Autisms drug problem (part-1)
Lauren Gravitz
Connor was diagnosed with autism early when he was just 18 months old. His condition was already obvious by then. He was lining things up, switching lights on and off, on and off, says his mother, Melissa. He was bright, but he didnt speak much until age 3, and he was easily frustrated. Once he started school, he couldnt sit still in class, called out answers without raising his hand and got visibly upset when he couldnt master a math concept or a handwriting task quickly enough. One time, he rolled himself up into the carpet like a burrito and wouldnt come out until I got there, Melissa recalls. (All families in this story are identified by first name only, to protect their privacy.)
Connor was prescribed his first psychiatric drug, methylphenidate (Ritalin), at age 6. That didnt last long, but when he was 7, his parents tried again. A psychiatrist suggested a low dose of amphetamine and dextroamphetamine (Adderall), a stimulant commonly used to treat attention deficit hyperactivity disorder (ADHD). The drug seemed to improve his time at school: He was able to sit still for longer periods of time and focus on what his teachers were saying. His chicken-scratch handwriting became legible. Then, it became neat. Then perfect. And then it became something Connor began to obsess over.
We were told that these are the gives and takes; if its helping him enough to get through school, you have to decide if its worth it, Melissa says. It was worth it for a while.
But when the Adderall wore off each day, Connor had a tougher time than ever. He spent afternoons crying and refusing to do much of anything. The stimulant made it difficult for him to fall asleep at night. So after a month or two, his psychiatrist added a second medication guanfacine (Intuniv), which is commonly prescribed for ADHD, anxiety and hypertension, but can also help with insomnia. The psychiatrist hoped it might both ease Connors afternoons and help him sleep.
In some ways, it had the opposite effect. His afternoons did get slightly better, but Connor developed intense mood swings and was so irritable that every evening was a struggle. Rather than simply tossing and turning in bed, he refused to even get under the covers. He wouldnt go to bed because he was always angry about something, Melissa says. He was getting himself all wound up, carrying on, getting upset at night and crying.
After seven months, his parents declared the combination unsustainable. They swapped guanfacine for over-the-counter melatonin, which helped Connor fall asleep with no noticeable side effects. But within a year, he had acquired a tolerance for Adderall. Connors psychiatrist increased his dosage and that, in turn, triggered tics: Connor began jerking his head and snorting. Finally, at his 9-year physical, his doctor discovered that hed only grown a few inches since age 7. He also hadnt gained any weight in two years; hed dropped from the 50th percentile in weight to the 5th.
That was the end of all the experiments. His parents took him off all prescription drugs, and today, at almost 13 years old, Connor is still medication-free. His tics have mostly disappeared. Although he has trouble maintaining focus in class, his mother says that the risk-benefit ratio of trying another drug doesnt seem worth it. Right now were able to handle life without it, so we do.
Connor is just one of the many, many children with autism who are given multiple prescriptions. Phoenix was only 4 when he started taking risperidone (Risperdal), a drug approved for irritability in autism. Now 15, he has taken more than a dozen different medications. Ben, 34, has autism, but for years he was misdiagnosed with other conditions.
He was in middle school when his mother insisted he take drugs for his depression and disruptive behaviors. His doctor tried one antidepressant after another; nothing worked. In high school, at 15, he was misdiagnosed again, this time with bipolar disorder, and given an anticonvulsant and an antidepressant.
For Connor, eliminating prescription drugs was difficult, but doable. For others, multiple medications may seem indispensable. Its not unusual for children with autism to take two, three, even four medications at once. Many adults with the condition do so, too. Data are scant in both populations, but what little information there is suggests multiple prescriptions are even more common among adults with autism than in children. Clinicians are particularly concerned about children with the condition because psychiatric medications can have long-lasting effects on their developing brains, and yet are rarely tested in children.
In general, polypharmacy most often defined as taking more than one prescription medication at once is commonplace in people with autism. In one study of more than 33,000 people under age 21 with the condition, at least 35 percent had taken two psychotropic medications simultaneously; 15 percent had taken three.
Psychotropic medications are used pretty extensively in people with autism because there arent a lot of treatments available, says Lisa Croen, director of the Autism Research Program at Kaiser Permanente in Oakland, California. Is heavy drug use bad? Thats the question. We dont know; it hasnt been studied.
Sometimes, as in Connors case, a second drug is prescribed to treat the side effects of the first. More often, doctors prescribe drugs for each individual symptom stimulants for focus, selective serotonin reuptake inhibitors (SSRIs) for depression, antipsychotics for aggression and so on. (Children with autism who have epilepsy also typically take anticonvulsants. But because those drugs are effective and easy to assess, theyre usually not seen as part of the polypharmacy problem.)
Kids come in on Zoloft, Depakote and risperidone, says Matthew Siegel, assistant professor of psychiatry and pediatrics at Tufts University in Medford, Massachusetts. Zoloft is an antidepressant, Depakote is a mood stabilizer, and risperidone is an antipsychotic three psychotropic medications that are being prescribed for one individual.
Other times, due to moves or changes in coverage or just a lack of rapport, people on the spectrum end up seeing multiple doctors, all of whom have their own ideas about treatment and may add a new drug without removing another.
The reason for this confusion: No existing medication treats the underlying condition.
The core characteristics of autism include repetitive behaviors, difficulty with social interactions and trouble communicating. Therapy can help, but no medication so far can improve these problems. Instead, drugs merely treat some of the peripheral features ADHD, irritability, anxiety, aggression, self-injury that make life challenging for people with autism.
This practice that can put people on a drug cocktail that may not be effective or appropriate. Each clinician must make her own best guess about what works and is safe, because theres simply not yet enough research. We have so few studies that have looked at single drugs, and so few studies that have even directly compared single drugs, says Bryan King, vice chair of child and adolescent psychiatry at the University of California, San Francisco. Theres such a long path to go down before we get to a point where we see these specific combinations studied.
The straight dope:
The U.S. Food and Drug Administration has approved only two drugs for children and adolescents with autism: risperidone and aripiprazole (Abilify), both atypical antipsychotics prescribed for behaviors associated with irritability, such as aggression, tantrums and self-harm. The drugs help ease these behaviors about 30 to 50 percent of the time, but leave others untouched. And thats a major gap: Psychiatric problems are common in children with autism. According to a 2010 study, more than 80 percent of children with autism at a psychiatric healthcare center also had ADHD, 61 percent had at least two anxiety disorders, and 56 percent had major depression.
Multiple diagnoses lead to drug cocktails, but no clinical trials have tested combinations of the most commonly used medications, so potential drug-drug interactions are unknown. Every drug has side effects, and when you start to mix them together youre looking at something thats not been studied, King says. And in autism, where you might have communication impairments, its even more worrisome because people are less likely to be able to tell you that your medicines are making them feel sick.
Beyond that, say researchers, is the fact that the medicines may not even work.
Many studies have looked at the use of ADHD meds to treat ADHD symptoms in people with autism. The same can be said for obsessive-compulsive disorder and repetitive behaviors, says Daniel Coury, a developmental pediatrician at Nationwide Childrens Hospital in Columbus, Ohio. And with virtually all of these, we find that they dont work as well as they do in people who dont have autism.
That research, too, is relatively sparse and is composed mostly of uncontrolled studies. One 2013 meta-analysis concluded that most studies of psychiatric drugs for autism features are either too small or dont have the right design to determine whether the drugs are effective. The research that does exist, the researchers wrote in that study, is only suggestive, and awaits true assessment in properly controlled studies.
Symptoms of depression, obsessive-compulsive disorder, ADHD and other conditions in people with autism seem similar to those that people without autism may experience. But because the underlying cause is different, the biochemistry may be different overall and also highly variable from person to person.
That is a big problem for any treatment in autism, Siegel says. With so many genetic variations underlying autism, each individuals situation is different, so any treatment needs to be tailored to that individual. Depending on the drug, as little as 20 percent of people may benefit from a drug, even within the ideal conditions of a clinical study. In this milieu, aripiprazole and risperidone stand out because they work up to 50 percent of the time; 50 percent is like a homerun, Siegel says.
Paradoxically, another reason children and adults with autism may take multiple drugs is because as in Connors case doctors prescribe a second medication to mitigate side effects from the first. Antipsychotics, for instance, can cause weight gain and metabolic problems, or even involuntary twitching. Some doctors add metformin to address the weight gain, or benztropine (Cogentin) to ease the jerky movements.
But each additional prescription comes with its own potential side effects. Metformin can cause muscle pain and, less commonly, anxiety and nervousness; benztropine can lead to confusion and memory problems. Doctors less experienced in treating autism might misinterpret these drug effects as new symptoms, and be tempted to medicate them in turn. The great majority of psychotropics are prescribed by primary care doctors who have little or no experience with autism, says Siegel. If people dont know what theyre doing, you might imagine that kids are more likely to end up on multiple medications. (...to be continued)
Source: Scientific American
