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N-Acetyl Cysteine in the Treatment of Grooming Disorders

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... Other drugs studied for treating TTM include olanzapine, inositol, and naltrexone with limited success [1,[27][28][29]. NAC has been studied in several clinical trials for TTM treatment (Table 1) [30][31][32][33][34][35][36][37][38][39][40][41]. In a 12-week randomized, double-blind, placebo-controlled trial of 50 adult patients with TTM ages 18-65 years, half of the patients received NAC (1200 mg/day), while the other half received placebo pills for six weeks. ...
... After 4 weeks, her hair pulling urges decreased. After another dose increase to 2400 mg/day for 2 weeks, the patient noted compete cessation of hair pulling behavior with maintenance of results after 5 months [41]. ...
... Other pharmacologic treatments include lamotrigine, atomoxetine, methylphenidate, and inositol [42,45]. In recent years, studies exploring the efficacy of NAC in excoriation disorder have revealed promising results (Table 2) [35,41,[46][47][48][49][50][51][52]. ...
Article
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Background: Trichotillomania (TTM), excoriation disorder, onychophagia, and onychotillomania are categorized as body focused repetitive behavior (BFRB) disorders, causing damage to the skin, hair, and/or nails with clinically significant psychosocial consequences. Currently, there are no standardized treatments for these compulsive, self-induced disorders. Studies on treatment of these disorders using psychotropic drugs (i.e., selective serotonin reuptake inhibitors, tricyclic antidepressants, anticonvulsants) have shown variable efficacy. Recently, there is a growing interest in N-acetylcysteine (NAC) for treating BFRBs. NAC is a glutamate modulator that has shown promise in successfully reducing the compulsive behaviors in BFRB disorders. This article provides an updated review of the literature on the use of NAC in TTM, excoriation disorder, onychophagia, and onychotillomania. Methods: Relevant articles were searched in the PubMed/MEDLINE database. Results: Twenty-four clinical trials, retrospective cohort studies, and case reports assessing the efficacy of NAC in TTM, excoriation disorder, and onychophagia were included. No studies for onychotillomania were found in our search. Conclusions: Although NAC has proven successful for treatment of BFRB disorders, data is derived from few clinical trials and case reports assessing small numbers of patients. Larger studies with longer durations are needed to fully establish the efficacy of NAC in these disorders.
... NAC (up to 2.7 g day À1 for 12 weeks) administration in children ( 3 months) therapy induced complete regrowth of their hair, and the positive results were maintained at the 6-month follow-up in the older female (Rodrigues- Barata et al., 2012). Similar results were presented by Odlaug and Grant (2007), who described a significant reduction in urges and cessation of compulsive behaviours after 3 weeks of NAC supplementation (1.2 g or 1.8 g day À1 ) in a 40-year-old female with treatment-resistant TTM or a 28-year-old male with chronic TTM and nail biting. ...
... Interestingly, women with excoriation who were supplemented with 1.2-1.8 g daily of NAC showed major improvements (n = 3) (Silva-Netto et al., 2014) or cessation of skin picking (n = 1) (Odlaug & Grant, 2007) in treatment-resistant disorder. In the case of a 52-yearold female, complete abstinence was maintained at the 4-month follow-up after daily treatment with 1.8 g of NAC (Odlaug & Grant, 2007). ...
... g daily of NAC showed major improvements (n = 3) (Silva-Netto et al., 2014) or cessation of skin picking (n = 1) (Odlaug & Grant, 2007) in treatment-resistant disorder. In the case of a 52-yearold female, complete abstinence was maintained at the 4-month follow-up after daily treatment with 1.8 g of NAC (Odlaug & Grant, 2007). On the other hand, one out of three of women showed a relapse in picking behaviours during the NAC-free period and improvements when the drug was reintroduced (Silva-Netto et al., 2014). ...
Article
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N‐acetylcysteine (NAC) is a well‐known and safe mucolytic agent used in patients with paracetamol overdose. In addition to the aforementioned effects, recent preclinical and clinical studies have shown that NAC exerts beneficial effects on different psychiatric disorders. Multiple potential mechanisms have been indicated to be involved in the therapeutic effects of NAC, including the regulation of several neurotransmitters, oxidative homeostasis, and inflammatory mediators. In this paper, we summarize the current knowledge on the ability of NAC to ameliorate symptoms and neuropathologies related to different psychiatric disorders, including attention deficit hyperactivity disorder, anxiety, bipolar disorder, depression, obsessive‐compulsive disorder, obsessive‐compulsive‐related disorder, posttraumatic stress disorder and schizophrenia. Preclinical studies have shown a positive effect of NAC on animal models of psychiatric disorders; however, the clinical efficacy of NAC is not fully established. NAC remains a strong candidate adjunct treatment for multiple psychiatric disorders in the clinic, but additional preclinical and clinical studies are needed.
... Thus, although UD is not a model for trichotillomania per se, trichotillomania (in humans) and barbering (in mice) are useful starting points to approach the problem of Skin Picking Disorder and UD. Although the mode of action is unclear, trichotillomania [10] and Skin Picking Disorder [11] both respond to N-Acetylcysteine (NAC). Ongoing work in our lab suggests a primary role for oxidative stress in barbering and UD [12]. ...
... NAC, however, was highly efficacious in treating trichotillomania in a randomized double blind placebo controlled trial [10], and open-label case reports suggest the same may be true for Skin Picking Disorder [11]. However, the mechanism of action is unclear: while authors with a psychiatric focus favor subtle interactions with glutamate receptors [10,11], authors with a neurological focus favor oxidative stress as a likely mechanism of NAC efficacy in other disorders [24]. ...
... NAC, however, was highly efficacious in treating trichotillomania in a randomized double blind placebo controlled trial [10], and open-label case reports suggest the same may be true for Skin Picking Disorder [11]. However, the mechanism of action is unclear: while authors with a psychiatric focus favor subtle interactions with glutamate receptors [10,11], authors with a neurological focus favor oxidative stress as a likely mechanism of NAC efficacy in other disorders [24]. Although these possibilities are not mutually exclusive (not least because GSH influences glutamate transmission via the redox modulatory site on the NMDA receptor), in our opinion the lack of reported glutamatergic side effects in patients treated with NAC argues against a primary role for glutamatergic modulation. ...
Article
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Skin Picking Disorder affects 4% of the general population, with serious quality of life impacts, and potentially life threatening complications. Standard psychoactive medications do not help most patients. Similarly, Mouse Ulcerative Dermatitis (skin lesions caused by excessive abnormal grooming behavior) is very common in widely used inbred strains of mice, and represents a serious animal welfare issue and cause of mortality. Treatment options for Ulcerative Dermatitis are largely palliative and ineffective. We have proposed mouse Ulcerative Dermatitis as a model for human Skin Picking Disorder based on similar epidemiology, behavior, and its comorbidity and mechanistic overlap with hair pulling (trichotillomania). We predicted that mouse Ulcerative Dermatitis would be treated by N-Acetylcysteine, as this compound is highly effective in treating both Skin Picking Disorder and Trichotillomania. Furthermore, we hypothesized that N-Acetylcysteine's mode of action is as a precursor to the production of the endogenous antioxidant glutathione in the brain, and therefore intranasal glutathione would also treat Ulcerative Dermatitis. Accordingly, we show in a heterogenous prospective trial, the significant reduction in Ulcerative Dermatitis lesion severity in mice receiving either N-acetylcysteine (oral administration) or glutathione (intranasal). The majority of mice treated with N-acetylcysteine improved slowly throughout the course of the study. Roughly half of the mice treated with glutathione showed complete resolution of lesion within 2-4 weeks, while the remainder did not respond. These findings are the first to show that the use of N-acetylcysteine and Glutathione can be curative for mouse Ulcerative Dermatitis. These findings lend additional support for mouse Ulcerative Dermatitis as a model of Skin Picking Disorder and also support oxidative stress and glutathione synthesis as the mechanism of action for these compounds. As N-Acetylcysteine is poorly tolerated by many patients, intranasal glutathione warrants further study as potential therapy in Skin Picking, trichotillomania and other body-focused repetitive behavior disorders.
... Given our findings of decreased brain GSH/Cr in OCD, interventions that increase GSH levels may represent novel treatments for OCD and possibly other OCRD. Indeed, the GSHprecursor, NAC, has demonstrated preliminary efficacy in the treatment of OCD (65)(66)(67) and other OCRD such as trichotillomania (68)(69)(70), excoriation disorder (69,71) and nail biting (69,72). While others have theorized that the beneficial effects of NAC in OCRD result from its ability to modulate glutamatergic neurotransmission (68), we propose that NAC's capacity to increase GSH synthesis may also play a significant role. ...
... Given our findings of decreased brain GSH/Cr in OCD, interventions that increase GSH levels may represent novel treatments for OCD and possibly other OCRD. Indeed, the GSHprecursor, NAC, has demonstrated preliminary efficacy in the treatment of OCD (65)(66)(67) and other OCRD such as trichotillomania (68)(69)(70), excoriation disorder (69,71) and nail biting (69,72). While others have theorized that the beneficial effects of NAC in OCRD result from its ability to modulate glutamatergic neurotransmission (68), we propose that NAC's capacity to increase GSH synthesis may also play a significant role. ...
... Given our findings of decreased brain GSH/Cr in OCD, interventions that increase GSH levels may represent novel treatments for OCD and possibly other OCRD. Indeed, the GSHprecursor, NAC, has demonstrated preliminary efficacy in the treatment of OCD (65)(66)(67) and other OCRD such as trichotillomania (68)(69)(70), excoriation disorder (69,71) and nail biting (69,72). While others have theorized that the beneficial effects of NAC in OCRD result from its ability to modulate glutamatergic neurotransmission (68), we propose that NAC's capacity to increase GSH synthesis may also play a significant role. ...
Article
Background: Several lines of evidence support the hypothesis that lower cerebral levels of glutathione (GSH), associated with increased oxidative stress, may contribute to obsessive-compulsive disorder (OCD). However, no studies to date have investigated brain GSH levels in individuals with OCD. Methods: Twenty-nine individuals with OCD and 25 age-, sex-, and race-matched comparison individuals without OCD underwent single voxel 2D J-resolved proton magnetic resonance spectroscopy (MRS) to examine GSH levels in the posterior cingulate cortex (PCC). MRS data were analyzed using LCModel and a simulated basis set. Group metabolite differences referenced to total creatine (Cr), as well as relationships between metabolite ratios and symptom severity as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), were analyzed using linear regression with adjustment for age, sex, and race. Results: One OCD participant failed to produce usable PCC MRS data. We found significantly lower PCC GSH/Cr in OCD participants compared with non-OCD participants (β = -0.027 [95% CI: -0.049 to -5.9 × 10(-3)]; P = 0.014). PCC GSH/Cr was not significantly associated with total Y-BOCS score in the OCD group (β = 5.7 × 10(-4) [95% CI: -4.8 × 10(-3) to 5.9 × 10(-3)]; P = 0.83). Conclusions: Lower PCC GSH/Cr may be indicative of increased oxidative stress secondary to hypermetabolism in this brain region in OCD. Future MRS studies are warranted to investigate GSH levels in other brain regions that comprise the cortico-striato-thalamo-cortical circuit thought to be abnormal in OCD.
... The other patient was a 40-year-old female with TTM who had previously failed several other pharmacologic therapies and was titrated from 600 to 2,400 mg over 10 weeks resulting in complete remission of hair-pulling behavior (Odlang & Grant, 2007). ...
... Ozcan et al. also reported of another pediatric case with two female patients (aged 14 and 30) treated with 1,200 mg/day of NAC for 4-6 months who has significant improvement in hair-pulling behavior and full regrowth of hair (Ozcan & Seckin, 2016). Case reports with this disorder include the aforementioned study by Odlang & Grant, (2007)) who described the titration of NAC from 600 to 1800 mg leading to complete cessation of skin picking in one patient, which was maintained at the 4-month follow-up. In addition, (Ghanizadeh et al., 2013). ...
... In addition, (Ghanizadeh et al., 2013). Case reports on this topic include the aforementioned study by Odlaug et al. with a patient with comorbid TTM and onychophagia who had a resolution of both disorders at a dose of 1800 mg/day (Odlang & Grant, 2007). Berk et al. also reported on three patients with comorbid bipolar disorder who had their nail-biting symptoms improve with treatment with NAC. ...
Article
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Treatment of psychodermatological conditions, particularly body focused repetitive behavior disorders, is often unsatisfactory. Various psychopharmacological and non‐pharmacological treatments have been used to ameliorate the symptoms of these disorders. N‐acetylcysteine (NAC) is a newer modality in the treatment of these disorders. This short review focuses on pharmacology, mode of action and use of NAC in common body focused repetitive disorders such as trichotillomania, skin picking disorders and onychotillomania (nail biting). Current research and literature review have been evaluated and will be discussed. This article is protected by copyright. All rights reserved.
... Similarly, anti-epileptic drugs that increase gamma-aminobutyric acid (GABA) activity and suppress the release of excitatory glutamate are also known to be effective in certain cases. Reports have suggested that glutamate can affect activity in the key reward circuitry, which may decrease the craving to indulge in reward-seeking compulsive skin picking behavior [84,100,101]. Consequently, anti-epileptic drugs can exert a positive influence on controlling skin picking behavior. ...
... Lithium carbonate is a mood stabilizer that acts by modulating glutamate receptors and has been shown to improve skin picking behavior as well as acne excoriee in an individual [102]. Other drugs that function on a similar basis include N-acetyl cysteine (NAC) [84,101] and Riluzole [100]. NAC is the only drug that has demonstrated the most promising results in treating SPD thus far. ...
... Additionally, in a 12-week randomized double-blind trial, administration of NAC resulted in improved profiles for 47% of the individuals, compared to 19% who were given a placebo [104]. Several other cases where NAC has been linked to the reduction or prevention of skin picking behavior have also been reported [84,101,[105][106][107]. Despite these promising results, NAC may often be poorly tolerated by individuals due to its mucolytic properties [108]. ...
Article
Full-text available
Dermatillomania or skin picking disorder (SPD) is a chronic, recurrent, and treatment resistant neuropsychiatric disorder with an underestimated prevalence that has a concerning negative impact on an individual’s health and quality of life. The current treatment strategies focus on behavioral and pharmacological therapies that are not very effective. Thus, the primary objective of this review is to provide an introduction to SPD and discuss its current treatment strategies as well as to propose biomaterial-based physical barrier strategies as a supporting or alternative treatment. To this end, searches were conducted within the PubMed database and Google Scholar, and the results obtained were organized and presented as per the following categories: prevalence, etiology, consequences, diagnostic criteria, and treatment strategies. Furthermore, special attention was provided to alternative treatment strategies and biomaterial-based physical treatment strategies. A total of six products with the potential to be applied as physical barrier strategies in supporting SPD treatment were shortlisted and discussed. The results indicated that SPD is a complex, underestimated, and underemphasized neuropsychiatric disorder that needs heightened attention, especially with regard to its treatment and care. Moreover, the high synergistic potential of biomaterials and nanosystems in this area remains to be explored. Certain strategies that are already being utilized for wound healing can also be further exploited, particularly as far as the prevention of infections is concerned.
... Given that NAC acts on glutamatergic transmission, glutathione, neurotrophin, apoptosis, mitochondrial function, and inflammation systems, research has been initiated recently on its action in neuropsychiatric disorders 1 . Clinical trials have reported that glutamatergic modulators may be effective on repetitive or compulsive behavior disorders [2][3][4] . For this reason, NAC has been considered as a single or additional drug therapy to be used in psychiatric disorders, and its use has increased in recent years 5 . ...
... The common aspect of the disorders included in OCRD is committing repetitive behaviors or cognitive acts to remove cognitive preoccupation and discomfort 20 . Their common etiology, similar clinical features and similar responses to treatment resulted in the grouping of these disorders within the same spectrum 3,[22][23][24][25] . ...
... One of these cases involved a 23-year-old female patient who displayed hair regrowth in the second month of treatment with NAC at a dose of 1200 mg/day. The other case involved a 19-yearold female patient who showed hair regrowth in the third month of NAC treatment at a dose of 1200 mg/day with no apparent side effects 3,111 . There are also case reports indicating that a 28-year-old female patient with nail biting and TTM showed recovery from both behaviors with 1200 mg/day of NAC, and a 40-year-old female patient recovered from her hair-pulling behavior with 2400 mg/day of NAC 3 . ...
Article
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Information on the use of N-acetylcysteine (NAC) in neuropsychiatric disorders has increased in recent publications. Although there are positive reports on the use of NAC in obsessive-compulsive and related disorders (OCRD), such data have not yet been validated. This article aims to review the research, case series and case reports that have been published about the use of NAC in OCRD. Research papers and case reports on the use of NAC in OCRD published within the last five years have been reviewed using the search engines of “Pubmed” and “Medline Central” databases. The search was performed by matching the terms “obsessive-compulsive disorder (OCD)”, “trichotillomania (TTM)”, “nail biting”, “skin picking”, “hoarding disorder”, and “body dysmorphic disorder” with “N-acetylcysteine”. The search identified 4 papers on TTM, 3 papers on nail biting behavior, 1 paper on OCD and 1 paper on skin-picking behavior. Three of these papers were double-blind, placebo-controlled studies and four were case reports/series. The results of 2 papers out of the 7 that we reviewed showed that there was no difference between NAC and placebo, while 5 papers reported that the response to the NAC therapy was positive. We did not find any papers on the use of NAC in either hoarding disorder or body dysmorphic disorder. NAC is thought to be a promising psychopharmacologic agent in OCD, which is defined under OCRD due to its common etiology, similar clinical features and similar response to treatment, as well as in TTM, skin picking and nail biting. The effectiveness of glutamatergic modulators on repetitive behaviors or OCD has increased interest in NAC. Although there are a few studies in the area, many research projects are being planned, with some already in progress (www.clinicaltrials. gov), a fact that emphasizes the importance of NAC in OCRD treatment. NAC has been used in a broad spectrum of conditions such as paracetamol intoxication, doxorubicin cardiotoxicity, ischemia-reperfusion-induced injury of the myocardium, acute respiratory distress syndrome, bronchitis, chemotherapy intoxication and heavy metal intoxication. In recent years, there has been an increase in the number of studies exploring the use of NAC in neuropsychiatric disorders such as schizophrenia, autism, bipolar disorder and OCRD. In this review, we have seen that the results of studies assessing the efficacy of NAC in psychiatric disorders are promising; however, there is a need for further studies to evaluate its mechanism of action, appropriate dose range and duration of treatment.
... Similarly, anti-epileptic drugs that increase gamma-aminobutyric acid (GABA) activity and suppress the release of excitatory glutamate are also known to be effective in certain cases. Reports have suggested that glutamate can affect activity in the key reward circuitry, which may decrease the craving to indulge in reward-seeking compulsive skin picking behavior [84,100,101]. Consequently, anti-epileptic drugs can exert a positive influence on controlling skin picking behavior. ...
... Lithium carbonate is a mood stabilizer that acts by modulating glutamate receptors and has been shown to improve skin picking behavior as well as acne excoriee in an individual [102]. Other drugs that function on a similar basis include N-acetyl cysteine (NAC) [84,101] and Riluzole [100]. NAC is the only drug that has demonstrated the most promising results in treating SPD thus far. ...
... Additionally, in a 12-week randomized double-blind trial, administration of NAC resulted in improved profiles for 47% of the individuals, compared to 19% who were given a placebo [104]. Several other cases where NAC has been linked to the reduction or prevention of skin picking behavior have also been reported [84,101,[105][106][107]. Despite these promising results, NAC may often be poorly tolerated by individuals due to its mucolytic properties [108]. ...
... There have been multiple case reports of successful treatment of trichotillomania with NAC, with target doses ranging from 1200 to 2400 mg/day and treatments lasting for as long 6 months [112][113][114][115][116][117][118][119]. However, only two RCTs have been published on NAC treating trichotillomania, and both were 12-week placebo-controlled trials with target doses of 2400 mg/day [109,120]. ...
... NAC might again treat skin-picking disorders by decreasing levels of glutamate in the NA, assisting the control of compulsive behavior [122]. There are several case reports (N = 10) published of NAC successfully treating skin-picking disorders, with doses ranging from 1200 to 1800 mg/day [29,112,115,119,[122][123][124]. There have been two interventional studies investigating NAC treating excoriation disorders; an open-label trial in 35 participants with Prader-Willi syndrome and a blinded RCT of 66 participants [125,126]. ...
... Onychophagia is also classified as an OCRD [110]. It is thought that NAC may reduce nail biting by modulating the glutamatergic system within the nucleus accumbens (NA), altering the subjective feeling of cravings and by reducing oxidative stress [112,127]. There are four case reports (N = 6) published on NAC treating nail biting, with treatment doses ranging from 800 to 2000 mg/day [28,112,119,127]. ...
Article
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N-acetyl-L-cysteine (NAC) is a compound of increasing interest in the treatment of psychiatric disorders. Primarily through its antioxidant, anti-inflammatory, and glutamate modulation activity, NAC has been investigated in the treatment of neurodevelopmental disorders, schizophrenia spectrum disorders, bipolar-related disorders, depressive disorders, anxiety disorders, obsessive compulsive-related disorders, substance-use disorders, neurocognitive disorders, and chronic pain. Whilst there is ample preclinical evidence and theoretical justification for the use of NAC in the treatment of multiple psychiatric disorders, clinical trials in most disorders have yielded mixed results. However, most studies have been underpowered and perhaps too brief, with some evidence of benefit only after months of treatment with NAC. Currently NAC has the most evidence of having a beneficial effect as an adjuvant agent in the negative symptoms of schizophrenia, severe autism, depression, and obsessive compulsive and related disorders. Future research with well-powered studies that are of sufficient length will be critical to better understand the utility of NAC in the treatment of psychiatric disorders.
... 31 On the whole, dropout rates were also relatively low, and were linked to an inability to comply with study demands 33 as well as adverse effects. [30][31][32] Positive therapeutic outcomes from less rigorous forms of investigation, including case studies, [37][38][39][40][41] have generated some initial excitement about NACs clinical potential, but the failure of the more methodologically robust work recorded here to replicate these findings serves as a caution in the utilization and interpretation of such weaker methods; indeed, some of these works did not use validated scales to measure change, relying instead on anecdotal description of symptom amelioration. [38][39][40][41] N-acetyl-cysteine is generally considered to be a relatively safe, well-tolerated agent, 42 and this was reflected in these results with generally low dropout rates and the mostly mild nature of the adverse effects. ...
... [30][31][32] Positive therapeutic outcomes from less rigorous forms of investigation, including case studies, [37][38][39][40][41] have generated some initial excitement about NACs clinical potential, but the failure of the more methodologically robust work recorded here to replicate these findings serves as a caution in the utilization and interpretation of such weaker methods; indeed, some of these works did not use validated scales to measure change, relying instead on anecdotal description of symptom amelioration. [38][39][40][41] N-acetyl-cysteine is generally considered to be a relatively safe, well-tolerated agent, 42 and this was reflected in these results with generally low dropout rates and the mostly mild nature of the adverse effects. It is also relatively cheap, and available without prescription, though there is concern about potential variation between over-the-counter preparations. ...
Article
Licensed pharmacological treatments for obsessive-compulsive disorders include selective serotonin reuptake inhibitors and tricyclic antidepressants. However, a large proportion of patients show minimal or no therapeutic response to these treatments. The glutamatergic system has been implicated in the etiology of obsessive-compulsive spectrum disorders, and it has been postulated that n-acetyl-cysteine (NAC) could have a therapeutic effect on these conditions through its actions on the glutamatergic system and the reduction of oxidative stress. A systematic review was conducted on the existing methodologically robust literature regarding the efficacy of NAC on obsessive-compulsive spectrum disorders in adults and children. Four randomized, double-blind placebo-controlled studies were identified, investigating the effects of NAC on obsessive-compulsive disorder, trichotillomania, and onychophagia. Results remain inconclusive, but NAC may still be useful as a treatment for obsessive-compulsive spectrum disorders on an individual level, particularly as the compound has a relatively benign side-effect profile. The dearth of methodologically robust work is clinically important: larger randomized controlled trials are required to inform of any meaningful clinical effectiveness, and to better determine which, if any, clinical populations might most benefit.
... There is limited evidence for the effectiveness of the NAC treatment in pediatric and adult populations, and the results published to date have been mixed [11][12][13][14]. However, one study found that the NAC decreased the extracellular concentration of the glutamate in the nucleus accumbens, reducing the symptoms of compulsive behaviors such as trichotillomania [15]. ...
Article
Full-text available
N-acetylcysteine (NAC) is a well-known antidote for acetaminophen toxicity and is easily available over the counter. It has antioxidant and anti-inflammatory properties and an established tolerance and safety profile. Owing to its neuroprotective effects, its clinical use has recently expanded to include the treatment of different psychiatric and non-psychiatric disorders. Although a number of randomized controlled trials have documented the clinical evidence for NAC, there are no reviews that summarize the evidence. The present scoping review summarizes the study designs, the patient characteristics, the evidence and the limitations in randomized controlled trials designed to explore the efficacy of NAC for psychiatric conditions in the pediatric population.
... He was then put on 600 mg TID which improved his symptoms. Three months after this therapy, the patient did not report any return of his symptoms [35]. ...
Article
Full-text available
Purpose Onychophagia, or habitual nail biting, is a common disorder, especially in children and young adults. Multiple factors contribute to its development, from emotional triggers to genetics and underlying psychiatric conditions. Nail biting can have a significant impact on one’s quality of life, and its complications are not limited to cosmetic distortion. In severe cases, uncontrolled onychophagia can cause serious physical, dental, and psychosocial consequences. In this article, we review the use of N-acetyl cysteine (NAC), selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), lithium, and silymarin as possible treatment modalities for chronic nail biting. Recent Findings There are many established behavioral and psychological interventions for the treatment of onychophagia, albeit modest in efficacy. And up until today, there is minimal evidence that supports effective pharmacotherapy. However, several of these drugs show promising results that warrant further exploration. Summary NAC was found to be more effective than placebo in the short term, while SSRIs showed contradictory results. TCAs (especially clomipramine), lithium, and silymarin have also exhibited potential in curbing nail biting behavior to different extents. Further studies are required to outline a definite treatment modality for onychophagia, along with corresponding therapeutic doses.
... SSRIs such as fl uoxetine, escitalopram, or citalopram, and opioid receptor antagonists such as naltrexone and NAC may demonstrate benefi t for the treatment of SPD (Banga and Connor 2012 ;Odlaug and Grant 2007b ). No sex differences have been reported in terms of therapeutic outcomes to pharmacotherapy. ...
Article
The obsessive-compulsive and related disorders (OCRDs) category in DSM-5 is comprised not only of OCD but also of body dysmorphic disorder (BDD), hoarding disorder, trichotillomania (hair-pulling disorder) (TTM), and skin picking (excoriation) disorder (SPD). A review of the literature on the phenomenology, psychobiology, pharmacotherapy, and psychotherapy of these OCRDs was undertaken with a specific focus on gender. OCRDs (e.g. BDD) may have a roughly equal gender ratio, may be more common in females (e.g. HPD) or may be more common in males (e.g. hoarding disorder). Comorbidity in OCRDs may also differ across gender; e.g. in SPD, females present with increased depressive symptomatology compared to males. The literature on treatment differences by gender in the OCRDs is, however, sparse. Thus, a range of questions arise for future research and for clinical practice.
... N-acetyl cysteine, an amino acid that restores extracellular glutamate concentration in the nucleus accumbens has demonstrated efficacy in reducing the reward-seeking behaviour in individuals with a range of substance addictions, including nicotine dependence and marijuana addiction (Asevedo et al., 2014). Nacetyl cysteine has also demonstrated promise in the treatment of behavioural addictions such as gambling disorder and trichotillomania (Grant et al., 2007a(Grant et al., , 2009bOdlaug and Grant, 2007). ...
Article
Full-text available
The term 'addiction' was traditionally used in relation to centrally active substances, such as cocaine, alcohol, or nicotine. Addiction is not a unitary construct but rather incorporates a number of features, such as repetitive engagement in behaviours that are rewarding (at least initially), loss of control (spiralling engagement over time), persistence despite untoward functional consequences, and physical dependence (evidenced by withdrawal symptoms when intake of the substance diminishes). It has been suggested that certain psychiatric disorders characterized by maladaptive, repetitive behaviours share parallels with substance addiction and therefore represent 'behavioural addictions'. This perspective has influenced the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which now has a category 'Substance Related and Addictive Disorders', including gambling disorder. Could other disorders characterised by repetitive behaviours, besides gambling disorder, also be considered 'addictions'? Potential examples include kleptomania, compulsive sexual behaviour, 'Internet addiction', trichotillomania (hair pulling disorder), and skin-picking disorder. This paper seeks to define what is meant by 'behavioural addiction', and critically considers the evidence for and against this conceptualisation in respect of the above conditions, from perspectives of aetiology, phenomenology, co-morbidity, neurobiology, and treatment. Research in this area has important implications for future diagnostic classification systems, neurobiological models, and novel treatment directions.
... Finally, another case study demonstrated that n-acetyl-cysteine (an antioxidant) may be an effective treatment for PSP (Odlaug and Grant, 2007b). ...
Chapter
Grooming disorders, such as trichotillomania (TTM), nail biting, and skin picking, are receiving increasing attention from researchers and clinicians. This is in part due to their possible link to obsessive–compulsive disorder (OCD). It is imperative that these disorders are categorized correctly in order to facilitate research and aid diagnosis and treatment. However, within current psychiatric classification systems TTM is currently conceptualized as an impulse control disorder and nail biting, lip biting, and skin picking are not yet included in the official nomenclature. It is therefore unclear whether these grooming disorders should form a category on their own (i.e., “grooming disorders” or “pathological grooming behaviors”), or whether they should be classified as obsessive–compulsive spectrum disorders (OCSD), impulse control disorders, or as body-focused repetitive behaviors. This chapter will discuss these diagnostic and taxonomic issues particularly as they pertain to clinical practice, fostering further discussion on the psychopathology of aberrant grooming behaviors. Introduction The positioning of TTM and other conditions characterized by self-directed repetitive behaviors (e.g., nail biting and pathological skin picking [PSP]) within existing psychiatric classification systems has recently been debated (e.g., Stein et al. 2007). Trichotillomania is classified in the most recent edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR; APA, 2000) as an impulse control disorder. However, some researchers suggest that TTM is an OCSD (Swedo and Leonard 1992).
... 9,20,21 The effectiveness of NAC to reduce binge eating of a highly caloric palatable food is consistent with other studies demonstrating the attenuation of compulsive behaviors such as drug taking, hair pulling and skin picking, and suggests that system xc-is a potential therapeutic target for the treatment of compulsive feeding disorders. 9,10,22 Pursuing effective treatments for compulsive eating disorders will require further understanding of the neural mechanisms that underlie hedonic drive. 7 System (90mg/kg; IP) and central (10μg/5μl) NAC alters binge behavior produced by daily limited access to a palatable food. ...
Article
Binge-eating behavior involves rapid consumption of highly palatable foods leading to increased weight gain. Feeding in binge disorders resembles other compulsive behaviors, many of which are responsive to N-acetylcysteine (NAC), which is a cysteine prodrug often used to promote non-vesicular glutamate release by a cystine-glutamate antiporter. To examine the potential for NAC to alter a form of compulsive eating, we examined the impact of NAC on binge eating in a rodent model. Specifically, we monitored consumption of standard chow and a high-fat, high carbohydrate western diet (WD) in a rodent limited-access binge paradigm. Before each session, rats received either a systemic or intraventricular injection of NAC. Both systemic and central administration of NAC resulted in significant reductions of binge eating the WD without decreasing standard chow consumption. The reduction in WD was not attributable to general malaise as NAC did not produce condition taste aversion. These results are consistent with the clinical evidence of NAC to reduce or reverse compulsive behaviors, such as, drug addiction, skin picking and hair pulling.International Journal of Obesity advance online publication, 15 March 2016; doi:10.1038/ijo.2016.31.
... Coming back to NAC, which is a precursor of glutathione, it has been shown that it can significantly improve the standard therapy, as a double-blind randomized placebocontrolled clinical study performed by Ng et al. in 2008 demonstrated [13]. In fact, NAC is considered a product which can modulate glutathione levels [149] and it is already cited as an adjuvant in BD therapy [278]. In addition, some studies showed that NAC could improve OCD-related trichotillomania (pathological nail-biting and skin-picking) [279]. ...
Article
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The correlation between the affective disorders and the almost ubiquitous pathological oxidative stress can be described in a multifactorial way, as an important mechanism of central nervous system impairment. Whether the obvious changes which occur in oxidative balance of the affective disorders are a part of the constitutive mechanism or a collateral effect yet remains as an interesting question. However it is now clear that oxidative stress is a component of these disorders, being characterized by different aspects in a disease-dependent manner. Still, there are a lot of controversies regarding the relevance of the oxidative stress status in most of the affective disorders and despite the fact that most of the studies are showing that the affective disorders development can be correlated to increased oxidative levels, there are various studies stating that oxidative stress is not linked with the mood changing tendencies. Thus, in this minireview we decided to describe the way in which oxidative stress is involved in the affective disorders development, by focusing on the main oxidative stress markers that could be used mechanistically and therapeutically in these deficiencies, the genetic perspectives, some antioxidant approaches, and the relevance of some animal models studies in this context.
... Third, preclinical data and research in mice and in adults with intellectual disabilities show that naltrexone, an opioid antagonist, can help in reducing excessive grooming behaviors and self-injurious behaviors [12,35]. Finally, there is significant evidence that N-acetylcysteine, which modulates glutamate, the main neurotransmitter in the frontostriato-thalamic-cortical circuit, may have efficacy in treating trichotillomania [36][37][38][39][40][41][42]. ...
Article
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Pathological hair-pulling or trichotillomania, which is commonly associated with anxiety and depression, obsessive-compulsive disorder, and neurodevelopmental disorders, has been rarely associated with dementing illnesses. Investigators have not clarified the neural correlates and treatment of trichotillomania in dementia. We report a patient who developed an early-onset cognitive decline with genetic, cerebrospinal fluid biomarker and structural and functional neuroimaging studies consistent with Alzheimer’s disease. Eight years into her disease, she developed severe, repetitive hair-pulling behavior leading to marked hair loss, along with other repetitive and “frontal” behaviors. Selective serotonin reuptake inhibitors (SSRIs) were ineffective in controlling her hair-pulling behavior, which subsequently responded to quetiapine 150 mg/day. This patient and a review of the literature suggest that trichotillomania may be a compulsive-related symptom in dementias of different etiologies as they involve frontal areas and release primitive grooming behavior from frontostriatal dysfunction. Dopamine blockade, rather than SSRIs, may be effective in managing trichotillomania in dementia.
... Several case reports in adults reported improved hair growth after the use of NAC at the mean dosage of 1400 mg/die [80,81,82], including the case of a severe, treatment-resistant form of the condition [67]. ...
Article
Introduction: N-acetylcysteine (NAC) is widely known for its role as a mucolytic and as an antidote to paracetamol overdose. There is increasing interest in the use of NAC in the treatment of several psychiatric disorders. The rationale for the administration of NAC in psychiatric conditions is based on its role as a precursor to the antioxidant glutathione, and its action as a modulating agent of glutamatergic, dopaminergic, neurotropic and inflammatory pathways. Areas covered: This study reviews the available data regarding the use of NAC in different psychiatric disorders including substance use disorders, autism, obsessive-compulsive spectrum disorders, schizophrenia, depression, bipolar disorder. Promising results were found in trials testing the use of NAC, mainly as an add-on treatment, in cannabis use disorder in young people, depression in bipolar disorder, negative symptoms in schizophrenia, and excoriation (skin-picking) disorder. Despite initial optimism, recent findings regarding NAC efficacy in autism have been disappointing. Expert opinion: These preliminary positive results require further confirmation in larger samples and with longer follow-ups. Given its high tolerability and wide availability, NAC represents an important target to investigate in the field of new adjunctive treatments for psychiatric conditions.
... An RCT trial using NAC for treatment of trichotillomania showed significant benefit [137]. ere are a number of case studies and short trials that show benefit in pathologic nail biting [138] and skin picking [139]. ...
Article
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Objective: To review the clinical usefulness of N-acetylcysteine (NAC) as treatment or adjunctive therapy in a number of medical conditions. Use in Tylenol overdose, cystic fibrosis, and chronic obstructive lung disease has been well documented, but there is emerging evidence many other conditions would benefit from this safe, simple, and inexpensive intervention. Quality of Evidence. PubMed, several books, and conference proceedings were searched for articles on NAC and health conditions listed above reviewing supportive evidence. This study uses a traditional integrated review format, and clinically relevant information is assessed using the American Family Physician Evidence-Based Medicine Toolkit. A table summarizing the potential mechanisms of action for N-acetylcysteine in these conditions is presented. Main Message. N-acetylcysteine may be useful as an adjuvant in treating various medical conditions, especially chronic diseases. These conditions include polycystic ovary disease, male infertility, sleep apnea, acquired immune deficiency syndrome, influenza, parkinsonism, multiple sclerosis, peripheral neuropathy, stroke outcomes, diabetic neuropathy, Crohn's disease, ulcerative colitis, schizophrenia, bipolar illness, and obsessive compulsive disorder; it can also be useful as a chelator for heavy metals and nanoparticles. There are also a number of other conditions that may show benefit; however, the evidence is not as robust. Conclusion: The use of N-acetylcysteine should be considered in a number of conditions as our population ages and levels of glutathione drop. Supplementation may contribute to reducing morbidity and mortality in some chronic conditions as outlined in the article.
... The potential benefit of NAC in ED has been suggested by case reports. 36 In addition, a recent randomized, double-blind trial (dosing range 1,200-3,000 mg/d) over 12 weeks found that NAC significantly reduced symptoms of ED. 37 Almost half of the sample (15/32, 47%) receiving NAC were much or very much improved compared to 19% (4/21) of participants receiving placebo. There were, however, no significant differences in psychosocial functioning between the active and placebo trial arms. ...
Article
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Christine Lochner,1 Annerine Roos,1 Dan J Stein2 1SU/UCT MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, South Africa; 2SU/UCT MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Mental Health, University of Cape Town, South Africa Abstract: Although pathological skin-picking has been documented in the medical literature since the 19th century, it has only recently been included as a distinct entity in psychiatric classification systems. In the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition and the proposed International Classification of Diseases, Eleventh Revision, excoriation (skin-picking) disorder (ED), also known as neurotic excoriation, psychogenic excoriation, or dermatillomania), is described as recurrent picking of skin, leading to skin lesions and significant distress or functional impairment. ED is listed as one of the obsessive–compulsive and related disorders, given its overlap with conditions such as trichotillomania (hair-pulling disorder). Arguably, its inclusion and delineation in the diagnostic nomenclature will lead to increased awareness of the condition, more research, and ultimately in treatment advances. This systematic review aims to provide readers with an up-to-date view of current treatment options for ED. A MEDLINE search of the ED treatment literature was conducted to collate relevant articles published between 1996 and 2017. The findings indicate that a number of randomized controlled trails on ED have now been published, and that current management options include behavioral therapy (habit reversal or acceptance-enhanced behavior therapy), and medication (selective serotonin reuptake inhibitors or N-acetyl cysteine). Keywords: excoriation, skin-picking, treatment, habit reversal therapy, behavioral therapy, pharmacotherapy, systematic review
... Anxiolytics used in SPD include lorazepam and buspirone (36). Also naltrexone (37) and N-acetylcysteine have shown to reduce SPD behavior (4,34,35,(38)(39)(40)(41)(42)(43)(44). ...
Article
Introduction: Repetitive skin manipulation is the key symptom in skin picking disorder (SPD), or acne excoriée des jeunes filles Brocq. The diagnostic and statistical manual of mental disorders (DSM-5) has recognized SPD as an independent disease, namely an obsessive-compulsive disorder. Thus, psychiatric treatment is indicated. Therefore, in a large cohort of SPD, we asked whether dermatologists’ treatment strategy includes routine referrals to psychiatry. In addition, we describe epidemiological data, treatments and follow up. Methods: We performed a retrospective study, searching in our hospital database between 01.01.2011-31.12.2016. Results: 154 (141 female, 13 male) patients were included in our study. In less than 5% a referral to a psychologist or psychiatrist occurred. More than 90% of all patients received topical and almost 40% systemical anti-acne treatment. The loss of follow-up was very high. Discussion: Our study shows that dermatologists focus on treating acne-like lesions in SPD, but rarely refer to psychiatry. Possible reasons include considerations of patients’ reactions who often reject the idea of a psychological origin of the disease. Our results suggest that new treatment strategies should be created to address SPD correctly, i.e. by combined consultations with psychiatrists or specific training of dermatologists in psychiatric therapy and diagnostics.
... The novelty in the current findings is that impulsivity predicts pathological grooming independent from other related factors, such as psychiatric distress. Perhaps this mechanism explains the beneficial effect of Nacetyl cysteine (NAC) medication (a modulator of the glutamatergic system involved in behavioural control) in the treatment of SP [69] and grooming [70]. Contrary to our expectations, BPD seems unrelated to pathological grooming. ...
Article
Full-text available
Although trichotillomania (TTM), skin picking (SP), and nail biting (NB) have been receiving growing scientific attention, the question as to whether these disorders can be regarded as separate entities or they are different manifestations of the same underlying tendency is unclear. Data were collected online in a community survey, yielding a sample of 2705 participants (66% women, mean age: 29.1, SD: 8.6). Hierarchical factor analysis was used to identify a common latent factor and the multiple indicators and multiple causes (MIMIC) modelling was applied to test the predictive effect of borderline personality disorder symptoms, impulsivity, distress and self-esteem on pathological grooming. Pearson correlation coefficients between TTM, SP and NB were between 0.13 and 0.29 (p < 0.01). The model yielded an excellent fit to the data (CFI = 0.992, TLI = 0.991, χ² = 696.65, p < 0.001, df = 222, RMSEA = 0.030, Cfit of RMSEA = 1.000), supporting the existence of a latent factor. The MIMIC model indicated an adequate fit (CFI = 0.993, TLI = 0.992, χ² = 655.8, p < 0.001, df = 307, RMSEA = 0.25, CI: 0.022–0.028, pclose = 1.000). TTM, SP and NB each were loaded significantly on the latent factor, indicating the presence of a general grooming factor. Impulsivity, psychiatric distress and contingent self-esteem had significant predictive effects, whereas borderline personality disorder had a nonsignificant predictive effect on the latent factor. We found evidence that the category of pathological grooming is meaningful and encompasses three symptom manifestations: trichotillomania, skin picking and nail biting. This latent underlying factor is not better explained by indicators of psychopathology, which supports the notion that the urge to self-groom, rather than general psychiatric distress, impulsivity, self-esteem or borderline symptomatology, is what drives individual grooming behaviours.
... In recent studies, it is showed that NAC may be effective in reducing TTM symptoms [6,12]. These effects can be the result of decreased extracellular glutamate concentrations in nucleus accumbens, which is the brain region responsible for compulsive behaviours in TTM [6,14]. In their double-blind randomized trial, Grant et al. found NAC to be significantly more effective in reducing TTM symptoms compared to placebo. ...
Article
Full-text available
Trichotillomania (TTM) is a disorder characterized by repetitive hair pulling resulting in hair loss and it is usually difficult to treat with a chronic course of illness. Currently, the selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed drugs for adults with TTM. Various studies and case reports give mixed results. Therefore, the treatment effectiveness of SSRIs remains uncertain. There is a growing interest regarding the use of glutamatergic agents in obsessive compulsive disorder and obsessive compulsive spectrum disorder. Here, we report an 18-year-old female patient with TTM, which successfully treated with glutamate modulator n-acetylcysteine.
... There are case reports describing the therapeutic benefit of using NAC in TTM (Odlaug & Grant, 2007;Rodrigues-Barata, Tosti, Rodriguez-Pichardo, & Camacho-Martinez, 2012;Silva-Netto, Jesus, Nogueira, & Tavares, 2014;Taylor & Bhagwandas, 2014). One large double-blind placebo-controlled study enrolled 50 adults who received either 1,200 mg/day of NAC over a 6-weeks period and 2,400 mg/day for another 6 weeks. ...
Article
Full-text available
Trichotillomania (hair pulling disorder) is a fairly common but underreported disorder characterized by recurrent episodes of pulling hair from different parts of the body. Currently classified in Diagnostic and Statistical Manual of Psychiatric Disorders (DSM-5) under the heading of the "Obsessive-compulsive spectrum and related disorders." The estimated prevalence data suggest that 0.5-2% of the general population suffers from this disorder. Stress and anxiety are directly correlated to the production of trichotillomania symptoms. The psychosocial aspects of trichotillomania are greatly underestimated, but recent literature suggests an increased interest in this neglected area. Although no FDA approved medications are available for the treatment of trichotillomania, a variety of medications including N-acetylcysteine have shown benefit in case reports. Combined liaison clinics, with an interdisciplinary approach, are highly advisable in the treatment of these cases.
... With regard to pharmacological treatment, patients with trichotillomania treated with the tricyclic serotonergic agent clomipramine reported a significant reduction in the frequency and intensity of their hair pulling urges and an increased ability to resist their urges, according to the findings of a relatively small trial (Swedo et al., 1989). In case reports, positive results have also been documented with the use of N-acetylcysteine (Odlaug and Grant, 2007;Rodrigues-Barata et al., 2012;Taylor and Bhagwandas, 2014). Our understanding of the relationship between awareness of sensory symptoms and effective pharmacological modulation of repetitive hair pulling is incomplete and requires further research. ...
Article
Tourette syndrome (TS) is a neurodevelopmental condition characterized by multiple tics. Sensory symptoms play a key role in the clinical phenomenology and pathophysiology of TS, as most patients report premonitory urges driving tic expression. Interestingly, sensory symptoms have also been reported in other conditions characterized by repeated behaviors. This review explores the nature of sensory symptoms reported by patients with body focused repetitive behaviors (BFRBs, especially trichotillomania and skin picking disorder) and restless legs syndrome (RLS) in comparison to TS. A sense of mounting inner tension and reinforcement mechanisms driven by gratification and relief on expression of the tic or repetitive behavior appear to be implicated across all conditions. Subjective urges can be temporarily suppressed by patients with TS and selected BFRBs, whereas patients with RLS tend to report dysesthesia more frequently than a suppressible urge to move. The observed similarities in the phenomenology of sensory symptoms across these conditions raise the possibility of a comparable underlying pathophysiology. Preliminary findings suggest an overlap of neural pathways encompassing the insula, basal ganglia (putamen), and posterior cingulate cortex.
... Current treatment approaches focus on interventions based on cognitive-behavioral therapy (CBT) (Flessner, Schuck, Keijsers, & Rinck, 2011), habit reversal (HR) (Moritz, Fricke, Treszl, & Wittekind, 2012;Teng, Woods, & Twohig, 2006), Acceptance and Commitment Therapy (ACT) (Twohig, Hayes, & Masuda, 2006) and pharmacotherapy, especially selective serotonin reuptakes inhibitors (SSRIs) (Bloch, Elliott, Thompson, & Koran, 2001;Keuthen et al., 2007;Simeon et al., 1997), lamotrigine (Grant, Odlaug, Chamberlain, & Kim, 2010;Grant, Odlaug, & Kim, 2007) and N-Acetylcysteine (Grant et al., 2016;Odlaug & Grant, 2007b). Nevertheless, research on skin picking disorder is still lacking adequately powered randomized controlled trials in samples diagnosed according to the official DSM-5 criteria (Schumer, Bartley, & Bloch, 2016;Selles, McGuire, Small, & Storch, 2016). ...
Article
Skin picking disorder is accompanied by substantial psychosocial impairment and requires adequate treatment. However, literature on help-seeking attitudes and healthcare utilization in affected individuals is scarce. Therefore, the present study sought to investigate help-seeking behavior and experiences, as well as attitudes and expectations towards healthcare utilization in individuals with skin picking. The current sample consisted of 133 affected individuals (mean age: M = 26.67, SD = 6.42; 93.2% female), enrolled in a pilot study examining an Internet-based self-help program for skin picking. Data were assessed via self-report within the online baseline assessment prior to randomization. Most participants reported a positive helpfulness expectancy towards professional support for skin picking, and 42% (N = 56) had sought help in at least one professional contact point. While psychotherapists and psychologists were commonly rated as helpful (76.0%/63.2%), dermatological counseling and treatments were mostly not perceived as helpful (83.9%). Common reasons for not seeking help were a low perceived need for treatment, insecurity about treatment providers and their expertise, as well as shame. The present results suggest that individuals with skin picking rarely receive adequate treatment despite an overall positive attitude towards professional support. Increasing awareness and knowledge in professionals and the general public is required to improve the currently insufficient healthcare situation.
... The mechanism of action of n-acetylcysteine in trichotillomania is believed to be the reduction of glutamate levels in the nucleus accumbens. 29 A double-blind, placebo-controlled trial was conducted on 50 patients of trichotillomania divided into two equal groups. Daily supplementation with 1200-2400 mg/day of n-acetylcysteine for a period of 12 weeks resulted in significant reductions in the severity of hair pulling compared to placebo. ...
Article
N-acetylcysteine is a mucolytic drug which is commonly used as an antidote for acetaminophen toxicity. It is a thiol compound, which acts as a donor of cysteine, leading to replenishment of glutathione and thus acts as an antioxidant. It also has anti-inflammatory effects, alters the levels of neurotransmitters, inhibits proliferation of fibroblasts and keratinocytes and causes vasodilatation. Due to these actions, n-acetylcysteine has found use in several dermatologic conditions in systemic and topical form. The drug has been used as an adjuvant in the management of conditions such as toxic epidermal necrolysis, drug hypersensitivity syndrome, trichotillomania, skin picking disorders and onychotillomania, ichthyoses, contact dermatitis, atopic dermatitis, melasma, pseudoporphyria, connective tissue diseases, wound healing and alopecia. It also has a role in protection from radiation-induced skin damage including photo-ageing, photocarcinogenesis and radiation dermatitis. Most indications in dermatology are supported by case reports, small case series and small trials. Higher quality of evidence is needed for its wider use. The drug is cheap and is generally safe with few adverse effects. Thus a greater role is possible for use of n-acetylcysteine in various skin conditions. This review explores the various uses of n-acetylcysteine in the field of dermatology, the evidence supporting the same, the possible mechanisms of action and the adverse effects of the drug.
... An RDBCT conducted by Grant et al. revealed significant improvement in trichotillomania patients after 12 weeks of treatment 126 ; this result was substantiated by a number of case reports. [127][128][129] In pediatric trichotillomania patients, an RDBCT found no significant reduction in hair pulling compared to placebo 130 ; in this trial, the authors suggested that the improvement was associated with psychoeducation about trichotillomania rather than drug treatment, since significant improvement in several measures of hair pulling was observed regardless of treatment time. A series of case reports showed that NAC is effective against excoriation disorder, 127,131-133 and an RDBCT concluded that NAC significantly reduced skin-picking symptoms. ...
Article
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Objective: Anxiety disorders are highly prevalent and the efficacy of the available anxiolytic drugs is less than desired. Adverse effects also compromise patient quality of life and adherence to treatment. Accumulating evidence shows that the pathophysiology of anxiety and related disorders is multifactorial, involving oxidative stress, neuroinflammation, and glutamatergic dysfunction. The aim of this review was to evaluate data from animal studies and clinical trials showing the anxiolytic effects of agents whose mechanisms of action target these multiple domains. Methods: The PubMed database was searched for multitarget agents that had been evaluated in animal models of anxiety, as well as randomized double-blind placebo-controlled clinical trials of anxiety and/or anxiety related disorders. Results: The main multitarget agents that have shown consistent anxiolytic effects in various animal models of anxiety, as well in clinical trials, are agomelatine, N-acetylcysteine (NAC), and omega-3 fatty acids. Data from clinical trials are preliminary at best, but reveal good safety profiles and tolerance to adverse effects. Conclusion: Agomelatine, NAC and omega-3 fatty acids show beneficial effects in clinical conditions where mainstream treatments are ineffective. These three multitarget agents are considered promising candidates for innovative, effective, and better-tolerated anxiolytics.
... NAC appears to be extremely well tolerated, with minimal adverse effects reported [743]. Mild gastrointestinal effects appear to be the most common symptom-flatulence (which ceased after two weeks of NAC supplementation), headache, skin rash, diarrhea and nausea and vomiting of mild-moderate intensity [68,77,78]. However, nausea and vomiting were also experienced in the placebo group of one particular trial, and was not evident in others [69]. ...
Article
Full-text available
Objective: Obsessive-compulsive disorder (OCD) is a disabling mental illness for which pharmacological and psychosocial interventions are all too often inadequate. This demonstrates the need for more targeted therapeutics. Recent preclinical and clinical studies have implicated dysfunction of glutamatergic neurotransmission in the pathophysiology of OCD. Moreover there are studies suggesting that neuroimmune abnormalities may play an important role in the pathogenesis of OCD. N-acetyl cysteine (NAC) is a safe and readily available agent that would modify the synaptic release of glutamate in subcortical brain regions via modulation of the cysteine-glutamate antiporter. The modulation of inflammatory pathways may also play a role in the benefits seen following NAC treatment. Therefore NAC can be considered a neuroprotective agent. Methods: This paper explores the role of NAC in the treatment of OCD conditions refractory to first-line pharmacological interventions, reviewing the clinical studies published in the last decade. Results: The possible benefit mechanisms of NAC for this disorder will be discussed, as well as the role of vitamin D supplementation, given its specific property of stimulating the formation of glutathione in the brain. Conclusions: Nutraceutical supplementation in treatment resistance OCD may be important not only for improving obsessive-compulsive symptomatology, but also from a psychological perspective, given its better acceptance by the patients compared to pharmacological treatment.
Article
Onychotillomania is a chronic psychodermatological disorder characterized by a repetitive, compulsive urge to pick nails that causes temporary or permanent trauma to the nail unit. Physical barrier methods, cognitive behavioural therapy and pharmacotherapy with psychotropic medications have shown some benefits in case reports, but no large clinical trials have been conducted to assess their efficacy. As a result, evidence-based treatment options for the management of onychotillomania are currently lacking.
Article
Background: The management of trichotillomania is challenging. The limited efficacy and side-effects of pharmacological medications and difficulty in long-term maintenance of behavioural therapies necessitates alternative treatment options. A dysregulated glutamatergic system has been implicated in the pathophysiology of trichotillomania. A limited number of reports indicate that N-acetylcysteine (NAC), a glutamate modulator, may be a promising treatment for this disorder. Objectives: We report two patients with trichotillomania for whom treatment with NAC was successful. Methods: The first patient was a 30-year-old female, and the second patient was a 14-year-old girl, both who were diagnosed with trichotillomania and prescribed NAC (1200 mg/d, p.o.). Results: Hair pulling behaviour subsided within 2 months and 2 weeks of initiating NAC in the first and second patient, respectively. Complete hair regrowth was observed after 4 and 6 months of NAC treatment in the first and second patient, respectively. No side-effects related to NAC were noted. Conclusion: NAC could be a well-tolerated and effective treatment option for trichotillomania.
Article
Background: Obsessive-compulsive disorder (OCD) is a disabling mental illness for which pharmacological and psychosocial interventions are all too often inadequate. Recent preclinical and clinical studies have implicated dysfunction of glutamatergic neurotransmission in the pathophysiology of OCD. The amino acid-based nutraceutical N-acetyl cysteine (NAC) is a safe and readily available agent that has been found to modify the synaptic release of glutamate in subcortical brain regions via modulation of the cysteine-glutamate antiporter. Objective: The aim of this study was to assess the efficacy and safety of NAC in treating OCD. Methods: A 16-week, double-blind, placebo-controlled, randomised trial using 3 g/day of NAC (1.5 g twice daily) in 44 participants (aged 18-70 years) with Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)-diagnosed OCD, during 2013-2015. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (YBOCS), conducted every 4 weeks. Results: Analysis of the full sample (intention-to-treat) with repeated measures mixed linear modelling revealed a nonsignificant time × treatment interaction for the YBOCS scale total score (p = 0.39). A per-protocol analysis removing protocol violators also failed to show a significant time × treatment interaction for YBOCS total score (p = 0.15). However, a significant time × treatment interaction was observed for the YBOCS 'Compulsions' subscale in favour of NAC (p = 0.013), with a significant reduction observed at week 12 (dissipating at week 16). At 16 weeks, only four (20 %) participants were considered 'responders' (YBOCS ≥35 % reduction at endpoint) versus four (27 %) in the placebo group. The NAC was well-tolerated, aside from more cases of heartburn occurring compared with placebo (p = 0.045). Conclusion: Further research involving NAC for OCD may require larger samples to detect moderate or small effect sizes, involve dosage or formulation differences, use in concert with exposure therapy, or an additional post-study observational period to mitigate study withdrawal. Trial registration: ACTRN12613000310763.
Article
Objectives We aimed to investigate the role of N-acetylcysteine (NAC), a glutamate-modulating agent, in the treatment of obsessive-compulsive disorder (OCD). Methods We searched PubMed, Scopus, and Medline for relevant clinical studies discussing the efficacy and safety of NAC in patients with OCD. Data from the Yale-Brown Obsessive-Compulsive Scale were extracted and pooled in a random effect model meta-analysis using RevMan version 5.3. Results Five RCTs were included with a total number of 212 patients who were assigned in a 1:1 ratio to either NAC or placebo. Doses ranged from 2000 to 3000 mg. Regarding the Yale-Brown Obsessive-Compulsive Scale, which was the primary outcome, the overall effect size favored NAC (MD=-2.97, 95% CI [-4.93, -1.02], P=0.003). Adverse events were not significantly higher in the NAC group compared to the placebo. Conclusion Evidence suggests that NAC may be a promising agent for the treatment of OCD patients. Further studies with larger sample sizes are still needed to support these findings and reach a conclusion regarding NAC's efficacy in reducing the symptoms of OCD.
Article
Background: Trichotillomania (TTM; hair-pulling disorder) is a prevalent and disabling disorder characterised by recurrent hair-pulling. Here we update a previous Cochrane Review on the effects of medication for TTM. Objectives: To assess the effects of medication for trichotillomania (TTM) in adults, children and adolescents compared with placebo or other medication. Search methods: We searched CENTRAL, MEDLINE, Embase, PsycINFO, eleven other bibliographic databases, trial registries and grey literature sources (to 26 November 2020). We checked reference lists and contacted subject experts. Selection criteria: We selected randomised controlled trials of medication versus placebo or other medication for TTM in adults, children and adolescents. Data collection and analysis: We used standard methodological procedures expected by Cochrane. Main results: Twelve studies were included. We identified 10 studies in adults (286 participants) with a mean sample size of 29 participants per trial; one study in children and adolescents (39 participants); and, one study in adults and adolescents (22 participants: 18 adults and 4 adolescents). All studies were single-centre, outpatient trials. Eleven studies compared medication and placebo (334 participants); one study compared two medications (13 participants). Studies were 5 to 13 weeks duration. We undertook meta-analysis only for opioid antagonists as other comparisons contained a single study, or reported insufficient data. Antioxidants versus placebo in adults There was little to no difference in treatment response between antioxidant (35.7%) and placebo groups (28.6%) after six weeks, based on a single trial of silymarin (risk ratio (RR) 2.25, 95% confidence interval (CI) 0.84 to 5.99; 36 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (18 participants; low-certainty evidence). Antioxidants versus placebo in adolescents There was little to no difference in treatment response between antioxidant (50%) and placebo groups (25%) after six weeks, based on a single trial of silymarin (RR 2.00, 95% CI 0.28 to 14.20; 8 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (8 participants; low-certainty evidence). Antipsychotics versus placebo in adults There may be greater treatment response in the antipsychotic group (85%) compared to the placebo group (17%) after 12 weeks, based on a single trial of olanzapine (RR 5.08, 95% CI 1.4 to 18.37; 25 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (25 participants; low-certainty evidence). Cell signal transducers versus placebo in adults There was little to no difference in treatment response between cell signal transducer (42.1%) and placebo groups (31.6%) after 10 weeks, based on a single trial of inositol (RR 1.33, 95% CI 0.57 to 3.11; 38 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (38 participants; low-certainty evidence). Glutamate modulators versus placebo in adults There is probably greater treatment response in the glutamate modulator group (56%) compared to the placebo group (16%) after 12 weeks, based on a single trial of N-acetylcysteine (RR 3.5, 95% CI 1.34 to 9.17; 50 participants; moderate-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (50 participants; low-certainty evidence). Glutamate modulators versus placebo in children and adolescents There was little to no difference in treatment response between the glutamate modulator (25%) and placebo groups (21.1%) in children and adolescents, based on a single trial of N-acetylcysteine (RR 1.19, 95% CI 0.37 to 3.77; 39 participants; low-certainty evidence). There was little to no difference in dropouts due to adverse events between glutamate modulator (5%) and placebo (0%) groups, based on a single trial (RR 2.86, 95% CI 0.12 to 66.11; 39 participants; low-certainty evidence). Opioid antagonists versus placebo in adults There may be little to no difference in treatment response between opioid antagonist (37.5%) and placebo groups (25%) after six to eight weeks, based on two studies of naltrexone, but the evidence is very uncertain (RR 2.14, 95% CI 0.25 to 18.17; 2 studies, 68 participants; very low-certainty evidence). No data were available regarding dropouts due to adverse events. Selective serotonin reuptake inhibitors (SSRIs) versus placebo in adults There were no data available for treatment response to SSRIs. There was little to no difference in dropouts due to adverse events in the SSRI group (5.1%) compared to the placebo group (0%) after 6 to 12 weeks, based on two trials of fluoxetine (RR 3.00, 95% CI 0.33 to 27.62; 2 studies, 78 participants; low-certainty evidence). Tricyclic antidepressants (TCAs) with predominantly serotonin reuptake inhibitor (SRI) actions versus placebo in adults There may be greater treatment response in the TCAs with predominantly SRI actions group (40%) compared to the placebo group (0%) after nine weeks, but the evidence is very uncertain, based on a single trial of clomipramine (RR 5.73, 95% CI 0.36 to 90.83; 16 participants; very low-certainty evidence). There may be increased dropouts due to adverse events in the TCAs with predominantly SRI actions group (30%) compared to the placebo group (0%), but the evidence is very uncertain (RR 4.45, 95% CI 0.27 to 73.81; 16 participants; very low-certainty evidence). TCAs with predominantly SRI actions versus other TCAs in adults There may be greater treatment response in the TCAs with predominantly SRI actions group compared to the other TCAs group after five weeks, based on a single trial comparing clomipramine to desipramine (mean difference (MD) -4.00, 95% CI -6.13 to -1.87; 26 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (26 participants; low-certainty evidence). Authors' conclusions: There was insufficient evidence from meta-analysis to confirm or refute the efficacy of any agent or class of medication for the treatment of TTM in adults, children or adolescents. Preliminary evidence suggests there may be beneficial treatment effects for N-acetylcysteine, clomipramine and olanzapine in adults based on four trials, albeit with relatively small sample sizes.
Article
Skin-picking disorder, also known as excoriation disorder or psychogenic skin excoriations, is an obsessive–compulsive and related disorder that is classified with other body-focused repetitive-behavior disorders in the most recent edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Skin-picking disorder is associated with significant comorbidity and psychosocial dysfunction. The disorder has a female predominance across studies, and the average age of onset is variable but commonly in adolescence and adulthood. A full clinical and dermatologic examination and multidisciplinary approach is important in the diagnosis of this condition. There is no specific or recommended treatment option, but cognitive–behavioral therapy, particularly habit-reversal therapy and acceptance and commitment therapy have shown promise. Various pharmacological interventions have also been described to treat this condition in case reports and open and controlled trials. Specific classes of agents implemented include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors, antipsychotics, and glutaminergic-modulating agents. SSRIs and N-acetylcysteine have been shown to be the most effective of the pharmacological interventions.
Article
Background Pathologic grooming disorders can lead to clinically significant distress and functional impairment. Studies on treatment of these disorders with selective serotonin reuptake inhibitors (SSRIs) and anticonvulsants have led to inconsistent findings. N‐acetylcysteine (NAC) has shown promise in treatment of obsessive‐compulsive and related disorders. The objective of this article is to perform an updated review of NAC in the treatment of grooming disorders. Methods PubMed was searched from inception to October 2017 to identify literature on the use of NAC in the management of trichotillomania, onychophagia, and pathological skin picking. Case reports, case series, and randomized controlled trials were included. Data on study design, dosing regimens, comorbidities, concurrent treatment, and side effects were extracted from the included articles. Results Fifteen articles were included in this review, which consisted of 10 case reports, one case series, and four randomized controlled trials. Dosing of oral NAC ranged from 450 to 2,400 mg per day, and treatment periods lasted from 1 to 8 months. Side effects were uncommon, mild, and usually gastrointestinal in nature, with severe aggression reported in one child. Conclusions While there are multiple reports of the safety and efficacy of NAC in the treatment of grooming disorders, there are currently few randomized controlled trials on this topic, and more research is needed to develop a formal treatment algorithm. While current data should be considered very preliminary, case reports have demonstrated mostly positive results and a lack of significant side effects. A trial of NAC may be a viable option for pathologic grooming disorders, especially in patients who have failed prior psychologic or pharmacologic treatment.
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N-acetyl-l-cysteine is a potent antioxidant that is commercially available as an over-the-counter supplement that has demonstrated efficacy for several medical applications.
Article
Onychotillomania is an uncommon and likely underreported condition in which patients repetitively manipulate the different constituents of the nail unit. Onychotillomania is characterized by a range of nonspecific findings, including bizarre morphology of the nail plate and damage to the nail bed and periungual skin. Histopathological changes are also nonspecific, but may be viewed as analogous to lichen simplex chronicus and prurigo nodularis of the skin. Clinical history is essential to making this diagnosis, as effective treatment modalities may focus on behavioral therapies and psychiatric medications.
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A Transdiagnostic Approach to Obsessions, Compulsions and Related Phenomena - edited by Leonardo F. Fontenelle January 2019
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This chapter will present evidence from human clinical trials regarding the efficacy of nutritional supplements which have emerged in recent years as viable treatments for anxiety disorders. B vitamins Magnesium Lysine and Arginine Myo-Inositol N-Acetyl-cysteine
Article
The skin and psyche are intimately related with various skin diseases caused by or resulting in psychiatric disturbances. Pruritus is a commonly reported symptom in psychiatric patients and likewise psychiatric co-morbidities including anxiety and depression are frequently seen in chronic pruritus patients. Primary psychodermatologic conditions such as somatic symptom disorder, dermatitis artefacta, obsessive compulsive and related disorders (excoriation disorder and prurigo nodularis), delusional infestation, and substance use disorder can all induce significant pruritus in patients, severely affecting their quality of life. Such entities can be challenging to manage and therefore a greater understanding of the underlying psychopathology and evaluation of associated psychosocial factors is necessary. In addition to proper skin hygiene and first line pharmacotherapies such as selective serotonin reuptake inhibitors, noradrenergic and selective serotonin anti-depressants, anti-epileptics, and anti-psychotics (for delusional and psychotic disorders), patients with psychopruritic disorders should be offered psychotherapy to maximize the therapeutic efficacy.
Article
Nail biting, a common behavior seen in children, is typically short-lived and does not cause significant problems. However, when nail biting remains unresolved, physical and emotional consequences may occur. Exploring the etiological factors and underly­ing function of nail biting may help providers recommend appropriate interventions.
Article
Onychotillomania, defined as self-induced trauma to the nail unit, either by picking or pulling at the nails, affects 0.9% of the population. It may lead to severe irreversible nail dystrophy, melanonychia, or infections. Although no large clinical trials have assessed the efficacy of treatments, cognitive-behavioral therapy, physical barrier methods, and pharmacological treatments have shown some benefits in case reports. The objective of this article is to review the prevalence, diagnostic criteria, etiology, historical and physical examination findings, pathological features, and current treatment methods. Onychotillomania remains a clinical challenge to dermatologists, pediatricians, internists, and psychiatrists in practice, as there are no evidence-based treatment methods.
Chapter
In this chapter we review the evidence of the effectiveness of N-acetylcysteine (NAC) in psychiatric disorders excluding disorders of addiction. Each of these disorders is reviewed individually with the most up-to-date evidence for the usage of NAC in their treatment along with recommendations when possible. There was not enough evidence to make recommendations for anxiety and attention deficit hyperactivity disorder, but the available studies were promising. More evidence was available for other psychiatric disorders reviewed with mixed recommendations for autism spectrum disorder, bipolar disorder, depression, impulse-control disorders (i.e., onychophagia, trichotillomania, excoriation disorder), obsessive-compulsive disorder, and schizophrenia. Given that NAC positively modulates many underlying pathophysiological mechanisms associated with psychiatric disorders, it is a very promising therapy that requires further study.
Chapter
Selective serotonin reuptake inhibitors (SSRIs) and SRIs have been consistently supported as a first-line pharmacological treatment for obsessive compulsive disorder (OCD). This chapter examines the published data regarding augmentation strategies for SSRI/SRIs in the treatment of OCD. It provides a general summary of available data from blinded, controlled studies assessing augmentation efficacy. Dosing information provided for each agent reflects the current levels reported in available studies meeting inclusion criteria, as is the case with treatment duration. Early promising responses with antipsychotics (both typical and atypical) may indicate that dopaminergic abnormalities are a core neural underpinning in OCD. The chapter also provides a brief summary of the antipsychotic medications. Clomipramine is a SRI commonly used in the treatment of OCD. Additionally, clomipramine has frequently been used as an acceptable primary medication in the majority of studies.
Article
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The effects of nitrous oxide-induced cobalamin inactivation on homocysteine and folate metabolism have been investigated. Plasma levels of cobalamin, folate, homocysteine, and methionine were determined in 40 patients before and after operation under nitrous oxide anesthesia (range of exposure time, 70 to 720 minutes). Twelve patients anesthetized with total intravenous anesthesia served as control subjects (range of exposure time, 115 to 600 minutes). Postoperative plasma levels of folate and homocysteine increased (p less than 0.001) up to 220% and 310%, respectively, in nitrous oxide-exposed patients, whereas plasma levels of methionine decreased (p less than 0.025). Response occurred after 75 minutes of nitrous oxide exposure. The percentage increase of plasma folate and homocysteine correlated significantly with exposure time (p less than 0.025 and p less than 0.0001, respectively). In eight patients receiving nitrous oxide anesthesia plasma homocysteine levels had not returned to preoperative levels within 1 week (p less than 0.01). Urinary excretion of folate and homocysteine increased during and after nitrous oxide exposure (p less than 0.01 and p less than 0.002, respectively) and correlated with exposure time (p less than 0.01 and p less than 0.005, respectively). It can be concluded that disturbance of homocysteine and folate metabolism by nitrous oxide develops with little delay and return to normal levels requires several days. Elevation of plasma homocysteine levels may therefore be used for monitoring nitrous oxide-induced cobalamin inactivation.
Article
A systematic review of published work concerning mirtazapine was undertaken to assess possible evidence of serotonergic effects or serotonin toxicity (ST) in humans, because drug toxicity and interaction data from human over-doses is an useful source of information about the nature and potency of drug effects. There is a paucity of evidence for mirtazapine having effects on any indicator of serotonin elevation, which leads to an emphasis on ST as an important line of evidence. Mirtazapine is compared with its analogue mianserin, and other serotonergic drugs. Although mirtazapine is referred to as a dual-action 'noradrenergic and specific serotonergic drug' (NaSSA) little evidence to support that idea exists, except from initial microdialysis studies in animals showing small effects; those have not subsequently been replicated or substantiated by independent researchers. Also, new data indicate its affinity for Alpha 2 adrenoceptors is not different to mianserin. It appears to exhibit no serotonergic symptoms or toxicity in over-dose by itself, nor is there evidence that it precipitates ST in combination with monoamine oxidase inhibitors, as would be expected if it raises intra-synaptic serotonin levels. Mirtazapine has no demonstrable serotonergic effects in humans and there is insufficient evidence to designate it as a dual-action drug. Copyright (c) 2005 John Wiley & Sons, Ltd.
Article
Objective: Neurophysiologic findings indicate an inhibition of dopaminergic neurotransmission by selective serotonin reuptake inhibitors (SSRIs). This article highlights the relationships between changes in dopaminergic neurotrans-mission induced by SSRIs and the occurrence of certain side effects such as hyperprolactinemia, extrapyramidal symptoms, sexual and cognitive dysfunction, galactorrhea, mammary hypertrophy, and, more rarely, gynecomastia. Data sources and selection: A systematic search of the literature in English, French, and German from 1980 to 2004 was performed in MEDLINE, EMBASE, and the Cochrane Library using the keywords SSRI, dopamine, serotonin, side effects, antidepressants, citalopram, escitalopram, sertraline, paroxetine, fluoxetine, fluvoxamine, and nefazodone. References cited in all trials were searched iteratively to identify missing studies. All studies concerning inhibition of dopaminergic neurotransmission by SSRIs and SSRI-related side effects were considered. We retained 62 significant articles debating the subject. Data extraction and synthesis: We critically reviewed the studies, depending on the methodologies (case reports, clinical reports, randomized studies), and assessed the pertinence of "dopamine-dependent" SSRI-related side effects. The analytic review of these articles suggests that some specific SSRI-related side effects be classified as dopamine-dependent. Conclusions: At a clinical level, it could be useful to underline dopamine-dependent characteristics of some SSRI-related side effects. This approach would allow clinicians the opportunity to search other dopamine-dependent side effects systematically. At a pharmacologic level, this approach could stimulate the development of molecules with a "corrective" function on dopamine-dependent side effects of SSRIs by facilitating dopaminergic neurotransmission.
Article
There is a considerable overlap of schizophrenia and obsessive-compulsive disorder (OCD) in the structural and functional brain abnormalities involved, role of the dopamine/serotonin neurotransmitter systems, and some demographic and clinical characteristics. Although OCD co-occurs in a substantial proportion of schizophrenia patients, a systematic evaluation of the clinical features and treatment of this population is lacking. This review critically evaluates findings of recent studies pertaining to the rate of occurrence of OCD or obsessive-compulsive symptoms (OCS) in schizophrenia and the clinical characterisation of the schizo-obsessive subtype. Specifically, interrelationships between obsessive-compulsive and schizophrenic symptoms in terms of temporal relationships and their association with specific schizophrenia subtypes and the effect of OCS on the severity of schizophrenia symptoms are addressed. In the absence of evidence-based data, tentative therapeutic approaches in this difficult-to-treat patient subgroup are suggested. These include monotherapy with atypical antipsychotic agents or a combination of either typical or atypical antipsychotic s with SSRIs or clomipramine. The clinical characteristics of antipsychotic-induced OCS/OCD are also presented to facilitate identification and management of this rare but clinically significant adverse effect. Finally, future directions of research in schizophrenia-OCD comorbidity relevant to clinical practice are discussed.
Article
Sexual problems are highly prevalent in both men and women and are affected by, among other factors, mood state, interpersonal functioning, and psychotropic medications.The incidence of antidepressant-induced sexual dysfunction is difficult to estimate because of the potentially confounding effects of the illness itself, social and interpersonal comorbidities, medication effects, and design and assessment problems in most studies. Estimates of sexual dysfunction vary from a small percentage to more than 80%. This article reviews current evidence regarding sexual side effects of selective serotonin reuptake inhibitors (SSRIs). Among the sexual side effects most commonly associated with SSRIs are delayed ejaculation and absent or delayed orgasm. Sexual desire (libido) and arousal difficulties are also frequently reported, although the specific association of these disorders to SSRI use has not been consistently shown. The effects of SSRIs on sexual functioning seem strongly dose-related and may vary among the group according to serotonin and dopamine reuptake mechanisms, induction of prolactin release, anticholinergic effects, inhibition of nitric oxide synthetase, and propensity for accumulation over time. A variety of strategies have been reported in the management of SSRI-induced sexual dysfunction, including waiting for tolerance to develop, dosage reduction, drug holidays, substitution of another antidepressant drug, and various augmentation strategies with 5-hydroxytryptamine-2 (5-HT2), 5-HT3, and [small alpha, Greek]2 adrenergic receptor antagonists, 5-HT1A and dopamine receptor agonists, and phosphodiesterase (PDE5) enzyme inhibitors. Sexual side effects of SSRIs should not be viewed as entirely negative; some studies have shown improved control of premature ejaculation in men. The impacts of sexual side effects of SSRIs on treatment compliance and on patients' quality of life are important clinical considerations. (J Clin Psychopharmacol 1999;19:67-85)
Article
• Twenty-five adult subjects with severe morbid onychophagia (nail biting) and no history of obsessive-compulsive disorder were enrolled in a 10-week double-blind crossover trial of clomipramine hydrochloride and desipramine hydrochloride. For the 14 subjects who completed the study, clomipramine hydrochloride (mean±SD dose, 120±48 mg/d) was superior to desipramine hydrochloride (mean± SD dose, 135±53 mg/d) in decreasing nail biting as measured by a repeated-measures analysis of variance on the Nail Biting Severity, Naiibiting Impairment, and Clinical Progress scales. The high dropout rate at every stage of the study was in sharp contrast to that seen with psychiatric populations. From a neuroethologic perspective, similar biologic systems are hypothesized to mediate a spectrum of grooming behaviors, including onychophagia, trichotillomania, and obsessive-compulsive disorder.
Article
Results of neuropathologic, spectroscopic, and neurochemical studies continue to confirm a major role for ammonia in the pathogenesis of the central nervous system complications of both acute and chronic liver failure. Damage to astrocytes characterized by cell swelling (acute liver failure) or Alzheimer Type II astrocytosis (chronic liver failure) can be readily reproduced by acute or chronic exposure of these cells in vitro to pathophysiologically relevant concentrations of ammonia. Furthermore, exposure of the brain or cultured astrocytes to ammonia results in similar alterations in expression of genes coding for key astrocytic proteins. Such proteins include the structural glial fibrillary acidic protein, glutamate transporters, and peripheral-type (mitochondrial) benzodiazepine receptors. Brain–blood ammonia concentration ratios (normally of the order of 2) are increased up to fourfold in liver failure and arterial blood ammonia concentrations are good predictors of cerebral herniation in patients with acute liver failure. Studies using 1H magnetic resonance spectroscopy in patients with chronic liver failure reveal a positive correlation between the severity of neuropsychiatric symptoms and brain concentrations of the brain ammonia-detoxification product glutamine. Increased intracellular glutamine may be a contributory cause of brain edema in hyperammonemia. Positron emission tomography studies using 13HN3 provide evidence of increased blood–brain ammonia transfer and brain ammonia utilization rates in patients with chronic liver failure. In addition to the use of nonabsorbable disaccharides and antibiotics to reduce gut ammonia production, new approaches to the treatment of hepatic encephalopathy by lowering of brain ammonia include the use of L-ornithine–L-aspartate and mild hypothermia.
Article
The treatment of negative symptoms of schizophrenia presents a major clinical challenge. This review examines the evidence pertaining to the efficacy, tolerability and safety of adding selective serotonin reuptake inhibitors (SSRIs) to antipsychotic agents in the treatment of negative symptoms in schizophrenia. Important methodological issues such as differentiating primary and secondary negative symptoms are discussed. The balance of available evidence indicates that at least some SSRIs, fluvoxamine and fluoxetine, can ameliorate primary negative symptoms in chronic schizophrenia patients who are treated with typical antipsychotics. The combination is safe and well tolerated although, as antipsychotic drug concentrations may be elevated, attention to dose and drug monitoring should be considered as appropriate. The effect of SSRI augmentation of atypical antipsychotics requires further study. Combination with clozapine may require particular caution because of potential toxicity if serum clozapine levels rise steeply. SSRI augmentation may be a useful addition to the treatment of schizophrenia.
Article
Psychogenic excoriation (also called neurotic excoriation, acne excoriée, pathological or compulsive skin picking, and dermatotillomania) is characterised by excessive scratching or picking of normal skin or skin with minor surface irregularities. It is estimated to occur in 2% of dermatology clinic patients and is associated with functional impairment, medical complications (e.g. infection) or substantial distress. Psychogenic excoriation is not yet recognised in the DSM. We propose preliminary operational criteria for its diagnosis that take into account the heterogeneity of behaviour associated with psychogenic excoriation and allow for subtyping along a compulsivity-impulsivity spectrum. Psychiatric comorbidity in patients with psychogenic excoriation, particularly mood and anxiety disorders, is common. Patients with psychogenic excoriation frequently have comorbid disorders in the compulsivity-impulsivity spectrum, including obsessive-compulsive disorder, body dysmorphic disorder, substance use disorders, eating disorders, trichotillomania, kleptomania, compulsive buying, obsessive-compulsive personality disorder, and borderline personality disorder. There are few studies of the pharmacological treatment of patients with psychogenic excoriation. Case studies, open trials and small double-blind studies have demonstrated the efficacy of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors in psychogenic excoriation. Other pharmacological treatments that have been successful in case reports include doxepin, clomipramine, naltrexone, pimozide and olanzapine. There are no controlled trials of behavioural or psychotherapeutic treatment for psychogenic excoriation. Treatments found to be effective in case reports include a behavioural technique called ‘habit reversal’ a multicomponent programme consisting of self-monitoring, recording of episodes of scratching, and procedures that produce alternative responses to scratching; and an ‘eclectic’ psychotherapy programme with insight-oriented and behavioural components.
Article
Amisulpride is a substituted benzamide. It is a dopamine antagonist with high selectivity for dopamine D2 and D3 receptors. In high doses, amisulpride exhibits dopaminergic blocking activity similar to that induced by classical antipsychotic agents, whereas in low doses it appears to facilitate dopaminergic transmission. In well controlled studies of patients with primary negative symptoms of schizophrenia who had high negative and low positive symptoms scores, amisulpride 50 to 300 mg/day was more effective than placebo. The drug was at least as effective as low-dose fluphenazine (2 to 12 mg/day) in less rigorous trials which included patients with negative symptoms of schizophrenia. At higher dosages (600 to 1200 mg/day), amisulpride exhibits efficacy similar to that of haloperidol 5 to 40 mg/day or flupenthixol 25 mg/day in patients with positive symptoms of schizophrenia. In low and high dosages, amisulpride is generally well tolerated. Extrapyramidal symptoms (EPS) induced by amisulpride can occur at both low and high dosages and are dose-dependent. Symptoms are generally mild or moderate. In comparative trials, amisulpride caused an incidence of EPS similar to that with placebo and lower than that caused by haloperidol, flupentixol or fluphenazine. Neuroendocrine adverse events were reported rarely with low-dose amisulpride and at similar incidences with amisulpride ≤600 mg/day and haloperidol 16 mg/day. Insomnia and excitation occurred rarely. As classical antipsychotic drugs are not generally effective in reducing negative symptoms of schizophrenia, amisulpride should be considered a promising agent in the management of patients with schizophrenia who have predominantly negative symptoms. While amisulpride does not offer superior efficacy over classical antipsychotics in the management of patients with positive symptoms of schizophrenia, its lower potential for causing EPS justifies consideration of its use, especially in patients intolerant of classical antipsychotics.
Article
Replies to D. A. Fishbain's (see record 1995-29412-001) comment on the similarity of kleptomaniacs to the compulsive buyers in the article by R. J. Christenson et al (see record 1994-29953-001). Christenson et al suggest that the 2 groups have different underlying psychological meaning; kleptomaniacs seek challenge, and compulsive buyers seek reward. Benefits of treatment with serotonin reuptake inhibitors for both are also discussed. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Presents 5 case histories of 23–52 yr old males to illustrate the potential for severe violence, as the result of akathisia, following the administration of neuroleptics for acute psychiatric symptoms. The experience of sensory dissociation associated with uncomfortable physical reactions, resulting in extreme acts of physical violence, is emphasized. It is suggested that because akathisia is primarily an internal sensation, clinicians must be certain to question patients before ruling out its presence. Patient histories should be taken prior to the use of neuroleptic agents in emergency rooms in order to elicit a potential for violence. (1 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
Treatment with clozapine may be associated with the appearance of obsessive-compulsive (OC) symptoms in up to 10% of schizophrenic patients. We present the first report of the emergence of de novo OC symptoms during clozapine withdrawal in two schizophrenic patients, associated in one with Tourette's syndrome-like tics. Resumption of clozapine led to the complete disappearance of the OC symptoms and a substantial alleviation of the tics. It is suggested that an imbalance between the dopamine and serotonin systems may account for this complication. (C) Williams & Wilkins 1998. All Rights Reserved.
Article
Controlled research has shown that supervised disulfiram is an effective treatment for alcoholism. Despite this, little is known about the effects of disulfiram in persons with alcoholism and severe mental illness. We conducted comprehensive chart reviews on 33 patients with alcoholism and severe mental illness (70% schizophrenia or schizoaffective disorder) who had been prescribed disulfiram. Twenty-one percent reported side effects from disulfiram, whereas significant psychiatric complications were not reported. Although 76%% of patients reported drinking while on disulfiram, only 28%o experienced negative reactions to alcohol. Sixty-four percent of the patients saw a remission of alcoholism for at least one year during a three-year follow-up, and 30%o experienced a two-year remission. Disulfiram treatment was associated with decreases in days hospitalized but not with changes in work status. The results suggest disulfiram may be a useful adjunctive treatment for alcoholism in patients with severe mental illness and that controlled research is needed to evaluate its effects in this population.
Article
The atypical antipsychotic clozapine is reported to have unique therapeutic effects and to produce minimal extrapyramidal side effects. However, in a blind survey, akathisia was observed to be similar in prevalence and severity in patients treated with clozapine and those receiving standard neuroleptic antipsychotic drugs. In addition, as with standard antipsychotic drugs, the presence of akathisia in patients receiving clozapine was associated with a worse overall clinical outcome. The results suggest that akathisia may be a common side effect of all antipsychotic drugs, that akathisia may be prodcued by a mechanism distinct from other locomotor effects of these medications, and that patients receiving clozapine, like patients receiving standard antipsychotic drugs, should be monitored for akathisia.
Article
Although the anticonvulsant hypersensitivity syndrome was first described in 1950, confusion still abounds regarding the syndrome. The triad of fever, rash and internal organ involvement occurring 1 to 8 weeks after exposure to an anticonvulsant heralds this rare (1 in 1,000 to 10,000 exposures) but serious reaction. Aromatic anticonvulsants [phenytoin, phenobarbital (phenobarbitone) and carbamazepine] are the most frequently involved drugs; however, there have also been several cases of anticonvulsant hypersensitivity syndrome associated with lamotrigine. Fever, in conjunction with malaise and pharyngitis, is often the first sign. This is followed by a rash which can range from a simple exanthem to toxic epidermal necrolysis. Internal organ involvement usually involves the liver, although other organs such as the kidney, CNS or lungs may be involved. Hypothyroidism may be a complication in these patients approximately 2 months after occurrence of symptoms. The aromatic anticonvulsants are metabolised to hydroxylated aromatic compounds, such as arene oxides. If detoxification of this toxic metabolite is insufficient, the toxic metabolite may bind to cellular macromolecules causing cell necrosis or a secondary immunological response. Cross-reactivity among the aromatic anticonvulsants may be as high as 75%. In addition, there is a familial tendency to hypersensitivity to anticonvulsants. Discontinuation of the anticonvulsant is essential in patients who develop symptoms compatible with anticonvulsant hypersensitivity syndrome. A minimum battery of laboratory tests, such as liver transaminases, complete blood count and urinalysis and serum creatinine, should be performed. Corticosteroids are usually administered if symptoms are severe. Patients with anticonvulsant hypersensitivity syndrome should avoid all aromatic anticonvulsants; benzodiazepines, valproic acid (sodium valproate) or one of the newer anticonvulsants can be used for seizure control. However, valproic acid should be used very cautiously in the presence of hepatitis. There is no evidence that lamotrigine cross-reacts with aromatic anticonvulsants. In addition, family counselling is a vital component of patient management.
Article
To study the pharmacokinetics of fluvoxamine when given in increasing doses to healthy volunteers. Ten healthy, non-smoking men were given maintenance treatment with fluvoxamine for 4 weeks. Eight subjects were CYP2D6 extensive metabolisers (EMs) and two were CYP2D6 poor metabolisers (PMs). As a measure of the CYP1A2 phenotype, the paraxanthine/caffeine ratio in saliva after intake of caffeine was studied. The fluvoxamine doses given were 25 mg day(-1) the first week, 50 mg day(-1) the second week, 100 mg day(-1) the third week and 200 mg day(-1) the fourth week, divided in two daily doses. On the seventh day every week, serum concentrations of fluvoxamine were followed for a dose interval of 12 h. After discontinuation of treatment, fluvoxamine concentrations were followed for 1 week. For each of the three two-fold increases in given dose, the mean AUC increased 3.25-fold, 3.17-fold and 3.14-fold, respectively (P < 0.0001), indicating a decrease in oral clearance with increasing dose. The elimination half-life based upon the serum concentrations 12-48 h after discontinuation of fluvoxamine was 32.1 +/- 11.0 h whereas the half-life based upon the concentrations 3-7 days after discontinuation was significantly shorter, 15.8 +/- 4.2h (means +/- s.d.; P < 0.001). There were no significant correlations between the CYP1A2 phenotype and fluvoxamine AUCs at different doses (r = -0.56; P = 0.095 for the correlation between the paraxanthine/caffeine ratio in saliva and fluvoxamine AUC at a dose of 50 mg day[-1]). The two CYP2D6 PMs had AUC values in the same range as the EMs. The present study conclusively demonstrates that fluvoxamine exhibits non-linear kinetics within the therapeutic dose interval. The reason for non-linearity is not Michaelis-Menten saturation kinetics of a single metabolic pathway, but rather a complex involvement of multiple parallel pathways.
Article
Our objective was to determine the efficacy of fluoxetine in the treatment of pathologic skin picking in a double-blind, placebo-controlled, parallel trial. Twenty-one adults with chronic pathologic skin picking agreed to participate and received 10 weeks of placebo or fluoxetine with a flexible dosing schedule up to 80 mg/day. Three skin-picking measures were employed: the Clinical Global Impression-Improvement (CGI-I) scale, the Skin Picking Treatment Scale (SPTS), and a visual analog scale of self-rated change (VAS). In addition, depression, anxiety, and obsessions-compulsions were rated using the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Spielberger State-Trait Anxiety Inventory (STAI), and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for the duration of the study. Seventeen subjects (6 treated with fluoxetine and 11 treated with placebo) completed the trial, at a mean fluoxetine dose of 55 mg/day. Fluoxetine was significantly superior to placebo in the treatment of skin picking according to two of the three measures for the completer analysis and to one of the three measures for the intent-to-treat analysis. Neither baseline level nor change in depression, anxiety, or obsessive-compulsive symptoms was significantly related to change in skin picking. This first controlled trial of the treatment of pathologic skin picking suggests that fluoxetine may be of therapeutic benefit. Larger controlled studies are warranted.
Article
An eleven item clinician-administered Mania Rating Scale (MRS) is introduced, and its reliability, validity and sensitivity are examined. There was a high correlation between the scores of two independent clinicians on both the total score (0.93) and the individual item scores (0.66 to 0.92). The MRS score correlated highly with an independent global rating, and with scores of two other mania rating scales administered concurrently. The score also correlated with the number of days of subsequent stay in hospital. It was able to differentiate statistically patients before and after two weeks of treatment and to distinguish levels of severity based on the global rating.
Article
Both the amygdala and the hippocampus are involved in the pathogenesis of a number of neurologic conditions, including temporal lobe epilepsy, postanoxic amnesia, and Alzheimer's disease. To enhance the investigation and management of patients with these disorders, we developed a protocol to measure the volumes of the amygdala and as much of the hippocampus as possible (approximately 90 to 95%) using high-resolution MRI. We present the anatomic basis of these two protocols and our results in normal control subjects. These volumetric studies of the amygdala may clarify the role of this structure in the pathogenesis of temporal lobe epilepsy.
Article
In treatment of alcohol dependence, disulfiram is most useful in conjunction with a structured, supervised, aftercare program. However, it has been reported to cause psychiatric side effects and to interact with various psychiatric medications. Many patients with alcohol dependence suffer from other psychiatric disorders and are treated with such psychiatric medications. This paper reviews the pertinent clinical pharmacology of disulfiram and the literature on potential psychiatric complications and drug interactions of disulfiram. At the usual dosage, about 250 mg/day, disulfiram does not appear to increase significantly the risk of psychiatric complications or of psychiatric drug interactions. Therefore, it can be considered a treatment option for patients with alcohol dependence and other psychiatric disorders.
Article
It has been proposed by some investigators that trichotillomania, a disorder of chronic hair pulling, is a variant of obsessive-compulsive disorder, and some studies have suggested that the antiobessional agents clomipramine and fluoxetine are useful in treating this disorder. The authors investigated the efficacy of fluoxetine in the treatment of trichotillomania. Twenty-one adult chronic hair pullers were recruited into an 18-week placebo-controlled, double-blind crossover study of fluoxetine, in doses up to 80 mg/day. The fluoxetine and placebo treatment phases consisted of 6-week trials of each agent separated by a 5-week washout period. Fifteen subjects (14 female and one male) completed the study; an additional female subject dropped out at 16 weeks after developing a drug reaction. No significant Drug by Period interactions were found in weekly subject ratings of hair pulling, weekly subject ratings of the urge to pull hair, weekly assessments of the number of hair-pulling episodes, or the estimated amount of hair pulled per week. The short-term efficacy of fluoxetine in the treatment of trichotillomania was not demonstrated in this study.
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Twenty-five adult subjects with severe morbid onychophagia (nail biting) and no history of obsessive-compulsive disorder were enrolled in a 10-week double-blind cross-over trial of clomipramine hydrochloride and desipramine hydrochloride. For the 14 subjects who completed the study, clomipramine hydrochloride (mean +/- SD dose, 120 +/- 48 mg/d) was superior to desipramine hydrochloride (mean +/- SD dose, 135 +/- 53 mg/d) in decreasing nail biting as measured by a repeated-measures analysis of variance on the Nail Biting Severity, Nailbiting Impairment, and Clinical Progress scales. The high dropout rate at every stage of the study was in sharp contrast to that seen with psychiatric populations. From a neuroethologic perspective, similar biologic systems are hypothesized to mediate a spectrum of grooming behaviors, including onychophagia, trichotillomania, and obsessive-compulsive disorder.