Abstract text (incl. figure legends and references)

BACKGROUND Observation examined effects of dextromethorphan, a manageable N-methyl-D-aspartate receptor antagonist involved with AMPA and kainate receptors trafficking, for medication overuse headache (MOH) and correlations of its effect with variables of patients. In 2006 we wrongly indicated the drug ineffectiveness. It was due to treatment shortness. The drug was shown needing a longer time for sensory remapping.

METHOD Participants 576 MOH. Presented data regard 378 (34.6+7.9SD 284 females) divided in 2 matched groups.

Procedure: dextromethorphan 1.5 mg/kg/PO vs amitriptyline 1 mg/kg day/PO, 2 months treatment-period. Baseline evaluation of: Adrenocorticotropic hormone (ACTH), cortisol, L-citrulline co-product in nitric oxide synthesis, microbiome, methylation, patterns, pineal gland volume (MRI), melatonin, psychometric tests.

RESULTS

Dextromethorphan Therapeutic and Side Effects

Drop-out n= 1

Effect decrease pain severity (87%), hrs./pain (72%) p>0.0001 vs amitriptyline (42%, 39% respectively)

Less than 35% benefit

Post-traumatic stress disorder n= 9 females,2 males

Opioids abusers n=25 females

Absolute Refractoriness n=2 females surgically treated pyneocitoma

Side effects

Drowsiness n=135 first week

Dextromethorphan: Therapeutic Effect Correlations

Positive

Cortisol abnormal pattern and high values p< 0.02

or low values p <0.01

ACTH abnormal pattern and value p>0.02

L-citrulline high p>0.009

Sleep rhythm alteration p<0.009

Depression Hamilton D p>0.01

Anxiety Hamilton A p<0.05

Microbiome disturbances p<0.001

Melatonin abnormalities p<0.02

Pineal dimensions RMN p<0.05

No/Poor

Methylation patterns NS

Social stress test TSST p<0.6

CONCLUSION

Hypothalamic-pituitary-adrenal axis function and pineal gland may play role in MOH mechanism and in dextromethorphan effectiveness