Today’s post is about Tardive Dyskinesia which is a side effect eventually experienced by about 30% of people taking antipsychotic drugs, like risperidone, widely prescribed in both autism and schizophrenia.
Enough money for your lifetime supply of a VMAT2 inhibitor?
It appears that the longer the drug is taken the greater the chance of developing Tardive Dyskinesia.
Tics are quite common in autism and not just in those taking psychiatric drugs.
Tourette’s syndrome is a well-known tic disorder that does overlap with autism, it used to be considered rare, but now 1% of children are thought to be affected. Some common Tourette’s tics are eye blinking, coughing, throat clearing, sniffing, and facial movements.
People diagnosed with Tourette’s might also be diagnosed with ADHD, OCD or indeed autism.
We saw in some Italian research that young children with Tourette’s type autism have a fair chance of seeing their symptoms of autism substantially fade away. It was called Dysmaturational Syndrome.
The part of the brain that is thought to be affected in Tardive Dyskinesia is that same part suspected in Tourette’s and indeed PANDAS/PANS; it is the basal ganglia.
Avoiding Tardive Dyskinesia
The best way to avoid Tardive Dyskinesia is not to use antipsychotic/ neuroleptic drugs.
It appears that high doses of melatonin and other antioxidants may give a protective effect from developing Tardive Dyskinesia.
Treating Tardive Dyskinesia
Much is written about treating Tardive Dyskinesia (TD), because nobody yet has found a cure for it, nonetheless there is a long list of partially effective therapies.
Given that the underlying basis of TD may very likely to overlap to some extent with Tourette’s and PANDAS/PANS it is over broader interest.
A Review of off-label Treatments for Tardive Dyskinesia
The Spanish study below gives a good overview of most therapies, but exclude the very recent therapies based on VMAT2.
All of the studies in the review were small, but you can see that some therapies did seem to help, including:-
· Vitamin E
· Vitamin B6
· Acetazolamide/Diamox
· Amino Acids
· Piracetam
I proposed Acetazolamide/Diamox to potentially treat some autism a while back and some readers of this blog do find it effective.
Piracetam is the world’s first cognitive enhancing (nootropic) drug. It was discovered by mistake when trying to make a cure for motion sickness.
Amino acids may look an odd choice, but in males, and only males, branched chain amino acids (BCAAs) valine, isoleucine, and leucine in a 3:3:4 ratio appears to be beneficial. Another amino acid called Phenylalanine is associated with tardive dyskinesia in men but not in women. It is an established fact that an increase in BCAAs will cause a reduction in phenylalanine in the brain, among a range of other effects.
Amino acids may look an odd choice, but in males, and only males, branched chain amino acids (BCAAs) valine, isoleucine, and leucine in a 3:3:4 ratio appears to be beneficial. Another amino acid called Phenylalanine is associated with tardive dyskinesia in men but not in women. It is an established fact that an increase in BCAAs will cause a reduction in phenylalanine in the brain, among a range of other effects.
Phenylalanine is a precursor for dopamine (as well as tyrosine, norepinephrine, and epinephrine).
One theory is that tardive dyskinesia results primarily from neuroleptic-induced dopamine supersensitivity. So if the BCAAs reduce the amount of dopamine produced, this might explain their effect.
VMAT2
VMAT2 transports monoamines - particularly neurotransmitters such as dopamine, norepinephrine, serotonin, and histamine - from cellular cytosol into synaptic vesicles. Inhibiting VMAT2 will reduce the release of dopamine.
In some circumstances VMAT2 is necessary for the release of the neurotransmitter GABA.
Drugs that inhibit VMAT2 appear to help treat Tardive Dyskinesia and one drug Valbenazine/Ingrezza was FDA approved for this purpose in April 2017. Not surprisingly, it is now being investigated to treat Tourette’s syndrome.
Valbenazine is known to cause a reversible reduction of dopamine release by selectively inhibiting VMAT2.
Conclusion
Since our regular reader Valentina is dealing with Tardive Dyskinesia, she will probably be very interested in Valbenazine.
The problem is the price. The drug will apparently cost $60,000 a year in the US.
So for the time being it is best to work through the list of very cheap interventions that do seem to be partially effective, at least in some people.