Thursday, May 28, 2009

Adventures with real time

I've added a link (on the left) to a really nice new blog by a fragile X parent who has just started her daughter on minocycline, and is blogging about the experience. I should say that I don't know these folks at all, other than getting permission to link. While they may well have gotten the idea to try minocycline from me and from this blog, I have no idea how it will all turn out---but check it out and follow the story.

Along the same lines, there is a recent paper from Japan suggesting that minocycline can act as a potent augmentation strategy for atypical antipsychotics (Risperdal, Abilify, etc.) in the treatment of schizophrenia:

Minocycline as adjunctive therapy for schizophrenia: an open-label study.

Clinical Neuropharmacology 2008 Sep-Oct;31(5):287-92.

Miyaoka T, Yasukawa R, Yasuda H, Hayashida M, Inagaki T, Horiguchi J.
Department of Psychiatry, Shimane University School of Medicine, Izumo, Japan.

Minocycline is a caspase inhibitor, decreases inducible nitric oxide synthase, and has been shown to delay disease in a mouse model of neuropsychiatric disorders. Recently, we reported the antipsychotic effects of minocycline in patients with schizophrenia. In a pilot investigation, we administered minocycline (150 mg/d) for 4 weeks as an open-label adjunct to antipsychotic medication to 22 patients with schizophrenia. The Positive and Negative Syndrome Scale for schizophrenia showed statistically significant and robust clinical improvements with minocycline treatment, which were maintained at follow-up evaluation 4 weeks after the end of minocycline treatment. There were no adverse events. These results suggest that minocycline may be a safe and effective adjunct to antipsychotic medications, and that augmentation with minocycline may prove to be a viable strategy for "boosting" antipsychotic efficacy and for treating schizophrenia.

This raises the interesting possibility that minocycline may (among many things) enhance the effectiveness of atypical antipsychotics. So far, I have seen fragile X patients respond to minocycline montherapy, but many of the most impressive responses have been in people taking atypical antipsychotics as well. This is oddly similar to the results obtained with Ampakines in clinical trials with schizophrenic subjects, and possibly in fragile X subjects as well (as suggested in Liz Berry-Kravis' CX 516 trial.)

This may also be a good time to address a question which I get asked a lot: will older people with fragile X respond to treatment with minocycline? Obviously, we are early in the game, so it is hard to say anything definitive at this point. However, I have seen some of the best responses to minocycline in adult patients, and some of the youngest patients I've seen treated have shown no observable effect. This may be related to co-administration of atypical antipsychotics, or other meds, as noted above, which tends to be more common in older individuals. Or, it may simply be that in younger patients minocycline is correcting synaptic defects before they can cause obvious behavioral problems, whereas older people with fragile X have had a longer time to form abnormal connections and develop symptoms, so correction (however partial) results in more apparent improvement. Generally speaking, I've seen impressive responses in most young adults (let's say 15-25), with a somewhat more gradual and prolonged response in older people. Some of the fragile X kids in the 5-8 age range have had little apparent benefit, and their parents have elected to discontinue, especially with the perceived risk of dental staining. We'll see if this observation amounts to anything, but it does contradict the general assumption that most drugs with a specific mechanism of action should work best in the youngest patients. In a way, this would be a favorable effect; if therapeutic effects are generally most easily observed in young adults with fragile X, this will make future trials with a wide range of agents much easier to conduct.