The aim of this article is to discuss the use of Abilify (generic name: aripiprazole) as a treatment for people with Fragile X syndrome (FXS). As an “off-label” prescription, Abilify targets behaviors such as irritability, aggression, self-injury and severe tantrums. I am a nurse and a family member of a person with Fragile X and I am familiar with this medication both personally and professionally.
I am curious, and I think there is still a lot to learn, about the mechanism of action of Abilify. Why does this medication work, and how does it affect the brain? Are there other side effects that family members of people with Fragile X who are placed on this medication should watch for or take into account? That is what I set out to learn more about this week.
Is There Evidence This Medication Works “In The Real World”?
My younger brother Matthew began taking Abilify two years ago. Many people with Fragile X, including Matthew, have some autism spectrum disorder tendencies that worsen with changes in routine. Matthew’s behavior problems increased as he started to go through puberty. Our major concern was self-injurious behavior. In Matthew’s case, Abilify has been instrumental in decreasing this behavior. He went from having self-injurious instances daily to maybe once or twice a month, only if he is extremely stressed/overwhelmed. His whole demeanor has changed for the better. Day to day, he seems happier and less overwhelmed by sensory stimuli. He handles crowds WAY better. Abilify has helped him focus and function both at school and in his everyday life.
Does Abilify Stop Aggressive, Irritable, or Injurious Behaviors?
Antipsychotics can be grouped into two categories: First generation antipsychotics (FGA) and second generation antipsychotics (SGA).
FGAs were developed in the 1950s and work only on the dopamine pathway and require higher doses over time to maintain effectiveness. SGAs were developed in the 1980s and work on both the dopamine and serotonin pathways.
FGAs can cause significant side effects, including unwanted physical symptoms. The most serious of these effects are extrapyramidal symptoms (EPS). EPS include continuous muscle spasms and contractions (dystonia), Parkinson’s disease like symptoms, tremors, and uncontrollable mouth movements (tardive dyskinesia). These side effects are more likely to occur with long-term use of FGAs. SGAs can cause these side effects in rare instances, but it is much less likely.
Abilify was approved by the US Food and Drug Administration as a SGA in 2002. It works as a dopamine partial agonist and serotonin blocker.
As a dopamine partial agonist, Abilify can diminish the effects of both dopamine excess (by decreasing dopamine action when there is too much of it) and deficit (by increasing dopamine action when there is too little of it). In the right amounts, dopamine works as a “feel good” chemical. Its major role is telling your brain that you are experiencing something pleasurable. However, too much dopamine can lead to feeling “the jitters”, aggressive, and in a state of mania. The more balanced your free-floating dopamine is, the better your body is at understanding pleasure and staying calm.
As a serotonin blocker, Abilify works to block the receptors that bind serotonin, causing more serotonin to be available. Serotonin is a mood stabilizer that helps with sleep, eating, digestion, and nausea. Low levels of serotonin cause depression while high levels of serotonin cause anxiety, irritability, and or aggression. When more serotonin is free-floating, mood is generally better and aggression is decreased.
Together, serotonin and dopamine help with many things:
- Executive functioning: your ability to make memories, think flexibly, and use self-control
- Stabilizing your mood and helping to control emotional flare-ups
- Motor control
- How you perceive pain
- Your response to stress i.e. your “fight or flight” response
What Are Side Effects of Abilify? Can It Increase Any Symptoms Of Fragile X?
Common side effects of Abilify include dizziness, lightheadedness, drowsiness, weakness, nausea, voting, stomach upset, tiredness, drooling, blurred vision, headache, weight gain, anxiety, insomnia, and constipation. One or more of these side effects are seen in every 1 of 100 people. I have found no evidence that Abilify increased other symptoms of Fragile X. In fact, Abilify seems to target not only unstable mood and aggression, but seems to help modulate some sensory sensitivities, such as hypersensitivity to loud noise or bright lights.
It is important to talk with a neurologist if you consider Abilify because it can interact with other medications including Banzel, Dilantin, Onfi, phenobarbital, Topamax, and Tegretol.
Where Can I Learn More About Abilify and Fragile X?
The article that piqued my interest was Aripiprazole as a Treatment for Fragile X Syndrome. It is the first systematic trial of aripiprazole in the treatment of FXS, and FRAXA was the organization which funded it.
Additional resources I found in the course of my own research included:
- Considering Available Drugs for Fragile X: My Favorite Combination (So Far)
- WebMD: Abilify
- RxList: Abilify
- GoodTherapy: Typical and Atypical Antipsychotic Agents
- National Alliance on Mental Illness (NAMI): Aripiprazole (Abilify)
- FDA: Abilify Medication Guide
- NIH: Aripiprazole in Autism Spectrum Disorders and Fragile X Syndrome
As always, FRAXA has a wealth of resources. If you are interested in more about Abilify or other drugs that can treat symptoms of Fragile X, visit Drug Repurposing.