N-Acetylcysteine Add-On Treatment in Refractory Obsessive-Compulsive Disorder

Afshar, Hamid; Roohafza, Hamidreza; Mohammad-Beigi, Hamid; Haghighi, Mohammad; Jahangard, Leila; Shokouh, Pedram; Sadeghi, Masoumeh; Hafezian, Hasan

doi:10.1097/jcp.0b013e318272677d

Cited by 124 publications

(102 citation statements)

References 30 publications

(31 reference statements)

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“…38 N-acetylcysteine has been shown to be potentially efficacious in a bewildering array of divergent disorders, from bipolar disorder 10,15,23 to schizophrenia, 6,14 obsessive-compulsive disorder, 39 nailbiting, 40 autism, 41 attention-deficit/hyperactivity disorder, 42 cocaine and cannabis abuse, 43 smoking, and blast traumatic brain injury, 44 although there are negative studies, including those in bulimia 45 and pediatric trichotillomania, 46 and the methodological quality of trials is highly variable. 4 As N-acetylcysteine has multiple mechanisms of action, it remains to be clarified if it works on common targets across disorders, such as oxidative stress or inflammation, or if some actions, such as glutamate-cysteine exchange, are more important to some disorders than others, such as addictions.…”

Section: Figure 2 Mean ± Se Estimates From Mixed-effects Model Repeamentioning

confidence: 99%

The Efficacy of AdjunctiveN-Acetylcysteine in Major Depressive Disorder

Berk

Dean²,

Cotton³

et al. 2014

J. Clin. Psychiatry

151

138

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Objective: Major depressive disorder (MDD) is one of the most common psychiatric disorders, conferring considerable individual, family, and community burden. To date, treatments for MDD have been derived from the monoamine hypothesis, and there is a paucity of emerging antidepressants, especially with novel mechanisms of action and treatment targets. N-acetylcysteine (NAC) is a redox-active glutathione precursor that decreases inflammatory cytokines, modulates glutamate, promotes neurogenesis, and decreases apoptosis, all of which contribute to the neurobiology of depression.Method: Participants with a current episode of MDD diagnosed according to DSM-IV-TR criteria (N = 252) were treated with NAC or placebo in addition to treatment as usual for 12 weeks and were followed to 16 weeks. Data were collected between 2007 and 2011. Results:The omnibus interaction between group and visit for the Montgomery-Asberg Depression Rating Scale (MADRS), the primary outcome measure, was not significant (F 1,520.9 = 1.98, P = .067), and the groups did not separate at week 12 (t 360.3 = −1.12, P = .265). However, at week 12, the scores on the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT) differed from placebo (P = .03). Among participants with a MADRS score ≥ 25, NAC separated from placebo at weeks 6, 8, 12, and 16 (P < .05). Additionally, the rate of change between baseline and week 16 was significant (t 221.03 = −2.11, P = .036). NAC treatment was superior to placebo at week 16 for secondary readouts of function and clinical impression. Remission and response were greater in the NAC group at week 16, but not at week 12. The NAC group had a greater rate of gastrointestinal and musculoskeletal adverse events. Conclusions:Being negative at the week 12 end point, and with some positive secondary signals, the study provides only limited support for the role of NAC as a novel adjunctive therapy for MDD. These data implicate the pathways influenced by NAC in depression pathogenesis, principally oxidative and inflammatory stress and glutamate, although definitive confirmation remains necessary.Trial Registration: www.anzctr.org.au Identifier: ACTRN12607000134426 Clin Psychiatry 2014;75(6):628-636 J

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Section: Figure 2 Mean ± Se Estimates From Mixed-effects Model Repeamentioning

confidence: 99%

The Efficacy of AdjunctiveN-Acetylcysteine in Major Depressive Disorder

Berk

Dean²,

Cotton³

et al. 2014

J. Clin. Psychiatry

151

138

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“…Moreover, directly disrupting glutamatergic transmission (ie, by deleting a postsynaptic scaffolding protein called SAPAP3; Bienvenu et al, 2008) triggered pathological OCD-like grooming behavior in mice that was reduced by SRI treatment (Welch et al, 2007). Finally, agents that modulate glutamate (eg, riluzole, N-acetylcysteine, and memantine) have been shown to ameliorate OCD symptoms in open (Aboujaoude et al, 2009;Coric et al, 2005;Feusner et al, 2009;Lafleur et al, 2006;Pittenger et al, 2011;Rodriguez et al, 2010;Stewart et al, 2010) and controlled trials (Afshar et al, 2012;Ghaleiha et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept

Rodríguez

Kegeles

Levinson

et al. 2013

Neuropsychopharmacol

303

204

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Serotonin reuptake inhibitors (SRIs), the first-line pharmacological treatment for obsessive-compulsive disorder (OCD), have two limitations: incomplete symptom relief and 2-3 months lag time before clinically meaningful improvement. New medications with faster onset are needed. As converging evidence suggests a role for the glutamate system in the pathophysiology of OCD, we tested whether a single dose of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, could achieve rapid antiobsessional effects. In a randomized, double-blind, placebo-controlled, crossover design, drug-free OCD adults (n ¼ 15) with nearconstant obsessions received two 40-min intravenous infusions, one of saline and one of ketamine (0.5 mg/kg), spaced at least 1-week apart. The OCD visual analog scale (OCD-VAS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) were used to assess OCD symptoms. Unexpectedly, ketamine's effects within the crossover design showed significant (po0.005) carryover effects (ie, lasting longer than 1 week). As a result, only the first-phase data were used in additional analyses. Specifically, those receiving ketamine (n ¼ 8) reported significant improvement in obsessions (measured by OCD-VAS) during the infusion compared with subjects receiving placebo (n ¼ 7). One-week post-infusion, 50% of those receiving ketamine (n ¼ 8) met criteria for treatment response (X35% Y-BOCS reduction) vs 0% of those receiving placebo (n ¼ 7). Rapid anti-OCD effects from a single intravenous dose of ketamine can persist for at least 1 week in some OCD patients with constant intrusive thoughts. This is the first randomized, controlled trial to demonstrate that a drug affecting glutamate neurotransmission can reduce OCD symptoms without the presence of an SRI and is consistent with a glutamatergic hypothesis of OCD.

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“…In addition, a proportion (n = 5, 14.3%) of the final group did not complete the full 16 weeks of the study, and four of these participants completed only until Week 4. Although ITT principles were employed in the statistical analysis, detecting a clinically relevant result may have been hindered further given that NAC has been repeatedly shown to produce therapeutic effects after 8 to 12 weeks (Afshar, et al, 2012;Berk et al, 2008;Grant, Odlaug, & Kim, 2009). A further limitation acknowledged is in regard to one of the methods of analysis used (i.e., dichotomizing the continuous data); however, other OCD studies have also assessed outcomes based on score cutoffs (see A. M. Garcia et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Participant Characteristics as Modifiers of Response to N-Acetyl Cysteine (NAC) in Obsessive-Compulsive Disorder

Sarris

Oliver

Camfield

et al. 2016

Clinical Psychological Science

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We previously reported on a 16-week, double-blind, randomized placebo-controlled trial (RCT) using 3 grams per day of N-acetyl cysteine (NAC) (1.5 grams twice per day) in 44 participants (aged 18–70) with DSM-5-diagnosed obsessive-compulsive disorder (OCD). We now report on an analysis of age, severity and duration of illness, OCD presentation type, baseline anxiety and depression scores, as well as the use of antidepressant medications as potentially modifying factors. Results revealed a significant effect ( p = .037) for younger participants (under mean age of 34) responding to NAC. This remained significant using OCD severity as a covariate ( p = .044). For those under 34 years of age with less than 17 years of OCD duration, this was also significant ( p = .037). Regression analysis within the NAC treatment group also revealed that duration of OCD presentation was a significant predictor of Yale-Brown Obsessive Compulsive Scale (YBOCS) change at study endpoint ( p = .019), whereas baseline Montgomery–Asberg Depression Rating Scale scores were also a trend-level predictor ( p = .060) of YBOCS change in the NAC group.

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N-Acetylcysteine Add-On Treatment in Refractory Obsessive-Compulsive Disorder

Abstract: This trial suggests that N-acetylcysteine may be a safe and effective option to augment standard treatment in patients with refractory obsessive-compulsive disorder.

Cited by 124 publications

References 30 publications

The Efficacy of AdjunctiveN-Acetylcysteine in Major Depressive Disorder

The Efficacy of AdjunctiveN-Acetylcysteine in Major Depressive Disorder

Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept

Participant Characteristics as Modifiers of Response to N-Acetyl Cysteine (NAC) in Obsessive-Compulsive Disorder

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