Autism symptoms and clinical trials
Trelles explains the three considerations doctors use to assess treatments for autistic children: behavioral interventions, affiliated disciplines, and pharmacological interventions (5:00). She discusses how autism is defined by subjective observations, such as deficits in social communication and restricted and repetitive behaviors. The speaker highlights that associated symptoms can cause impairment and that treating these and other co-occurring medical conditions can help with quality of life (7:00).
Unlike other conditions, there are no clinical markers or known biomarkers for autism, and this greatly impacts research on pharmacological interventions. Due to the heterogeneity of autism, it is very difficult to define and test the population, making standard treatment recommendations difficult (8:50). Therefore, it is important for clinicians to assess the entirety of a child’s diagnosis, co-occurring conditions, and general environment. The speaker notes that a “failed” clinical trial is one in which the majority did not experience improvements. But because autism is so heterogeneous (different presentations), the few participants who did see improvements could help identify a subgroup for which a medication may work (13:00).
Symptom domain approach
Trelles outlines the symptom domain approach, highlighting that atypical brain development sets the standard of approach for autistic patients. She discusses the clinical process of teasing apart symptoms to determine where they are relative to a baseline, and then using available evidence and what we know to see if a medication would be helpful (14:55). The speaker lists common symptoms or conditions they consider when deciding on medications. Commonly presented symptoms that use medication include irritability, aggression, and other destructive behaviors, ADHD symptoms (hyperactivity and inattention), anxiety and depression, and sleep problems (17:35).
Atypical antipsychotics
The presenter lists some common antipsychotics, including Risperidone, Clozapine, Aripiprazole, Quetiapine, Ziprasidone, Haloperidol, and Olanzapine. Risperdone and Aripiprazole are the only two FDA-approved medications for the management of disruptive behaviors in autism (18:25). Trelles details some of these medications and their clinical validity.
Risperidone and Aripiprazole
Risperidone is the most studied medication, with its efficacy established by two large randomized controlled trials in 2002 and 2004, leading to FDA approval in 2006. Major studies show a significant decrease in challenging behaviors, but also side effects, including weight gain and other metabolic symptoms. The speaker emphasizes that side effects are dose-dependent and that parent training helps with symptomologies (19:26).
Apriprazole was FDA-approved in 2009 and is dose-dependent, with about a 50% reduction at 15 mg. Its weight-gain profile is better than risperidone’s, though clinical practice shows we really do not know how it will affect each child. Trelles reiterates that clinicians must work with more than what the research tells us, taking small steps and having many discussions with parents and caregivers. If Risperidole is the only thing that will help, metformin can assist with weight gain, but not necessarily with other metabolic issues (21:44).
Mood stabilizer – Valproate
Valproate has been found to be effective in reducing irritability. It works, but doesn’t have the best side-effect profile, and many are hesitant to use it because of this (23:45).
ADHD Symptoms
Methylphenidate
Trelles explains that there is some evidence showing methylphenidate to be helpful with attention, but autistic kids are more likely to have side effects. She suggests a slow step-wise approach. The speaker says that treating ADHD can be very helpful for autistic people, especially if they are in behavior therapies that require a lot of attention. While treating ADHD may not improve autism symptoms, it can make the child available for treatment and thus act synergistically with other therapies (24:30). She notes a systematic review showing positive outcomes at half the dosage used in typically developing kids.
Guanfacine and Atomoxetine
Guanfacine is a non-stimulant that has been shown to improve symptoms and help a bit with anxiety. The speaker reiterates how treating ADHD can help children access a wider range of care (27:00). Atomoxetine shows significant improvement in hyperactivity, but can only be taken if a child can swallow the capsule. There was a large study showing improvement in anxiety. Research also shows that using it in combination with parent training yields better results. Trelles reiterates the impact of equipping parents with the skills and resources they need to better support their loved ones (28:00).
Restrictive repetitive behaviors
Serotonergic drugs (SSRIs)
Serotonergic drugs include SSRIs, and open-label studies in children and adults show mostly positive results. There are activating side effects in most studies, and the research on autism is mixed. The largest study done was with Citalopram, which showed no difference between the placebo and the test group. Trelles suggests beginning with low dosages and moving slowly (29:50).
Risperidone and Abilify
These have seen huge success. So much so that in some cases, patients halt behavioral therapies. Trelles stresses the importance of maintaining various interventions and suggests holding off on starting Risperidone and Abilify until they are identified as the only options (33:00).
Sleep
The speaker notes that sleep changes with age and underscores the importance of remembering this when considering children with atypical brain development. Sleep, she explains, is a pervasive problem that is significantly associated with family quality of life and caregiver stress (33:40). Melatonin is the most studied sleep medication in autism and is very safe. It has a short duration, and some children cannot put themselves back to sleep after it wears off.
Conclusions
Trelles reiterates the importance of clinical trials and of using all available information to determine pharmacological interventions in autism (36:50). She emphasizes that, while many medications lack clear studies, they have been well vetted and appear to have minimal side effects. Despite “negative” studies, some medications are used in clinical practice. The speaker reiterates the importance of considering the patient’s overall context and current research (38:00). Trelles summarizes the main points of her presentation before the Q&A (42:00).
- Foundations of treatment rely on behavioral and educational interventions.
- Pharmacological approaches in autism use a symptom domain-specific approach.
- The heterogeneity of autism and related conditions presents major challenges in research.
- Treatment will be a dynamic and evolving process that responds to the needs of the child and family, as well as the demands of the environment.
- A strong alliance with your treatment team (school, therapy, medical providers, etc.) will be critical to identify the best treatment option.
