication or may be affected by learning or social-emotional disabilities. Additionally, even if they meet the criteria for ASD, some may identify with the Asperger syndrome label and fear they will be stigmatized should they be classified as having the more general ASD.^6,7

Although future revisions to the DSM may include further changes in classification, grouping adults with ASD according to their functional and cognitive ability may allow for pragmatic characterization of their needs. At least 3 informal groupings of autistic adults have been described that integrate cognitive ability and independence⁸:

• Those with low cognitive and social abilities, who need lifelong support
• Those with midrange cognitive and social limitations but who can complete their work in special education classes; they often find employment in supervised workshops or other work with repetitive tasks
• Those who have greater cognitive ability and some social skills; they may proceed to college and employment and live independently.

UNCERTAIN PROGNOSIS

Prognostication for people with ASD remains an area of research. Some adults experience a reduction in symptoms as they age, with significant improvements in speech and, sometimes, modest improvements in restrictive and repetitive behaviors.^9,10

Nevertheless, autism remains a lifelong disorder for many. Adults may still require significant support and may experience impairment, particularly in social interaction.¹⁰ In longitudinal studies, only 15% to 27% of patients with ASD are characterized as having a positive outcome (often defined as variables related to independent function, near-normal relationships, employment, or a quantified reduction in core symptoms), and many experience significant dependency into adulthood.^10–13

IQ has been cited as a possible prognostic factor,^10,13 with an IQ below 70 associated with poorer outcome, although an IQ above 70 does not necessarily confer a positive outcome. Less-severe impairment in speech at baseline in early childhood also suggests better outcomes in adulthood.¹⁰

As we see more adults with autism, studies that include both children and adults, such as the Longitudinal European Autism Cohort, will be important to characterize the natural history, comorbidities, and genetics of ASD and may help provide more specific predictors of disease course into adulthood.¹⁴

While many patients are recognized as having autism in early to mid-childhood, some adults may not receive a formal diagnosis until much later in life. Those with fluent language and normal-range IQ are likely to be overlooked.¹⁵ People with ASD may have had mild symptoms during childhood that did not impair their functioning until demands of daily life exceeded their capacities in adulthood. Alternatively, parents of a child with newly diagnosed ASD may realize that they themselves or another adult family member also show signs of it.

The UK National Institute of Health and Care Excellence suggests that assessment should be considered if the patient meets psychiatric diagnostic criteria and one of the following:

• Difficulty obtaining or sustaining employment or education
• Difficulty initiating or sustaining social relationships
• Past or current contact with mental health or learning disability services
• History of a neurodevelopmental or mental health disorder.^15,16

Currently, diagnosis typically involves a multidisciplinary approach, with psychiatric assessment, neuropsychological testing, and speech and language evaluation.¹⁷ Providers may need to refer patients for these services, sometimes at the patient’s request, if previous mental health misdiagnoses are suspected, if patients report symptoms or impairment consistent with ASD, or if benefits, services, or accommodations, such as a coach in the workplace, are needed.

Diagnosing ASD in adults can be difficult, given that the gold-standard diagnostic tests such as the Autism Diagnostic Observation Schedule-2 (ADOS-2)¹⁸ and the Autism Diagnostic Interview-Revised (ADI-R)¹⁹ are typically used to diagnose autism in children. However, Module 4 in the ADOS-2 was developed for adolescents and older patients with fluent language and has shown at least moderate power to distinguish adults with ASD from those without ASD.^18,20

An initial psychiatric assessment should include a thorough history taken from the patient and, if applicable, the patient’s caregiver, as well as a psychiatric interview of the patient. Neuropsychological testing should include evaluation of cognitive function, social functioning (using the ADOS-2 for adults without intellectual disability, the ADI-R, or both), and adaptive functioning (using the Vineland Adaptive Behavior Scales, second edition²¹).

Evaluation of speech and language is particularly important in patients with limited language ability and should include both expressive and receptive language abilities. Serial testing every few years, as is often recommended in childhood, may help establish the pattern of impairment over time.

Comorbid psychiatric disorders are common

Many people with ASD also have other psychiatric disorders,^17,22 which clinicians should keep in mind when seeing an adult seeking evaluation for ASD.

Attention-deficit/hyperactivity disorder is present at higher rates in patients of average intellectual function with ASD than in the general population.²³

Anxiety disorders, including obsessive-compulsive disorder, were found to often coexist with autism in a sample of adults with autism without intellectual disability,^24,25 and approximately 40% of youths with ASD have at least 1 comorbid anxiety disorder.²⁶

Mood disorders are also prevalent in adults with ASD, with a small study showing that 70% of adults with DSM-IV Asperger syndrome had at least 1 depressive episode in their lifetime.²⁷

BEHAVIORAL AND PHARMACOLOGIC THERAPIES FOR THE ADULT PATIENT

Services and medications for adults with ASD are discussed below. These will vary by individual, and services available may vary by region.

Historically, vocational and social outcomes have been poor for adults with ASD. It is estimated that most larger universities may be home to 100 to 300 students with ASD. To combat isolation, the University of California, Los Angeles, the University of Alabama, and others provide special support services, including group social activities such as board games and individual coaching.⁸ Nevertheless, half of the students with autism who attend institutions of higher learning leave without completing their intended degree.²⁹ Many still struggle to establish meaningful friendships or romantic relationships.²⁹

Planning for a transition of care

Healthcare transition planning is important  but is strikingly underused.³⁰ Individual providers, including adult psychiatrists, vary in their level of training and comfort in diagnosing, treating, and monitoring adults with autism. Youths with ASD are half as likely to receive healthcare transition services as other youths with special healthcare needs.³¹

Pediatric providers, including pediatric psychiatrists, developmental behavioral specialists, and pediatric neurologists, may be best equipped to treat young adult patients or to refer patients to appropriate generalists and specialists comfortable with autism-specific transition of care. The question of eligibility for services is important to patients and families during the transition period, with many parents and professionals unaware of services available to them.³² Receiving adequate transition services is enabled by having a medical home during childhood—that is, a comprehensive, centralized medical record, culturally competent care, interaction with schools, and patient access to clear, unbiased information.³¹

Ideally, in our experience, transitioning should be discussed well before the child ages out of the pediatric provider’s practice. If necessary, healthcare transition services should include 4 components:

• Discussing the switch to a new physician who treats adults
• Discussing changing healthcare needs as an adult
• Planning insurance coverage as an adult
• Encouragement by the physician for the child to take age-appropriate responsibility for his or her healthcare.^31,33

Tools such as the Got Transition checklist from the National Health Care Transition Center can provide support during this process.³⁴

Other services

Other services provided as an extension or adjunct to the medical home in early adulthood may include customized vocational or employment training, specialized mentorship or support in a college setting, housing support, and psychological services.³⁵

Community-based programs that emphasize leisure have been shown to improve participants’ independence and quality of life.³⁶ Similarly, participants in programs that emphasized supported employment, with a job coach, on-the-job support, collaboration with the participant’s larger social support network, and selection of tasks to match an individual’s abilities and strengths, demonstrated improved cognitive performance, particularly executive functioning,³⁷ and employment.^38,39 These programs work best for patients who have mild to moderate symptoms.^37,39

Patients with symptoms that are more severe may do better in a residential program. Many of these programs maintain an emphasis on vocational and social skills development. One such long-standing program is Bittersweet Farms, a rural farming community in Ohio for adults with ASD, where individuals with moderate to low function live in a group setting, with emphasis on scheduled, meaningful work including horticulture, animal care, carpentry; and activities of daily living.⁴⁰

Studies of patients across the autism spectrum have generally found better outcomes when vocational support is given, but larger and randomized studies are needed to characterize how to best support these individuals after they leave high school.⁴¹

Psychological services such as applied behavioral therapy, social cognition training, cognitive behavioral therapy, and mindfulness training may be particularly useful in adults.^42–44

Some versions of applied behavioral therapy, such as the Early Start Denver Model,⁴⁵ have been found to be cost-effective and offset some expenses in the care of children with autism, using play-based and relationship-based interventions to promote development across domains while reducing symptoms.

In randomized controlled trials, modified cognitive behavioral therapy⁴³ and mindfulness⁴⁴ were shown to reduce symptoms of anxiety, obsessive-compulsive disorder, and depression.

Dialectical behavior therapy, used to find a balance between accepting oneself and desiring to change, may help in some circumstances to regulate emotions and reduce reactivity and lability, although large randomized clinical trials have not been conducted in the ASD population.⁴⁶

Drug therapy

Medications may be appropriate to manage symptoms or comorbid conditions in adults with ASD. Over 75% adults with ASD have been found to use psychotropic medications.⁴⁷ However, although these drugs have been approved for treating behaviors commonly associated with ASD, none of them provide definitive treatment for this disorder, and they have not been rigorously tested or approved for use in adults with ASD.⁴⁸

Irritability and aggression associated with ASD can be treated with risperidone (approved for children over age 5), aripiprazole (approved for children ages 6–17), clozapine, or haloperidol.⁴⁹

Aberrant social behavior can be treated with risperidone.⁵⁰ Treatments under investigation include oxytocin and secretin.⁴⁹

While no approved drug has been shown to improve social communication,⁵¹ balovaptan, a vasopressin V1a agonist, has shown potential and has been granted breakthrough status by the US Food and Drug Administration for treating challenging behaviors in adults, with additional studies ongoing in children.^52,53

Repetitive behaviors, if the patient finds them impairing, can be managed with selective serotonin reuptake inhibitors.⁴⁹

Much more study of drug therapy in adults with ASD is needed to fully understand the best approaches to psychotropic medication use, including appropriate classes and effective dosage, in this population.

SEX: UNEXPLORED TERRITORY

The reproductive health needs of people with autism remain largely underexplored.⁵⁴ Historically, individuals with ASD were thought to have little interest in sexual activity or parenthood, owing to the nature of the core symptoms of the disorder. This has been shown to be untrue, particularly as studies on this topic began to engage in direct interviews with people with ASD, rather than solely gathering information from caregivers or parents. The findings reinforce the importance of broaching this component of health in this population, for the following reasons:

Adults with ASD are at increased risk of sexual victimization, with nearly 4 out of 5 reporting unwanted sexual advances, coercion, or rape.⁵⁵

They have a smaller pool of knowledge with respect to sexual health. They report⁵⁶ that they learned about sex from television and from “making mistakes.” They use fewer sources. They are less likely to speak to peers and figures of authority to gain knowledge about sexually transmitted infections, sexual behaviors, and contraception. And they are more likely to use forms of nonsocial media, such as television, for information.⁵⁵

They report more concerns about the future with respect to sexual behavior, suggesting the need for targeted sexual education programs.⁵⁶

College-age young adults with ASD who misread communication may be particularly affected by Title IX, which requires schools to promptly investigate reports of sexual harassment and sexual assault, should they struggle to comport themselves appropriately.⁵⁷ Early and frank conversations about issues of consent and appropriate displays of interest and affection may better equip youth to navigate new social scenarios as they plan to leave a supervised home environment for college or the workforce.

Gender identification: Male, female, other

In one study, 77.8% of birth-sex males with ASD said they identified as men, and 67.1% of birth-sex females identified as women,  compared with 93.1% of birth-sex males and 87.3% of birth-sex females without ASD. Many of the remaining individuals with ASD reported a transgender, genderqueer, or other gender identity.⁵⁸ Some studies have found females with ASD report a gay or bisexual orientation more often than males with ASD.^59–61

Adolescents and young adults may be exploring their changing bodies, sexual preferences, and gender roles, and as for all people at this age, these roles emerge against a backdrop of familial and societal expectations that may or may not be concordant with their own projected path regarding sexuality and reproductive health.⁶²

Having the conversation

As with non-ASD patients, a thorough sexual history should be collected via open-ended questions when possible to determine types of sexual activity and partners.

Education of the patient, alongside caregivers and parents, about healthy and safe sexual practices, screening for sexual violence, and hormonal and nonhormonal contraception options are important components of care for this population.

CAREGIVER STRESS MAY PERSIST INTO PATIENT’S ADULTHOOD

Caregiver burden is a monumental concern for parents or others who may have lifelong primary responsibility for these neurodiverse adults.⁶³ Family members may feel isolated and may feel they have encountered many barriers to services.⁶⁴ Remaining sensitive, knowledgeable, and inquisitive about the types of support that are needed may help forge a trusting relationship between the provider and the family.

Parents of children with ASD have been reported to experience worse physical and emotional health than parents whose children do not have developmental disabilities.^63,65 These disparities have been found to persist  as their children enter adolescence and young adulthood.^66,67 Parents of children with ASD report more anxiety, depression, and distress compared with parents of children without ASD,⁶³ and parents themselves may be affected by ASD symptoms, which has been linked to increased parenting stress.⁶⁸ Some studies have found blunted cortisol responses,^63,69,70 and some,⁷¹ but not all,⁶³ have found elevated blood pressure in caregivers of children with developmental disabilities. Headache, backache, muscle soreness, and fatigue may also be commonly reported.⁶⁷

In our experience, caregivers are tremendously appreciative when provided connections to adult ASD services and support systems as their child ages. The school system and other formal support systems often assist until the time of transition into adulthood. This transition can be stressful for the adolescent and family alike, and informal support systems such as friends and family may become increasingly crucial, particularly if the adolescent still lives at home.^72,73

The affected young adult’s unmet needs, as perceived by the caregiver, have been found to be significantly associated with caregiver burden, whereas the severity of the adult patient’s ASD symptoms has not.⁶⁶ Therefore, it may be helpful to ask caregivers whether they perceive any unmet needs, regardless of the clinician’s perception of the severity of the patient’s ASD symptoms. Providing support to address these needs, particularly those relating to the child’s mood disorders, communication, social needs, safety, and daytime activities, may be the domains of support that most effectively reduce the caregiver burden in this population.⁶⁶

Caregiver positivity, lower stress levels, and increased social support, particularly in the form of friends and family members providing no-cost assistance to caregivers whose children do not live independently,⁷⁴ have been linked to better outcomes for caregivers.^70,74,75 Rigorous studies that examine caregiver burden as individuals with ASD enter mid- and late-adulthood are limited.

THE ROLE OF THE INTERNIST IN CARING FOR ADULTS WITH AUTISM

A major challenge for many adults with ASD is the transition from services provided during childhood to those provided in adulthood. While children with autism have subspecialty providers who diagnose and manage their condition, including developmental-behavioral pediatricians, pediatric neurologists, and child psychiatrists, adults with autism may have fewer options.

Autism centers are becoming more available across the nation, and many provide care across the life span. However, depending on a patient’s needs, the primary care provider may need to manage residual symptoms as the patient transitions from pediatric to adult care, ultimately deciding when and where to refer the patient.

The patient’s family should pay close attention to function and mood around the time the patient leaves the structure of high school, and they should build rapport with a primary care provider they can turn to if problems persist or arise. Referrals for behavioral therapy and for social work, job training, and vocational support can greatly benefit patients as they transition to young adulthood. Referrals and suggestions for social support can also help caregivers.

Medical care

Deciding when and how to medicate the patient for symptoms of autism and related behaviors necessitates consideration of the patient’s impairment, side effects of the medication, and the impact medications may have on the patient’s other conditions. Disordered eating, mood problems, anxiety, and attention-deficit/hyperactivity disorder should be considered, and, as in all patients, regular screenings of mental health status should be conducted.^76,77

Comorbid medical conditions may cause worsening of a patient’s known behavioral symptoms or may precipitate new behaviors or aggression as a result of pain or discomfort, particularly in patients with limited speech. A change in stereotypes or increased irritability warrants a thoughtful investigation for a cause other than ASD before adding or increasing behavioral medications. Common comorbid conditions include gastrointestinal distress, most commonly constipation and diarrhea in an idiopathic ASD population, with increasing ASD symptom severity correlating with increased odds of a gastrointestinal problem.⁷⁸ Allergies, sleep disorders, seizures, and other psychiatric conditions are also frequent.⁷⁹

Preventive care, including vaccinations, should be given as scheduled. Caregivers and patients can be reminded if needed that vaccines do not cause or worsen autism, and vaccination is intended to improve the safety of the patient and those around them, protecting against potentially life-threatening disease. Regular dental care visits, particularly for patients who are using medications that may affect tooth or gingival health,⁸⁰ and regular visits to an optometrist or ophthalmologist for screening of vision are also advised.

Adverse effects. Weight gain and metabolic syndrome are common adverse effects of medications used for behavioral management, and the primary care physician may uncover diabetes, cardiac disorders, and hyperlipidemia. Patients with ASD may be particularly sensitive to the effects of medications and therefore may require a lower dose or a slower titration than other patients. Working with a behavioral team, careful weaning of psychiatric medications to the minimum needed is strongly recommended whenever possible.⁸¹

TAKE-HOME POINTS

As more adults with autism enter society, they may require varying levels of support from the healthcare community to ensure that therapeutic gains from childhood persist, allowing them to achieve maximal functional potential.

Adults with ASD may have a high, normal, or low IQ and intellectual capability. Knowledge of this and of the patient’s symptom severity and presence of comorbid psychiatric and other health conditions can help the clinician guide the patient to appropriate social services and pharmacologic treatments.

Individualized support in the workplace, as well as education regarding sexual health, can help improve outcomes for affected individuals.

Caregiver burden for individuals with autism can be high, but it can be mitigated by social support.

Further research regarding appropriate diagnostic instruments in adulthood and appropriate treatments for impairing autism-related symptoms across the life span may be particularly helpful in supporting this patient population.

Eating disorders are debilitating biopsychosocial illnesses associated with serious medical illness and a high risk of death.¹

Primary care physicians are often the first to see young women who have these problems, diagnose them, and start their evaluation and treatment.^2–4 Many patients require acute medical interventions as well as long-term care for chronic medical issues. Therefore, primary care physicians play essential front-line and long-term roles in the multidisciplinary treatment team.

DEFINITIONS OF EATING DISORDERS HAVE CHANGED

Several problems existed in the category of eating disorders in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-4) and in the DSM-4 Text Revision (DSM-4-TR). These problems have been addressed in the fifth edition (DSM-5), released in 2013.⁵

One problem in the earlier editions was that many patients referred for treatment of eating disorders—more than 50% in one study⁶—did not meet the criteria for anorexia nervosa or bulimia nervosa and thus had to be categorized as having “eating disorder not otherwise specified.” Further, the earlier editions did not recognize that young children and adolescent males can be affected.⁷

Eating disorders are now recognized as an equal-opportunity disease, with all ethnic and socioeconomic groups affected. Children can run into medical trouble with even a small amount of weight loss or falling off the growth curve. Moreover, children and adolescents do not “experience” their bodies in the same way adults do; they may lack the vocabulary for eating-disorder thoughts.

For these reasons, the definitions of eating disorders have changed in the DSM-5.⁵

Anorexia nervosa. Older editions of the DSM listed amenorrhea as a criterion. This has been eliminated in DSM-5, since amenorrhea does not necessarily predict medical risk or treatment outcome; also, it is not applicable to males or premenorrheal girls and postmenopausal women.⁸ In addition, the requirement of low weight is now defined in the context of “age, sex, developmental trajectory, and physical health,” rather than the old threshold of 85% of expected weight.⁹

What remains unchanged is that anorexia nervosa is still characterized by self-starvation in order to maintain an abnormally low body weight, along with an intense fear of being fat and a disturbed self-image.

Bulimia nervosa. In both the old and the new editions of the DSM, bulimia nervosa is characterized by episodes of binge eating followed by inappropriate compensatory behaviors to avoid weight gain, such as vomiting, laxative abuse, diuretic abuse, and overexercise. In DSM-5, bulimia nervosa no longer has subtypes and requires only one binge per week with compensatory behavior, for at least 3 months. This change was based on the finding that there is no clear difference in psychopathology or treatment outcome between patients with one and two binge-purge episodes a week.¹⁰

“Eating disorder not otherwise specified” was a wastebasket category, lumping all those who did not meet the criteria for anorexia nervosa or bulimia nervosa or who did not neatly fit into a specific category.¹⁰ In DSM-5, subcategories were designed to help distinguish different treatment needs and outcomes between various subtypes.

Binge-eating disorder, one of the new subcategories, is characterized by binge eating without inappropriate compensatory behaviors.⁹ Patients with binge-eating disorder are often obese, have greater functional impairment, and are more likely to develop components of metabolic syndrome than obese patients without eating disorders.¹¹

Avoidant/restrictive food intake disorder is another new DSM-5 diagnosis, characterized by failure to meet nutritional needs for reasons other than weight control. Reasons include disinterest in eating, dislike of sensory characteristics of food, or avoidance of consequences of eating. This disorder replaces the category “feeding disorder of infancy or early childhood,” since the condition can also occur in adolescents and adults.¹²

Other new diagnoses are:

• Atypical anorexia nervosa (if the patient is not underweight)
• Purging disorder
• Subthreshold bulimia nervosa (if the patient has < 1 episode per week or has had them for < 3 months)
• Subthreshold binge eating disorder (< 1 time a week or < 3 months)
• Night eating syndrome
• Pica and rumination disorder.

Regardless of the diagnostic label, the medical evaluation and treatment of anyone with an eating disorder should be tailored to the specific behaviors of the eating disorder. Medical complications can be subdivided into those from starvation, from purging, and from refeeding.

MEDICAL COMPLICATIONS OF STARVATION

Cardiovascular effects of starvation

Malnutrition and starvation have multiple adverse effects on the heart.

Electrophysiologic effects. Sinus bradycardia (< 60 bpm) and hypotension are common cardiac manifestations of starvation.¹³ Bradycardia has been attributed to an adaptive increase in parasympathetic vagal tone.¹⁴ QTc prolongation is also seen in patients with malnutrition.¹⁵

Together, these electrocardiographic abnormalities predispose the patient to ventricular arrhythmia and sudden cardiac death.¹⁶ The risk of ventricular arrhythmia is particularly relevant when treating psychiatric symptoms, since antipsychotics and tricyclic antidepressants are among several drug classes that can cause further QTc prolongation (Table 1).^17,18

In patients with QTc prolongation, bradycardia, or both, the standard of care involves acute hospitalization for refeeding using continuous telemetric monitoring until normal rhythm is restored and the heart rate is above 40 at night and 50 by day.^4,19

Structural changes. Starvation also causes structural changes in the heart. Loss of lean body mass can reduce cardiac muscle mass, compromise cardiac output, and lead to mitral valve prolapse.²⁰ These changes are fully reversible with restored nutrition and regaining of heart mass.^21,22

Effects of starvation on the brain

Starvation can affect brain structure and cognitive function. Undernourished patients have reduced volumes of white and gray matter, a change that can occur within months. Cortical volumes may increase with weight gain, but a reduction in gray matter volume may not be completely reversible.²³

Furthermore, starvation impairs cognitive functions that are needed to stop eating-disorder behaviors; namely, decision-making, emotional control, regulation of appetite, and reward path-ways. Therefore, undernourished patients may not have sufficient insight into the disease to be able to make the best choices for recovery. This finding lends support for using the Maudsley method in adolescents, in which parents take control of their child’s eating until the child can maintain a healthy weight.²⁴

Gastrointestinal consequences of starvation

Patients with malnutrition have prolonged gastric emptying and colonic transit time with solid foods.²⁵ They often complain of early satiety, abdominal pain, bloating, and constipation, all symptoms that complicate the refeeding process. A prokinetic such as metoclopramide (Reglan), given 1 hour before meals and at bedtime, may provide some relief from gastrointestinal symptoms.²⁶

Patients may also experience transient lactose or fructose intolerance after prolonged starvation. Taking a lactase supplement (eg, Lactaid 1–10 tabs) before consuming dairy products and dextrose (contained in candies such as Smarties) before eating fruit or fructose-containing foods can sometimes partially relieve symptoms. In general, gastrointestinal function returns over time as nutritional status improves.

Patients with severe or prolonged starvation can develop steatosis accompanied by elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In reports of starvation-induced steatosis, liver enzyme levels rapidly normalize with nutritional rehabilitation.²⁷

Endocrine consequences of starvation

Amenorrhea. Dysregulation of the hypothalamic-pituitary-gonadal axis is a major endocrine complication of nutritional in-sufficiency. Weight loss disrupts the normal pulsatile secretion of gonadotropin-releasing hormone, reduces secretion of luteinizing hormone and follicle-stimulating hormone, and decreases estrogen levels.²⁸ Leptin deficiency likely plays a role in suppressing gonadotropin secretion with subsequent development of amenorrhea. With weight gain, levels of leptin and gonadotropins normalize and menstruation eventually returns.^29,30

Hypothyroidism. Starvation can also lead to dysregulation of the hypothalamic-pituitary-thyroid axis. Typically, the concentration of triiodothyronine (T3) is reduced, the ratio of thyroxine (T4) to T3 is elevated, and thyroid-stimulating hormone (TSH) is close to or within the normal range, creating a euthyroid sick syndrome. In eating disorders, this thyroid disturbance is a result of starvation and resolves with weight restoration. Therefore, thyroid hormone replacement therapy is not medically indicated.²⁸

Osteoporosis. Amenorrhea resulting from low estrogen levels in undernourished patients can raise the risk of osteoporosis and fractures, particularly in patients with a low body mass index. Osteopenia results from a negative balance between bone deposition and resorption.

Lack of bone deposition can be especially problematic when disordered eating occurs during peak bone mass development, ie, ages 11 to 14 for girls, and ages 15 to 17 for boys.^31,32 Even a 5% to 10% decrease in bone deposition can result in significant risk of osteopenia.³³ However, after age 30, bone resorption is a greater contributor.³⁴

Does hormone therapy correct bone loss? Given the association between estrogen deficiency and bone loss, estrogen supplementation was expected to be an effective treatment for bone loss in patients with eating disorders.³⁵ Also, the restoration of menses through hormone replacement may give underweight patients a false sense of achieving a “healthy” weight.³⁶

Golden et al³⁷ prospectively studied 50 adolescents and found no significant difference in bone mineral density at 1 year of follow-up between patients treated with estrogen and those who received only standard nutritional therapy. However, increased bone mineral density was achieved in adolescents with anorexia nervosa treated with transdermally administered estrogen dosed to mimic physiologic pubertal levels.³⁸

Klibanski et al³⁹ found that hormone therapy resulted in a 4% gain in bone density in an extremely low-weight subset of women with anorexia nervosa (< 70% of ideal body weight), whereas similar patients in the control group lost 20%. However, in all groups, only weight gain correlated with bone gain in women who were within 70% of their ideal body weight.

Divasta et al⁴⁰ evaluated 60 girls and women ages 13 to 27 with anorexia nervosa, randomized to receive either placebo or dehydroepiandrosterone combined with an estrogen-progestin oral contraceptive, and followed for 18 months. As in the study by Klibanski et al,³⁹ bone loss was prevented in the treatment group, but significant bone gain occurred only in the context of weight gain.

The bottom line is that only weight gain has resulted in significant increases in bone density in patients with anorexia nervosa, and hormone therapy without weight gain has not been shown to increase bone density effectively in this population. Although calcium and vitamin D in oral therapeutic doses through foods or through supplementation are required for bone gain, the combination is not enough to augment bone density in the absence of weight gain.³⁷ Although not curative, weight gain is currently the best option for treating bone loss, and no single pharmacologic treatment is effective.

COMPLICATIONS OF PURGING

Oral complications of purging

Patients who purge by vomiting are at risk of complications from exposure of the esophagus, pharynx, and mouth to acidic gastric contents.

Dental problems. Over time, contact with gastric acid wears down enamel on the lingual and occlusal surfaces of teeth, resulting in dental caries and periodontal disease. Until they can give up purging, patients should be instructed to rinse with mouthwash or water immediately after vomiting to reduce the acidity in the mouth.^41,42 We recommend that patients not brush their teeth after vomiting, because brushing can deliver acid to otherwise unreachable surfaces and thus worsen tooth erosion. For patients who are determined to brush after vomiting, a bicarbonate toothpaste might mitigate harm.⁴²

Sialadenosis (hypertrophy of the salivary glands) is another consequence of repeated vomiting, with elevated salivary amylase. Both the size of the glands and the salivary amylase level generally normalize on their own after vomiting is stopped, but parotitis can take up to a year to resolve. Similar to smoker’s cough, parotitis may acutely worsen when the patient abruptly stops vomiting and may worsen before it improves.

To reduce discomfort, patients can use hot compresses or sugarless hard candies.⁴⁴ However, the latter should not be substituted as a chronic habit in a patient with disordered eating. Patients need to be reassured that the swelling is not permanent, since they often interpret it as having fat cheeks (the “chipmunk sign”).

Hypokalemia, metabolic alkalosis, renal dysfunction

Chronic vomiting can cause electrolyte and acid-base imbalances, the most worrisome of which is hypokalemia. With repeated vomiting, loss of potassium and gastric acid causes metabolic alkalosis with hypokalemia, hypochloremia, and hypomagnesemia. Loss of water and the resultant volume contraction activates the renin-angiotensin-aldosterone system, and elevated aldosterone further decreases serum potassium.

In patients with eating disorders, who often have other factors contributing to electrolyte imbalance, vomiting-induced hypokalemia heightens the risk of cardiac arrhythmias.⁴³

Hypokalemia can also cause rhabdomyolysis and kidney damage.^41,43 Prolonged hypokalemia and reduced kidney perfusion in the setting of volume depletion causes acute kidney injury and impaired concentrating ability of the renal tubules. Hypovolemia can cause prerenal azotemia and increases the risk for nephrolithiasis and nephrocalcinosis.^44,45

When a patient stops vomiting, elevated aldosterone from prior hypovolemia results in water retention and can manifest in significant edema associated with hypochloremic alkalosis. This condition, known as pseudo-Bartter syndrome, usually resolves without treatment. In the meantime, salt restriction and leg elevation can help reduce edema.²⁶

Laxative abuse: A mode of purging

Many patients with eating disorders abuse laxatives to lose weight or to prevent weight gain. Believing that laxatives will prevent calorie absorption, patients commonly take them to compensate for caloric intake (eg, during a binge episode). The immediate weight loss, albeit artificial, is highly reinforcing for an eating-disorder patient. In some cases, patients with eating disorders also abuse laxatives to self-treat the constipation that results from chronic starvation.⁴⁶

Over time, tolerance to laxatives develops, and patients use increasingly larger doses. This can lead to activation of the renin-angiotensin-aldosterone system.⁴⁷ Patients interpret the resultant edema as true weight gain and again take laxatives to get rid of it. If laxatives are stopped abruptly, the patient may need inpatient and outpatient support for the resultant fluid shifts.

Gastrointestinal complications of laxative abuse include reflex hypofunction of the bowel, malabsorption, steatorrhea, and gastrointestinal bleeding.⁴⁷ Reflex hypofunction during laxative withdrawal is a consequence of the bowel becoming tolerant of laxatives.⁴⁸ Cathartic colon syndrome is a rare complication characterized by loss of the normal haustral markings and slowed or absent peristalsis in segments of the colon.⁴⁹

Systemically, the major risk of laxative abuse relates to electrolyte and acid-base imbalance. Loss of potassium and water in the stool can cause hypokalemia and metabolic alkalosis.⁴⁸ The disturbances caused by laxative abuse are similar to those caused by vomiting and diuretic use and have the same treatment.

The most important component of treating laxative abuse is giving patients realistic expectations to help them tolerate temporary discomfort and to help manage the edema and fluid shifts that can happen acutely with shifting of fluid into the intracellular space. In extreme cases, this may need to be managed in the hospital. To help relieve the initial anxiety, doctors should emphasize that any bloating the patient experiences is not true weight gain and will go away within a few days to weeks. In addition, explaining that laxatives reduce nutrient absorption only minimally may lessen the temptation to resume taking them.⁴⁸

Diuretic abuse: Another form of purging

Diuretic abuse is yet another mode of purging, with its own set of medical complications. Like laxatives, diuretics are not effective weight-loss agents, and the weight reduction they cause is only temporary.

As with vomiting, there is a compensatory activation of the renin-angiotensin-aldosterone system, and therefore subsequent fluid intake will lead to water retention, which encourages further diuretic use.⁴¹ Diuretics can also contribute to hypokalemia, hypomagnesemia, hypochloremia, and metabolic alkalosis.

Ipecac abuse can lead to heart failure

Ipecac syrup has long been used to induce vomiting, but this practice has become much less common since ipecac has become harder to obtain in the United States.⁵⁰ The emetine base contained in ipecac binds irreversibly to cardiac and skeletal muscle. With continued use, irreversible cardiomyopathy develops and can lead to heart failure. Treatment should include supportive care and immediate cessation of ipecac use.

Diabetic patients may skip insulin to lose weight

Patients with diabetes, especially those with type 1 that begins in childhood, are at greater risk of eating disorders over time.⁵¹ They may withhold insulin to lose weight, a practice referred to in the nonmedical literature as “diabulimia,” and they seem particularly more likely to develop bulimia nervosa than those without diabetes.⁵²

The medical prognosis is poor for patients with diabetes who develop eating disorders and do not receive intensive treatment.⁵¹ In addition, if a diabetic patient on an insulin pump becomes depressed in addition to having an eating disorder, careful monitoring for suicidal thoughts and a rapid follow-up with mental health services are in order.

REFEEDING SYNDROME

When refeeding is started, a high glucose load stimulates insulin secretion, resulting in cellular uptake of phosphorus along with potassium, magnesium, and glucose. In addition, total body phosphorus is depleted by the increased demand for adenosine triphosphate and 2,3-diphosphoglycerate for cellular metabolism.

When liver enzyme levels increase, the astute clinician will closely monitor the patient for evidence of refeeding syndrome. In a child, adolescent, or young adult, the standard of care is inpatient monitoring for acute stabilization.^4,19

Hypophosphatemia is the hallmark of refeeding syndrome, although hypomagnesemia, hypokalemia, and hypoglycemia can also occur.⁵³ In addition, sodium and water retention can lead to fluid overload, with shifting of fluid into the intracellular space, resulting in dependent edema.

Cardiovascular complications are the most worrisome manifestations of refeeding syndrome. Electrolyte shifts and increased fluid volume can cause arrhythmias and heart failure. Furthermore, severely undernourished patients may have reduced myocardial mass as well as electrocardiographic abnormalities associated with starvation, which further increase their vulnerability to electrolyte shifts and fluid retention during refeeding.¹⁵

Other manifestations of refeeding syndrome include delirium, seizures, rhabdomyolysis, and respiratory failure. In the most extreme cases, refeeding syndrome causes sudden death.⁵³

Fortunately, refeeding syndrome is easily preventable and treatable when recognized early. Electrolytes and cardiovascular and renal function must be carefully monitored, especially during the first week of nutritional restoration.⁵³ In patients with extremely low body mass (< 70% of ideal body weight) or with precipitous weight loss, close monitoring of the complete metabolic panel including electrolytes, AST, ALT, calcium, magnesium, and phosphorus may be required to detect changes that can affect cardiac status. Specific suggestions for refeeding are discussed below and in Table 2.⁴⁵

ACUTE CARE OF PATIENTS WITH EATING DISORDERS

Refeeding in the inpatient setting

The decision to hospitalize an eating-disorder patient is based on the current or potential risk of serious medical complications and the likelihood of success at home. Medical criteria for hospital admission are outlined in Table 3.^4,54

In refeeding undernourished patients, the challenge is to maximize weight gain while preventing refeeding syndrome. Undernourished patients are generally hypometabolic at baseline but become hypermetabolic once refeeding begins.

How many calories should refeeding start with? The traditional principle of “start low and go slow” has been recently challenged.⁵⁵ Starting at 1,200 kcal/day or less in the typical patient can result in failure to gain weight or even in weight loss in the first week of refeeding.⁵⁶ The goal is to achieve a weight gain of 0.2 kg/day while the patient is in the hospital. Thus, we start higher, and to date we have seen no cases of life-threatening refeeding syndrome. In all patients who need hospitalization or who are beginning the refeeding process as outpatients, caloric intake should be started at 1,500 to 2,000 kcal/day.^45,57 However, for exceptionally low-weight patients, intake may be started lower.

In Australia, patients are started at 1,900 kcal/day.⁵⁶ All patients in one program there receive nasogastric feeding initially in an intensive care unit and then are moved to a regular nursing floor where they graduate to full oral feeding as they improve cardiovascularly and behaviorally. In the United States, some programs use nasogastric feeding at night for caloric restoration; our program and others use nasogastric feeding as a behavioral modification strategy for patients who refuse food or supplements by mouth.

Phosphorus supplementation. Many centers give phosphorus supplements preventively. In our center, we give potassium phosphate (Neutra-Phos) 500 mg orally twice daily for 5 days, and we have seen no life-threatening cases of refeeding syndrome with that regimen. Other centers give phosphorus supplements in a dose of 250 mg orally twice a day for 5 days, while still others only supplement phosphorus reactively once a deficit has been identified. The latter method requires daily blood draws for monitoring and is reactive rather than proactive. Further studies can help clarify the optimal dosing and timing of phosphorus supplementation.

Managing fluid balance. Fluid-loading these patients may tip them over the edge into refeeding syndrome. Except in cases of shock, patients with eating disorders should not be given intravenous fluids, as it is safer to rehydrate and feed them orally. Electrolyte imbalances can be corrected orally with no need for intravenous supplementation. To avoid fluid overload, fluids can be started at 1,500 mL to 2,000 mL per day, with strict monitoring of intake and output. Fluids are liberalized if ALT and AST levels remain normal and to gradually correct orthostatic hypotension; caloric fluids are ideal to help address energy needs and improve bradycardia.

Laboratory monitoring. On admission, a urinalysis, complete blood cell count, complete metabolic panel, TSH, erythrocyte sedimentation rate, serum magnesium, and phosphorus should be obtained.²⁶ In addition, continuous electrocardiographic recording should begin on admission.⁴⁵ Inpatient use of a telemetry bed helps identify extreme tachycardia with arrhythmia, as well as profound bradycardia.^45,56

Some protocols call for daily laboratory monitoring, although that degree of testing is less cost-effective. If initial results are normal, clinical judgment can be used on when to repeat laboratory evaluation. For instance, patients with edema require repeat complete metabolic panels to assess for elevated ALT and AST, electrolyte imbalances, and other abnormalities.

Signs of refeeding syndrome include tachycardia, hepatosplenomegaly, peripheral edema, altered mental status, and electrolyte disturbances, specifically, acute or severe hypophosphatemia or hypokalemia.^26,45 If refeeding syndrome is suspected, the rate of caloric intake should be reduced or not advanced, fluid intake should be urgently reassessed for volume overload, and supportive care with close monitoring should be provided.

KNOWLEDGE SAVES LIVES

Eating disorders can lead to potentially life-threatening medical complications that require attentive care by the primary care clinician and subspecialist. Without thoughtful consideration, it is easy for even a caring medical team to unintentionally enable patients with these illnesses or to cause active harm in the case of underrecognized pathology.⁵⁸

Acute medical stabilization on an inpatient unit trained to recognize pathology and treat sequelae can be lifesaving. Arming patients and families with medical knowledge, as provided in the Academy for Eating Disorders’ brochure, “Critical Points for Early Recognition and Medical Risk Management in the Care of Individuals with Eating Disorders”⁵⁹ can help save patients’ lives.

Eating disorders are debilitating biopsychosocial illnesses associated with serious medical illness and a high risk of death.¹

Primary care physicians are often the first to see young women who have these problems, diagnose them, and start their evaluation and treatment.^2–4 Many patients require acute medical interventions as well as long-term care for chronic medical issues. Therefore, primary care physicians play essential front-line and long-term roles in the multidisciplinary treatment team.

DEFINITIONS OF EATING DISORDERS HAVE CHANGED

Several problems existed in the category of eating disorders in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-4) and in the DSM-4 Text Revision (DSM-4-TR). These problems have been addressed in the fifth edition (DSM-5), released in 2013.⁵

One problem in the earlier editions was that many patients referred for treatment of eating disorders—more than 50% in one study⁶—did not meet the criteria for anorexia nervosa or bulimia nervosa and thus had to be categorized as having “eating disorder not otherwise specified.” Further, the earlier editions did not recognize that young children and adolescent males can be affected.⁷

Eating disorders are now recognized as an equal-opportunity disease, with all ethnic and socioeconomic groups affected. Children can run into medical trouble with even a small amount of weight loss or falling off the growth curve. Moreover, children and adolescents do not “experience” their bodies in the same way adults do; they may lack the vocabulary for eating-disorder thoughts.

For these reasons, the definitions of eating disorders have changed in the DSM-5.⁵

Anorexia nervosa. Older editions of the DSM listed amenorrhea as a criterion. This has been eliminated in DSM-5, since amenorrhea does not necessarily predict medical risk or treatment outcome; also, it is not applicable to males or premenorrheal girls and postmenopausal women.⁸ In addition, the requirement of low weight is now defined in the context of “age, sex, developmental trajectory, and physical health,” rather than the old threshold of 85% of expected weight.⁹

What remains unchanged is that anorexia nervosa is still characterized by self-starvation in order to maintain an abnormally low body weight, along with an intense fear of being fat and a disturbed self-image.

Bulimia nervosa. In both the old and the new editions of the DSM, bulimia nervosa is characterized by episodes of binge eating followed by inappropriate compensatory behaviors to avoid weight gain, such as vomiting, laxative abuse, diuretic abuse, and overexercise. In DSM-5, bulimia nervosa no longer has subtypes and requires only one binge per week with compensatory behavior, for at least 3 months. This change was based on the finding that there is no clear difference in psychopathology or treatment outcome between patients with one and two binge-purge episodes a week.¹⁰

“Eating disorder not otherwise specified” was a wastebasket category, lumping all those who did not meet the criteria for anorexia nervosa or bulimia nervosa or who did not neatly fit into a specific category.¹⁰ In DSM-5, subcategories were designed to help distinguish different treatment needs and outcomes between various subtypes.

Binge-eating disorder, one of the new subcategories, is characterized by binge eating without inappropriate compensatory behaviors.⁹ Patients with binge-eating disorder are often obese, have greater functional impairment, and are more likely to develop components of metabolic syndrome than obese patients without eating disorders.¹¹

Avoidant/restrictive food intake disorder is another new DSM-5 diagnosis, characterized by failure to meet nutritional needs for reasons other than weight control. Reasons include disinterest in eating, dislike of sensory characteristics of food, or avoidance of consequences of eating. This disorder replaces the category “feeding disorder of infancy or early childhood,” since the condition can also occur in adolescents and adults.¹²

Other new diagnoses are:

• Atypical anorexia nervosa (if the patient is not underweight)
• Purging disorder
• Subthreshold bulimia nervosa (if the patient has < 1 episode per week or has had them for < 3 months)
• Subthreshold binge eating disorder (< 1 time a week or < 3 months)
• Night eating syndrome
• Pica and rumination disorder.

Regardless of the diagnostic label, the medical evaluation and treatment of anyone with an eating disorder should be tailored to the specific behaviors of the eating disorder. Medical complications can be subdivided into those from starvation, from purging, and from refeeding.

MEDICAL COMPLICATIONS OF STARVATION

Cardiovascular effects of starvation

Malnutrition and starvation have multiple adverse effects on the heart.

Electrophysiologic effects. Sinus bradycardia (< 60 bpm) and hypotension are common cardiac manifestations of starvation.¹³ Bradycardia has been attributed to an adaptive increase in parasympathetic vagal tone.¹⁴ QTc prolongation is also seen in patients with malnutrition.¹⁵

Together, these electrocardiographic abnormalities predispose the patient to ventricular arrhythmia and sudden cardiac death.¹⁶ The risk of ventricular arrhythmia is particularly relevant when treating psychiatric symptoms, since antipsychotics and tricyclic antidepressants are among several drug classes that can cause further QTc prolongation (Table 1).^17,18

In patients with QTc prolongation, bradycardia, or both, the standard of care involves acute hospitalization for refeeding using continuous telemetric monitoring until normal rhythm is restored and the heart rate is above 40 at night and 50 by day.^4,19

Structural changes. Starvation also causes structural changes in the heart. Loss of lean body mass can reduce cardiac muscle mass, compromise cardiac output, and lead to mitral valve prolapse.²⁰ These changes are fully reversible with restored nutrition and regaining of heart mass.^21,22

Effects of starvation on the brain

Starvation can affect brain structure and cognitive function. Undernourished patients have reduced volumes of white and gray matter, a change that can occur within months. Cortical volumes may increase with weight gain, but a reduction in gray matter volume may not be completely reversible.²³

Furthermore, starvation impairs cognitive functions that are needed to stop eating-disorder behaviors; namely, decision-making, emotional control, regulation of appetite, and reward path-ways. Therefore, undernourished patients may not have sufficient insight into the disease to be able to make the best choices for recovery. This finding lends support for using the Maudsley method in adolescents, in which parents take control of their child’s eating until the child can maintain a healthy weight.²⁴

Gastrointestinal consequences of starvation

Patients with malnutrition have prolonged gastric emptying and colonic transit time with solid foods.²⁵ They often complain of early satiety, abdominal pain, bloating, and constipation, all symptoms that complicate the refeeding process. A prokinetic such as metoclopramide (Reglan), given 1 hour before meals and at bedtime, may provide some relief from gastrointestinal symptoms.²⁶

Patients may also experience transient lactose or fructose intolerance after prolonged starvation. Taking a lactase supplement (eg, Lactaid 1–10 tabs) before consuming dairy products and dextrose (contained in candies such as Smarties) before eating fruit or fructose-containing foods can sometimes partially relieve symptoms. In general, gastrointestinal function returns over time as nutritional status improves.

Patients with severe or prolonged starvation can develop steatosis accompanied by elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In reports of starvation-induced steatosis, liver enzyme levels rapidly normalize with nutritional rehabilitation.²⁷

Endocrine consequences of starvation

Amenorrhea. Dysregulation of the hypothalamic-pituitary-gonadal axis is a major endocrine complication of nutritional in-sufficiency. Weight loss disrupts the normal pulsatile secretion of gonadotropin-releasing hormone, reduces secretion of luteinizing hormone and follicle-stimulating hormone, and decreases estrogen levels.²⁸ Leptin deficiency likely plays a role in suppressing gonadotropin secretion with subsequent development of amenorrhea. With weight gain, levels of leptin and gonadotropins normalize and menstruation eventually returns.^29,30

Hypothyroidism. Starvation can also lead to dysregulation of the hypothalamic-pituitary-thyroid axis. Typically, the concentration of triiodothyronine (T3) is reduced, the ratio of thyroxine (T4) to T3 is elevated, and thyroid-stimulating hormone (TSH) is close to or within the normal range, creating a euthyroid sick syndrome. In eating disorders, this thyroid disturbance is a result of starvation and resolves with weight restoration. Therefore, thyroid hormone replacement therapy is not medically indicated.²⁸

Osteoporosis. Amenorrhea resulting from low estrogen levels in undernourished patients can raise the risk of osteoporosis and fractures, particularly in patients with a low body mass index. Osteopenia results from a negative balance between bone deposition and resorption.

Lack of bone deposition can be especially problematic when disordered eating occurs during peak bone mass development, ie, ages 11 to 14 for girls, and ages 15 to 17 for boys.^31,32 Even a 5% to 10% decrease in bone deposition can result in significant risk of osteopenia.³³ However, after age 30, bone resorption is a greater contributor.³⁴

Does hormone therapy correct bone loss? Given the association between estrogen deficiency and bone loss, estrogen supplementation was expected to be an effective treatment for bone loss in patients with eating disorders.³⁵ Also, the restoration of menses through hormone replacement may give underweight patients a false sense of achieving a “healthy” weight.³⁶

Golden et al³⁷ prospectively studied 50 adolescents and found no significant difference in bone mineral density at 1 year of follow-up between patients treated with estrogen and those who received only standard nutritional therapy. However, increased bone mineral density was achieved in adolescents with anorexia nervosa treated with transdermally administered estrogen dosed to mimic physiologic pubertal levels.³⁸

Klibanski et al³⁹ found that hormone therapy resulted in a 4% gain in bone density in an extremely low-weight subset of women with anorexia nervosa (< 70% of ideal body weight), whereas similar patients in the control group lost 20%. However, in all groups, only weight gain correlated with bone gain in women who were within 70% of their ideal body weight.

Divasta et al⁴⁰ evaluated 60 girls and women ages 13 to 27 with anorexia nervosa, randomized to receive either placebo or dehydroepiandrosterone combined with an estrogen-progestin oral contraceptive, and followed for 18 months. As in the study by Klibanski et al,³⁹ bone loss was prevented in the treatment group, but significant bone gain occurred only in the context of weight gain.

The bottom line is that only weight gain has resulted in significant increases in bone density in patients with anorexia nervosa, and hormone therapy without weight gain has not been shown to increase bone density effectively in this population. Although calcium and vitamin D in oral therapeutic doses through foods or through supplementation are required for bone gain, the combination is not enough to augment bone density in the absence of weight gain.³⁷ Although not curative, weight gain is currently the best option for treating bone loss, and no single pharmacologic treatment is effective.

COMPLICATIONS OF PURGING

Oral complications of purging

Patients who purge by vomiting are at risk of complications from exposure of the esophagus, pharynx, and mouth to acidic gastric contents.

Dental problems. Over time, contact with gastric acid wears down enamel on the lingual and occlusal surfaces of teeth, resulting in dental caries and periodontal disease. Until they can give up purging, patients should be instructed to rinse with mouthwash or water immediately after vomiting to reduce the acidity in the mouth.^41,42 We recommend that patients not brush their teeth after vomiting, because brushing can deliver acid to otherwise unreachable surfaces and thus worsen tooth erosion. For patients who are determined to brush after vomiting, a bicarbonate toothpaste might mitigate harm.⁴²

Sialadenosis (hypertrophy of the salivary glands) is another consequence of repeated vomiting, with elevated salivary amylase. Both the size of the glands and the salivary amylase level generally normalize on their own after vomiting is stopped, but parotitis can take up to a year to resolve. Similar to smoker’s cough, parotitis may acutely worsen when the patient abruptly stops vomiting and may worsen before it improves.

To reduce discomfort, patients can use hot compresses or sugarless hard candies.⁴⁴ However, the latter should not be substituted as a chronic habit in a patient with disordered eating. Patients need to be reassured that the swelling is not permanent, since they often interpret it as having fat cheeks (the “chipmunk sign”).

Hypokalemia, metabolic alkalosis, renal dysfunction

Chronic vomiting can cause electrolyte and acid-base imbalances, the most worrisome of which is hypokalemia. With repeated vomiting, loss of potassium and gastric acid causes metabolic alkalosis with hypokalemia, hypochloremia, and hypomagnesemia. Loss of water and the resultant volume contraction activates the renin-angiotensin-aldosterone system, and elevated aldosterone further decreases serum potassium.

In patients with eating disorders, who often have other factors contributing to electrolyte imbalance, vomiting-induced hypokalemia heightens the risk of cardiac arrhythmias.⁴³

Hypokalemia can also cause rhabdomyolysis and kidney damage.^41,43 Prolonged hypokalemia and reduced kidney perfusion in the setting of volume depletion causes acute kidney injury and impaired concentrating ability of the renal tubules. Hypovolemia can cause prerenal azotemia and increases the risk for nephrolithiasis and nephrocalcinosis.^44,45

When a patient stops vomiting, elevated aldosterone from prior hypovolemia results in water retention and can manifest in significant edema associated with hypochloremic alkalosis. This condition, known as pseudo-Bartter syndrome, usually resolves without treatment. In the meantime, salt restriction and leg elevation can help reduce edema.²⁶

Laxative abuse: A mode of purging

Many patients with eating disorders abuse laxatives to lose weight or to prevent weight gain. Believing that laxatives will prevent calorie absorption, patients commonly take them to compensate for caloric intake (eg, during a binge episode). The immediate weight loss, albeit artificial, is highly reinforcing for an eating-disorder patient. In some cases, patients with eating disorders also abuse laxatives to self-treat the constipation that results from chronic starvation.⁴⁶

Over time, tolerance to laxatives develops, and patients use increasingly larger doses. This can lead to activation of the renin-angiotensin-aldosterone system.⁴⁷ Patients interpret the resultant edema as true weight gain and again take laxatives to get rid of it. If laxatives are stopped abruptly, the patient may need inpatient and outpatient support for the resultant fluid shifts.

Gastrointestinal complications of laxative abuse include reflex hypofunction of the bowel, malabsorption, steatorrhea, and gastrointestinal bleeding.⁴⁷ Reflex hypofunction during laxative withdrawal is a consequence of the bowel becoming tolerant of laxatives.⁴⁸ Cathartic colon syndrome is a rare complication characterized by loss of the normal haustral markings and slowed or absent peristalsis in segments of the colon.⁴⁹

Systemically, the major risk of laxative abuse relates to electrolyte and acid-base imbalance. Loss of potassium and water in the stool can cause hypokalemia and metabolic alkalosis.⁴⁸ The disturbances caused by laxative abuse are similar to those caused by vomiting and diuretic use and have the same treatment.

The most important component of treating laxative abuse is giving patients realistic expectations to help them tolerate temporary discomfort and to help manage the edema and fluid shifts that can happen acutely with shifting of fluid into the intracellular space. In extreme cases, this may need to be managed in the hospital. To help relieve the initial anxiety, doctors should emphasize that any bloating the patient experiences is not true weight gain and will go away within a few days to weeks. In addition, explaining that laxatives reduce nutrient absorption only minimally may lessen the temptation to resume taking them.⁴⁸

Diuretic abuse: Another form of purging

Diuretic abuse is yet another mode of purging, with its own set of medical complications. Like laxatives, diuretics are not effective weight-loss agents, and the weight reduction they cause is only temporary.

As with vomiting, there is a compensatory activation of the renin-angiotensin-aldosterone system, and therefore subsequent fluid intake will lead to water retention, which encourages further diuretic use.⁴¹ Diuretics can also contribute to hypokalemia, hypomagnesemia, hypochloremia, and metabolic alkalosis.

Ipecac abuse can lead to heart failure

Ipecac syrup has long been used to induce vomiting, but this practice has become much less common since ipecac has become harder to obtain in the United States.⁵⁰ The emetine base contained in ipecac binds irreversibly to cardiac and skeletal muscle. With continued use, irreversible cardiomyopathy develops and can lead to heart failure. Treatment should include supportive care and immediate cessation of ipecac use.

Diabetic patients may skip insulin to lose weight

Patients with diabetes, especially those with type 1 that begins in childhood, are at greater risk of eating disorders over time.⁵¹ They may withhold insulin to lose weight, a practice referred to in the nonmedical literature as “diabulimia,” and they seem particularly more likely to develop bulimia nervosa than those without diabetes.⁵²

The medical prognosis is poor for patients with diabetes who develop eating disorders and do not receive intensive treatment.⁵¹ In addition, if a diabetic patient on an insulin pump becomes depressed in addition to having an eating disorder, careful monitoring for suicidal thoughts and a rapid follow-up with mental health services are in order.

REFEEDING SYNDROME

When refeeding is started, a high glucose load stimulates insulin secretion, resulting in cellular uptake of phosphorus along with potassium, magnesium, and glucose. In addition, total body phosphorus is depleted by the increased demand for adenosine triphosphate and 2,3-diphosphoglycerate for cellular metabolism.

When liver enzyme levels increase, the astute clinician will closely monitor the patient for evidence of refeeding syndrome. In a child, adolescent, or young adult, the standard of care is inpatient monitoring for acute stabilization.^4,19

Hypophosphatemia is the hallmark of refeeding syndrome, although hypomagnesemia, hypokalemia, and hypoglycemia can also occur.⁵³ In addition, sodium and water retention can lead to fluid overload, with shifting of fluid into the intracellular space, resulting in dependent edema.

Cardiovascular complications are the most worrisome manifestations of refeeding syndrome. Electrolyte shifts and increased fluid volume can cause arrhythmias and heart failure. Furthermore, severely undernourished patients may have reduced myocardial mass as well as electrocardiographic abnormalities associated with starvation, which further increase their vulnerability to electrolyte shifts and fluid retention during refeeding.¹⁵

Other manifestations of refeeding syndrome include delirium, seizures, rhabdomyolysis, and respiratory failure. In the most extreme cases, refeeding syndrome causes sudden death.⁵³

Fortunately, refeeding syndrome is easily preventable and treatable when recognized early. Electrolytes and cardiovascular and renal function must be carefully monitored, especially during the first week of nutritional restoration.⁵³ In patients with extremely low body mass (< 70% of ideal body weight) or with precipitous weight loss, close monitoring of the complete metabolic panel including electrolytes, AST, ALT, calcium, magnesium, and phosphorus may be required to detect changes that can affect cardiac status. Specific suggestions for refeeding are discussed below and in Table 2.⁴⁵

ACUTE CARE OF PATIENTS WITH EATING DISORDERS

Refeeding in the inpatient setting

The decision to hospitalize an eating-disorder patient is based on the current or potential risk of serious medical complications and the likelihood of success at home. Medical criteria for hospital admission are outlined in Table 3.^4,54

In refeeding undernourished patients, the challenge is to maximize weight gain while preventing refeeding syndrome. Undernourished patients are generally hypometabolic at baseline but become hypermetabolic once refeeding begins.

How many calories should refeeding start with? The traditional principle of “start low and go slow” has been recently challenged.⁵⁵ Starting at 1,200 kcal/day or less in the typical patient can result in failure to gain weight or even in weight loss in the first week of refeeding.⁵⁶ The goal is to achieve a weight gain of 0.2 kg/day while the patient is in the hospital. Thus, we start higher, and to date we have seen no cases of life-threatening refeeding syndrome. In all patients who need hospitalization or who are beginning the refeeding process as outpatients, caloric intake should be started at 1,500 to 2,000 kcal/day.^45,57 However, for exceptionally low-weight patients, intake may be started lower.

In Australia, patients are started at 1,900 kcal/day.⁵⁶ All patients in one program there receive nasogastric feeding initially in an intensive care unit and then are moved to a regular nursing floor where they graduate to full oral feeding as they improve cardiovascularly and behaviorally. In the United States, some programs use nasogastric feeding at night for caloric restoration; our program and others use nasogastric feeding as a behavioral modification strategy for patients who refuse food or supplements by mouth.

Phosphorus supplementation. Many centers give phosphorus supplements preventively. In our center, we give potassium phosphate (Neutra-Phos) 500 mg orally twice daily for 5 days, and we have seen no life-threatening cases of refeeding syndrome with that regimen. Other centers give phosphorus supplements in a dose of 250 mg orally twice a day for 5 days, while still others only supplement phosphorus reactively once a deficit has been identified. The latter method requires daily blood draws for monitoring and is reactive rather than proactive. Further studies can help clarify the optimal dosing and timing of phosphorus supplementation.

Managing fluid balance. Fluid-loading these patients may tip them over the edge into refeeding syndrome. Except in cases of shock, patients with eating disorders should not be given intravenous fluids, as it is safer to rehydrate and feed them orally. Electrolyte imbalances can be corrected orally with no need for intravenous supplementation. To avoid fluid overload, fluids can be started at 1,500 mL to 2,000 mL per day, with strict monitoring of intake and output. Fluids are liberalized if ALT and AST levels remain normal and to gradually correct orthostatic hypotension; caloric fluids are ideal to help address energy needs and improve bradycardia.

Laboratory monitoring. On admission, a urinalysis, complete blood cell count, complete metabolic panel, TSH, erythrocyte sedimentation rate, serum magnesium, and phosphorus should be obtained.²⁶ In addition, continuous electrocardiographic recording should begin on admission.⁴⁵ Inpatient use of a telemetry bed helps identify extreme tachycardia with arrhythmia, as well as profound bradycardia.^45,56

Some protocols call for daily laboratory monitoring, although that degree of testing is less cost-effective. If initial results are normal, clinical judgment can be used on when to repeat laboratory evaluation. For instance, patients with edema require repeat complete metabolic panels to assess for elevated ALT and AST, electrolyte imbalances, and other abnormalities.

Signs of refeeding syndrome include tachycardia, hepatosplenomegaly, peripheral edema, altered mental status, and electrolyte disturbances, specifically, acute or severe hypophosphatemia or hypokalemia.^26,45 If refeeding syndrome is suspected, the rate of caloric intake should be reduced or not advanced, fluid intake should be urgently reassessed for volume overload, and supportive care with close monitoring should be provided.

KNOWLEDGE SAVES LIVES

Eating disorders can lead to potentially life-threatening medical complications that require attentive care by the primary care clinician and subspecialist. Without thoughtful consideration, it is easy for even a caring medical team to unintentionally enable patients with these illnesses or to cause active harm in the case of underrecognized pathology.⁵⁸

Acute medical stabilization on an inpatient unit trained to recognize pathology and treat sequelae can be lifesaving. Arming patients and families with medical knowledge, as provided in the Academy for Eating Disorders’ brochure, “Critical Points for Early Recognition and Medical Risk Management in the Care of Individuals with Eating Disorders”⁵⁹ can help save patients’ lives.

Eating disorders are debilitating biopsychosocial illnesses associated with serious medical illness and a high risk of death.¹

Primary care physicians are often the first to see young women who have these problems, diagnose them, and start their evaluation and treatment.^2–4 Many patients require acute medical interventions as well as long-term care for chronic medical issues. Therefore, primary care physicians play essential front-line and long-term roles in the multidisciplinary treatment team.

DEFINITIONS OF EATING DISORDERS HAVE CHANGED

Several problems existed in the category of eating disorders in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-4) and in the DSM-4 Text Revision (DSM-4-TR). These problems have been addressed in the fifth edition (DSM-5), released in 2013.⁵

One problem in the earlier editions was that many patients referred for treatment of eating disorders—more than 50% in one study⁶—did not meet the criteria for anorexia nervosa or bulimia nervosa and thus had to be categorized as having “eating disorder not otherwise specified.” Further, the earlier editions did not recognize that young children and adolescent males can be affected.⁷

Eating disorders are now recognized as an equal-opportunity disease, with all ethnic and socioeconomic groups affected. Children can run into medical trouble with even a small amount of weight loss or falling off the growth curve. Moreover, children and adolescents do not “experience” their bodies in the same way adults do; they may lack the vocabulary for eating-disorder thoughts.

For these reasons, the definitions of eating disorders have changed in the DSM-5.⁵

Anorexia nervosa. Older editions of the DSM listed amenorrhea as a criterion. This has been eliminated in DSM-5, since amenorrhea does not necessarily predict medical risk or treatment outcome; also, it is not applicable to males or premenorrheal girls and postmenopausal women.⁸ In addition, the requirement of low weight is now defined in the context of “age, sex, developmental trajectory, and physical health,” rather than the old threshold of 85% of expected weight.⁹

What remains unchanged is that anorexia nervosa is still characterized by self-starvation in order to maintain an abnormally low body weight, along with an intense fear of being fat and a disturbed self-image.

Bulimia nervosa. In both the old and the new editions of the DSM, bulimia nervosa is characterized by episodes of binge eating followed by inappropriate compensatory behaviors to avoid weight gain, such as vomiting, laxative abuse, diuretic abuse, and overexercise. In DSM-5, bulimia nervosa no longer has subtypes and requires only one binge per week with compensatory behavior, for at least 3 months. This change was based on the finding that there is no clear difference in psychopathology or treatment outcome between patients with one and two binge-purge episodes a week.¹⁰

“Eating disorder not otherwise specified” was a wastebasket category, lumping all those who did not meet the criteria for anorexia nervosa or bulimia nervosa or who did not neatly fit into a specific category.¹⁰ In DSM-5, subcategories were designed to help distinguish different treatment needs and outcomes between various subtypes.

Binge-eating disorder, one of the new subcategories, is characterized by binge eating without inappropriate compensatory behaviors.⁹ Patients with binge-eating disorder are often obese, have greater functional impairment, and are more likely to develop components of metabolic syndrome than obese patients without eating disorders.¹¹

Avoidant/restrictive food intake disorder is another new DSM-5 diagnosis, characterized by failure to meet nutritional needs for reasons other than weight control. Reasons include disinterest in eating, dislike of sensory characteristics of food, or avoidance of consequences of eating. This disorder replaces the category “feeding disorder of infancy or early childhood,” since the condition can also occur in adolescents and adults.¹²

Other new diagnoses are:

• Atypical anorexia nervosa (if the patient is not underweight)
• Purging disorder
• Subthreshold bulimia nervosa (if the patient has < 1 episode per week or has had them for < 3 months)
• Subthreshold binge eating disorder (< 1 time a week or < 3 months)
• Night eating syndrome
• Pica and rumination disorder.

Regardless of the diagnostic label, the medical evaluation and treatment of anyone with an eating disorder should be tailored to the specific behaviors of the eating disorder. Medical complications can be subdivided into those from starvation, from purging, and from refeeding.

MEDICAL COMPLICATIONS OF STARVATION

Cardiovascular effects of starvation

Malnutrition and starvation have multiple adverse effects on the heart.

Electrophysiologic effects. Sinus bradycardia (< 60 bpm) and hypotension are common cardiac manifestations of starvation.¹³ Bradycardia has been attributed to an adaptive increase in parasympathetic vagal tone.¹⁴ QTc prolongation is also seen in patients with malnutrition.¹⁵

Together, these electrocardiographic abnormalities predispose the patient to ventricular arrhythmia and sudden cardiac death.¹⁶ The risk of ventricular arrhythmia is particularly relevant when treating psychiatric symptoms, since antipsychotics and tricyclic antidepressants are among several drug classes that can cause further QTc prolongation (Table 1).^17,18

In patients with QTc prolongation, bradycardia, or both, the standard of care involves acute hospitalization for refeeding using continuous telemetric monitoring until normal rhythm is restored and the heart rate is above 40 at night and 50 by day.^4,19

Structural changes. Starvation also causes structural changes in the heart. Loss of lean body mass can reduce cardiac muscle mass, compromise cardiac output, and lead to mitral valve prolapse.²⁰ These changes are fully reversible with restored nutrition and regaining of heart mass.^21,22

Effects of starvation on the brain

Starvation can affect brain structure and cognitive function. Undernourished patients have reduced volumes of white and gray matter, a change that can occur within months. Cortical volumes may increase with weight gain, but a reduction in gray matter volume may not be completely reversible.²³

Furthermore, starvation impairs cognitive functions that are needed to stop eating-disorder behaviors; namely, decision-making, emotional control, regulation of appetite, and reward path-ways. Therefore, undernourished patients may not have sufficient insight into the disease to be able to make the best choices for recovery. This finding lends support for using the Maudsley method in adolescents, in which parents take control of their child’s eating until the child can maintain a healthy weight.²⁴

Gastrointestinal consequences of starvation

Patients with malnutrition have prolonged gastric emptying and colonic transit time with solid foods.²⁵ They often complain of early satiety, abdominal pain, bloating, and constipation, all symptoms that complicate the refeeding process. A prokinetic such as metoclopramide (Reglan), given 1 hour before meals and at bedtime, may provide some relief from gastrointestinal symptoms.²⁶

Patients may also experience transient lactose or fructose intolerance after prolonged starvation. Taking a lactase supplement (eg, Lactaid 1–10 tabs) before consuming dairy products and dextrose (contained in candies such as Smarties) before eating fruit or fructose-containing foods can sometimes partially relieve symptoms. In general, gastrointestinal function returns over time as nutritional status improves.

Patients with severe or prolonged starvation can develop steatosis accompanied by elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In reports of starvation-induced steatosis, liver enzyme levels rapidly normalize with nutritional rehabilitation.²⁷

Endocrine consequences of starvation

Amenorrhea. Dysregulation of the hypothalamic-pituitary-gonadal axis is a major endocrine complication of nutritional in-sufficiency. Weight loss disrupts the normal pulsatile secretion of gonadotropin-releasing hormone, reduces secretion of luteinizing hormone and follicle-stimulating hormone, and decreases estrogen levels.²⁸ Leptin deficiency likely plays a role in suppressing gonadotropin secretion with subsequent development of amenorrhea. With weight gain, levels of leptin and gonadotropins normalize and menstruation eventually returns.^29,30

Hypothyroidism. Starvation can also lead to dysregulation of the hypothalamic-pituitary-thyroid axis. Typically, the concentration of triiodothyronine (T3) is reduced, the ratio of thyroxine (T4) to T3 is elevated, and thyroid-stimulating hormone (TSH) is close to or within the normal range, creating a euthyroid sick syndrome. In eating disorders, this thyroid disturbance is a result of starvation and resolves with weight restoration. Therefore, thyroid hormone replacement therapy is not medically indicated.²⁸

Osteoporosis. Amenorrhea resulting from low estrogen levels in undernourished patients can raise the risk of osteoporosis and fractures, particularly in patients with a low body mass index. Osteopenia results from a negative balance between bone deposition and resorption.

Lack of bone deposition can be especially problematic when disordered eating occurs during peak bone mass development, ie, ages 11 to 14 for girls, and ages 15 to 17 for boys.^31,32 Even a 5% to 10% decrease in bone deposition can result in significant risk of osteopenia.³³ However, after age 30, bone resorption is a greater contributor.³⁴

Does hormone therapy correct bone loss? Given the association between estrogen deficiency and bone loss, estrogen supplementation was expected to be an effective treatment for bone loss in patients with eating disorders.³⁵ Also, the restoration of menses through hormone replacement may give underweight patients a false sense of achieving a “healthy” weight.³⁶

Golden et al³⁷ prospectively studied 50 adolescents and found no significant difference in bone mineral density at 1 year of follow-up between patients treated with estrogen and those who received only standard nutritional therapy. However, increased bone mineral density was achieved in adolescents with anorexia nervosa treated with transdermally administered estrogen dosed to mimic physiologic pubertal levels.³⁸

Klibanski et al³⁹ found that hormone therapy resulted in a 4% gain in bone density in an extremely low-weight subset of women with anorexia nervosa (< 70% of ideal body weight), whereas similar patients in the control group lost 20%. However, in all groups, only weight gain correlated with bone gain in women who were within 70% of their ideal body weight.

Divasta et al⁴⁰ evaluated 60 girls and women ages 13 to 27 with anorexia nervosa, randomized to receive either placebo or dehydroepiandrosterone combined with an estrogen-progestin oral contraceptive, and followed for 18 months. As in the study by Klibanski et al,³⁹ bone loss was prevented in the treatment group, but significant bone gain occurred only in the context of weight gain.

The bottom line is that only weight gain has resulted in significant increases in bone density in patients with anorexia nervosa, and hormone therapy without weight gain has not been shown to increase bone density effectively in this population. Although calcium and vitamin D in oral therapeutic doses through foods or through supplementation are required for bone gain, the combination is not enough to augment bone density in the absence of weight gain.³⁷ Although not curative, weight gain is currently the best option for treating bone loss, and no single pharmacologic treatment is effective.

COMPLICATIONS OF PURGING

Oral complications of purging

Patients who purge by vomiting are at risk of complications from exposure of the esophagus, pharynx, and mouth to acidic gastric contents.

Dental problems. Over time, contact with gastric acid wears down enamel on the lingual and occlusal surfaces of teeth, resulting in dental caries and periodontal disease. Until they can give up purging, patients should be instructed to rinse with mouthwash or water immediately after vomiting to reduce the acidity in the mouth.^41,42 We recommend that patients not brush their teeth after vomiting, because brushing can deliver acid to otherwise unreachable surfaces and thus worsen tooth erosion. For patients who are determined to brush after vomiting, a bicarbonate toothpaste might mitigate harm.⁴²

Sialadenosis (hypertrophy of the salivary glands) is another consequence of repeated vomiting, with elevated salivary amylase. Both the size of the glands and the salivary amylase level generally normalize on their own after vomiting is stopped, but parotitis can take up to a year to resolve. Similar to smoker’s cough, parotitis may acutely worsen when the patient abruptly stops vomiting and may worsen before it improves.

To reduce discomfort, patients can use hot compresses or sugarless hard candies.⁴⁴ However, the latter should not be substituted as a chronic habit in a patient with disordered eating. Patients need to be reassured that the swelling is not permanent, since they often interpret it as having fat cheeks (the “chipmunk sign”).

Hypokalemia, metabolic alkalosis, renal dysfunction

Chronic vomiting can cause electrolyte and acid-base imbalances, the most worrisome of which is hypokalemia. With repeated vomiting, loss of potassium and gastric acid causes metabolic alkalosis with hypokalemia, hypochloremia, and hypomagnesemia. Loss of water and the resultant volume contraction activates the renin-angiotensin-aldosterone system, and elevated aldosterone further decreases serum potassium.

In patients with eating disorders, who often have other factors contributing to electrolyte imbalance, vomiting-induced hypokalemia heightens the risk of cardiac arrhythmias.⁴³

Hypokalemia can also cause rhabdomyolysis and kidney damage.^41,43 Prolonged hypokalemia and reduced kidney perfusion in the setting of volume depletion causes acute kidney injury and impaired concentrating ability of the renal tubules. Hypovolemia can cause prerenal azotemia and increases the risk for nephrolithiasis and nephrocalcinosis.^44,45

When a patient stops vomiting, elevated aldosterone from prior hypovolemia results in water retention and can manifest in significant edema associated with hypochloremic alkalosis. This condition, known as pseudo-Bartter syndrome, usually resolves without treatment. In the meantime, salt restriction and leg elevation can help reduce edema.²⁶

Laxative abuse: A mode of purging

Many patients with eating disorders abuse laxatives to lose weight or to prevent weight gain. Believing that laxatives will prevent calorie absorption, patients commonly take them to compensate for caloric intake (eg, during a binge episode). The immediate weight loss, albeit artificial, is highly reinforcing for an eating-disorder patient. In some cases, patients with eating disorders also abuse laxatives to self-treat the constipation that results from chronic starvation.⁴⁶

Over time, tolerance to laxatives develops, and patients use increasingly larger doses. This can lead to activation of the renin-angiotensin-aldosterone system.⁴⁷ Patients interpret the resultant edema as true weight gain and again take laxatives to get rid of it. If laxatives are stopped abruptly, the patient may need inpatient and outpatient support for the resultant fluid shifts.

Gastrointestinal complications of laxative abuse include reflex hypofunction of the bowel, malabsorption, steatorrhea, and gastrointestinal bleeding.⁴⁷ Reflex hypofunction during laxative withdrawal is a consequence of the bowel becoming tolerant of laxatives.⁴⁸ Cathartic colon syndrome is a rare complication characterized by loss of the normal haustral markings and slowed or absent peristalsis in segments of the colon.⁴⁹

Systemically, the major risk of laxative abuse relates to electrolyte and acid-base imbalance. Loss of potassium and water in the stool can cause hypokalemia and metabolic alkalosis.⁴⁸ The disturbances caused by laxative abuse are similar to those caused by vomiting and diuretic use and have the same treatment.

The most important component of treating laxative abuse is giving patients realistic expectations to help them tolerate temporary discomfort and to help manage the edema and fluid shifts that can happen acutely with shifting of fluid into the intracellular space. In extreme cases, this may need to be managed in the hospital. To help relieve the initial anxiety, doctors should emphasize that any bloating the patient experiences is not true weight gain and will go away within a few days to weeks. In addition, explaining that laxatives reduce nutrient absorption only minimally may lessen the temptation to resume taking them.⁴⁸

Diuretic abuse: Another form of purging

Diuretic abuse is yet another mode of purging, with its own set of medical complications. Like laxatives, diuretics are not effective weight-loss agents, and the weight reduction they cause is only temporary.

As with vomiting, there is a compensatory activation of the renin-angiotensin-aldosterone system, and therefore subsequent fluid intake will lead to water retention, which encourages further diuretic use.⁴¹ Diuretics can also contribute to hypokalemia, hypomagnesemia, hypochloremia, and metabolic alkalosis.

Ipecac abuse can lead to heart failure

Ipecac syrup has long been used to induce vomiting, but this practice has become much less common since ipecac has become harder to obtain in the United States.⁵⁰ The emetine base contained in ipecac binds irreversibly to cardiac and skeletal muscle. With continued use, irreversible cardiomyopathy develops and can lead to heart failure. Treatment should include supportive care and immediate cessation of ipecac use.

Diabetic patients may skip insulin to lose weight

Patients with diabetes, especially those with type 1 that begins in childhood, are at greater risk of eating disorders over time.⁵¹ They may withhold insulin to lose weight, a practice referred to in the nonmedical literature as “diabulimia,” and they seem particularly more likely to develop bulimia nervosa than those without diabetes.⁵²

The medical prognosis is poor for patients with diabetes who develop eating disorders and do not receive intensive treatment.⁵¹ In addition, if a diabetic patient on an insulin pump becomes depressed in addition to having an eating disorder, careful monitoring for suicidal thoughts and a rapid follow-up with mental health services are in order.

REFEEDING SYNDROME

When refeeding is started, a high glucose load stimulates insulin secretion, resulting in cellular uptake of phosphorus along with potassium, magnesium, and glucose. In addition, total body phosphorus is depleted by the increased demand for adenosine triphosphate and 2,3-diphosphoglycerate for cellular metabolism.

When liver enzyme levels increase, the astute clinician will closely monitor the patient for evidence of refeeding syndrome. In a child, adolescent, or young adult, the standard of care is inpatient monitoring for acute stabilization.^4,19

Hypophosphatemia is the hallmark of refeeding syndrome, although hypomagnesemia, hypokalemia, and hypoglycemia can also occur.⁵³ In addition, sodium and water retention can lead to fluid overload, with shifting of fluid into the intracellular space, resulting in dependent edema.

Cardiovascular complications are the most worrisome manifestations of refeeding syndrome. Electrolyte shifts and increased fluid volume can cause arrhythmias and heart failure. Furthermore, severely undernourished patients may have reduced myocardial mass as well as electrocardiographic abnormalities associated with starvation, which further increase their vulnerability to electrolyte shifts and fluid retention during refeeding.¹⁵

Other manifestations of refeeding syndrome include delirium, seizures, rhabdomyolysis, and respiratory failure. In the most extreme cases, refeeding syndrome causes sudden death.⁵³

Fortunately, refeeding syndrome is easily preventable and treatable when recognized early. Electrolytes and cardiovascular and renal function must be carefully monitored, especially during the first week of nutritional restoration.⁵³ In patients with extremely low body mass (< 70% of ideal body weight) or with precipitous weight loss, close monitoring of the complete metabolic panel including electrolytes, AST, ALT, calcium, magnesium, and phosphorus may be required to detect changes that can affect cardiac status. Specific suggestions for refeeding are discussed below and in Table 2.⁴⁵

ACUTE CARE OF PATIENTS WITH EATING DISORDERS

Refeeding in the inpatient setting

The decision to hospitalize an eating-disorder patient is based on the current or potential risk of serious medical complications and the likelihood of success at home. Medical criteria for hospital admission are outlined in Table 3.^4,54

In refeeding undernourished patients, the challenge is to maximize weight gain while preventing refeeding syndrome. Undernourished patients are generally hypometabolic at baseline but become hypermetabolic once refeeding begins.

How many calories should refeeding start with? The traditional principle of “start low and go slow” has been recently challenged.⁵⁵ Starting at 1,200 kcal/day or less in the typical patient can result in failure to gain weight or even in weight loss in the first week of refeeding.⁵⁶ The goal is to achieve a weight gain of 0.2 kg/day while the patient is in the hospital. Thus, we start higher, and to date we have seen no cases of life-threatening refeeding syndrome. In all patients who need hospitalization or who are beginning the refeeding process as outpatients, caloric intake should be started at 1,500 to 2,000 kcal/day.^45,57 However, for exceptionally low-weight patients, intake may be started lower.

In Australia, patients are started at 1,900 kcal/day.⁵⁶ All patients in one program there receive nasogastric feeding initially in an intensive care unit and then are moved to a regular nursing floor where they graduate to full oral feeding as they improve cardiovascularly and behaviorally. In the United States, some programs use nasogastric feeding at night for caloric restoration; our program and others use nasogastric feeding as a behavioral modification strategy for patients who refuse food or supplements by mouth.

Phosphorus supplementation. Many centers give phosphorus supplements preventively. In our center, we give potassium phosphate (Neutra-Phos) 500 mg orally twice daily for 5 days, and we have seen no life-threatening cases of refeeding syndrome with that regimen. Other centers give phosphorus supplements in a dose of 250 mg orally twice a day for 5 days, while still others only supplement phosphorus reactively once a deficit has been identified. The latter method requires daily blood draws for monitoring and is reactive rather than proactive. Further studies can help clarify the optimal dosing and timing of phosphorus supplementation.

Managing fluid balance. Fluid-loading these patients may tip them over the edge into refeeding syndrome. Except in cases of shock, patients with eating disorders should not be given intravenous fluids, as it is safer to rehydrate and feed them orally. Electrolyte imbalances can be corrected orally with no need for intravenous supplementation. To avoid fluid overload, fluids can be started at 1,500 mL to 2,000 mL per day, with strict monitoring of intake and output. Fluids are liberalized if ALT and AST levels remain normal and to gradually correct orthostatic hypotension; caloric fluids are ideal to help address energy needs and improve bradycardia.

Laboratory monitoring. On admission, a urinalysis, complete blood cell count, complete metabolic panel, TSH, erythrocyte sedimentation rate, serum magnesium, and phosphorus should be obtained.²⁶ In addition, continuous electrocardiographic recording should begin on admission.⁴⁵ Inpatient use of a telemetry bed helps identify extreme tachycardia with arrhythmia, as well as profound bradycardia.^45,56

Some protocols call for daily laboratory monitoring, although that degree of testing is less cost-effective. If initial results are normal, clinical judgment can be used on when to repeat laboratory evaluation. For instance, patients with edema require repeat complete metabolic panels to assess for elevated ALT and AST, electrolyte imbalances, and other abnormalities.

Signs of refeeding syndrome include tachycardia, hepatosplenomegaly, peripheral edema, altered mental status, and electrolyte disturbances, specifically, acute or severe hypophosphatemia or hypokalemia.^26,45 If refeeding syndrome is suspected, the rate of caloric intake should be reduced or not advanced, fluid intake should be urgently reassessed for volume overload, and supportive care with close monitoring should be provided.

KNOWLEDGE SAVES LIVES

Eating disorders can lead to potentially life-threatening medical complications that require attentive care by the primary care clinician and subspecialist. Without thoughtful consideration, it is easy for even a caring medical team to unintentionally enable patients with these illnesses or to cause active harm in the case of underrecognized pathology.⁵⁸

Acute medical stabilization on an inpatient unit trained to recognize pathology and treat sequelae can be lifesaving. Arming patients and families with medical knowledge, as provided in the Academy for Eating Disorders’ brochure, “Critical Points for Early Recognition and Medical Risk Management in the Care of Individuals with Eating Disorders”⁵⁹ can help save patients’ lives.