The Treatment of Autism With Low-Dose Phenytoin
The Treatment of Autism With Low-Dose Phenytoin
Introduction The drug treatment of autism spectrum disorders is often poorly tolerated and has traditionally targeted associated conditions (such as inattention or irritability) that frequently coexist, with limited benefit for the core social deficits. Here, I describe the novel use of a low dose of the anti-epileptic phenytoin to enhance social functioning in a patient with an autism spectrum disorder.
Case presentation I present the case of a 19-year-old Caucasian man with autism spectrum disorder treated with stimulant medication since early childhood. He experienced long-standing difficulties in establishing and maintaining relationships and reading social cues, and was socially isolated. Within 10 minutes of a single sublingual low dose of phenytoin there was an immediate observable improvement in his eye contact and integration of both verbal and non-verbal communication. This enhanced social functioning associated with his adherence to the low-dose phenytoin therapy was maintained for over 18 months of follow-up. These clinical observations were supported by ratings using the Autism-Spectrum Quotient and the Depression, Anxiety and Stress Scales, recorded pre-treatment and after seven months on 5mg phenytoin.
Conclusion This case report provides the first potential evidence that a low dose of phenytoin, a widely used and well tolerated anti-epileptic medication, may be capable of modifying the core social cognitive deficits associated with autism spectrum disorders. While acknowledging this is a single case study, the lack of availability of safe and effective treatments to address the important core deficits associated with autism spectrum disorders makes this case noteworthy.
Autism is a neurodevelopmental disorder characterized by dysfunction in three core behavioral dimensions: repetitive behaviors, social deficits and language abnormalities. Autism is assigned to a spectrum of disorders that are referred to as autism spectrum disorders (ASDs), distinguishable in the severity of symptoms. Autism is the model disorder of social dysfunction - a key inability to respond appropriately to social cues, including failure to accurately interpret facial expressions. Additional social deficits include unusual eye contact, limitations in facial expression directed to other people, atypical social engagement and responsiveness, difficulty with peer relationships, lack of awareness of other people's thoughts and feelings, poor communication skills, and difficulty initiating social contacts through verbal or non-verbal means.
Only two medications, risperidone and aripiprazole, have so far been approved by the United States Food and Drug Administration for the treatment of autism, and these are for the associated behavioral disturbance. Although effective treatments, they are associated with side-effects including sedation, cognitive impairment, weight gain and metabolic disturbance.
I observed that patients with attention deficit hyperactivity disorder (ADHD) who on their stimulant therapy often still experienced persistent affective instability. The addition of sodium valproate was undertaken in an attempt to improve these symptoms. Unexpectedly, a number of patients reported an improvement in their ability to maintain eye contact during conversations, which in turn enabled them to better read non-verbal social cues and enhanced their comprehension and enjoyment of social interaction. Significantly, this beneficial effect of sodium valproate appeared to have a narrow therapeutic window, with the optimal range between 50 and 200mg daily. A complete loss of efficacy frequently occurred above a dose of 400mg. Similarly, phenytoin is an anti-epileptic that has shown to have some benefit in the treatment of bipolar mood disorder.
I present a case of a man with a childhood diagnosis of ASD and co-morbid ADHD with persistent disruptive behavioral difficulties despite long-term treatment with stimulant medication. Following the addition of a very low dose of phenytoin there was an improvement in multiple areas of his functioning, in particular in the core areas of social interaction impaired in ASDs. He was for the first time able to sustain eye contact, demonstrated more spontaneous facial expression, and began to use gestures during conversation. He also appeared to enjoy and benefit from the company of others.
Evaluations of the effects of medication pre- and post-treatment with phenytoin were two-fold: behavioral observations (for example, client and carer reports, clinician's observations) and formal ratings on behavioral scales (The Depression Anxiety and Stress Scales (DASS) and The Autism-Spectrum Quotient (AQ)).
The DASS is a 42-item self-administered questionnaire designed to measure the magnitude of three negative emotional states: depression, anxiety and stress. This instrument is considered to be an appropriate and reliable measure of overall improvement that may correlate with overall functioning. Depression and anxiety are among the most common ASD co-morbidities and correlate to significantly poorer life functioning.
The AQ, although not a diagnostic instrument, is useful in identifying the extent of autistic traits shown by an adult of normal intelligence. It was designed as a screening tool but also provides a quantitative approach to the measurement of ASD symptoms and is considered to have established test-retest reliability. It was therefore useful in the assessment of clinical improvement.
Abstract and Introduction
Abstract
Introduction The drug treatment of autism spectrum disorders is often poorly tolerated and has traditionally targeted associated conditions (such as inattention or irritability) that frequently coexist, with limited benefit for the core social deficits. Here, I describe the novel use of a low dose of the anti-epileptic phenytoin to enhance social functioning in a patient with an autism spectrum disorder.
Case presentation I present the case of a 19-year-old Caucasian man with autism spectrum disorder treated with stimulant medication since early childhood. He experienced long-standing difficulties in establishing and maintaining relationships and reading social cues, and was socially isolated. Within 10 minutes of a single sublingual low dose of phenytoin there was an immediate observable improvement in his eye contact and integration of both verbal and non-verbal communication. This enhanced social functioning associated with his adherence to the low-dose phenytoin therapy was maintained for over 18 months of follow-up. These clinical observations were supported by ratings using the Autism-Spectrum Quotient and the Depression, Anxiety and Stress Scales, recorded pre-treatment and after seven months on 5mg phenytoin.
Conclusion This case report provides the first potential evidence that a low dose of phenytoin, a widely used and well tolerated anti-epileptic medication, may be capable of modifying the core social cognitive deficits associated with autism spectrum disorders. While acknowledging this is a single case study, the lack of availability of safe and effective treatments to address the important core deficits associated with autism spectrum disorders makes this case noteworthy.
Introduction
Autism is a neurodevelopmental disorder characterized by dysfunction in three core behavioral dimensions: repetitive behaviors, social deficits and language abnormalities. Autism is assigned to a spectrum of disorders that are referred to as autism spectrum disorders (ASDs), distinguishable in the severity of symptoms. Autism is the model disorder of social dysfunction - a key inability to respond appropriately to social cues, including failure to accurately interpret facial expressions. Additional social deficits include unusual eye contact, limitations in facial expression directed to other people, atypical social engagement and responsiveness, difficulty with peer relationships, lack of awareness of other people's thoughts and feelings, poor communication skills, and difficulty initiating social contacts through verbal or non-verbal means.
Only two medications, risperidone and aripiprazole, have so far been approved by the United States Food and Drug Administration for the treatment of autism, and these are for the associated behavioral disturbance. Although effective treatments, they are associated with side-effects including sedation, cognitive impairment, weight gain and metabolic disturbance.
I observed that patients with attention deficit hyperactivity disorder (ADHD) who on their stimulant therapy often still experienced persistent affective instability. The addition of sodium valproate was undertaken in an attempt to improve these symptoms. Unexpectedly, a number of patients reported an improvement in their ability to maintain eye contact during conversations, which in turn enabled them to better read non-verbal social cues and enhanced their comprehension and enjoyment of social interaction. Significantly, this beneficial effect of sodium valproate appeared to have a narrow therapeutic window, with the optimal range between 50 and 200mg daily. A complete loss of efficacy frequently occurred above a dose of 400mg. Similarly, phenytoin is an anti-epileptic that has shown to have some benefit in the treatment of bipolar mood disorder.
I present a case of a man with a childhood diagnosis of ASD and co-morbid ADHD with persistent disruptive behavioral difficulties despite long-term treatment with stimulant medication. Following the addition of a very low dose of phenytoin there was an improvement in multiple areas of his functioning, in particular in the core areas of social interaction impaired in ASDs. He was for the first time able to sustain eye contact, demonstrated more spontaneous facial expression, and began to use gestures during conversation. He also appeared to enjoy and benefit from the company of others.
Evaluations of the effects of medication pre- and post-treatment with phenytoin were two-fold: behavioral observations (for example, client and carer reports, clinician's observations) and formal ratings on behavioral scales (The Depression Anxiety and Stress Scales (DASS) and The Autism-Spectrum Quotient (AQ)).
The DASS is a 42-item self-administered questionnaire designed to measure the magnitude of three negative emotional states: depression, anxiety and stress. This instrument is considered to be an appropriate and reliable measure of overall improvement that may correlate with overall functioning. Depression and anxiety are among the most common ASD co-morbidities and correlate to significantly poorer life functioning.
The AQ, although not a diagnostic instrument, is useful in identifying the extent of autistic traits shown by an adult of normal intelligence. It was designed as a screening tool but also provides a quantitative approach to the measurement of ASD symptoms and is considered to have established test-retest reliability. It was therefore useful in the assessment of clinical improvement.
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