Psychopharmacology in Autism: Thoughtful, Individualized Care for Co-Occurring Mental Health Needs

Autism spectrum disorder (ASD) is a neurodevelopmental variation characterized by differences in communication, sensory processing, and behavior. Autism itself is not a psychiatric illness and does not require medication. However, many autistic children and adolescents experience co-occurring mental health conditions that can significantly impact daily functioning, safety, and quality of life.

Current CDC estimates indicate that approximately 1 in 31 children are identified as autistic. Research consistently shows that co-occurring psychiatric conditions are far more common in autistic youth than in the general population, with estimates ranging from 55% to over 90% having at least one additional mental health diagnosis. The most frequently observed conditions include ADHD, anxiety disorders, depression, and sleep disorders. These challenges—not autism itself—are often what bring families into crisis care settings.

Autistic youth are approximately 6.6 times (some literature indicates 11 times) more likely to experience psychiatric hospitalization than their neurotypical peers. Emergency departments are often ill-equipped to meet their sensory, communication, and behavioral needs, making these visits costly and traumatic.  Because of this, families will frequently attempt to avoid taking their child to an ED however this can lead to escalating dangerous behavior and poor outcomes within the home. Expanding access to specialized outpatient psychiatric and therapeutic services for autistic youth is one of the most effective ways to reduce unnecessary emergency care and improve long-term outcomes.

When to Consider Medication

When an autistic child presents with escalating distress or behaviors—such as aggression, self-injury, severe anxiety, food refusal, sleep disruption, or mood changes—the first step is NOT MEDICATION. A comprehensive evaluation should always occur first to consider:

• Underlying medical issues or pain

• Recent life changes or stressors

• Communication barriers

• Sensory overload or unmet support needs
  

Only when these factors have been addressed or ruled out, and when significant functional impairment or safety concerns remain, should medication be considered—particularly if evidence-based therapies have been ineffective or inaccessible.

Medication is not a replacement for supports, accommodations, or therapy. It is a tool, sometimes helpful, sometimes not, and always requiring careful consideration.

Understanding the Evidence Base

Psychopharmacology research in autism remains limited for several reasons:

• Autistic individuals were historically excluded from many psychiatric trials

• Study samples are often small

• Autism is highly heterogeneous, with wide variability in communication, cognition, and support needs
  

Because of this, clinicians must rely on the strongest available evidence, clinical experience, and individualized decision-making.

FDA-Approved Medications for Irritability in Autism

Currently, only two medications are FDA-approved for the treatment of irritability in autistic children and adolescents:

• Risperidone (approved in 2006)

• Aripiprazole (Abilify) (approved in 2009)

These medications target severe symptoms such as aggression, self-injury, and intense emotional dysregulation—not autism itself. While both have demonstrated efficacy in randomized controlled trials, they also carry meaningful risks, including weight gain, metabolic changes, movement disorders, and hormonal effects. Their use requires careful monitoring and ongoing reassessment.

Other antipsychotic medications have not demonstrated the same level of evidence and are generally not recommended as first-line options.

Common Co-Occurring Conditions and Medication Considerations

Anxiety and Depression

There are no medications FDA-approved specifically for anxiety or depression in autistic youth. SSRIs and other commonly used medications for depression and anxiety are often prescribed to autistic individuals based on evidence from studies on neurotypical children.  Research on how effective they are for depression/anxiety in children  who are also diagnosed with autism is ongoing.  Recent studies have not shown strong support for medications such as mirtazapine or propranolol for anxiety in ASD, although research is ongoing.

ADHD

ADHD is one of the most common co-occurring diagnoses in autism. Stimulant medications such as methylphenidate can be effective but often carry a higher risk of irritability, appetite suppression, and sleep disruption in autistic children. Alpha-agonists (such as guanfacine or clonidine) are often better tolerated, though occasionally cause sedation and are less robust in effect. Medication choice should be guided by looking at the child’s unique medical and sensory characteristics in combination with the medication’s risks and benefits.  The side effect profile of medications should always be reviewed and explored for possible side effects that might be viewed as beneficial in a particular child.  For example, if a child is diagnosed with both ADHD and obesity, the side effect profile of a stimulant medication might be beneficial given the suppressed appetite.

Sleep

Sleep challenges are extremely common in autistic children. Behavioral and environmental interventions such as “sleep hygiene,” should always be the foundation of treatment. When medication is needed, melatonin (which also is available in extended-release formulations) has the strongest evidence base. Other sedating medications may be considered cautiously.  Adjusting the timing/dosage of a medicine (that has a side effect of drowsiness) the child is already taking is ideal since it avoids adding another medication (polypharmacy) to their daily regimen. 

Polypharmacy and Ethical Prescribing

Polypharmacy—the use of multiple psychiatric medications simultaneously—is common in autistic youth and requires particular caution. Every medication trial should be clearly documented and thoughtfully monitored:

• Was it an adequate dose?

• Was it used for a sufficient duration? (Was it taken long enough for it to start having a therapeutic effect on the mind/body)

• Were benefits meaningful?

• Were side effects tolerable?
  

Medications should be regularly reassessed and discontinued when risks outweigh benefits.  It is also important to discontinue a medication when no clear benefit has been observed.  If this is not done, medications will pile up and the number of daily medications a child is taking can increase to unsafe levels.

What the Evidence Does Not Support

Current evidence does not support the use of:

• Chelation Therapy

• Medical marijuana or isolated cannabinoids

• CBD products
  

Professional organizations, including the American Academy of Child and Adolescent Psychiatry, strongly advise against these interventions for autistic children outside of rigorous research settings.

The Art of Medicine

Evidence-based care does not mean one-size-fits-all care. The American Academy of Child and Adolescent Psychiatry emphasizes that treatment decisions should integrate:

• The scientific evidence

• Side-effect profiles

• Clinical expertise

• The child’s individual strengths, needs, and values
  

In addition to this guidance, it is important to start and stop medications in a safe and planful manner.  Experienced, thoughtful clinicians improve clarity by avoiding starting or stopping multiple medications at once.  Also by taking into account other environmental factors and life stressors that may be influencing a child’s behaviors in addition to the medication. This is where the art of medicine lives—at the intersection of data, experience, and humanity.

Conclusion

Autistic children do not need to be “fixed.” They need to be understood as the unique individual they are and to be supported and respected as such.  Improving outcomes for autistic youth requires more than medications—it requires focusing on the whole child, access to specialized outpatient care & trained clinicians, and systems designed to meet neurodivergent needs. When we invest in these supports, we reduce crises, improve quality of life, and help children thrive in their own authentic way.