TRIPASS XR تري باس

 

Overall, it seems that melatonin is the most well-studied, effective, and safe

medication option for treating sleep disturbance in individuals with developmental

disabilities. Although promising evidence for ramelteon, trazodone, mirtazapine, and

clonidine exists, further research is needed in individuals with developmental

disabilities. Research evidence does not seem to support the wide use of

diphenhydramine for sleep disorders in children, and although zolpidem and

benzodiazepines may be of benefit for sleep in some, they should be used with

caution, and primarily in adults for zolpidem, and those with parasomnias for

benzodiazepines.

CASE 88-4

QUESTION 1: T.T. is a 10-year-old boy with ASD and significant sleep disturbances. His father has tried

diphenhydramine for the last few weeks but has not seen any meaningful improvement in T.T.’s total sleep

time. Last year, T.T. had a trial of melatonin 2.5 mg daily with only a small recognized improvement. T.T.’s

clinician is thinking about starting a low-dose benzodiazepine, however, is weighing the concerns for adverse

effects. T.T.’s clinician asks for your opinion.

You note that the dose of melatonin last year may have been on the lower range

and you would recommend another trial of melatonin before considering a controlled

substance. The dose you would recommend is 5 mg taken approximately 1 hour to

T.T.’s bedtime. You note that this dose can be increased to 10 mg if an adequate

response is not seen.

Table 88-2

Summary of Target Symptoms and Pharmacologic Treatment

Target Symptom Treatment Medications/Classes to Consider

Hyperactivity Stimulants, atomoxetine, α2

agonists

Irritability/aggression Risperidone, aripiprazole

Repetitive behaviors Risperidone, aripiprazole, fluoxetine, clomipramine, fluvoxamine,

Self-injurious behavior Risperidone, clomipramine, naltrexone

Anxiety/depression SSRIs

Sleep Melatonin, ramelteon, clonidine, trazodone, mirtazapine, zolpidem,

benzodiazepines

SSRI, selective serotonin reuptake inhibitors.

p. 1861

p. 1862

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT11e. Below are the key references and websites for this

chapter, with the corresponding reference number in this chapter found in parentheses

after the reference.

Key References

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the literature. Res Dev Disabil. 2011;32:939–962. (108)

Mahajan R et al. Clinical practice pathways for evaluation and medication choice for attention-deficit/hyperactivity

disorder symptoms in autism spectrum disorders. Pediatrics. 2012;130:s125–s138. (45)

Minshawi NF et al. Multidisciplinary assessment and treatment of self-injurious behavior in autism spectrum

disorder and intellectual disability: integration of psychological and biological theory and approach. J Autism Dev

Disord. 2015;45:1541–1568. (82)

Volkmar F et al. Practice parameter for the assessment and treatment of children and adolescents with autism

spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2014;53(2):237–257.

Wong C et al. Evidence-based practices for children, youth, and young adults with autism spectrum disorder: a

comprehensive review. J Autism Dev Disord. 2015;45:1951–1966. (29)

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p. 1862

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous

psychiatric disorder that consists of multiple subtypes, including

inattention, hyperactivity/impulsivity, and a combination of these two

types. For diagnostic criteria to be met, there must be evidence that

these symptoms are present in multiple settings and that the individual

exhibited this psychopathology before the age of 12 years. These

symptoms cannot be because of other illnesses.

Case 89-1 (Question 1),

Table 89-1

Behavioral therapy is an important component of any effective treatment

plan and typically includes educational interventions, creation of a

structured environment for the child, and introducing contingency

training.

Case 89-1 (Questions 1-3)

Stimulant medications are highly effective for the rapid relief of ADHD

symptoms and substantially improve a child’s prognosis. Individuals who

fail to respond adequately to one type of stimulant will often do well

with another, suggesting that subtle differences exist in the

pharmacologic mode of action. Although the duration of pharmacologic

action is relatively brief for stimulants, a variety of preparations have

been approved that can prolong the relief of ADHD symptoms and

permit once-daily dosing.

Case 89-1 (Questions 3-5),

Table 89-2

There are a number of non-stimulant medications that have proven to be

effective for ADHD over the years, including atomoxetine a NE

reuptake inhibitor, and α-agonists. These medications may be viable

options for the management of treatment-resistant illness as well as in

patients with a history of substance abuse. They also possess a different

side effect profile than stimulants and have a delay until therapeutic

effects are evident.

Case 89-1 (Question 6),

Table 89-2

Many people are reluctant to consider stimulant medications for ADHD

treatment because of unfounded fears about drug tolerability and abuse.

As a result, there have been a wide variety of alternative treatments

considered for use, including changes in dietary habits, ingestion of

herbs and supplements, and other somatic interventions. At the present

time, the evidence supporting these options is sparse, although the rigor

of investigations has steadily improved in recent years, and there is hope

that some of these options may prove to be beneficial.

Case 89-2 (Question 1)

ADHD is commonly associated with several psychiatric and medical

comorbidities, and these concurrent conditions often influence treatment

plans. Tic disorders such as Tourette syndrome are frequently found in

children with ADHD, but research evidence suggests that stimulants

are not only safe but also effective in this particular population.

Case 89-1 (Question 1)

Some children with ADHD will continue to have symptoms of their

illness well into their adult years, usually of the inattention subtype.

There is a growing awareness that adults with ADHD have significant

social and occupational impairments. Fortunately, medications used to

treat ADHD in children appear to be equally effective in adults.

Stimulants are the most effective agents but have the unique side effect

risk of abuse and diversion. Monitoring for this is essential. If abuse or

diversion occurs then a reevaluation of the diagnosis is necessary as

well as a change to a medication with less risk of misuse.

Case 89-2 (Question 2)

p. 1863

p. 1864

Although the diagnosis and treatment of attention deficit and hyperactivity disorder

(ADHD) have been associated with considerable controversy, ADHD is a serious

psychiatric condition that has been well described in the medical literature for more

than two centuries.

1 There are highly effective pharmacologic treatments that

ameliorate the core symptoms of the illness. These agents are generally safe and have

been shown to improve long-term prognosis.

2

By definition, ADHD symptoms manifest in childhood and will often persist into

adulthood in many cases. If left untreated, ADHD can produce significant

impairments in academic performance and social functioning; adults with ADHD are

often hindered in occupational settings as well.

3 Psychiatric comorbidities are

commonly encountered among individuals suffering from ADHD, including

developmental disorders, mood disorders, and substance abuse.

Although hyperactivity had been recognized as a troublesome childhood behavior

for many years, ADHD was not formally described in the Diagnostic and Statistical

Manual of Mental Disorders until the third edition was released in 1980. The

recently released DSM-5 describes three different subtypes of ADHD including

“Predominantly inattentive presentation,” “Predominantly hyperactive/impulsive

presentation,” and “Combined presentation.”

4 The DSM-5 also requires the diagnosis

by age 12, in contrast to DSM IV that required the onset of impairment before age 7.

Qualitatively the core symptoms of ADHD will differ according to gender, with boys

more likely to exhibit the hyperactive/impulsive subtype (vs. girls).

5 These symptoms

often change with time as hyperactive and impulsive behaviors recede during

adolescence, and inattention predominates among adolescents and adults with

ADHD.

6

Although the effectiveness of pharmacologic treatments for ADHD has been

widely replicated, many children and adolescents with ADHD will receive

suboptimal treatment for a variety of reasons, including parental reluctance to

consider psychotropic medications, the perceived stigma of mental illness, and welldescribed deficiencies in the delivery of health care to persons with psychiatric

conditions.

7

It is important to note that ADHD poses a huge economic burden to

Western society. A meta-analysis by Doshi et al. reports overall national incremental

costs of $143 to $266 billion in the United States.

8 The economic impact related to

adults with the disorder from productivity and income loss is greatest, although there

are also significant costs associated with youth with the disorder from educational

and health expenses. Further, the study documents significant “spillover costs” for

family members of individuals with ADHD.

8

Stimulants such as methylphenidate and amphetamine have been the mainstay of

ADHD treatment in children for more than 30 years, and recent studies have

demonstrated acute and long-term benefits in adolescents as well as adults.

1,9-11

Unfortunately, stimulants have not been consistently shown to decrease delinquency

rates. They have also been implicated with rare but serious side effects, and they

carry an elevated risk of diversion and abuse.

11–13 Pharmacologic alternatives to

stimulants have been identified in recent years and have proven to be useful, albeit

often as second-line agents among individuals who have significant side effects and

those with medical or psychiatric comorbidities.

11 The benefits of cognitive

behavioral psychotherapy have also been emphasized in recent years, and most

experts now contend that the combination of pharmacotherapy with family-based

cognitive behavioral interventions will generate the best long-term prognosis for

individuals with this disorder.

2

Recent landmark studies have helped clarify important aspects of diagnosis and

treatment with regard to ADHD. The Multimodal Treatment of Attention Deficit

Hyperactivity Disorder Study (MTA) is considered a groundbreaking study of

ADHD treatments and outcomes. The main findings were released in 1999, but

additional findings have been subsequently released. MTA was a multisite study that

differed from earlier studies of ADHD in that the duration of the study was

significantly longer (up to 14 months) and that the study compared the use of both

medication and cognitive behavior therapy, both alone and in combination with

routine community-based treatment. The central findings of MTA included the

following: (1) Medication alone and in combination with CBT was more effective

than intensive behavioral treatment alone or routine community-based care, (2) youth

receiving combined treatment required lower doses of medication, and (3) youth with

associated mental health issues, in addition to ADHD, had better outcomes with

combined treatment than with medication alone.

14,15

The question of medication treatment for preschool children presenting with

ADHD symptoms is a controversial issue. The “Preschool ADHD Treatment Study”

(PATS) is considered a landmark study in this arena. The majority of the findings

were released in 2006. The central findings include (1) preschool children tend to

respond better and with fewer adverse effects with lower doses of medication and

(2) preschool children are more sensitive to the adverse effects of psychostimulants

and require closer monitoring. In particular, younger children tend to have more

emotional adverse effects such as irritability and a tendency toward crying.

16,17

EPIDEMIOLOGY

ADHD is a chronic neurobehavioral disorder, with an overall estimated prevalence

of 6% to 12% in school-aged children worldwide.

18 The Centers for Disease Control

and Prevention analyzed data from the 2006 National Survey of Children’s Health

and reported that the incidence of ADHD diagnoses has risen annually by an average

of 3% between 1997 and 2006.

19

In 2006, 7.4% of US children aged 4 to 17 years

were diagnosed with ADHD. The DSM-5 reports that “ADHD occurs in most

cultures in about 5% of children and about 2.5% of adults.” The diagnosis is more

common in males with a ratio of 2:1 in children and 1.6:1 in adults.

4

It is

hypothesized, however, that this gender predominance may be exaggerated because

the more overt hyperactive subtype is more common in boys and the less overt

inattentive subtype is more common in girls. As ADHD transitions into adulthood, the

prevalence falls to 4.4% (standard error 0.6), with a higher risk found in previously

married men who are unemployed and non-Hispanic white.

19

PATHOPHYSIOLOGY

Various abnormal genetic and neurochemical abnormalities are associated with

ADHD. Estimates of heritability of ADHD range in the area of 0.7, indicating that

ADHD is one of the most heritable conditions in psychiatry.

20 Family studies have

demonstrated that the relative risk of ADHD is 6 to 8 times higher among first-degree

relatives of persons with ADHD compared with the general ADHD population.

21

Several candidate genes associated with ADHD have been identified, such as the

dopamine receptor, dopamine-transporter receptor, and serotonin transporter

gene.

22,23 Despite a small causal effect, no single gene is responsible for the

symptoms seen with ADHD, but rather these symptoms are likely the result of

interactions among several genes, which influence multiple neurotransmitters,

including serotonin, dopamine, and norepinephrine.

22

p. 1864

p. 1865