Can Medication Management Smooth the Journey for Families of Autistic Children?

Barbara J. Howard, MD


February 22, 2023

Caring for a child with autism is a long haul for families and not often a smooth ride. Medications can help improve child functioning and family quality of life but the evidence may require our careful consideration.

Although I am discussing medication treatment here, the best evidence-based treatments for autism symptoms such as poor social communication and repetitive restricted behavior (RRB) are behavioral (for example, applied behavior analysis), cognitive-behavioral therapy (CBT), and parent training. These modalities also augment the effectiveness of medications in many cases. Educational adjustments and specific therapies, when indicated, such as speech-language, occupational, and physical therapy are also beneficial.

Barbara J. Howard, MD

Autism symptoms change with age from early regression, later to RRB, then depression, and they are complicated by coexisting conditions. Not surprisingly then, studying the effectiveness and side effects of medications is complex and guidance is in flux as reliable data emerge.

Because of the shortage of specialists and increasing prevalence of autism, we need to be prepared to manage, monitor, and sometimes start medications for our autistic patients. With great individual differences and the hopes and fears of distressed parents making them desperate for help, we need to be as evidence-based as possible to avoid serious side effects or delay effective behavioral treatments.

Our assistance is mainly to address the many co-occurring symptoms in autism: 37%-85% ADHD, 50% anxiety, 7.3% bipolar disorder, and 54.1% depression (by age 30). Many autistic children have problematic irritability, explosive episodes, repetitive or rigid routines, difficulty with social engagement, or trouble sleeping.

We need to be clear with families about the evidence and, whenever possible, use our own time-limited trials with placebos and objective measures that target symptoms and goals for improvement. This is complicated by that fact that the child may have trouble communicating about how they feel, have hypo- or hypersensitivity to feelings, as well as confounding coexisting conditions.

The Food and Drug Administration has approved the atypical antipsychotics risperidone (ages 5-16) and aripiprazole (ages 6-17) for reducing symptoms of irritability by 25%-50% – such as agitation, stereotypy, anger outbursts, self-injurious behavior, and hyperactivity within 8 weeks. The Aberrant Behavior Checklist can be used for monitoring. These benefits are largest with behavior therapy and at doses of 1.25-1.75 mg/day (risperidone) or 2-15 mg/day (aripiprazole). Unfortunately, side effects of these medications include somnolence, increased appetite and weight gain (average of 5.1 kg), abnormal blood lipids and glucose, dyskinesia, and elevated prolactin (sometimes galactorrhea). Aripiprazole is equivalent to risperidone for irritability, has less prolactin and fewer metabolic effects, but sometimes has extrapyramidal symptoms. Other second-generation atypical antipsychotics have less evidence but may have fewer side effects. With careful monitoring, these medications can make a major difference in child behavior.

ADHD symptoms often respond to methylphenidate within 4 weeks but at a lower dose and with more side effects of irritability, social withdrawal, and emotional outbursts than for children with ADHD without autism. Formulations such as liquid (short or long acting) or dermal patch may facilitate the important small-dose adjustments and slow ramp-up we should use with checklist monitoring (for example, Vanderbilt Assessment). Atomoxetine also reduces hyperactivity, especially when used with parent training, but has associated nausea, anorexia, early awakening, and rare unpredictable liver failure. Mixed amphetamine salts have not been studied. Clonidine (oral or patch) and guanfacine extended release have also shown some effectiveness for hyperarousal, social interaction, and sleep although they can cause drowsiness/hypotension.

Sleep issues such as sleep onset, duration, and disruptions can improve with melatonin, especially combined with CBT, and it can even sometimes help with anxiety, rigidity, and communication. Use a certified brand and prevent accidental ingestion of gummy forms. Note that obstructive sleep apnea is significantly more common in children with autism spectrum disorder (ASD) and should be evaluated if there are signs. The Childhood Sleep Questionnaire can be used to monitor.

There aren’t data available for selective serotonin reuptake inhibitors in treating depression and anxiety in autistic children but CBT may help. Buspirone improved RRB (at 2.5 mg b.i.d.) but did not help mood. Mood-stabilizing antiepileptics have had mixed results (valproate reduced irritability but with serious side effects), no benefits (lamotrigine and levetiracetam), or no trials (lithium, oxcarbazepine, and topiramate). In spite of this, a Cochrane report recommends antidepressants “on a case by case basis” for children with ASD, keeping in mind the higher risks of behavioral activation (consider comorbid bipolar disorder), irritability, akathisia, and sleep disturbance. We can monitor with Short Moods and Feelings Questionnaire and Problem Behavior Checklist.

NMDA and GABA receptors are implicated in the genesis of ASD. Bumetanide, a GABA modulator, at 1 mg b.i.d., improved social communication and restricted interests, but had dose-related hypokalemia, increased urination, dehydration, loss of appetite, and asthenia. Donepezil (cholinesterase inhibitor) in small studies improved autism scores and expressive/receptive language. N-acetylcysteine, D-cycloserine, and arbaclofen did not show efficacy.

Currently, 64% of children with ASD are prescribed one psychotropic medication, 35% more than two classes, and 15% more than three. While we may look askance at polypharmacy, several medications not effective as monotherapy for children with ASD have significant effects in combination with risperidone; notably memantine, riluzole, N-acetylcysteine, amantadine, topiramate, and buspirone, compared with placebo. Memantine alone has shown benefits in 60% of autistic patients on social, language, and self-stimulatory behaviors at 2.5-30 mg; effective enough that 80% chose continuation.

Families often use complementary or alternative medicines (CAM) so we need to ask about them because CAM may interact with prescribed drugs or complicate determining the source of side effects or benefits. Oxytocin has promising but inconclusive data for improving social cognition but only for 3-8 year olds. Omega-3 fatty acid had benefits for young child stereotypy and lethargy but only by parent report. Vitamin B12, folinic acid, vitamin D3, and digestive enzymes may help but lack data. It is important that families not replace evidence-based treatments with CAM when there are significant symptoms needing treatment.

Being a person with autism, beyond the stress of rigid routines and social difficulties, may include being a target of physical or sexual abuse or bullying, which are risks for suicide. Suicide is eightfold greater in people with autism, especially those who are high functioning; thus, we need to include children with ASD in our routine suicide screening.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at

This article originally appeared on, part of the Medscape Professional Network.

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