Journal Article Annotations
2021, 4th Quarter

Psychodermatology

Annotations by J. Jewel Shim, MD
December, 2021

Pharmacotherapy for trichotillomania.
Is Isotretinoin in Acne Patients a Psychological Boon or a Bane: A Systematic Review.

PUBLICATION #1 — Psychodermatology

Pharmacotherapy for trichotillomania.

Jacob Hoffman, Taryn Williams, Rachel Rothbart, Jonathan C Ipser, Naomi Fineberg, Samuel R Chamberlain, Dan J Stein

Abstract: Cochrane Database Syst Rev. 2021 Sep 28;9(9):CD007662. doi: 10.1002/14651858.CD007662.pub3.

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.

Annotation

The finding:
This is a Cochrane review of effectiveness of different pharmacotherapies for the treatment of trichotillomania (TTM) in children, adolescents, and adults. Twelve studies were included in this review, 10 in adults and 2 in children/adolescents. Pharmacotherapeutic agents included antioxidants, antipsychotics, cell signal transducers, glutamate modulators, opioid antagonists, SSRIs, TCAs. Studies were each from a single center with small numbers of subjects (average n= 29 in adult studies). Most studies were found to have low certainty or very uncertain evidence, except in the case of N-acetylcysteine (NAC), which was judged to have moderate certainty evidence. The authors’ conclusion was that there is insufficient evidence to support the effectiveness of any one agent or class of medications, though there is some evidence to suggest that the most effective treatments among those studied are NAC, clomipramine, and olanzapine.

Strength and weaknesses:
This meta-analysis was limited by the quality of the studies, as well as the small sample sizes in each study. While the data suggest that SSRIs with high serotonergic effects, olanzapine, and NAC may be the most effective for TTM symptoms, the certainty of the evidence is not high.

Relevance:
TTM remains a difficult to treat psychodermatological condition, and it is important to establish the evidence base for the most effective treatments.

PUBLICATION #2 — Psychodermatology

Is Isotretinoin in Acne Patients a Psychological Boon or a Bane: A Systematic Review.

Savitri Chandrasekaran, Joaquim Francisco Maria De Sousa, Smit Paghdar, Taheseen M Khan, Nishant P Patel, Nicholas Tsouklidis

Abstract: Cureus. 2021 Aug 2;13(8):e16834. doi: 10.7759/cureus.16834. eCollection 2021 Aug.

Acne vulgaris is a frequently encountered dermatological condition in clinical practice. Isotretinoin is one of the drugs prescribed for this condition. However, it is unclear whether the use of this drug worsens or improves the psychological effects in an acne patient and whether it is advisable to use this drug commonly. This systematic review aims to assess the relationship between Isotretinoin and psychiatric side effects in acne patients. A literature search was conducted using PubMed, Cochrane, and Google Scholar databases in accordance with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Articles published within the last 10 years were taken into account and a review was conducted on the relevant articles after critical appraisal. Nine studies were finalized for discussion and out of the nine studies, two studies concluded that Isotretinoin could cause psychiatric effects. Five studies showed no association between them. Two studies unexpectedly found that psychiatric symptoms improved because of Isotretinoin use. Lack of adequate sample size and absence of randomized controlled trials are the limitations of this study. To conclude, Isotretinoin can be prescribed as a treatment option for severe acne despite some evidence of link with psychiatric effects. However, bearing the side effects in mind, a detailed evaluation before initiating the drug and a thorough monitoring while using the drug should be done as a standard practice in order to be on the safer side.

Annotation

The finding:
This is a systematic review of 9 studies examining whether isotretinoin used in patients with acne were associated with adverse psychological effects. The study authors found inconsistent evidence across these studies as to whether isotretinoin used in patients with acne caused or exacerbated psychological symptoms, was not associated with psychological symptoms, or even improved psychological symptoms. In regard to this latter result, there is some question of whether psychological symptoms improved as a result of the beneficial effects of isotretinoin, leading to an increased sense of well-being and confidence in those who suffer from acne. The authors concluded that isotretinoin could be used with caution with careful monitoring, particularly in patients with a pre-existing psychiatric disorder.

Strengths and weaknesses:
The authors noted that there are no randomized controlled trials examining the association between isotretinoin and psychiatric symptoms, and existing studies generally had small sample sizes.

Relevance:
Isotretinoin, when used in acne patients, has long been associated with exacerbation/onset of psychological symptoms, including depression, anxiety, and suicidal ideation. It is important for the C-L psychiatrist to be aware of the existing evidence in regard to this potential association.