N-Acetylcysteine for Pediatric Obsessive-Compulsive Disorder: A Small Pilot Study

Abstract

Background: Many children and adults with Obsessive-Compulsive Disorder (OCD) fail to respond to first-line pharmacological and behavioral treatments. Glutamate dysfunction may contribute to the development of OCD. N-acetylcysteine (NAC), a glutamate modulating drug, has shown to be a promising agent in adults with OCD. Methods: We conducted a double-blind, placebo-controlled clinical trial from July 2012 to January 2017. Children ages 8 to 17 years with OCD were assigned to receive NAC (up to 2700 mg/day) or the matching placebo for a period of 12 weeks. Children were required to be on stable psychiatric treatment (both medication and therapy) but were not required to be treatment-refractory. The primary outcome was OCD symptom severity as measured by the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). We used linear mixed models to analyze the effect of NAC compared to placebo. Results: Due to poor recruitment and eventual expiration of the study medication, enrollment was stopped at 11 children out of a planned sample size of 40. Nonetheless, NAC was associated with significant reduction in CY-BOCS total score compared to placebo (Satterthwaite's test: t (37) = 2.36, p = 0.024) with effects separating from placebo beginning at week 8. Mean CY-BOCS total score decreased in the NAC group from 21.4-4.65 at baseline to 14.4-5.55 at week 12. In the placebo group, mean CY-BOCS total score remained unchanged (21.3-4.65). In the NAC group, 1 out of 5 participants achieved >35% improvement in CY-BOCS total score, while none of the six patients in placebo group reached this improvement level. NAC and placebo were well tolerated. One mild adverse event was reported in each group. Conclusions: Our trial suggests that there may be some initial improvement in OCD symptom severity with NAC treatment. NAC was well tolerated in the study population. Future trials should employ multiple sites and have a larger study population to further confirm any benefits of NAC.

N‐acetylcysteine as a new prominent approach for treating psychiatric disorders

“…Although the effects of NAC on SSRI‐resistant OCD are ambiguous, the administration of NAC (1 g day −1 for a week followed by 2 g day −1 for 9 weeks) in combination with the SSRI citalopram significantly decreased OCD symptoms in 34 paediatric and adolescent outpatients (age: 10–21 years) with OCD in a 10‐week multicentre randomized double‐blind placebo‐controlled trial (Ghanizadeh et al, 2017). The same conclusion was obtained from a recent, small ( n = 11) double‐blind, placebo‐controlled clinical trial on the effects of NAC on paediatric patients with OCD (Li et al, 2020). NAC (up to 2.7 g day −1 for 12 weeks) administration in children (age: 8–17 years) who were also on stable psychiatric treatment (drug and therapy) evoked a significant reduction in OCD symptoms beginning at week 8.…”

“…(n = 11) double-blind, placebo-controlled clinical trial on the effects of NAC on paediatric patients with OCD (Li et al, 2020). NAC (up to 2.7 g day À1 for 12 weeks) administration in children (age: 8-17 years) who were also on stable psychiatric treatment (drug and therapy) evoked a significant reduction in OCD symptoms beginning at week 8.…”

Investigational and Experimental Drugs to Treat Obsessive-Compulsive Disorder

“…[46][47][48][49][50] Of note, a recent small open trial on pediatric OCD patients showed some initial positive effects of NAC on OCD symptoms. 51 On the other hand, L-carnosine has been less investigated for OCD, but the only available controlled trial (1 g of L-carnosine as add on to fluvoxamine) showed good results. 55,56 Lamotrigine and Topiramate Lamotrigine and topiramate are two inhibitors of the glutamate AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate) receptors.…”

N-Acetylcysteine Mitigates Social Dysfunction in a Rat Model of Autism Normalizing Glutathione Imbalance and the Altered Expression of Genes Related to Synaptic Function in Specific Brain Areas

“…N-acetylcysteine (NAC) is a synthetic derivative of the endogenous amino acid L-cysteine that is able to modulate glutamatergic neurotransmission and the excitatory/inhibitory ratio (26,27). Furthermore, the anti-oxidant properties of NAC are relevant to the pathogenesis of several neuropsychiatric disorders (28)(29)(30)(31)(32)(33). Indeed, NAC is an essential substrate for the enzyme γ-glutamyl-cisteine synthetase (GCL) in the synthesis of glutathione (GSH), the main antioxidant in tissues (34).…”