Autism spectrum disorder: Practice guidelines for pharmacists

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental condition that is present at birth and whose first manifestations generally appear around 2 years of age. ¹ ASD as defined by the DSM-5-TR encompasses the 4 historical types of autism (autistic disorder, childhood disintegrative disorder not otherwise specified, pervasive developmental disorder and Asperger’s syndrome).^2,3 Restrictive and repetitive behaviours are a key feature of ASD (Figure 1). It is a condition that impacts the child’s ability to communicate and relate to others, as well as restricts their interests, with different degrees of severity ranging from 1 (requiring support) to 3 (requiring substantial support). ² The cause or the exact mechanism of ASD is still unknown. ⁴ Genetics and environment that affect the developing brain seem to play a role in the pathophysiology.^5-8

Figure 1.

Diagnostic criteria for autism spectrum disorder (according to the US Centers for Disease Control and Prevention)*

*In order to meet the diagnostic criteria for ASD in accordance with DSM-5-TR, a child must have persistent deficits in each of 3 areas of social communication and interaction (A) plus at least 2 of 4 types of restricted, repetitive behaviours (B). Furthermore, symptoms must be present in the early developmental period and cause clinically significant impairment in social, occupational or other important areas of current functioning and are not explained by intellectual disability or global developmental delay.

In the United States, the overall prevalence of ASD was 23 per 1000 children aged 8 years in 2018. ⁹ The prevalence varied from 16.5 per 1000 in Missouri to 38.9 per 1000 in California. ⁹ According to this report, ASD prevalence estimates have increased from 6.7 per 1000 children aged 8 years to 18.5 between 2000 and 2016. ⁹ In Canada, among children and youth aged from 1 to 17 years, 1 in 50 (2%) were diagnosed with ASD in 2019 according to the Public Health Agency of Canada, and the prevalence of this disorder was 4 times higher in boys than in girls.^2,10 In the United States, the lifetime cost of supporting an autistic individual ranges from $1.4 million without intellectual disability to $2.4 million with intellectual disability. ¹¹

While there is no cure for ASD, pharmacological and nonpharmacological measures can help manage the specific symptoms of ASD and/or comorbidities associated with autism.^12,13 ASD is a condition that often requires medication, with more than half of patients using prescription drugs.^12,13 Psychotropics are often prescribed in this population, with antipsychotics being the most prevalent treatment.^12,13 The US Food and Drug Administration (FDA) approved the use of 2 antipsychotics for the treatment of irritability in autistic patients: risperidone and aripiprazole.^12,13 No drug has been approved specifically for autism by Health Canada, but several drugs are available for typical comorbidities of autistic patients. Since autistic patients prefer identity-first language (i.e., “autistic patients”) over person-first language (“patients with autism”), for the remainder of this article, we have used identity-first language. ¹⁴

According to the literature, pharmacists and pharmacy students are not sufficiently familiar with ASD and the medications related to this condition. A study conducted at the University of Mississippi reported that 87.7% of pharmacy students had never had training on autism during their academic careers. ¹⁵ In this study, 91% of pharmacy students felt that autism should be more discussed in their academic program. ¹⁵ In addition, a study in Australia found that pharmacists lacked confidence when interacting with autistic patients and their parents, which limited the quality of their advice. ¹⁶ Furthermore, in an online survey of pharmacists in Mississippi, less than 47% of participants reported confidence in providing quality advice to parents of children regarding recommended therapies and their adverse reaction profile in ASD. ⁵

Due to the rising prevalence of autism, increasing disease awareness, the high rates of medication usage in this group and the fact that pharmacists are first-line health care providers specialized in drug treatment, the pharmacist’s role in the treatment of autistic patients is becoming more and more crucial. There is a significant lack of education in pharmacy schools on ASD symptoms and treatments and a resulting lack of knowledge among pharmacists. Furthermore, pharmacists are not mentioned in clinical practice guidelines for ASD care, in contrast to many other professions. Given the lack of knowledge and familiarity of pharmacists about autistic patients, ⁵ the aim of these guidelines is to inform pharmacists about the symptoms and various pharmacological and nonpharmacological treatments of ASD, provide them with tools for efficient communication with autistic patients and propose measures that can be implemented in community pharmacies to adapt the environment and provide better health care for autistic patients.

Step 1: Assess and engage with patient

ASD manifests with a broad range of neuropsychiatric symptoms and affects patients very differently. These symptoms often require pharmacological treatment (Table 1). ¹² Increasing pharmacists’ awareness of these symptoms and the recommended treatments can improve the quality of care provided to autistic patients. The pharmacist’s role is to be aware of ASD symptoms and their pharmacological treatments, assess the patient’s medical chart, engage with the patient and/or the caregiver and ask open-ended questions to learn more about the individual patient (Figure 2). In this section, we provide information on the most common ASD symptoms and recommended pharmacological treatments.

Table 1.

Symptoms associated with ASD with respective pharmacological treatments recommended by the Canadian Paediatric Society ¹³

ADHD	Mood and behavioural issues	Anxiety	Depression	Sleep disturbances
Stimulants (methylphenidate, amphetamine) Alternatives: norepinephrine reuptake inhibitor atomoxetine and alpha-adrenergic agonists (long-acting guanfacine, clonidine)	Atypical antipsychotics: aripiprazole, a risperidone b	SSRIs such as fluoxetine and sertraline	SSRIs	Melatonin

ADHD, attention-deficit/hyperactivity disorder; SSRIs, selective serotonin uptake inhibitors.

^aApproved by the US Food and Drug Administration (FDA) for 6- to 17-year-old pediatric patients with irritability associated with autistic disorder.

^bApproved by the FDA for 5- to 16-year-old pediatric patients with irritability associated with autistic disorder, including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums and quickly changing moods.

Figure 2.

Proposed procedure for pharmacists to support autistic patients

ADHD, attention-deficit/hyperactivity disorder; OTC, over-the-counter; SSRIs, selective serotonin uptake inhibitors.

Attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) includes symptoms such as inattention, hyperactivity and impulsivity and is one of the most common psychiatric comorbidities in autistic patients, with a population prevalence of 14% to 75%. ¹⁷ In Canada, 36.5% of autistic youth and children were also diagnosed with ADHD, according to the 2019 Canadian health survey by the Public Health Agency of Canada. ¹⁰ Several drug therapies are recommended for these symptoms, including stimulants (methylphenidate, amphetamine), ¹⁸ the norepinephrine reuptake inhibitor atomoxetine, the alpha-2-adrenergic agonist guanfacine and antipsychotics. Good-quality data exist on the use of methylphenidate in this population, as several randomized controlled studies have been published.^19,20 However, there is a lack of data in the literature regarding the long-term efficacy and safety of these treatments in ASD patients.

A study in 24 autistic children demonstrated statistically significant improvements in symptoms of hyperactivity and impulsivity at home and at school with morning long-acting methylphenidate and afternoon short-acting methylphenidate at weight-adjusted doses in autistic patients. ²¹ The improvements observed in this study were dose-dependent: the most significant improvements were observed at the highest doses of methylphenidate, according to parents and teachers. ²¹ Adverse reactions included decreased appetite and difficulty falling asleep. ²¹ Another study compared the efficacy of methylphenidate in 40 children and autistic adolescents with and without comorbid ADHD. ²² In autistic patients with ADHD, there was a significant clinical improvement in the first 2 years of treatment and amelioration of global functioning.

Mood and behaviour issues

Mood and behaviour issues encompass irritability, aggression, anger, self-injury and depression. ²³ The prevalence of this comorbidity in ASD patients is high, with estimates ranging from 55% to 97%. ²³ The antipsychotics risperidone and aripiprazole are the only medications approved by the FDA for the treatment of irritability, self-injury and aggression in autistic children. A combination of pharmacological and nonpharmacological interventions is the most beneficial approach, where the latter can identify triggering situations and help modulate behaviour.^12,13,24

Risperidone is FDA approved for the treatment of irritability with aggression, tantrums and/or self-injury in autistic children ≥5 years of age. ²⁵ Randomized controlled studies and systematic reviews demonstrate benefit in autistic patients and challenging behaviours. ²⁵ A multicenter, double-blind trial assessed irritability and aberrant behaviour scores at 8 weeks in patients on risperidone or placebo. ²⁵ Despite the short duration of the study, the authors were able to demonstrate statistically significant results in relation to the treatment of tantrums, aggressivity or self-harm behaviour in autistic children. ²⁵ Another double-blind randomized controlled trial evaluated risperidone vs. placebo for the treatment of autistic patients concomitant with tantrums, aggressivity or self-injurious behaviour. ²⁶ The results were statistically significant and demonstrated the efficacy of risperidone on irritability and lethargy in patients with moderate to severe ASD symptoms. ²⁶

Aripiprazole is also approved by the FDA for the treatment of irritability in autistic children (6-17 years). A review of the literature of randomized controlled studies showed that aripiprazole is effective in the short term for decreasing irritability and hyperactivity. ²⁷ In the long term, 1 study found that relapse rates did not differ between the aripiprazole and placebo groups. ²⁷ Re-evaluation of aripiprazole use is recommended after the patient is stable. ²⁷

Antipsychotics like olanzapine, clozapine, quetiapine, ziprasidone, haloperidol, anticonvulsants, alpha-2 agonists, mood stabilizers, selective serotonin reuptake inhibitors (SSRIs) and beta-blockers are used off-label. ²⁸ However, most of these treatments do not have high-quality evidence and some of their adverse effects profiles do not support their use. ²⁸

Depressive disorders are characterized by debilitative sadness and lack of interest or pleasure. ²⁹ According to a meta-analysis published in 2019, the prevalence of comorbid depressive disorder in the ASD population is 14.4%. ³⁰ Existing tools to assess depressive disorder in the ASD population have yet to be validated given the complexity of symptom overlap, creating a grey zone between diagnosis and some behaviours from an underlying ASD. ²⁹ In patients with professionally identified depressive disorders, the use of SSRIs or serotonin and norepinephrine reuptake inhibitors (SNRIs) is warranted and extrapolated to this population, given the lack of quality evidence. ²⁹ A few randomized double-blind studies of pharmacological treatments for depressive disorder in these patients have been published but are of low quality. ³¹ Given the low level of evidence regarding depressive disorders in autistic individuals, this comorbidity needs to be developed in the literature.

Anxiety and obsessive-compulsive disorder

Anxiety is defined as excessive worry and apprehensive expectations about events or activities, such as work or school. It is another common psychiatric comorbidity seen in autistic patients. A 2019 report published by the Canadian Public Health Agency on ASD found that 22.5% of autistic youth and children suffered from anxiety. ¹⁰ Anxiety is associated with functional impairment in autistic patients. ³² In clinical practice, the treatments recommended for autistic patients with anxiety disorders include SSRIs in the first line of treatment followed by second-generation antipsychotics.^12,13 Some autistic individuals also have coexisting obsessive-compulsive disorder. Obsessions are recurrent, unwanted and persistent thoughts, images or urges that result in distress. Compulsions are repetitive behaviours with rigid rules that are performed in order to reduce anxiety. In addition to behavioural approaches adapted to the language and cognitive level of the patient and cognitive behavioural therapy, SSRIs are recommended to treat obsessive-compulsive disorder in autistic patients. ¹²

Restricted and repetitive behaviour

Restricted and repetitive behaviours (stereotypies) are repetitive, rhythmic, semi-voluntary, non-goal-oriented movements. ³³ They can manifest themselves in several forms. The movements may be motor (e.g., hand flapping, body swaying, repetitive jumping, etc.) or other (object alignment, echolalia). ³³ Several observational studies have shown that stereotypies may increase following a stressful situation. ³³ Autistic patients might perform these movements to calm their minds, particularly in heightened sensory environments. ³³ In some patients, stereotypies may be associated with an underlying anxiety disorder, which may explain the use of SSRIs and their indirect improvement on stereotypies. ³⁴

There are currently no recommended pharmacological treatments for stereotypies due to limited data. ¹⁹ Results from studies assessing the efficacy of SSRIs in this behaviour in the past decade have been mixed. Smaller studies showed improvement in repetitive behaviours on fluoxetine, ¹⁹ but these effects have not been reproduced in large-scale randomized clinical trials. Studies evaluating citalopram in autistic children found no significant differences compared to a placebo. ¹⁹ Randomized controlled trials conducted with other antidepressants like clomipramine showed good efficacy in the treatment of stereotypies, although they were associated with significant adverse effects. ¹⁹

Sleep disturbances

Sleep problems affect 50% to 80% of autistic children, and these include late onset, frequent night and morning waking and decreased sleep duration. ¹³ Autistic adults also report high rates of sleep disturbances. ³⁵ According to the Canadian Paediatric Society, counselling to improve sleep hygiene and reinforce behavioural techniques should be considered. ¹³ Furthermore, melatonin combined with appropriate sleep hygiene and behavioural modification strategies appears to be effective in reducing sleep onset times and increasing sleep duration. ¹³ Some of the typically used drugs in the autistic population, such as methylphenidate, might add to sleeping disturbances if taken too late in the day, at high dosages or in case of slow-release formulations—here pharmaceutical counselling might be of primary importance.

Nonpharmacological treatments

The primary modalities of treatment for autism come from a psychosocial approach. This includes behavioural and developmental interventions, social skills training, parent-mediated training, communication training and other approaches. Due to the interindividual variability of social impairment in autistic patients, there is no universal psychosocial intervention—interventions are selected based on the patient’s age, developmental stage, difficulties and family needs.^13,36

Behavioural interventions are the primary treatment for autistic children. ¹³ The goal of these interventions is to help develop social skills and teach prosocial behaviours in a social context. ³⁷ The use of this intervention has been repeatedly shown to be effective in the management of specific problem behaviours, ³⁸ improvements in social interaction, language acquisition and academic achievement compared to control groups. ³⁷ Recently published guidelines for nonmedical interventions for children with autism spectrum disorders concluded that early intensive behavioural intervention programs significantly improve language, adaptive skills and intelligence quotient. However, it was noted that there is limited evidence to suggest the superiority of one behavioural program over another. ³⁶

Step 2: Communication strategy

One of the main challenges for pharmacists and other health professionals is effective communication with autistic patients.^39,40 Communication barriers are related to difficulties of autistic patients in understanding nonverbal or figurative language and difficulties in dealing with environmental distractions. ³⁹ As ASD can differ in clinical presentation, the pharmacist needs to adapt their communication to the patient’s symptoms, severity and individual preferences and include the caregiver if needed. As communication skills vary greatly among autistic patients, ³⁹ the pharmacist should document the preferred communication mode (e.g., via caregiver, in person, on the phone) in the medical chart if possible.

First, it is important to note that the pharmacist may communicate primarily with the patient or with the caregiver depending on the autonomy of the patient. If the patient is accompanied by a caregiver, the pharmacist will convey the most important information to the caregiver but should still interact directly with the patient. Seeing the pharmacist communicate with their caregiver can help create a bond of trust between the pharmacist and the autistic patient. ⁴¹

When speaking with an autistic patient, the pharmacist should try to reduce the sensory load. ⁴² First, the pharmacist should bring the patient to a private space. The room should be quiet, dimly lit and free of other employees. For patients with language difficulties, it is best to convey information briefly at a low rate of speech. ³⁹ To engage the patient, the pharmacist can start sentences with the patient’s name so that they know that they are being addressed (Table 2). ⁴³ It is preferable to use simple sentences and go straight to the point in order to avoid confusing the patient. ³⁹ When conveying information, it is recommended to limit the number of words used, repeat key words specific to the situation, accompany words with simple gestures or pictures/videos if possible and pause between words and sentences so that the patient can fully understand what is being said. ³⁹ For example, instead of saying “Take one tablet in the morning, either when you wake up or at breakfast, whatever you prefer,” start the sentence with the patient’s name and say, “Take one tablet at breakfast,” pause and repeat the same sentence. If engaging the patient is challenging, it can be useful to start the conversation with a topic of interest to the patient such as one of their hobbies. Furthermore, it is important to adapt the communication to the person’s level.^39,42 There is a risk that the autistic person will feel infantilized by the pharmacist if the adjustment is not appropriate, which could have a negative impact on establishing a bond of trust.

Table 2.

Communication strategies for pharmacists interacting with autistic patients

Recommended

To avoid

Always evaluate and adapt communication to each patient’s ability level, needs and situation Mention patient’s name at the beginning of interaction and use simple sentences and specific words • (Name of patient), take one tablet at breakfast, please. Speak slowly and repeat key words • (Name of patient), take this tablet at breakfast, please. One tablet at breakfast. Pause between words and sentences Use visual support if possible • (Name of patient), take the green tablet at breakfast, please.

Reliance on nonverbal language (body language, facial expressions, tone of voice) Multiple questions at once • When was your last doctor’s appointment? What did they tell you? Did you mention your adverse reactions? Figurative language (metaphors, sarcasm, exaggeration) • This drug helps you concentrate; it makes your focus laser-sharp • This drug will make you calm as a sloth Words that are too personal or familiar • Honey, tell me what your doctor said at the last appointment • Sweetie, have you taken your tablets every day?

Autistic patients often have difficulty understanding nonverbal language such as tone of voice, body language and facial expressions and may have difficulty maintaining eye contact. ⁴⁴ The pharmacist should avoid any form of nonverbal communication, such as relying on facial expressions and body language. ⁴⁵ They should also avoid communicating with the patient using figurative language (e.g., metaphors, sarcasm, exaggeration), because autistic patients tend to take in most information literally. ⁴⁶ Also, pharmacists should avoid using words that are too personal, such as “honey” or “sweetie.” ⁴⁷ Finally, some patients are more comfortable communicating in written form. ³⁹ By entertaining this option, the pharmacist can show their willingness to respect the patient’s preferences and thus build trust.

Routine is very important in the lives of autistic patients. A disruption in routine can trigger anxiety in these patients. ⁴⁸ For this reason, monthly appointments can be a relevant option for these patients in order to maintain a stable routine during medication renewals. For example, the pharmacist can suggest that the patient come in every Friday at the end of the month to renew medications.

Step 3: Assess pharmacy infrastructure

Autistic patients are often sensitive to sensory stimuli such as noise and light and can get easily distracted by crowds. Therefore, pharmacists need to be aware of the impact of pharmacy infrastructure on the autistic patient’s experience, as well as its potentially negative effects on communication, and proactively take steps to create an autism-friendly pharmacy environment.

The pharmacy is a place with many visual and auditory distractions, which can negatively impact interactions between the pharmacist and the ASD patient. Reducing these distractions could improve the experience of the autistic patient and the transmission of information. Several studies have shown that an alteration in the perception of sensory stimuli in an environment is one of the main issues in ASD. ⁴⁹ Patients are sensitive to the different stimuli (visual, auditory) in their environment: a heightened sensory environment can worsen patients’ anxiety levels and decrease concentration and self-control. ⁴⁹ Thus, the design of different environments can be adapted to this population. In a study of 97 pharmacists in Australia, 55.7% of pharmacists reported that pharmacy design made access difficult for autistic patients. ¹⁶ However, only 39.2% felt that the environment should be redesigned to accommodate the needs of these patients and their caregivers. ¹⁶

Pharmacists may offer ASD patients the option to conduct the consultation in the pharmacy’s private space, where the noise level is lower. Another suggestion would be for ASD patients to come to the pharmacy at a less busy time, depending on the pharmacy in question. Hours of accommodation can be established: at these times, it could be possible to reduce the brightness and noise of the radio. Another option would be to offer a delivery service with the possibility of receiving telephone advice if the pharmacy environment is not suitable for the patient.

As ASD patients can have very different symptoms and severities, it is important for the pharmacist to know the patient’s level of functioning within the spectrum in order to individualize pharmaceutical care and communication. A questionnaire to help community pharmacists to understand an individual ASD patient’s strengths, challenges and needs could be a helpful tool. This questionnaire could include the patient’s drug therapy, symptoms, level of autonomy, communication preferences and the names of other health professionals, caregivers and emergency contacts. The implementation of this tool would allow the pharmacist to provide optimal care for each individual ASD patient.

Conclusion

ASD is a neurodevelopmental condition with an increasing prevalence in North America. ASD symptoms often require complex pharmacological treatments, including antipsychotics, stimulants and antidepressants. ASD patients are generally supported by an interdisciplinary team of health professionals and educators. As pharmacists are not mentioned in current clinical practice guidelines and many studies show limited ASD knowledge among them, we are providing practice guidelines to make community pharmacists central players in the care team of ASD patients. Pharmacists are patient-centric health professionals and uniquely positioned to improve disease management in autistic patients thanks to their pharmacological expertise, communication skills and ability to create a welcoming environment in the community pharmacy. ■