August 26, 2013

Might Galantamine Help Some Autistic Patients?

Award Winning Non-Fiction Blogs - BlogCatalog Blog DirectoryA few years ago, my son had a fMRI that showed blunted choline. This has always bothered me. So, after a ton of research, I asked my son's psychiatrist why not try Galantamine, a substance extracted from a flowering plant called the snowdrop (and marketed both as a nutrient and as a drug under the name Reminyl), to see if will enhance choline? I faxed him the research. He wrote a prescription.

 Within a few weeks of giving our autistic son 4mg Galantamine H.S. (at night) we saw a MAJOR increase in eye contact. It's been several months, and the increased eye contact continues.

Any other evidence Galantamine helps autistic individuals? Yes.

In a 2006 study, published in the Journal of Child Adolescent Psychopharmacology,  Rob Nicolson and colleagues administered galantamine for 12 weeks to 13 autistic children in an open-label trial, where parents and a physician rated children monthly using two different behavioral scales.

According to this study: “Patients showed a significant reduction in parent-rated irritability and social withdrawal on the Aberrant Behavior Checklist as well as improvements in emotional lability and inattention on Conners’ Parent Rating Scale. Similarly, clinician ratings showed reductions in the anger subscale of the
Children’s Psychiatric Rating Scale.”

Additionally, 8 out of the 13 children were judged to be responders on the Clinical Global Impressions scale. Based on these findings, researchers suggest Galantamine may be particularly beneficial for autistic children who exhibit aggression, out-of-control behavior, and inattention. They further note that while galantamine’s effects in this study were more modest than the effects of risperidone (one of the most common drug treatments for autism), galantamine—unlike risperidone— appears to have few significant side effects.

Good news, considering late night commercials show recent lawsuits suing makers of Risperdal after the drug gave autistic males boobs. Yes, boobies. Breasts. Boobs. Not only boobs, but lactating boobs.
How weird is that? One can only imagine what the heck is in Risperdal that would cause that to happen....

Anyway, the above study on Galantamine is consistent with those of an earlier study by Helmut Niederhofer et al. (see ARRI 16/4), which found that Galantamine was at least moderately effective in reducing the behavior problems of autistic children who did not respond to other medications. 

Historical fact: Back in the 1950's, Russian doctors isolated Galantamine from a plant called the Caucasian Snowdrop.

Is Galantamine contraindicated for patients who also have epilepsy? According to one study, the answer is no. And from what we've seen, there has been no increase in our autistic son's seizure activity with the adding of 4mg of Galantamine at night. See below study for further insight....

The safety and tolerability of galantamine in patients with epilepsy and memory difficulties.


Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294-0017, USA. rlgriffith@uabmc.edu


Individuals with epilepsy commonly experience memory loss. We investigated the safety and tolerability of galantamine in treatment of memory loss in a pilot study of 28 patients with epilepsy, randomly assigned to galantamine (n=13) or placebo (n=15) and followed for a total of 12 weeks. Participants underwent blinded memory assessment at baseline and 12 weeks (Selective Reminding Test, 7/24 Spatial Recall). One participant in the galantamine group had a suspected recurrence of brain neoplasm and increased seizures; all other participants receiving galantamine showed no increase in seizure activity during the trial. Patients in both groups reported mild, tolerable side effects (headache, appetite suppression), with no difference between groups. No significant differences were observed on the memory measures when both groups were retested at Week 12. Galantamine appears to be safe and tolerable in patients with epilepsy.

A recent study, published in October 2013, from researchers in Iran, further supports Galantamine in treating autism. See, "Galantamine efficacy and tolerability as augmentative therapy in autistic children. A randomized, double-blind, placebo study."

 2010 Jan;40(1-2):211-6. doi: 10.1007/s12031-009-9236-1.

Mechanisms of neuroprotective effects of nicotine and acetylcholinesterase inhibitors: role of alpha4 and alpha7 receptors in neuroprotection.


Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. aakaike@pharm.kyoto-u.ac.jp


Neurotoxicity induced by glutamate and other excitatory amino acids has been implicated in various neurodegenerative disorders including hypoxic ischemic events, trauma, and Alzheimer's and Parkinson's diseases. We examined the roles of nicotinic acetylcholine receptors (nAChRs) in survival of CNS neurons during excitotoxic events. Nicotine as well as other nicotinic receptor agonists protected cortical neurons against glutamate neurotoxicity via alpha4 and alpha7 nAChRs at least partly by inhibiting the process of apoptosis in near-pure neuronal cultures obtained from the cerebral cortex of fetal rats. Donepezil, galanatamine and tacrine, therapeutic acetylcholinesterase (AChE) inhibitors currently being used for treatment of Alzheimer's disease also protected neuronal cells from glutamate neurotoxicity. Protective effects of nicotine and the AChE inhibitors were antagonized by nAChR antagonists. Moreover, nicotine and those AChE inhibitors induced up-regulation of nAChRs. Inhibitors for a non-receptor-type tyrosine kinase, Fyn, and janus-activated kinase 2, suppressed the neuroprotective effect of donepezil and galantamine. Furthermore, a phosphatidylinositol 3-kinase (PI3K) inhibitor also suppressed the neuroprotective effect of the AChE inhibitors. The phosphorylation of Akt, an effector of PI3K, and the expression level of Bcl-2, an anti-apoptotic protein, increased with donepezil and galantamine treatments. These results suggest that nicotine as well as AChE inhibitors, donepezil and galantamine, prevent glutamate neurotoxicity through alpha4 and alpha7 nAChRs and the PI3K-Akt pathway.
Galantamine augments dopaminergic neurotransmission within the hippocampus by enhancing the activity of acetylcholine receptors. Low dose Galantamine treatment sounds like a promising new treatment in autistic patients who suffer from difficulty sustaining eye contact and controlling behaviors. 

[PubMed - indexed for MEDLINE]

August 15, 2013

Self-Injurious Behavior in Autism: Where it may Start in the Brain

Award Winning Non-Fiction Blogs - BlogCatalog Blog DirectoryMight Deep Brain Stimulation Targeting Specific Areas of Brain, Help Autistic People Plagued by Self-injurious Behavior?

Doctors at University Hospital in Cologne Germany wanted to help an autistic boy who couldn’t stop hurting himself. The 13 yr old non-verbal, autistic boy was suffering from life-threatening self-injurious behavior (SIB). Doctors treated him with deep brain stimulation (DBS) targeting the amygdaloid complex of his brain, says a 2012 Frontiers in Human Neuroscience Report.

Results were surprising. 

And may give new hope to finding a cure to chronic self-injurious behavior in autistic patients.

When doctors positioned electrodes in various parts of the autistic boy’s brain, they noted only electrodes positioned to stimulate a specific part of amygdala, the basolateral (BL) area of amygdala, improved both SIB and autism related symptoms.

Stimulation of only the basolateral area with electrodes not only radically reduced SIB, but improved socialization, nocturnal sleep and sparked rudimentary speech. Conversely, stimulating other areas of brain made SIB and autism related symptoms worse.
The basolateral amygdala is located in the limbic related area of brain. 

Stimulating other brain areas had no effect or worsened self-injurious behaviors.  

According to the Journal of Neuroscience, the basolateral amygdala controls emotions, learning and memory.

What’s more, after 8 weeks of continuous electrical stimulation of the basolateral region, the autistic boy became higher functioning. Going from severely autistic to moderately autistic. 

44 weeks into this implanted deep brain stimulation treatment, the battery on device malfunctioned, and during the month long lull in treatment, the boy’s self-injurious behavior exploded. Imagine the parents despair. Once battery was replaced his symptoms improved.

Scientists caution more studies are needed to validate DBS as a treatment for chronic self-injurious behavior in children and adults with autism. 

However, this case is “intriguing and promising,” said Ali Rezai of the Ohio State University Wexner Medical Center.

Of interest: 

·         This part of the brain called amygdala is involved in the etiopathogenesis (where it's speculated self-abuse stems from) of autism and self-injurious behavior.
·         DBS in the basolateral amygdala was effective and did not evoke side-effects, thus having potential for treatment of patients with severe autism and related SIB.

In our autistic son's case, I've noticed something interesting. When he's given Ativan for seizures, it's effective, but if you give him Ativan for self-injurious behavior, it worsens his behavior. Why? One possible reason is that Ativan deactivates parts of the brain that need to be activated to control self-injurious behavior. 

Another thing I've noticed is certain epilepsy drugs seem to increase his self-injurious behavior, even if they're effectively controlling seizures. For instance, Topamax (topiramate). Why is this? One reason could be that Topamax reduces excitability in the basolateral amygdala. If the study using DBS says activating this region reduces SIB, then it would make sense that deactivating this brain area would increase SIB. 

Clearly, pharmaceutical and autism research studying autistic people who have both seizures and self-injurious behavior is lacking. 

The development of a drug that activates the basolateral amygdala, while also deactivating parts of brain involved in seizure spread, would be helpful. Or the development of a drug that activates basolateral amygdala, so it could be an adjunct to work synergistically with seizure medication.  Currently, it doesn't seem there are pharmaceutical drugs that activate this region. 


  • Representing 19 San Diego County children diagnosed with Autism Spectrum Disorder (ASD) in their appeal of the San Diego Regional Center's termination of funding for a crucial therapy. The victory resulted in a complete reinstatement of funding and set a precedent that allows other children to obtain the treatments they need.