How fascinating and clever is this research study done to find already FDA approved drugs to treat seizures in Dup15q Syndrome!!! This bypasses drug discovery starting from scratch which can take decades to create the drug, do clinical trials and then get FDA approval, time my son can't afford to loose. This group must have felt the urgency of parents to find seizure treatment and bypassed all that work and went straight to a databank of already FDA approved drugs and engineered drosophila flies that mimic Dup15q Syndrome and screened them for seizure reduction against a variety of drugs. It turns out that drugs that showed most promising belong to a class of antidepressants notably Mirtazapine (trade name, Remeron). In jist, these drugs modulate serotonin levels in the brain much like SSRI's. The mechanism of action is by stimulation of serotonin receptor 5-HT1A while inhibiting another receptor 5-HT2. They showed that if 5-HT1A is inhibited and receptor 5-HT2 activated, the seizures get worse. The results showed over 55% reduction in seizures with Remeron followed closely by Lyrica and wellbutrin. The principal investigator stated in an interview that a new antidepresant drug trintellix/Brintellix may have more specificity to a target site than Remeron! That is exciting and promising news! About 10 years ago, I suggested to a parent support group that given the symptoms so many with the syndrome experience such as anxiety and GI issue that serotonin levels were low and maybe SSRi's could help with the syndrome, although I wasn't thinking of seizure control at the time. I considered adding 5HTP or other serotonin supplements to Luki's diet but gave up pursuing the idea because he was so young at the time and I was already experimenting with DHA, accupuncture, CBD oils, creatine, CoQ, etc... I wonder now how his seizures would have been controlled had I started him on the supplements. It is really hard when there is no one else giving it to their children and all I am going off is my hunches and intuition with no confirmed scientific data. I had to wait 10 years for that! I need to listen to my intuition more often! The thing is, when I first got the diagnosis, I was in fight or flight mode and we've heard of people who obtain supernatural abilities and strength in dangerous predicaments. There have been stories of mothers able to lift heavy trucks to save their babies in danger. I think in the beginning when I was in the flight or fight mode, I had so many ideas come to me (not so much now, I've grown accustomed to the condition) most of which I had no ability to pursue. Had I gone to our neurologist 10 years ago and requested SSRI or Remeron for Lucas, they would have labeled me as "that crazy mom" and shrugged me off. I also remember a lively discussion with another mom linking sodium channel modulators in the brain of Dup15 to control seizures. I never followed up with it but now I wonder if there is something do it. Maybe I need to wait another 10 years for research to make the connection...
It’s so ironic that such widely used medications right under our noses may be potential treatments! I’ve always felt shooting random AED’s without actually understanding the underlying pathology is missing the mark and may do more harm than good - or at most only serve as a band-aid for a bigger problem. We need a med that works like a key to open a lock, something specific to this disorder rather than using a hammer to break open the lock which is why I prefer to live with the few seizures he has at night than add another AED or two. I worry these meds will irretrievably remodel his brain chemistry over time and do more harm in the long run. I wish clinical trials for trintellix can happen soon. I hate seeing so many drug commercials on tv but Trintellix is so familiar to me from the ads. The study suggests Trillentix/Brillentix may be more specific than Remeron. If Remeron reduces seizures by 50%, I wonder what the percentage reduction will be with trillentix!
For 3 nights, we have had Luki on dopamine/serotonin supplements. I haven't started the 5 HTP, yet as I am trying one at a time. The last two nights, his seizures have not reduced in frequency, but they seem to be milder. While on most nights he thrashes about in bed with arms flapping and legs kicking; after the supplements, he no longer kicks his legs. On his first seizure at 1 am, he just jolted up and stared off as if in surprise. Usually, he will thrash about. This morning he had another one and we noticed that he did not kick his legs but just flapped his arms. Coincidence? We will wait and see. The dopamine/serotonin supplement needs to be taken for 5 days then off for two days. I am a bit concerned that the data shows only 33.3% seizure reduction with serotonin itself versus over 55% reduction with Remeron. And how the heck does an eye drop dorzolamide reduce seizures by 50%? And meclizine, an anti-nausea medication reduces seizures by 43.8%?? Although Felbamate (50% reduction), works well for some individuals with Dup15, we have not had much luck with it. The results kind of seem to be everywhere and nowhere.
I only give Luki half the recommended dose of the serotonin/ dopamine supplement and only at nighttime. I break open the capsule and mix it with his yogurt. I will also present the data to his neurologist to see if he will be agreeable to prescribing Remeron. Although, prescription medications have their side effects, too one being increased thoughts of suicidal ideations. It baffles me how an antidepressant actually makes you want to kill yourself??? Also, starting and stopping SSRI's need to be done judiciously and titrated carefully. If the supplements do their magic, maybe I don't need to get prescription drugs. Let's wait and see what happens.
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Day 4 update:
On day 3 I reduced his night time dose of lamictal to half and skipped his morning dose. Bad idea. He woke up crying for about 5 minutes. It seemed like he was having pain (headache?). He also had one of his usual "wake up" seizures. Maybe taking away the lamictal was too soon? I will give him his morning dose and only half his night time dose and see what happens. I am keeping him home today to monitor more closely. So far so good. He is back to his cheerful self and ate a very good breakfast.
Day 5 update: No morning seizures noted.
Day 6 update: AM seizure with flapping and kicking.
Day 7 update: day 1 of 2 OFF day of supplement. Wake up seizure noted.
Day 8 update: Day 2 of 2 OFF day of supplement. Wake up seizure noted.
Day 9 update: Took supplement at night. No morning seizure on day 10. Giggling noted around 2 am.
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