Autism and Medications
Guest Article by Dr. Ranjan Ghosh
We at PlayStreet believe in sharing information as well as inviting people to share their knowledge and experiences.
This week we have invited renowned and skilled Adult and Pediatric Psychiatrist, Dr. Ranjan Ghosh to write a guest blog for us on antipsychotic drugs and when parents should think about it for their children with Autism.
You have read that there’s no known medical cure for autism, yet your doctor is prescribing medication. What’s that about? The answer is simple. Your doctor is not treating Autism: he or she is treating specific symptoms of autism. Often, when symptoms are treated, people with autism are better able to learn, communicate, and generally connect with others. Through this article you will see words like FDA (Federal Drug Administration) and US (United States of America) standards. These are the toughest standards and I feel it is best to be very tough when it comes to mental health management of children. A whole separate subset of medications can apply for adolescents but again with varying side effects. Still, there is a necessity to monitor, as you will see in the following.
Symptoms of Autism That Can Be Treated with Drugs
Not everyone with an Autism Spectrum Disorder has the same symptoms, and not all symptoms can be treated with pharmaceuticals. Most often, when drugs are prescribed for people with autism, they are intended to address specific symptoms including behavioural issues (aggression, self-injurious behaviour and difficulties with day to day functioning), anxiety, depression, obsessive-compulsive disorder, attentional issues, hyperactivity, and mood swings.
Treating Anxiety and Depression
Selective serotonin reuptake inhibitors (SSRIs) are prescribed for anxiety, depression, and/or obsessive-compulsive disorder (OCD). Of these, only Fluoxetine and Sertraline are approved by the FDA for children age 7 and older with obsessive-compulsive disorder. Fluoxetine is also approved for children age 8 and older for the treatment of depression. Also, clomipramine for kids age 10 and older is used to treat OCD.
Two SSRIs, Fluoxetine and Sertraline, have been approved by the FDA to treat obsessive compulsive disorder (OCD) in children who are also diagnosed with autism spectrum disorder. Fluoxetine has been used to treat children with major depressive disorder (MDD) and OCD for over 14 years in the US. Sertraline was approved by the FDA for children age 7 and older with obsessive-compulsive disorder. Despite the relative safety and popularity of SSRIs and other antidepressants, some studies have suggested that they may have unintentional effects on some people, especially adolescents and young adults.
The FDA adopted a “black box” warning label to be noted on all antidepressant medications about the potential increased risk of suicidal thinking or attempts in children and adolescents taking antidepressants. In 2007, the agency extended the warning to include young adults up to age 25. A “black box” warning is the most serious type of warning on prescription drug labeling. It states that patients of all ages should be closely monitored, especially in the beginning phases of treatment, if depression is worsening, or if there is suicidal thinking or behaviour. If there are unusual changes in behaviour such as sleeplessness, agitation, or withdrawal from normal social situations, it is important to notify your physician. This is especially important at the beginning of treatment or when doses are changed.
Treating Behavioural Problems
Many autistic children have significant behavioural problems. Some can be managed by non-pharmaceutical treatments such as applied behaviour analysis (ABA), Hanen Programs, Floortime therapy, etc. But when behaviour is out of control or dangerous, it may be time to consider antipsychotic medications. These work by reducing the activity of the neurotransmitter dopamine in the brain.
Improving these problems could help a person with autism spectrum disorder function more effectively in all areas of their lives. However, risperidone and aripiprazole can actually ease these core symptoms, because relieving irritability often improves sociability while reducing tantrums, aggressive outbursts and self-injurious behaviour.
There are two types of antipsychotics, including:
Older antipsychotic medications:
Older antipsychotic medications such as haloperidol, thioridazine, fluphenazine, and chlorpromazine, may be effective in treating serious behavioural problems. But all, including haloperidol, can have serious side effects such as sedation, muscle stiffness, and abnormal movements, so these medications are only used if newer antipsychotics do not do the job. It would be rare to utilize the medications.
Newer antipsychotic medications:
Some of the newer “atypical” antipsychotics may be a better choice, particularly for children. Both risperidone and aripiprazole were approved by the Food and Drug Administration (FDA) for autism-related irritability. These two drugs are in a class known as atypical antipsychotics and are believed to produce better results than previously used “typical” antipsychotics. In addition to addressing irritability, these drugs also may reduce behaviour such as aggression, deliberate self-injury, and “lashing out” or temper tantrums. The drugs address these behaviours about 30 to 50 percent of the time, but don’t address all behaviour issues — and psychiatric problems are common in children with autism. Even if they are approved medications, they still come with side effects. With risperidone we must continually monitor for hyperprolactinemia, breast enlargement and galactorrhea. With aripiprazole we must monitor for tremors.
Other atypical antipsychotics that have been studied recently with encouraging results are olanzapine, quetiapine, and ziprasidone. Ziprasidone has not been associated with significant weight gain, though some side effects of these medications can include increased appetite and weight gain. It is important to consult with your doctor to monitor these side effects, and also make a commitment to a healthy diet and exercise.
The medications used for autism spectrum disorder may be used to treat similar symptoms in other disorders. Many of these medications are prescribed “off-label.” This means they have not been officially approved by the U.S. Food and Drug Administration (FDA) for use in children, but the doctor prescribes the medications if he or she feels they are appropriate for your child. Further research needs to be done to ensure not only the efficacy but the safety of psychotropic agents used in the treatment of children and adolescents.
Olanzapine and other antipsychotic medications are used “off-label” for the treating symptoms such as aggression in addition to other serious behavioural disturbances in children, including children with autism.
One in four people with autism spectrum disorder (ASD) also has a seizure disorder. Usually, they are treated with anticonvulsants such as Tegretol (carbamazepine), Lamictal (lamotrigine), Topamax (topiramate), or Depakote (valproic acid). The level of the medication in the blood should be monitored carefully and adjusted so that the least amount possible is used to be effective. Although medication usually reduces the number of seizures, it cannot always eliminate them. These medications act as both anti-seizure as well as mood stabilization.
Treating Inattention and Hyperactivity
Stimulant medications such as Methylphenidate and Atomoxetine used safely and effectively in people with attention-deficit hyperactivity disorder (ADHD) have also been prescribed for children with autism. These medications may decrease impulsivity and hyperactivity in some children, especially those with higher functioning. Clonidine, an antihypertensive, is sometimes prescribed for hyperactivity and impulsiveness as well.
Let me be as up front and frank here. I feel that this is the most over diagnosed condition. There are exceedingly rare circumstances that you may need to use stimulants in the ASD population. The problem with this class is that it also increases obsessions, compulsions and additionally makes it even harder for a person with ASD to express themselves.
Assessing Drug Options
All pharmaceuticals described in this article have the potential for side effects. Some, when prescribed for autism, are prescribed “off-label,” meaning that they are prescribed for purposes other than that for which they were approved. Just remember that no pharmaceutical intervention comes without potential risks. We will summarize the risks in Table 1-1.
Consult with a Doctor
Typically developing children and children with autism may respond differently to certain medications. It is important that parents work with a doctor who has experience with children with autism. Children taking any medications should be monitored closely. The doctor should prescribe the lowest dose possible to be effective. Ask the doctor about any side effects the medication may have and keep a record of how your child responds to the medication.
Because of the risk of any pharmaceutical intervention, it makes sense to use drugs only if and when symptoms are severe or uncontrollable by other means. Even then, it’s critically important that you consult a medical doctor with experience in autism and, if appropriate, pediatrics. Be sure that you understand the potential side effects. Ask your doctor whether any of these side effects could be dangerous and be sure you know what to do if any problems arise. Make a follow-up appointment too so your doctor can assess the success of the treatment and recommend any changes to the dosage.
The Food and Drug Administration (FDA) has approved two drugs for treating irritability associated with the autism (risperidone and aripiprazole). The prevalent behavioural problems associated with autism spectrum disorder, including repetitive behaviour, communication, and social issues, have not been able to be improved by medication at this time, since there are no drugs are currently approved to address these core symptoms.
However, a breakthrough may be on the horizon. A major Swiss pharmaceutical company, Roche, says it has received a designation from the Food and Drug Administration to help expedite what could be the first drug to treat these core characteristics of autism. Roche released news in January 2018 that the FDA has granted its breakthrough therapy designation for the development of balovaptan, a drug that has the potential to improve “core social interaction and communication” in those with autism. Results from a clinical trial in adults with autism released in 2017 indicated that balovaptan was successful in helping to improve challenging social behaviour. Additionally, it was deemed safe and well tolerated.
Another trial looking at children and adolescents on the spectrum is underway and additional studies are in the works.
Ranjan Ghosh, MBBS, MD (USA)
Sr. Consultant Dept. of Psychiatry
American Board Certified Adult and Paediatric Psychiatry
Reg # 80063 WBMC
Reg# 125679 KMC
Table 1-1 (All names of medicine are in their generic composition form). Some side effects to look out for and not a comprehensive list.
|Medication||Usage||Side Effects||Special Consideration|
|Selective Sertonin Reuptake Inhibitor (SSRI)|
|Fluoxetine||Major Depressive Disorder, Obsessive Compulsive Disorder||Akathisia, worsening of mood, Suicidal black box warning||Need to monitor for sleeplessness and increased energy.|
|Sertraline||Obsessive Compulsive Disorder||Akathisia, worsening of mood, Suicidal black box warning||Need to monitor for sleeplessness and increased energy.|
|Clomipramine||Obsessive Compulsive Disorder, Behavioural problems||Movement disorders- dystonia, tardive dyskinesia, and Extrapyramidal symptoms. Tremor and Orthostatic hypotension. Withdrawal effects.||Older agent which in current thinking is a second line agent after trying atypical antipsychotics. Seizure, Serotonin syndrome, Depression, Mania, and Suicidality.|
|Haloperidol||Behavioural Problems (aggression and Mood) and psychosis||Movement disorders- dystonia, tardive dyskinesia, and Extrapyramidal symptoms.||Older agent which in current thinking is a second line agent after trying atypical antipsychotics.|
|Thioridazine||Behavioural Problems (aggression and Mood) and psychosis||Movement disorders- dystonia, tardive dyskinesia, and Extrapyramidal symptoms.||Older agent which in current thinking is a second line agent after trying atypical antipsychotics. Look for ocular pigmentation.|
|Fluphenazine||Behavioural Problems (aggression and Mood) and psychosis||Movement disorders- dystonia, tardive dyskinesia, and Extrapyramidal symptoms.||Older agent which in current thinking is a second line agent after trying atypical antipsychotics. Retinal/ corneal deposits. Seizure risk|
|Less likely to cause movement disorders.|
|Risperidone||Behavioural Problems (aggression and Mood) and psychosis||Appetite increase for carbohydrates, hyperprolactinemia, galactorrhea, and possible diabetes mellitus.||Prolactin levels need to be checked along with Fasting blood sugar and Lipid profile. ECG also needed to assess for QTc after prolonged usage.|
|Aripiprazole||Behavioural Problems (aggression and Mood) and psychosis||Appetite increase for carbohydrates, tremors, and possible diabetes mellitus.||Fasting blood sugar and Lipid profile needs to be taken. ECG also needed to assess for QTc after prolonged usage.|
|Olanzapine||Behavioural Problems (aggression and Mood) and psychosis||Appetite increase for carbohydrates and diabetes mellitus and increased lipids and cholesterol.||Works best but has most likelihood of carbohydrate craving and weight gain.
Fasting blood sugar and Lipid profile needs to be taken. ECG also needed to assess for QTc after prolonged usage.
|Quetiapine||Behavioural Problems (aggression and Mood) and psychosis||Appetite increase for carbohydrates, and possible diabetes mellitus.||Fasting blood sugar and Lipid profile needs to be taken. ECG also needed to assess for QTc after prolonged usage.|
|Ziprasidone||Behavioural Problems (aggression and Mood) and psychosis||Akathisia, QTc prolongation and Torsades de Pointes.||Most QTc prolongation in this class but no increased risk of Diabetes.|
|All have withdrawal seizure if abruptly stopped.|
|Carbamazepine||Mood stabilization (aggression and Mood)/ Seizure disorder||Dizziness, rash, blood dyscrasias: agranulocytosis, thrombocytopenia, leukopenia, pancytopenia, and hepatotoxicity.||Levels of the medication should be taken along with CBC and LFT.|
|Lamotrigine||Mood stabilization (aggression and Mood, Tx depression)/ Seizure disorder||Dizziness, rash, blood dyscrasias, angioedema and hepatic failure.||Levels of the medication should be taken along with CBC and LFT. Look out for life threatening rash (Steven Johnson Syndrome)|
|Topiramate||Mood stabilization (aggression and Mood)/ Seizure disorder||Dizziness, weight loss, metabolic acidosis, and cognitive dysfunction.||Cognitive dullness and decreased appetite/ weight loss.|
|Valproic Acid||Mood stabilization (aggression and Mood)/ Seizure disorder||Dizziness, thrombocytopenia, hepatotoxicity, pancreatitis, pancytopenia, and hyponatremia.||Levels of the medication should be taken along with CBC and LFT.|
|Methylphenidate||ADHD, Narcolepsy||Anorexia, headache, insomnia, nausea/vomiting, weight loss, motor tics and emotional lability.||Dependency, abuse, psychosis, hallucinations, mania and aggressive behaviour. Should not be dosed more than 1mg/kg.|
|Atomoxetine||ADHD||Anorexia, headache, insomnia, nausea/vomiting, weight loss and irritability.||Psychosis, hallucinations, mania and aggressive behaviour, depression, suicidal ideation and orthostasis.|
|Clonidine||ADHD||Somnolence, headache, hypotension||Severe hypotension and rebound hypertension possible.|
|Balovaptan||ASD- core social interaction and communication|