Annotated Abstracts of Journal Articles
2015, 1st Quarter
Annotations by J. Jewel Shim, MD, FAPM
ANNOTATION (J. Jewel Shim)
The Finding: This is a systematic review of 12 randomized, controlled trials and 7 open-label trials for the pharmacotherapy for trichotillomania (TTM). The authors categorized the trials according to type of pharmacological agent: serotonin reuptake inhibitors, tricyclic antidepressants, opioid antagonists, glutamate modulators, cannabinoid agonists, and antipsychotics. Overall, study sizes were small, with the largest study containing 51 subjects, and the majority were 6-12 weeks in duration. Three of the RCTs had a behavioral therapy comparison group; in all of the studies therapy was found to be superior to active agent and placebo. In general, open trials found a statistically significant treatment effect of the medication studied, but of the 12 RCTs, only 3 of them found a significant treatment effect of the active agent vs. placebo: a clomipramine study, an investigation examining the efficacy of N-acetylcysteine (NAC), and an olanzapine trial. However, the clomipramine study was small (n= 13) and its results have not been replicated.
Strengths and Weaknesses: A strength of this study is that it gives a review of the existing pharmacological studies for treatment of TTM. It also describes the rationale behind the different pharmacological approaches of the studies, e.g., cannabinoid agents have been found to have some success in treating disorders with motoric compulsions such as tic disorders. Also, behavioral therapy was highlighted as perhaps the most successful treatment overall for TTM. However, the major weakness is that it is not a true meta-analysis and there was no determination of an overall effect size, due to the heterogeneity of the studies as well as the large number of open trials included.
Relevance: This paper provides a good review of the literature regarding the current medication studies for TTM which may guide the PM psychiatrist in choosing an evidence-based treatment approach for this population of patients.
Introduction: Individuals affected by trichotillomania (TTM) (hair-pulling disorder) consciously or non-consciously pull out their own body hair. The disorder has recently been incorporated into a chapter entitled, ‘Obsessive-Compulsive and Related Disorders’ in the diagnostic and statistical manual of mental disorders, fifth edition.
Areas Covered: The review describes the literature currently available on the pharmacotherapy for TTM, including both randomized controlled trials and open-label trials of pharmacotherapy for TTM in adults or children.
Expert Opinion: Early work focused on the serotonin reuptake inhibitors; however, the majority of the trials have been negative. There is a small body of evidence focused on pharmacotherapy for TTM. In future, larger trials are required to expand on the preliminary evidence available for N-acetylcysteine, olanzapine and dronabinol in recent trials.
ANNOTATION (J. Jewel Shim)
The Finding: This cross-sectional, multicenter study which included 4994 subjects—3635 subjects recruited from dermatology clinics and 1359 controls—was undertaken to investigate the co-occurrence of depression, anxiety, and suicidal thoughts in patients with common skin conditions. The authors cited the importance of defining the burden of dermatological disease and the role of associated psychiatric illnesses in worsening this burden in the evidence-based allocation of resources from a global health perspective. Each dermatological subject underwent a physical exam and all subjects completed the Hospital Anxiety and Depression Scale (HADS). The results showed the both depression and anxiety symptoms were more prevalent in the dermatological subjects than in the controls (10.1% vs. 4.1% and 17.2% vs. 11.1% respectively). Subjects with chronic leg ulcers had the highest rates of depression. Psoriasis and hand eczema were the skin conditions associated with the highest rate of anxiety. Overall, suicidal ideation was more prevalent in the dermatological subjects but this difference was not significant, though when broken down by specific disease, psoriasis was the only skin condition that had a significant association with suicidal thoughts.
Strengths and Weaknesses: Strengths include study size as well as its multicenter nature, which included many different kinds of skin disease as well as a diverse subject pool, making its findings more representative of the general population. An additional strength is that it included a control group that served as a reference population. The HADS allowed a comparison of severity of depression and anxiety symptoms among the different dermatological illnesses. The results replicated and supported the findings of other similar studies, demonstrating a consistent association between skin disease and depression and anxiety states.
A major weakness is the cross-sectional design, which did not allow the authors to draw any conclusions regarding causality or the specific relationship between the skin diseases and psychiatric disorders/symptoms. Moreover, while comorbid mental and physical conditions were recorded, there is no mention of the medications the subjects were taking. This is of importance because many medications, including psychotropics agents, have dermatological as well as psychiatric side effects, which could have affected the results. Additionally, the HADS is not a diagnostic tool, it is a self-report of symptoms of depression and anxiety; these symptoms were not confirmed with a diagnostic interview.
Relevance: This study highlights the co-occurring nature of psychiatric diseases and common dermatological conditions, in which both may contribute to the overall burden of disease.
The contribution of psychological disorders to the burden of skin disease has been poorly explored, and this is a large-scale study to ascertain the association between depression, anxiety, and suicidal ideation with various dermatological diagnoses. This international multicenter observational cross-sectional study was conducted in 13 European countries. In each dermatology clinic, 250 consecutive adult out-patients were recruited to complete a questionnaire, reporting socio-demographic information, negative life events, and suicidal ideation; depression and anxiety were assessed with the Hospital Anxiety and Depression Scale. A clinical examination was performed. A control group was recruited among hospital employees. There were 4,994 participants—3,635 patients and 1,359 controls. Clinical depression was present in 10.1% patients (controls 4.3%, odds ratio (OR) 2.40 (1.67-3.47)). Clinical anxiety was present in 17.2% (controls 11.1%, OR 2.18 (1.68-2.82)). Suicidal ideation was reported by 12.7% of all patients (controls 8.3%, OR 1.94 (1.33-2.82)). For individual diagnoses, only patients with psoriasis had significant association with suicidal ideation. The association with depression and anxiety was highest for patients with psoriasis, atopic dermatitis, hand eczema, and leg ulcers. These results identify a major additional burden of skin disease and have important clinical implications.
Chen MH, Su TP, Chen YS, Hsu JW, Huang KL, Chang WH, et al
ANNOTATION (J. Jewel Shim)
The Finding: This is a longitudinal cohort study of 14,812 atop subjects diagnosed before age 3 and 6944 control subjects with no lifetime atopic disease born between 1997-2000 and followed until the diagnosis of ADHD or autism spectrum disorder (ASD), December 2010, or death. They were drawn from the Taiwan National Health Insurance Research Database (NHIRD). The atopic subjects had a higher incidence of ADHD (6.3% vs. 2.9% p< 0.001) and ASD (0.8% vs. 0.2% p< 0.001). 64.6% of ASD subjects also had comorbid ADHD, and among ADHD subjects, 7.4% also had ASD. Primary Cox regression models demonstrated that subjects with any atopic disease had an almost two-fold (HR 1.97, 95% CI 1.69-2.29) increase in risk of developing ADHD and were over three times (HR 3.40, 95% CI 1.95-5.93) as likely to have a subsequent diagnosis of ASD. Further, secondary Cox regression models showed that the likelihood of developing ADHD or ASD in later life increased with the number of atopic diseases. Male gender was identified as an independent risk factor for ADHD and ASD.
Strengths and Weaknesses: The primary strengths of this study are its large sample size and the length of follow-up, with the study following participants from birth. Diagnoses of psychiatric and physical conditions were made by board-certified physicians. A weakness mentioned by the authors is that the incidence of ADHD and ASD may have been underestimated because the study only identified those who sought treatment. While the study included a control group, only an association between atopic diseases and ADHD and ASD could be identified; however, the researchers cited a number of studies investigating the relationship between them, which suggested the role of immunological responses in the development of ADHD and ASD in patients with atopic disease.
Relevance: Children with atopic diseases may be identified as a higher risk group for the development of ADHD and ASD.
Objective: Previous studies have found a temporal concordance in the increased prevalence of atopic diathesis/atopic diseases, attention-deficit hyperactivity disorder (ADHD), and autistic spectrum disorder (ASD) worldwide. But, the temporal association among these 3 distinct diseases is unknown.
Method: 14,812 atopic subjects diagnosed with any atopic disease (asthma, atopic dermatitis, allergic rhinitis, or allergic conjunctivitis) before the age of 3 (atopic cohort) and 6944 non-atopic subjects with no lifetime atopic disease (non-atopic cohort), born between 1997 and 2000, were enrolled and followed to December 31, 2010 to identify the development of ADHD and ASD.
Results: The presence of any atopic disease in early childhood increased the risk of developing ADHD (hazard ratio [HR]: 1.97) and ASD (HR: 3.40) in later life. Greater numbers of atopic comorbidities (4 comorbidities: ADHD: HR: 2.53; ASD: HR: 4.29) were significantly related to a greater risk of developing ADHD and ASD.
Discussion: Atopic diathesis in early childhood elevated the risk of developing ADHD and ASD in later life, with the dose-dependent relationship of more atopic comorbidities with a greater likelihood of ADHD and ASD.