Monday, February 6, 2023

Clinical Trial of some FDA Approved SSRI's for treatment of seizures in Dup15q Syndrome and serotonin/dopamine supplements




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. 

2022

As I bid farewell to 2022, I say adieu with some bittersweetness but also with some relief.  It has been an amazing year of travel adventure for the family as we stayed at a oceanfront airBNB at Oceanside for Gabriel's birthday and went on an amazing cruise to Alaska.  It has also been a busy year for Liam as he has graduated from mommy homeschool Abeka curriculum and started kindergarten at Heights Christian Elementary school.  He has also had quite a busy year of extracurricular activities since the pandemic lockdown has lifted.  He finished a dance class, went to summer camp at Heights, went to Lego Camp for a few days in the summer, swam throughout the whole summer and is now in level 2 and hopefully he can continue on this summer.  Through church, he participated in basketball clinic, golf class and soccer.  He even took 6 weeks of yoga for children through the community center.  He also is finishing up his beginner's piano class and had his first recital at a hall in Mt. Sac College. Liam enrolled in cooking classes as well as Chess master through his school and we made tons and tons of Christmas cookies for the holiday.   Lucas went kayaking and paddle boarding for the first time and did great!  He has always loved water. For Halloween, Liam went as an angel and Lucas as Spiderman.  Lucas is on this last year of elementary school before starting junior high next year.  We are lucky he found a really great 6th grade teacher who is working with him and showing me things I didn't think he could do but is mastering in the classroom such as matching letters and numbers!  His seizures are still at bay with 1-2 occurring almost every morning as he wakes up. 

 Liam had his first school Christmas concert where he fell so hard as he tried to get down the steps that the whole audience gasped with concern.  Luckily, he was not injured and said his line "An angel appeared to Joseph" like a pro. He dressed as a cowboy for a school cowboy themed day and I am sure everyone thought he was just adorable, I know I did.  We spent Christmas with Gabe's parents and visited the Cathedral of our Lady in downtown for mass and surprisingly bumped into the priest who married Gabe and I.  We learnt that he has been promoted to Monsignor and is serving at the cathedral.  Seeing him was such a beautiful coincidence and it was the best Christmas present Spirit could have given me.  For dinner, we did something unconventional and had dinner at Spire76, the top of one of the tallest builings in downtown Los Angeles.  The lights illuminating the city was more beautiful than Christmas light shows we've paid to see and found it awe inspiring to see the city change so much (for the better) over the 42 years since I've been here.  We then visited The Bloc where they had some beautiful lights and show for free and took some memorable family Christmas pictures! After Christmas, the family went to Las Vegas and stayed at Paris hotel for some good food and relaxation.  We had an extravagant dinner at Gordon Ramsay's steakhouse and visited Bellagio to view their beautiful Christmas decorations in the atrium.  In the new year, the family had dduk-guk and went for a walk at the Sequoia forest at Carbon Canyon Park then went to Mt. Baldy for the kids to play in the snow.  New Year in 2023, we spent a quiet day with Gabe's parents and I took all the ingredients for dduk guk and made it at their house.   Liam bowed "sebae" and received money from his grandparents, a tradition I am trying to teach him every year. 

Overall, it's been a great and memorable year.  The only downside has been the mess in the cryptocurrency world where my investments totally tanked compared to the previous year.  There has been scandals and the collapse of reputable (or so we thought) centralized exchanges such as FTX and Celsius and I've lost money with the collapse of a certain stablecoin. Although not directedly tied to FTX, some of my investments are locked for withdrawal through its contagion.  But, I am still hopeful there will be an upturn eventually but not necessarily in 2023.  I have hope and conviction that cryptocurrency is good for mankind and that it will help humanity to be on a level playing field to get ahead.