With Autism numbers climbing, there are those who look to the profit margin of knowing thousands of children, teens and young adults may need medications to "target behavior." It is unfortunate and incorrect that Autism is still being looked at as a behavioral and developmental disability for many instead of a neuroimmune disease that manifests in repetitive behaviors, anxiety and verbal/social regression. For many, like my daughter, that regression came about after vaccinations. These children tend to be very vulnerable canaries to toxins, thus medications can prove to be problematic for many. It is important to know the mechanism of action in treating symptoms short term, but especially long term as some of these drugs have severe side effects that increase with dosage as well as duration.
Recently, I wrote about a new study showing that over a third of children with an autism diagnosis had high levels of S100B in their blood, a calcium-binding protein that is produced primarily by astrocytes and is indicative of active brain injury. While reading about S100B, I started to realize that some abstracts and research about Risperdal and other anti-psychotic medications were appearing that seemed to show a pattern.
(Note: below is a public video from a parent unrelated to AofA showing her son's Risperdal-related side effect. Her message attached to the video reads, This is my son Nathan he is 13yrs old and started with the neck twitching about 3 months ago. He has been on Risperdal (risperdone) for about 8 years now. I have seen his doctors on a regular basis to discuss the side effects and to see what we can do about weening him off. However he did not say this was Tardive Dyskinasia, he gave me another medication to help with this side effect, but I am not going to keep giving my son medication to solve the problem of a drug side effect. I am trying to get answers, he is scheduled for a Neurologist appt in July and in the mean time we are currently at .05 mg risperdone, he was taking 3 mg before then dropped down to 2, then 1 and now 0.5. I am so confused everything I have looked up on Tardive Dyskinasia shows me that this is what my son has. Nathan is autistic and his doctor recently prescribed us Congentin to help with the neck twitching, but what I have read on Congentin says this is not for patients with Tardive Dyskinesia, its so confusing. All i know is that his twitching gets really bad to where he is so sore from his neck and his doctor also reccomended us taking Benadryl has anyone ever heard of that..???)
Some Facts About the S100B Autism Study
- High S100B levels offer an indicator of cell damage when standard diagnostic procedures are still silent.
- Increased serum S100B protein levels reflect neurological damage.
- Elevated S100B protein may be indicative of active cell injury and can reflect an axonal and glial pathology.
- Serum and cerebrospinal fluid (CSF) levels of S100B protein levels are raised in some autoimmune neuropsychiatric disorders, reflecting the presence of glial cell pathology and continuing neurological damage.
- S100B protein levels were elevated in autistic children, and they were significantly correlated with the degree of the severity of autism
- patients with associated allergic, inflammatory or autoimmune disorders; and patients who were receiving any medications -- were excluded.
I thought it would be helpful to set this up with an "abstract" that is based on studies connecting these dots. Their is a longer version also for any who want to read the corresponding studies:
Instead, the pattern has been this:
----"When you put all the data together, you get a strong biochemical plausibility that this is a Risperdal effect," Doraiswamy tells WebMD.>>>"But we cannot rule out the possibility it is a spurious association. >>> No one should stop Risperdal because of this. Even if Risperdal is linked to pituitary tumors, it may turn out to be fairly rare." >>> Johnson & Johnson is a WebMD sponsor."----
- A lack of association between elevated serum levels of S100B protein and autoimmunity in autistic children
"S100B protein is chiefly found in glial cells and Schwann cells in the central nervous system (CNS) . The clinical significance of S100B protein has substantially increased throughout several areas of clinical neuroscience as it can be used as a reliable and early predictor of poor physiological and cognitive neurological outcomes . Serum and cerebrospinal fluid (CSF) levels of S100B protein levels are raised in some autoimmune neuropsychiatric disorders, reflecting the presence of glial cell pathology and continuing neurological damage [6-8]."
[1a]- S100B in Brain Damage and Neurodegeneration
"This was shown by several different approaches:......Also, an increase of serotonin levels by fluoxetine [PROZAC] administration increased S100B concentrations (Haring et al., 1993; Manev and Manev, 2001).
[2a]- In this context, we have investigated the effect of risperidone on astroglial cells, evaluating morphology, membrane integrity, viability, secretion of S100B, a neurotrophic astrocyte-derived protein and glutamate metabolism (glutamate uptake, glutamine synthetase activity and glutathione synthesis). We demonstrate for the first time that risperidone was able to modulate cell morphology and glial adhesion (Quincozes-Santos et al., 2008), contributing to the proposal that glial cells also are targets of antipsychotics. In addition, risperidone also increased S100B secretion by astroglial cells. S100B is a calcium-binding protein involved in the regulation of cytoskeleton and the proliferation of astrocytes. Beyond its intracellular role, S100B,depending on its concentration, works as a cytokine for neighboring cells (astrocytes, neurons, and microglia) and is able to protect hippocampal neurons against glutamate toxicity. "
[2b] Stanford School of Medicine-Psychiatric Medications
"Risperdal is the brand name for Risperidone, an antipsychotic agent used to treat certain types of psychotic thinking. It has been found to improve both positive and negative symptoms of schizophrenia. The exact mechanism of action of risperidone is unknown."
"The exact mechanism of action of risperidone is not known, but, like other anti-psychotics, it is believed that risperidone affects the way the brain works by interfering with communication among the brain's nerves. Nerves communicate with each other by making and releasing chemicals called neurotransmitters. The neurotransmitters travel to other nearby nerves where they attach to receptors on the nerves. The attachment of the neurotransmitters either stimulates or inhibits the function of the nearby nerves. Risperidone blocks several of the receptors on nerves including dopamine type 2, serotonin type 2, and alpha 2 adrenergic receptors. It is believed that many psychotic illnesses are caused by abnormal communication among nerves in the brain and that by altering communication through neurotransmitters, risperidone can alter the psychotic state.
- Astrocyte -Wikipedia:
"They are the most abundant cell of the human brain. They perform many functions, including biochemical support of endothelial cells that form the blood-brain-barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, and a role in the repair and scarring process of the brain and spinal cord following traumatic injuries."
-Effect of the atypical neuroleptic risperidone on morphology and S100B secretion in C6 astroglial lineage cells.
"We investigated the effect of the atypical neuroleptic risperidone on morphology and S100B secretion in C6 glioma cells, considering the putative involvement of astroglial cells in neuropsychiatric disorders. In the presence of high experimental doses of risperidone, C6 cells become stellate, with process-bearing cells and partial retraction of the cell body followed by detachment from the adhesion surface with practically no cell death. These results indicate that risperidone is able to interfere with C6 cell adhesion without toxic effects. RhoA activator LPA prevented the effects of risperidone on cell morphology. From 6 h risperidone induced a statistically significant increment of about 80% in S100B secretion. These data contribute to the proposal that glial cells are targets of risperidone, which could be involved in the therapeutic response of risperidone to improve autism symptoms."
[5a]- S100B in Brain Damage and Neurodegeneration
"Secreted glial S100B exerts trophic or toxic effects depending on its concentration. At nanomolar concentrations, S100B stimulates neurite outgrowth and enhances survival of neurons during development. In contrast, micromolar levels of extracellular S100B in vitro stimulate the expression of proinflammatory cytokines and induce apoptosis. In animal studies, changes in the cerebral concentration of S100B cause behavioral disturbances and cognitive deficits. In humans, increased S100B has been detected with various clinical conditions. Brain trauma and ischemia is associated with increased S100B concentrations, probably due to the destruction of astrocytes. In neurodegenerative, inflammatory and psychiatric diseases, increased S100B levels may be caused by secreted S100B or release from damaged astrocytes. "
[5b]- The S100B protein in biological fluids: more than a lifelong biomarker of brain distress
".. the S100B protein was detected for the first time in extracellular biological fluids (CSF) of MS patients in concomitance with the acute phase of exacerbation, being essentially undetectable during remission. At that time the appearance of the protein in biological fluids was regarded as a consequence of leakage from damaged cells. Today, the growing recognition that S100B may be regarded as a released neuroinflammatory protein makes it possible to reinterpret the original data as indicating the active participation of S100B in the exacerbation phase of MS. A subsequent longitudinal study that monitored the CSF of MS patients revealed a peak followed by a decrease."
- Increased serum S100B levels in chronic schizophrenic patients on long-term clozapine or typical antipsychotics
"These findings suggest that serum S100B levels in chronic schizophrenia under antipsychotic medication may be increased, suggesting that a dysfunction of astrocytes and/or oligodendrocytes may play a role in the pathogenesis of schizophrenia. Long term treatment with both typical and atypical antipsychotics may produce similar effects on the S100B serum levels, which however remains to be characterized in a large sample of first-episode, medication-naïve patients with schizophrenia using a longitudinal design."
[6a]- Increased serum S100B in never-medicated and medicated schizophrenic patients.
"Our results showed significantly increased serum S100B levels in both never-medicated and medicated patients compared to normal controls "
[6b]- Serum S100B is increased during early treatment with antipsychotics and in deficit schizophrenia.
"Previous studies reported controversial results concerning alterations of astrocytes in schizophrenia. Because S100B may be regarded as a marker for astrocytes, the objective of this study was to examine S100B serum concentrations in 30 patients with schizophrenia with a monoclonal two-site immunoluminometric assay that specifically detects S100B. An ANOVA revealed medication (p<0.005) and deficit vs. nondeficit syndrome (p<0.05) as factors that influenced S100B significantly. S100B was higher in schizophrenic patients treated with antipsychotic drugs for approximately 3 weeks (241.1+/-152.5 ng/l) in comparison with unmedicated patients (111.4+/-31.8 ng/l, p<0.005), and healthy age-matched controls (112.8+/-53.4 ng/l, p<0.001; Bonferroni corrected two-tailed Student's t-test). There was no difference of S100B between unmedicated patients and controls (p>0.05)."
- Increased S100B serum levels in schizophrenic patients with tardive dyskinesia: Association with dyskinetic movements
"Several studies show that calcium-binding protein S100B is increased in schizophrenia and may be involved in the pathogenesis of tardive dyskinesia (TD). We therefore compared serum S100B levels in normal controls (n=60), schizophrenic patients with (n=32) and without TD (n=50). Assessments included the abnormal involuntary movement scale (AIMS) and the positive and negative syndrome scale (PANSS). Serum S100B levels were measured by enzyme-linked immunosorbent assay (ELISA). The results indicated that patients with TD had higher serum S100B levels than normals and those without TD. Serum S100B levels were positively correlated with AIMS scores in patients with TD. These data suggest that increased S100B levels may be related to neuro-degeneration, associated with TD pathophysiology. "
- Tardive Dyskinesia With Risperidone and Anticholinergics
"To the Editor: The following are reports on three Japanese women who developed early-onset tardive dyskinesia during short-term risperidone treatment while taking an anticholinergic agent. "
[8a]- Risperidone-Induced Tardive Dyskinesia http://ajp.psychiatryonline.org/article.aspx?volume=156&page=1290
"Here we report a case of tardive dyskinesia that developed while a patient was on a regimen of risperidone"
[8b]- Tardive dyskinesia following risperidone treatment in Tourette's syndrome
" We discuss the case of a 24-year-old male who first exhibited repetitive head and neck twisting movements that started at 15 years of age....Oral risperidone was started as well as maintained at 1mg with dinner and fluoxetine was increased to 40mg with breakfast. Although his tics were minimal at this dose (YGTSS = mild), he developed severe TD of the lower jaw (oro-mandibular dyskinetic movements) after four months of treatment [Abnormal Involuntary Movement Scale (AIMS) rating = severe]. This movement was entirely different from the initial symptoms both anatomically and phenomenologically... We wish to highlight the need for awareness among clinicians and patients about the potential risk of getting new movement disorders during the course of treatment with risperidone for tic disorders."
[8c]- Risperidone and Tardive Dyskinesia: A Case of Blepharospasm
"We present the case of a young male diagnosed with schizophrenia who developed a blepharospasm form of tardive dyskinesia in association with risperidone."
[8d]- Risperidone-induced tardive movements in young adult patients
"Here, we report a series of four cases with risperidone-induced tardive dyskinesia and dystonia and discuss their management."
- IMPORTANT SAFETY INFORMATION FOR RISPERDAL
"RISPERDAL ® and similar medications can raise the blood levels of a hormone known as prolactin, causing a condition known as hyperprolactinemia. Blood levels of prolactin remain elevated with continued use. Some side effects seen with these medications include the absence of a menstrual period; breasts producing milk; the development of breasts by males; and the inability to achieve an erection. The connection between prolactin levels and side effects is unknown."
- Atypical antipsychotics and pituitary tumors: a pharmacovigilance study.
"Risperidone had the highest adjusted reporting ratios for hyperprolactinemia (EBGM 34.9, 90% confidence interval [CI] 32.8-37.1]), galactorrhea (EBGM 19.9, 90% CI 18.6-21.4), and pituitary tumor (EBGM 18.7, 90% CI 14.9-23.3) among the seven antipsychotics, and one of the highest scores for all drugs in the AERS database. Some tumors were associated with visual field defects, hemorrhage, convulsions, surgery, and severe (>10-fold) prolactin elevations. The EBGM values for risperidone for these adverse events were higher in women, but high EBGM values for these events were also seen in men and children. Moreover, the rank order of the EBGM values for pituitary tumors corresponded to the affinities of these seven drugs for D2 receptors."
- S100 proteins as cancer biomarkers with focus on S100B in malignant melanoma.
"S100B concentrations reflect tumor mass. Serum S100B levels predict efficacy of treatment. Decreasing S100B concentrations reflect response to therapy while increasing S100B concentrations indicate tumor progression."
[11a]- Regulation Of Pituitary Hyperlasia and Neoplasia
"The development of prolactin cell hyperplasia and the transformation to neoplastic prolactin producing pituitary tumors will be investigated in rats using morphological, immunohistochemical and biochemical methods. Morphological and immunohistochemical studies at the light and electron microscopic levels will be used to characterize various subtypes of prolactin cells and mammosomatotropic cells (which produced both prolactin and growth hormone) in hyperplastic and neoplastic MtT/W15 and MtT/F4 tissues. The functions of the pituitary folliculostellate cells in normal, hyperplastic and neoplastic pituitaries will be investigated by immunohistochemical and ultrastructural studies. The role of S100 protein in regulating prolactin secretion will be investigated. Preliminary findings indicate that S100 protein which is present in pituitary folliculo-stellate cells can stimulate prolactin releases in vitro suggesting that these cells may exert a paracrine type regulation of prolactin release.
- Schizophrenia Drugs May Up Tumor Risk
"A statistical "signal" links Risperdal and other schizophrenia drugs to pituitary tumors, FDA researchers report....Seventy percent of these reports were in patients taking Risperdal. "When you put all the data together, you get a strong biochemical plausibility that this is a Risperdal effect," Doraiswamy tells WebMD.