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.

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.

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.