Q: My son is 21 years old. He has been described as a higher functioning fragile x boy. Unfortunately, he has aggressive tendencies which have mysteriously gotten worse in the past month.
He is on citalopram, low dose Tenex, and a very tiny dose of BuSpar every day. We tried Abilify a couple of years ago, but stopped it. My recollection was that he began reporting hearing sirens and voices. Obviously not good. However, he has had some very violent episodes just lately - as many as six in the space of four days. We are back to trying Abilify because of this. (Two days into it, and no episode)
I'm wondering about the drug trials I heard were happening in Boston, or about any other thing you might suggest. I'm somewhat hopeful that the Abilify might work, but obviously want to look beyond that in case.
Our son has been working at a restaurant and at a nursery and is quite sociable when he is not having a bad day. He has had to spend the last three years being tutored at home, because the school decided they couldn't (or wouldn't) school him anymore because of his episodes. We were unable to find an out-of-district placement, and, being mistrustful of the school system, decided it was best for him to be tutored at home. The school has paid for this, but this program runs out this month.
It would be possible to find a work placement for him, except for this fear of aggressive episodes. I guess we're on the verge of desperation here.
A: Aggression in fragile X can be treated a few different ways, and you're actually already trying a couple of them. Ordinarily, we think of episodic aggression (sometimes classified as "Intermittent Explosive Disorder") in fragile X as a phenomenon which occurs as a result of severe and intolerable anxiety. For this reason, SSRIs (like citalopram) are often used. However, proper dosage is often the key to getting the best response; since you didn't specify the dose, let me say that ordinary doses like 20-30 mg/d may be somewhat helpful, but not give the best effect. Higher doses, more like those we might use for OCD, are often much more effective---40-60 mg/d would not be considered excessive, and you could even go higher, if needed, since it's so non-toxic.
BuSpar (buspirone) is also used to treat anxiety, and can be very effective in treating aggression, either alone or in combination with SSRIs. However, dosage matters here, too. A few people with severe episodic aggression will respond to amazingly low doses of buspirone (as little as 5 mg three times a day) but most require quite a bit more, up to 60 mg/d in divided doses. Aggression usually also involves some degree of physical hyperarousal, so Tenex is often used to damp down the autonomic nervous system in people with autism and fragile X. As you might guess, I'd suggest that a very low dose isn't enough to stop whatever is going on, so it could be worth trying more. Doses of about 2 mg three times a day would be considered average in a young adult male, so check your dosage and see how it compares.
Generally, I recommend optimizing the meds you're already on before adding new ones, but now that your son has gotten started on Abilify, I'll state that it is an excellent choice for severe behavioral problems in people with fragile X, although his prior poor response might have led me to try something a little different. Still, sometimes adverse effects are reported with a drug when they are really just coincidence; this is especially true with behavioral and psychiatric side effects. It sounds as though the Abilify trial is going well so far, though Abilify has a very long half life, so it accumulates in the system for about 10 days after starting it. In other words, the effective dose (in the bloodstream) will continue to go up, even if you give the same daily dose by mouth. If Abilify works for your son, it might be a good opportunity to clean up the rest of his med regimen but getting rid of the low doses of Tenex and BuSpar (gradually, of course, and over a long time---people with fragile X do seem unusually sensitive to drug discontinuation effects.)
The drug trials that are currently recruiting are mostly looking for subjects who are not on any meds already---this is to try to see the purest effect from the study drug. However, one drug which just finished a small but successful trial in fragile X subjects is widely available: lithium. Many people are scared off by potential toxic effects, but lithium has been taken safely by millions of people around the world, for a range of psychiatric disorders, and it can be remarkably effective. Even before we had specific evidence of efficacy in fragile X, lithium was recognized as an especially effective treatment for episodic aggression, so there is a clear rationale for using it here. Furthermore, there is substantial evidence from basic research and the previously noted clinical trial that lithium can have specific beneficial effects in fragile X, perhaps even improving development over time. The disadvantage is that only a psychiatrist would usually even consider prescribing lithium, since other medical professionals rarely have any experience with it; lithium use also requires regular blood tests, and this makes it unacceptable for many people.
In case you haven't seen it, check out my Xmas entry on minocycline. This may be of interest to you; while it's not something we think of as a psychiatric treatment effective in an emergency, minocycline is showing real promise as an off-label treatment for fragile X, and it often has rather rapid effects. My experience so far is that the best responses often occur in young adults already on atypical antipsychotics (like Abilify), so your son is in the right demographic.