Autism: Celecoxib COX-2 nonsteroidal antiinflammatory agent improves symptoms

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Inflammation and dysfunctional immune system have been implicated in neuropsychiatric disorders like autism spectrum disorders, attention deficit hyperactivity disorder and schizophrenia. In fact, there is a significant overlap in pathogenic factors, structural and functional abnormalities of brain, and clinical manifestations.

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Evidence for role of inflammation and immune dysfunction

1. Increased pro-inflammatory cytokines
2. Altered levels of antibodies
3. Altered levels of natural killer cells
4. Altered white blood cell function
5. Presence of auto-antibodies against brain of patients with autism spectrum disorders
6. Altered genes due to gene-gene, gene-environment, and epigenetic interactions giving rise to wide spectrum of clinical manifestations

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Similarities between ASD and schizophrenia

1. Shared pro-inflammatory andf immune dysfunction markers
2. Shared immune related genetic abnormalities
3. Overlap of altered genetic architecture including  individual, rare mutations
4. Neurotoxic role of glutamatergic neurotransmitter system in brain
5. Excitotoxicity and brain inflammation related to neuro-toxicity of glutamatergic system
6. Increased excitatory receptor activity in brain
7. Increased pro-inflammatory cytokines
8. Enhanced cyclooxygenase-2 (COX2) activity

Role of nonsteroidal anti-inflammatory drugs especially COX-2 inhibitor celecoxib

1. COX-2 inhibitor effective against inflammatory conditions like arthritis
2. COX-2 inhibitors rebalance type-1 and type-2 immune dysfunction
3. COX-2 inhibitors prevent death of brain cells
4. Beneficial effects of celecoxib  in early schizophrenia (Muller 2011)
5. Beneficial effect of celecoxib as adjunct to risperidone in schizophrenia (Akhondzadeh 2007)
6. Beneficial effect Aspirin as adjuvant to usual antipsychotic treatment of schizophrenia (Laan et al 2010)
7. Beneficial effects in major depression

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Dr. Asadabadi and colleagues examined the effect of adjunctive treatment using celecoxib for treatment of autism. The results of the study were published in the journal Psychopharmacology (2012).

Hypothesis of celecoxib-autism study

• Celecoxib has beneficial effects on aberrant behavior in autism

Study design of celecoxib-autism study

• Tertiary care referral center
• Double-blind randomized controlled trial for 10 weeks
• 40 children with autism between 5 and 11 years of age

Intervention

• Celecoxib (Celebrrex®) or placebo in addition to risperidone (Risperdal®)
• Celecoxib dose: 100 mg for first week and then 200 mg/d if body weight less than 30 kg and 300 mg/d for patients with bodyweight greater than 30 kg

Outcome measures studied

• Autism Behavior Checklist ABC-C, a 58-item tool to study disruptive behaviors
• Sub-domains of ABC-C studied included lethargy/social withdrawal, stereotypic behavior, inappropriate speech, irritability and hyperactivity/noncompliance

Results design of celecoxib-autism study

1. Complete response was attained in 55% of treatment group as compared to only 20% in placebo
2. Partial resoonse  was attained in 100% of treatment group as compared to only 60% in placebo
3. Celecoxib addition to risperidone significantly improved autism as compared to placebo:

• Irritability
• Lethargy/social withdrawal
• Stereotypic behavior

4. Celecoxib treatment did not help hyperactivity/noncompliance or inappropriate speech

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Dr. Minocha's comments

Celecoxib adjunctive treatment is beneficial for stereotypic behavior, lethargy/social withdrawal, irritability in patients wit autism spectrum disorders.

Natural Compounds with biochemical effects similar to celecoxib Cox2 

Curcumin, quercetin, green tea and white tea catechins, balcalein, luteolin in celary and parsley, omega-3 fatty acids, resveratrol, naringenin, milk thistle (silymarin), chyrsin, apigenin, blueberry extract, butyrate, baicalein, wogonin, a component in the plant Scutellaria baicalensis, N-Acetyl-L-cysteine, amentoflavone which is a component in Ginkgo biloba and magnesium.

Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health

Is It Leaky Gut or Leaky Gut Syndrome? 

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[Mary Tormey]

This research is unethical and inhuman. People with Autism want safe food, stop abusing them with drugs that cause painful diarrhea.