The neuropsychiatric disorders such as obsessive-compulsive disorder (OCD), autism-spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) lead to certain traits such as impulsivity and compulsivity, and increased irritability. Research has indicated that these disorders in early childhood can persist to impulsivity and addictive behavior in adulthood (1,2). Addictions in adulthood can stem from a simple pleasure that turns into a compulsion with several neural and brain adaptations that occur as a result of changes on the neural-transmission in the brain, and physiology associated with the chemical / behavior leading to deficiencies in motivation and learning (3).
One proposed hypothesis in the etiology of these disorders, based on observations in neuro-imaging studies, are the glutamatergic interactions in the frontal area of the brain. Glutamate is the most abundant excitatory neurotransmitter in the nervous system.
European researchers have heavily investigated the role of glutamate modulators as a potential therapeutic strategy. Information can be found about the research on these findings on this website: https://www.tactics-project.eu/. This project concluded last year.
Moving from mechanism (lab studies, animal studies) to clinical efficiency/safety/ and tolerability is the name of the game in medical science.
A recent systematic review was conducted to assess different therapeutic strategies in the above mentioned conditions in children and adolescents, including medications and one natural compound, N-acetyl cysteine (NAC) either in isolation or as an augmentation to medication and/or cognitive-behavioral therapy (CBT) (4). The authors discuss the major limitations in pediatric research, which include the lack of properly conducted research trials by investigators, the study design (i.e. pilot trials or open label studies), and high levels of statistical heterogeneity. The authors also mention that the proposed mechanism of action between treatments all involve the glutamatergic pathways but differ widely between each group. Additionally, aspects such as adverse events methods of reporting were not properly outlined in most studies.
It is too early to have any definitive answers based on the evidence in the available literature based on this study, however the authors concluded that it is worthwhile to further investigate two therapies, memantine and NAC, in the pediatric population as they demonstrate the greatest risk-to-benefit ratio, and riluzole in adults.
More information to follow this blog post. Stay tuned or contact me for questions.
1. Billstedt, E., at al. (2007). Autism in adults: symptom patterns and early childhood predictors. Use of the DISCO in a community sample followed from childhood. J Child Psychol Psychiatry, 48(11):1102-1110.
2. Lewin, A. B., et al (2006). A neuropsychiatric review of pediatric obsessivecompulsive disorder: etiology and effi cacious treatments. Neuropsychiatr Dis Treat, 2(1), 21–31.
3. Tomko, RL et al. (2018). N-acetylcysteine : A potential treatment for substance use disorders. Curr Psychiatr. 17(6): 30-55.
4. Mechler, K et al. (2018). Glutamatergic agents in the treatment of compulsivity and impulsivity in child and adolescent psychiatry: a systematic review of the literature. Z Kinder Jugendpsychiatr Psychother. 46(3): 246-263.