Annotated Abstracts of Journal Articles
2015, 2nd Quarter
Annotations by J. Jewel Shim, MD, FAPM
Also of interest:
ANNOTATION (J. Jewel Shim)
The Finding: The study investigators describe a growing body of evidence reporting an association between atopic diseases (AD), depression, and anxiety disorders but point out that results of these studies have been either inconsistent or did not control for atopic comorbidities. In their investigation they examined the risk for depression and anxiety disorders in a sample of over 8200 adolescents and adults with a history of AD compared to a matched group of over 8200 controls. Over the study period between 1998-2011, they found that adolescents and adults with AD did have an increased risk of subsequently developing a depressive or anxiety disorder. This risk was consistent after controlling for atopic comorbidities, as well as when results were stratified by age group (adolescents vs. adults).
Strengths and Weaknesses: A major strength is the sample size, which was large, and the longitudinal study design. The statistical analyses did control for comorbid atopic illnesses to better identify the independent effect of AD in the development of depression and anxiety disorders. Psychiatric diagnoses were made by board-certified psychiatrists instead of by self-report measures, though the authors pointed out a potential lack of consistency due the absence of standardized measurements.
The investigators also acknowledged that the results may have underestimated the incidence of psychiatric disorders in subjects because only those who sought treatment were enrolled. The database, though large, did not provide information regarding a number of factors, such as disease severity and environmental factors, and thus their potential influence on the results could not be assessed. Further, there was no information regarding treatments, including medications, some of which may have psychiatric side effects such as depression and anxiety (i.e., steroids, isotretinoin, beta agonists).
Relevance: This study reports a potential association between AD and depression and anxiety disorders. Knowledge of this link may help the PM psychiatrist aid their primary care and dermatology colleagues in the identification of depression and anxiety symptoms in this population of patients who may be at greater risk for the development of these disorders.
Background: Previous cross-sectional studies have suggested a comorbid association between atopic dermatitis (AD) and depressive disorder as well as anxiety disorders, but the temporal relationship was not determined.
Methods: Using the Taiwan National Health Insurance Research Database, 8208 AD patients aged 12 and older without psychiatric history and age-/sex-matched (1:1) controls between 1998 and 2008 were enrolled in our study and followed to the end of 2011. Subjects who developed major depression, any depressive disorder, and anxiety disorders during the follow-up were identified.
Results: The Cox regression analysis after adjusting for demographic data and atopic comorbidities demonstrated that patients with AD had an elevated risk of developing major depression (hazard ratio [HR]: 6.56, 95% confidence interval [CI]: 3.64-11.84), any depressive disorder (HR: 5.44, 95% CI: 3.99-7.44), and anxiety disorders (HR: 3.57, 95% CI: 2.55-4.98). Stratified by age group, both adolescents and adults with AD were prone to developing major depression (HR: 4.26, 95% CI: 1.39-13.13; HR: 7.56, 95% CI: 3.75-15.23), any depressive disorder (HR: 4.38, 95% CI: 2.09-9.18; HR: 5.66, 95% CI: 4.01-7.99), and anxiety disorders (HR: 5.40, 95% CI: 2.02-14.39; HR: 3.36, 95% CI: 2.38-4.80).
Conclusions: AD in both adolescence and adulthood increased the risk of developing major depression, any depressive disorder, and anxiety disorders in later life. Further studies would be required to clarify the possible underlying mechanism between AD and depression as well as anxiety disorders.
ANNOTATION (J. Jewel Shim)
The Finding: This is a review of clinical trials and case reports using N-acetyl cysteine (NAC) for the treatment of OCD and obsessive-compulsive related disorders (OCRD) which include excoriation disorder and trichotillomania (TTM). The authors describe the rationale for using NAC in this population of patients—there is growing evidence that the cortico-striato-thalamic-cortical (CSTC) circuit is a key factor underlying the pathophysiology of OCD and OCRD. Glutamine is the primary neurotransmitter within this circuit and abnormal glutamate transmission has been implicated in patients with OCD. Thus, glutamine-modulating agents have been studied in the regulation of impulse control in patients with impulse control related disorders such as OCD, OCRD, and substance use disorders.
The authors presented case reports and clinical trials examining the use of NAC in OCD and OCRD. The results of most of the case reports for NAC treatment for OCD were negative. Only one RCT of 39 subjects studied NAC in OCD, and it showed significant improvement in OCD symptoms over placebo. The results also suggested that NAC may only be effective in a subset of OCD patients.
In terms of the use of NAC in OCRD, case reports suggested that NAC is effective in TTM, nail biting, and excoriation disorder. There have been 4 RCTs for OCRD: two for TTM, one for skin picking, and one examining nail biting. NAC performed better than placebo in reducing TTM symptoms in a study of 44 subjects, and showed significant improvements in skin picking behaviors in a sample of 35 children and adults with Prader-Willi Syndrome. NAC demonstrated initial improvement in nail biting in a study of 25 children and adolescents, but this effect was not sustained over the two-month study period. NAC showed no difference over placebo in another study of 35 pediatric patients with TTM.
Strengths and Weaknesses: This study, which was described as a systematic review, was actually just a review. Data on the use of NAC in OCD is currently quite limited, with most of the data with OCD being from case reports. While there have been more clinical trials examining NAC in the treatment of OCRD, sample sizes were small and the results have not been particularly robust nor consistent in support of the efficacy of NAC in this patient population. The strengths of this paper are that it provided a fairly inclusive review of the available studies of NAC in the treatment of OCD and OCRD, and it gives a good background on the rationale for the use of NAC in these disorders. It also highlights, based on the results of these studies, that only certain subsets of patients afflicted with OCD/OCRD may respond to NAC and suggests that future studies also aim to identify these subsets.
Relevance: This paper describes data on NAC, a potentially effective alternative treatment for patients with refractory symptoms of OCD and OCRD.
Objective: Obsessive compulsive and related disorders are a collection of debilitating psychiatric disorders in which the role of glutamate dysfunction in the underpinning neurobiology is becoming well established. N-acetyl cysteine (NAC) is a glutamate modulator with promising therapeutic effect. This paper presents a systematic review of clinical trials and case reports exploring the use of NAC for these disorders. A further objective was to detail the methodology of current clinical trials being conducted in the area.
Methods: PubMed, Web of Science and Cochrane Library Database were searched for human clinical trials or case reports investigating NAC in the treatment of obsessive compulsive disorder (OCD) or obsessive compulsive related disorders. Researchers with known involvement in NAC studies were contacted for any unpublished data.
Results: Four clinical trials and five case reports/series were identified. Study durations were commonly 12-weeks, using 2,400-3,000 mg/day of NAC. Overall, NAC demonstrates activity in reducing the severity of symptoms, with a good tolerability profile and minimal adverse effects. Currently there are three ongoing randomized controlled trials using NAC for OCD (two adults and one pediatric), and one for excoriation.
Conclusions: Encouraging results have been demonstrated from the few pilot studies that have been conducted. These results are detailed, in addition to a discussion of future potential research.