May is a 62 year old female with intellectual disability who presents to the regional hospital emergency room from a residential care facility (RCF). She was brought to the hospital due to complaints from staff members of increased combativeness and agitation when staff try to help her complete her activities of daily living. May had a similar episode of increased agitation in the winter and was found at that time to have a urinary tract infection. She is otherwise relatively easy to care for at the facility.

May's caregiver states that the psychiatrist who sees May at the RCF has recently increased the doses of a few of her medications (specifically her risperidone, quetiapine, and clonazepam) due to her agitation and combative behaviors. The caregiver is concerned these adjustments may actually be contributing to May's behaviors.

Upon exam, the patient is essentially nonverbal, making no direct eye contact and is unable to answer directed questions. She gestures to her stomach and winces, suggesting possible abdominal pain. She is unable to comply with a full review of systems. Information on May's medical history is limited; however, an old admission note lists her medical conditions as GERD, seizure disorder, and hypothyroidism. Her medication list is documented as follows:

  • Risperidone 3 mg po BID

  • Quetiapine 400 mg po BID

  • Clonazepam 1 mg po TID

  • Fluvoxamine 100 mg po BID

  • Divalproex 500 mg po BID

  • Phenytoin 300 mg po daily

  • Gabapentin 800 mg po BID

  • Hydrocodone/Acetaminophen 5/500 1-2 po Q6h prn pain

  • Levothyroxine 125 mcg po daily

  • Benztropine 1 mg po BID

  • Calcium Carbonate antacids 2 po TID

  • Aspirin 325 mg 1 po daily

  • Calcium carbonate 600 mg + Vitamin D 125 IU 1 po BID

  • Multivitamin 1 po daily

  • Pink Bismuth 30 mL po daily

  • Docusate sodium 100 mg po daily

  • Metoclopramide 10 mg po BID prn constipation

  • Ferrous sulfate 325 mg po BID

  • Ranitidine 300 mg po BID

  • Omeprazole 20 mg po BID

Overwhelmed by the number of medications on the patient's profile, May's physician asks you what types of comorbid disorders are most common in patients with developmental disabilities. He also asks if you can help determine if any of these medications may be contributing to her behavioral changes.

Patients with developmental disabilities can present with symptoms or complaints that may be difficult to interpret and even harder to manage. Developmental disabilities (DD) is a term used to describe a chronic physical or mental disability present before the age of twenty two years old that cause significant physical or mental impairment. This classification includes a variety of diagnoses, such as Fragile X syndrome, Down syndrome, and autism spectrum disorders.1,2 Literature examining the epidemiology of these disorders estimates a prevalence of 0.7% of the population is affected with a disability that may be classified as a developmental disorder.3 

Due to the genetic origin of these disorders, many patients with developmental disorders also have a wide range of medical and psychiatric comorbidities that require treatment. However, diagnostic overshadowing is a common problem in the treatment of patients with DD.4 The symptoms a patient presents with may be inappropriately attributed to their developmental disorder rather than treated as a separate condition. These patients are also less likely to undergo basic medical and psychiatric screenings for comorbid conditions and are less likely to receive adequate treatment.3 

Difficulties in treating a patient with developmental disabilities may also occur due to the way in which the patient presents to the health care provider. Some patients are unable to communicate to the provider that there is a problem. Small changes in behavior may be the only clue to the provider that something is wrong. This can be seen in May's case above, in which her increased agitation and irritability were likely due to gastrointestinal discomfort rather than new onset of behavioral problems. The issue of behavioral outbursts as indication of new onset of illness has been highlighted in the literature as well, leading authors to suggest that any and all changes in behavior should be investigated as a possible indication of medical or mental illness.3–5 

Behavioral actions of these patients may lead to the addition of medications used to control behaviors. Psychiatric pharmacists are essential to the medical team to help streamline medication regimens and ensure adequate treatment of medical conditions in these patients. Thus it is imperative that they are also aware of the most common comorbid medical and psychiatric conditions to which these patients are susceptible.

In a New Zealand study of annual health check-ups in patients with DD, the authors noted that 73% of participants with DD needed follow-up interventions for health concerns identified during the screening.6 The high incidence of untreated comorbidities was also seen in the study by Lee and colleagues in which approximately 50% of Australian patients with intellectual disabilities who were enrolled in the study were referred to a specialist for additional follow-up of their medical conditions.7 The authors of both studies suggest that screenings be completed annually in all patients with DD in order to identify comorbidities earlier and allow for more timely interventions.6,7 These recommendations have also been echoed by Prater and Zylstra in their discussion of medical care of patients with mental retardation.5 The authors also highlight preventative care guidelines from the Massachusetts Department of Mental Retardation for use in the care of patients with DD and to ensure adequate and timely monitoring of medical conditions guidelines available).

Some medical conditions may be more prevalent in patients with DD than in the general population due to genetic factors. For example, patients with Down syndrome have been shown to be more likely to develop cataracts and obstructive sleep apnea than in patients with other genetic disorders.5,8,9 Other patients with DD may have chronic gastroesophageal reflux disease (GERD), resulting in difficulties with feedings and providing meals for these patients.5,9 The patient in the case above suffers from chronic GERD, and her medication list reflects the various treatment strategies that were used to attempt to control her symptoms. GERD is a common problem for patients with DD and some literature suggests it may actually be a component of the developmental disorder.9 Dysphagia can also be a common problem in patients with DD, causing difficulty with feedings and even resulting in need for feeding tubes and alternative forms of nutrition for some patients.7 In the study conducted by Lee and colleagues, almost 30% of patients screened for problems had swallowing difficulties.7 

Constipation (and subsequent impaction) is another common gastrointestinal complaint for patients and can be a frequent and serious problem in patients with DD.5 These patients are at an increased risk of constipation due to inactivity and immobility and are susceptible to the constipating side effects of the multiple medications they may be taking. Patients should be monitored for changes in bowel patterns, as constipation and impaction is a common cause of acute behavioral changes in patients with DD.5 

Lastly, many patients with DD will struggle with weight gain and obesity due to sedentary lifestyles and side effects of medication use. In the study by Lee and colleagues, 30% of study patients were either overweight or obese.7 Chronic, unaddressed obesity can lead to long-term complications in these patients and increased mortality, particularly when hypertension or hyperlipidemia are comorbid with obesity.

Patients with DD also have an increased incidence of comorbid psychiatric and neurologic disorders. One study cites 41% of patients with intellectual disabilities also had a psychiatric diagnosis.3 Similarly, Kwok and Cheung report a much larger prevalence of comorbid psychiatric disorders in patients with DD when compared to the general population (32.2% vs 11.2%).9 Rates of use of psychiatric medications was also seen in the study by Lee and colleagues in which 20% of study patients with DD were taking antidepressant medications and 26% were prescribed antipsychotics. The authors also note that 47% of these patients were taking multiple classes of psychiatric medications.7 The use of multiple psychotropic medications may be due to the difficult nature of diagnosing a patient's psychiatric illness in the presence of a developmental disorder. Rather than presenting with an expected set of symptoms (such as sadness, difficulty concentrating, and loss of appetite in depression), patients with DD may act out or demonstrate aggression towards others. These signs should serve as a warning to the provider that further examination is needed and may be the only clues of untreated psychiatric illness.

These patients may also have inherent behavioral issues, such as self-injurious behaviors, aggression, or impulsivity. In the study conducted by Lee and colleagues, 35% of study patients were indicated as having “behavioral issues” and were given medication to treat their symptoms. Medications such as atypical antipsychotics or mood stabilizers are often used to control or minimize these behaviors, but data to support the use of these agents for these behaviors is variable. Risperidone and aripiprazole are FDA-approved for management of irritability with autism and mental retardation, while divalproex has shown limited benefits in small studies of pediatric patients.10,11 Although potentially beneficial, these medications are not benign. Use of antipsychotics and mood stabilizers may predispose patients to weight gain, increases in lipids or blood sugar, and changes in hepatic enzymes or prolactin levels. When using these medications for behavioral management of patients with DD, providers must ensure that patients are receiving adequate follow-up and that proper blood work and laboratory monitoring are completed to carefully assess patients for adverse effects.

Other medications that are frequently used for behavioral disturbances are the benzodiazepines. Although useful for many psychiatric disorders, these medications have been shown to disinhibit patients with developmental disorders and may lead to worsening of aggression and irritability.5,12 Patients receiving these medications should be monitored for changes in behaviors, and dose reductions should be considered for patients taking a benzodiazepine with worsening behavioral symptoms.

Patients with DD have also been shown to have comorbid neurologic disorders, such as epilepsy. In a study of 162 patients with DD, 52% were taking anticonvulsant medications for a seizure disorder. In spite of this, one-third of these patients were still experiencing recurrent seizures.7 These patients were more likely to receive multiple antiepileptics, which predisposes them to an increase in side effects and drug interactions. Monitoring of antiepileptic therapy can also be a problem for patients with DD, who may not be receiving adequate medical follow-up for their disorders. Laboratory values such as hepatic enzymes and blood counts should be monitored at initiation of therapy and at regular intervals throughout treatment. Patients who are newly started on therapy for epilepsy will need more frequent monitoring until their seizures are adequately controlled and the patient is tolerating the new medication.

Other neurologic disorders common to patients with DD are dementias. Alzheimer's disease and dementia is particularly common in patients with Down syndrome, who are estimated to be three times more likely to develop dementia when compared to the general population. These patients will also develop symptoms at a younger age, often around age 40.5,8 Screening for early symptoms of dementia may be difficult in these patients, who may not be able to complete a mini mental exam or a thorough evaluation. As the patient ages and their dementia progresses, the patient's may develop more challenging behaviors that can become increasingly difficult to manage.9 

After reviewing May's diagnoses and medication list, the psychiatric pharmacist and physician decided to hold many medications to allow for a thorough physical exam and assessment. All medications were discontinued except for phenytoin, levothyroxine, and vitamin supplementation. Clonazepam was restarted at 1 mg at bedtime with the option to give another dose during the day if needed for agitation. The patient's caregiver was given a prescription for risperidone at a lower dose of 1 mg BID as needed if psychiatric symptoms returned. Upon physical exam, the patient was believed to be constipated; a KUB was completed that confirmed these findings and indicated bowel obstruction. After use of laxatives and disimpaction, the patient's aggression and agitation subsided and behaviors returned to baseline. The patient was restarted on docusate with senna at twice daily dosing and caregivers were instructed to monitor the patient for regular bowel movements.

Assessment and determination of appropriate medication use in patients with intellectual disabilities can often be difficult. These patients may be more sensitive to the effects of medication but may also have comorbid psychiatric and medical illnesses that warrant treatment and close monitoring. Pharmacists caring for these patients need to be aware of the complicated nature of these patients and work closely with other health care providers to identify and address any unmet needs of the patients. Collaboration of psychiatric pharmacists with providers will help to ensure that patients receive only necessary medications to control their symptoms and that risks associated with the use of these medications are minimized.

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