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Living with Autism

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April 15, 2011

Anti-Psychotics and Other Medications for Autism and Chronic SIB

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           Let me say this about anti-psychotics in the treatment of autism and chronic self-injurious behavior (CSIB): They seldom work. 

Why? 

Anti-psychotics attach to multiple “receptors” in the brain. Each “receptor”—as if God did this to show us who’s really in charge, has subtypes--- all with unique mechanisms of action. 

For additional ego-crushing lessons, neurotransmitter systems (histamine, adrenergic, dopaminergic, etc) that may cross talk and recruit each other. Hey, you, D1, yea it’s a2, activate, researchers closing in. Hurry. Tweak your mechanism of action and show low affinity for incoming agent.

For years, researchers have been obsessing over how to treat SIB. Well, Ok, I don’t know if they’ve been obsessing, but if they haven’t, they should be. Obsessive people get shit done.

Anyway, one the things that research shows is Dopamine (mainly D1 in corpus striatum—an area rich in receptors) dysfunction is implicated in chronic, refractory SIB. In case you’re wondering: 

There are no pure D1 antagonist drugs for clinical use in USA.

Consequently, psychiatrists prescribe multiple drugs to target SIB. 

Problem is, “Overblocking” or “underblocking” one receptor can throw brain into reverse, neutral, forward, or all three, within hours, depending on onset, peak and steady state of drug, and interactions with other drugs taken.

Don’t panic. It’s not hopeless. Finding synergistic (where all the receptors play nicely together) combination involves a LOT of cross-analysis, adjustments, trials and errors. It may take years. It may take weeks. Whatever it takes, don’t give up. SIB has to be STOPPED. At the very least, reduced. 

Atypical Anti-psychotics used to treat our Son’s Autism and Self-Injurious Behavior (SIB):

 DRUG                    What Happened After Drug Given              

  *(Typical)
1. Haldol:           Retrocollis, oculogyric crisis, laryngeal
                                        pharyngeal Dystonia. Increased seizures.
                        Not effective on SIB. Given @ hospital
                     
2. Risperdal:         Slight reduction SIB, slight increase
                          Seizures; Tongue paralysis & tremor

3. Geodon:             Little effect on SIB, restless, crying,
                           Confused look on face, possible drug-
                           induced headache, dizziness, slight
                           increase seizures. Given @ hospital.

4. Seroquel:           Little effect on SIB outside sedation @
                           300 mg PRN. Slight seizure elevation
                           noted.

5. Zyprexa:            5mg zydis disintegrating tablet, slight
                           reduction SIB, tongue edema (swelled),
                           slight increase seizures.


What to do when bad reaction to anti-psychotic happens:

1.    Stop giving/taking them!

2.    Report side effects to health care provider

3.    If you’re having trouble breathing, call 911

Anti-dotes given to reverse adverse reactions to anti-psychotics:

1.   Cogentin  Intra-muscular (IM)
2.   Benadryl  PO (by mouth) or (IM)     


Thoughts on why these drugs didn’t work so well:

Haldol: Has high affinity for D2 in temporal and prefrontal areas, blocks dopamine in nigrostriatal pathways, which raises risk of extra pyramidal symptoms (EPS), slight affinity for D1 and D4, minimal affinity for serotonin and alpha-adrenergic receptors

Risperdal: High affinity for D2, slight affinity for D1 receptors. Targets various serotonin, histamine, alpha-adrenergic receptors

Geodon: High affinity for D2, D3 receptors, targets various serotonin, histamine, alpha-adrenergic receptors; doesn’t touch D1

Seroquel: Low affinity for D1, slightly higher for D2; high affinity for 5 HT2a and histamine receptors. Little, if any affinity for D4. Interestingly, a norepinephrine reuptake inhibitor, which should pump brain up, but is probably countered by the potent (H1)histamine effect

Zyprexa: High affinity for D1, D2, 5 HT 2a & c.


WARNING: Atypical Anti-psychotics: GEODON and SEROQUEL have high prolonged QTc interval risk. (Geodon wins 1st place, Seroquel 2nd). What does QTc risk mean? A high QTc score means high risk of elevating your heart rate, as in tachycardia. Rapid heart rate. Risperdal and Zyprexa come in 3rd & 4th place, in that order.

The utmost goal of physicians should be to rapidly achieve and manage neurotransmitter homeostasis in brain to promote and restore health to autistic persons suffering from chronic SIB. 

This may be, in my opinion, the most promising first-line-treatment in controlling devastating chronic SIB in autistic persons. The utmost goal of parents is to work with physicians to achieve this goal, which will most likely include using adjunct treatments, such as special diets, vitamins, herbs, massage, ABA therapy, exercise or whatever research supports as reasonable adjunct to target goal of achieving neurotransmitter homeostasis in brain.


What is showing promise for our son as of this month:
(This has changed now, of course)
1.    Topamax 100 mg Given 7a (50mg) & 7p(50mg) (Brand name also seems to be better at controlling atonic, but again, tachphylaxis occurs and you have to adjust meds as needed)
2.    Keppra 3000 mg  Given 7a (750mg) 1pm (750mg) 7p (1500mg) (keppra has always been a mainstay drug, seems to be very good for our's son's epilepsy, however, only the BRAND NAME, by UCB, as everytime we tried any generic, it caused increase in seizure activity)
3.    Clonazepam (1 mg) 1p (0.5mg) 7p (0.5mg) (had to be increased then decreased when increasing it caused more atonic seizures)
4.    Lamictal 300 mg  Given 7a (150 mg), 1p (150mg) (ended up increasing myoclonus)
5.    Seroquel  50 mg   Given 1p (ended up increasing seizures)
6.    Guanfacine 4mg   Given 7a (2mg)  1p (2mg)
7.    Mirtazapine 15mg  Given H.S. (night) 8p  (D/C: ended up causing RLS, aka restless leg syndrome)

Adjuncts: B-Vitamin/Iron complex
               Calcium/Vit D3 complex
               Multi-vitamin children’s chewable
               Himalaya Bacopa monnieri (herb)
               MRM Liver X with Bio-Sorb



Okay, so that’s what he’s on NOW, and I know it’s way too many meds, but our GOAL is to keep REDUCING meds, because goal is always LOWEST and LEAST drugs possible. This takes time. And careful thought. For example, NOW that we’ve reached final titration of the newest seizure med, Topamax, we will begin to scale DOWN on Keppra, seek to have clonazepam only as PRN (as needed for breakthrough seizure activity or agitation), and eventually, fade out Seroquel.

As for other new drug—Guanfacine--this drug has been a real surprise. I learned about this drug during one of my marathon research adventures. I then asked psychiatrist if we could try it, since I believe my son’s SIB could be fueled by episodic states of hyper-arousal: No doubt, hyperarousal being a ‘chaotic and frightening flood of affect that threatens and overwhelms brain’ could fuel SIB. Guanfacine is an alpha-2a receptor agonist, used to treat high blood pressure, thus decreasing body’s release of adrenaline and stress hormones. After all the anti-psychotic side effects, Guanfacine seemed like bite of a brown sugar and buttercream chocolate.

The great thing about Jamey, my son, by the way, is that no matter how horrible things get, he is an amazing autistic person. He blows everyone away with his ability to bounce back, as if the hammering he does to himself, and the panic and pain of it all, is somehow, for such a time as this, a useful tool in the hands of God.

For the things which are seen are temporal, but the things which are not seen are eternal.” 2 Corinthians

2 comments:

Selene said...

Wanted to post and tell you how compelling your story is, I've read from the beginning, it's amazing and moving. Thanks so much for sharing it here, and thinking of you and your family.

Karl said...

It's great that there are other medications for that kind of disorder. Thanks a lot for sharing that valuable information.

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