Pharmacological Interventions for Primary Psychodermatologic Disorders: An Evidence Mapping and Appraisal of Randomized Controlled Trials

Abstract

Background

The lack of clinical guidelines for the treatment of primary psychodermatologic disorders (PPDs) hinders the delivery of optimal care to patients. The review aimed to identify, appraise, and summarize the currently available evidence about the safety and effectiveness of pharmacological management of PPDs through randomized controlled trials (RCTs).

Methods

The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRIMSA) statement and the Global Evidence Mapping Initiative guidance were followed. Medline, Embase, PsycInfo, Cochrane and Scopus were searched, and two reviewers independently completed article review, data extraction, and quality assessment.

Results

Among 2618 unique studies, full texts of 83 were reviewed and 21 RCTs were included. Five PDDs were identified: trichotillomania (n = 12), pathologic skin picking (n = 5), nail biting (n = 2), delusional parasitosis (n = 1), and dermatitis from compulsive hand washing (n = 1). Seven different classes of medications were investigated: SSRIs (i.e., fluoxetine, sertraline, and citalopram), tricyclic antidepressants (i.e., clomipramine and desipramine), antipsychotics (i.e., olanzapine and pimozide), anticonvulsant (i.e., lamotrigine), N-acetylcysteine, inositol, and milk thistle. RCT-derived evidence supports the use of antidepressants in trichotillomania (sertraline and clomipramine), pathologic skin picking (fluoxetine), pathologic nail biting and dermatitis from compulsive hand washing (clomipramine or desipramine); antipsychotics in trichotillomania (olanzapine) and delusional parasitosis (pimozide); N-acetyl cysteine in trichotillomania and skin picking.

Conclusion

Few pharmacotherapies for primary psychodermatologic disorders are assessed through controlled trials in the literature. This review serves as a roadmap for researchers and clinicians to reach informed decisions with current evidence, and to build on it to establish guidelines in the future.

Introduction

Primary psychiatric disorders with dermatologic symptoms are often referred to as “primary psychodermatologic disorders,” for example, delusional parasitosis. ¹ These are different from “secondary psychodermatologic disorders,” which are dermatologic conditions with secondary or accompanying psychiatric symptoms, for example, acne vulgaris causing increased anxiety. ¹ Primary psychodermatologic disorders (PPDs) present with a skin complaint that has a primary psychiatric origin, and the most commonly reported PPDs are delusional parasitosis (DP), trichotillomania (TTM), pathologic skin picking (PSP), pathologic nail biting, tanning dependence, psychogenic pruritus, and dermatitis artefacta. ^{1 -3}

The clinical management of PPDs is challenging, especially for dermatologists who often are the first to see patients with PPDs. ⁴ Treatment challenges include patients’ limited insight into the nature of their condition, leading to frequent reluctance of considering psychological and psychiatric intervention. ^{5 -7} Other challenges include dermatologists’ insufficient training and time constraint to treat psychiatric conditions. ^{5 -7} The lack of clinical practice guidelines for dermatologists for PPDs is therefore particularly challenging in this context. ⁴ Few PPDs have been investigated systematically, including skin picking disease and trichotillomania: a meta-analysis from 2016 found that selective serotonin reuptake inhibitors (SSRIs) and an anticonvulsant (lamotrigine) were the only medications for PDDs investigated in controlled trials that showed potential benefits for skin picking. ⁸ One meta-analysis on trichotillomania found that several pharmacological treatments demonstrated efficacy in single trials, and reproducing and validating the outcomes of these trials was recommended. ⁹ For delusional parasitosis, the currently available evidence is mostly derived from case series and small-scale uncontrolled trials. ¹⁰ Although the most commonly reported medications are pimozide and risperidone, there is a lack of consensus on the dosage of antipsychotics for delusional parasitosis. ¹⁰ The effectiveness of pharmacological interventions for treatment of PPDs, compared to psychotherapy, or the combination of medications and psychotherapy has been debated in the literature with little consensus. ¹¹ Consequently, clinicians and researchers are currently left with inadequate guidance on how to best approach and investigate PPDs. ¹² This can affect the quality of care and the conduct of targeted research to enhance psychodermatology practice.

Evidence mapping is a research method used to systematically describe the availability and extent of scientific evidence. ¹³ The aim of the review is to identify gaps and determine the sufficiency of current evidence to support informed decision making, and to identify specific areas of need for future research and interventions. In this evidence mapping study, we aim to identify, appraise, and summarize the currently available evidence about the pharmacological management of PPDs through randomized controlled trials (RCTs). We also aim to identify the areas with sufficient clinical evidence for specific pharmacological interventions for PPDs, and to give an overview of investigated medications and regimens.

Methods

A protocol was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement and the Global Evidence Mapping Initiative. ^13,14

Search Strategy and Data Sources

Team members (TT, CL, and LD) created a list of relevant psychodermatology search terms and a health sciences librarian (LD) conducted searches in Medline, Embase, PsycInfo, Cochrane Trials database (CENTRAL), and Scopus in November 2020. The search strategy combined an extensive list of subject headings and keywords for primary psychodermatologic disorders (Supplemental Appendix). The search was limited to randomized controlled trials (RCTs) using relevant filers. ¹⁵ No language or date restrictions were applied. The reference lists of included studies were also screened for additional studies.

Studies Selection

All studies identified from the search were uploaded to the Covidence systematic review software. Two reviewers (TT and CL) independently screened titles and abstracts of retrieved studies to identify relevant studies. Full-text reviews were completed independently using pre-defined inclusion/exclusion criteria. Disagreements were first discussed between the two reviewers and then by consultation among the research team.

Controlled clinical trials were included if they evaluated any pharmacological intervention for the following PDDs: delusional parasitosis, pathologic skin picking, trichotillomania, tanning dependence, psychogenic pruritus, psychogenic purpura, dermatitis artefacta, and skin manifestations of obsessive-compulsive disorder, phobias, or body dysmorphic disorder. There was no limitation on the age of study participants.

Data Extraction and Quality Assessment

Two reviewers (TT and CL) independently extracted data. Details extracted included: study year, geographical location, psychodermatologic disorder, population age and gender, details of the interventions and controls, clinical effectiveness as measured by the study using standardized criteria or validated scales, and side effects. Next, two reviewers independently conducted a quality assessment using the rating scheme endorsed by JAMA Dermatology, which was modified from the Oxford Centre of Evidence-based Medicine. ¹⁶ Disagreements were discussed between the two independent reviewers followed by a third-party adjudication when needed.

Results

A total of 2618 unique studies (including 6 studies from searching the reference lists of included studies) were identified from the search and 83 of them were subjected to full-text review after the initial screening. A total of 21 met the pre-defined criteria for data analysis (Figure 1). Figure 2 demonstrates the mapping of current evidence on all identified medications and studies, along with sample sizes and clinical outcomes.

Figure 1

Study Selection for Data Analysis.

Figure 2

Evidence Mapping of Controlled Trials on the Pharmacological interventions for Primary Psychodermatologic Disorders.

Study Characteristics

Among the 21 studies published from 1982 to 2019, 16 were conducted in the US, ^{17 -32} one in Canada, ³³ one in the Netherlands, ³⁴ one in Denmark, ³⁵ and two in Iran. ^36,37 Five PDDs were identified: trichotillomania (n = 12 studies), ^{17 -26,33,34} skin picking (n=5), ^{27 -30,36} nail biting (n = 2), ^31,37 delusional parasitosis (n = 1), ³⁵ and dermatitis from compulsive hand washing (n = 1). ³² Seven different classes of medications were investigated: SSRIs (i.e., fluoxetine, sertraline, and citalopram), tricyclic antidepressants (i.e., clomipramine and desipramine), antipsychotics (i.e., olanzapine and pimozide), anticonvulsants (i.e., lamotrigine), N-acetylcysteine (NAC), inositol, and milk thistle. Supplemental Table 1 provides a summary of safety and side effects for the investigated interventions (Supplemental Table 3summarizes the characteristics of all studies and the investigated outcomes measures).

Trichotillomania (TTM)

TTM was the most studied condition with the most diverse pharmacological interventions.

SSRI (fluoxetine and sertraline)

Three studies investigated the efficacy of fluoxetine for TTM (Supplemental Table 1), including an 18 week cross-over double-blind placebo-controlled trial (20, 80 mg/d fluoxetine) of 16 patients (93.8% females), a 31 week double-blind, placebo-controlled crossover trial (20, 80 mg/d fluoxetine) of 23 patients (87.0% females), and a 12 week randomized, waiting-list controlled study (60 mg/d fluoxetine) of 43 patients (88.4% females). ^17,18,34 None of the studies demonstrated efficacy of fluoxetine for treating TTM. In a 22 week double-blind trial, 13 patients received single-modality treatment with either sertraline (50, 200 mg/d) or with a psychological intervention, i.e., habit reversal training (HRT), and 11 received both modalities. ¹⁹ TTM symptoms improved in both groups, but dual therapy was more effective than sertraline alone.

N-acetylcysteine (NAC)

There was conflicting evidence regarding the efficacy of NAC for TTM. In 2009, a 12 week randomized double-blinded placebo-controlled add-on trial on 50 patients demonstrated that NAC (1200, 2400 mg) led to statistically significant reduction in TTM symptoms measured by the Massachusetts General Hospital Hairpulling Scale (MGH-HPS) (P < .001) and Psychiatric Institute Trichotillomania Scale (PITS) (P = .001). ²¹ The study showed improvement in 56.0% of participants on NAC versus 16.0% on placebo. Another 12 week of 39 participants randomized double-blinded placebo-controlled add-on trial, however, found no significant difference between NAC (1200 mg BID) and placebo on any of their primary or secondary outcome measures regarding TTM. ²⁰

Tricyclic antidepressants (clomipramine and desipramine)

Thirteen women with severe TTM completed a 10 week double-blind, crossover trial of clomipramine and desipramine. Clomipramine (180.8 ± 56.0 mg/d) was more effective in improving TTM symptoms than desipramine (173.1 ± 33.0 mg/d), demonstrated by TTM-impairment scale and physician-rated clinical progress. ²² In another 9 week placebo-controlled randomized parallel treatment trial of a total of 23 patients comparing clomipramine of average dose of 116.7 mg/d (n = 10), cognitive-behavioral therapy (CBT) (n = 7), and placebo (n = 6), clomipramine was not significantly better at reducing TTM symptoms than placebo. ²¹

Olanzapine

A 12 week randomized, double-blind, placebo-controlled trial demonstrated 11 of 13 patients on olanzapine (10.8 ± 5.7 mg/d) responded to treatment, compared to 2 of 12 patients in the placebo group. ³³ Outcome measures included pre-to-post-trial scores on the Clinical Global Impression-Improvement (CGI-I) scale (P < .001), the Yale-Brown Obsessive-Compulsive Scale (YBOCS) (P < .01), and the Clinical Global Impression-Severity of Illness (CGI-S) (P < .001).

Naltrexone, Inositol, and Milk Thistle

An 8 week double-blind, placebo-controlled study investigated naltrexone 150 mg/d in 51 patients (86.3% females) with TTM. ²⁴ A 10 week double-blind, placebo-controlled trial studied inositol 6-18 mg/d in 38 patients (92.1% females), and a 12 week double-blind, placebo-controlled crossover study investigated milk thistle 150-300 mg BID in 20 patients (95.0% females). ^25,26 None of the studies demonstrated significant improvement in hair pulling behaviors measured by different assessment tools (Supplemental Table 1).

Skin Picking

Five studies investigated the efficacy of SSRIs, lamotrigine, and NAC for patients with skin picking. ^{27 -30,36} Treatment outcomes were measured via various assessment tools. SSRIs and NAC, but not lamotrigine, demonstrated treatment efficacy for improving skin picking.

SSRI (fluoxetine and sertraline)

Two studies investigated the efficacy of fluoxetine for skin picking. ^27,28 One study had 15 female patients going through 6 week open-label treatment with fluoxetine (up to 60 mg/d), 8 of the 15 were responders and were enrolled in a 6 week double-blinded, placebo-controlled trial (4 fluoxetine:4 placebo). ²⁷ Patients on fluoxetine maintained clinically significant improvement of their skin picking, measured by modified Y-BOCS and MGH-SPS, while the 4 patients receiving placebo returned to their baseline symptom level. Another 10 week double-blinded, placebo-controlled, parallel trial studied fluoxetine (average 55 mg/d) in 21 patients (76.19% females) with skin picking (10 on fluoxetine and 11 on placebo). ²⁸ Intent-to-treat analysis showed fluoxetine superior to placebo according to one of the three primary outcome measures (i.e., a visual analogue scale of self-rated change). There was no significant improvement in CGI-I or Skin Picking Treatment Scale (SPTS). In a 4 week double-blind, placebo-controlled trial, treatment group of citalopram 20 mg/d (n = 23) achieved significant improvement in quality of life, general health status and obsession-compulsion severity (P < .05), but not in pathologic skin picking severity when compared with the placebo group (n = 22). ³⁶

Lamotrigine

In a 12 week double-blind, placebo-controlled trial, 32 patients (90.6% females) with skin picking were randomized into a lamotrigine group (n = 16) or a placebo group (n = 16). ²⁹ No significant overall differences were noted between lamotrigine (12.5, 300 mg/d) and placebo in the Yale-Brown Obsessive-Compulsive Scale Modified for Neurotic Excoriation (NE-YBOCS), the Skin Picking Symptom Assessment Scale (SP-SAS), and a number of self-rated skin picking scales. Despite the lack of efficacy for skin picking, lamotrigine responders exhibited significantly impaired cognitive flexibility (extradimensional shifting) measured by the intradimensional/extradimensional shift task at baseline before treatment compared to lamotrigine non-responders (P = .017). The authors suggested that lamotrigine may be valuable in a subset of patients who exhibit relatively impaired cognitive flexibility and future trials with lamotrigine and other glutamatergic agents may selectively enroll patients with impaired cognitive flexibility. ²⁹

N-acetylcysteine (NAC)

Grant et al. randomized 66 patients (89.4% females) with skin picking into an NAC group (1200, 3000 mg/d) or a placebo group. ³⁰ Comparing with placebo (21/31 completed the study), the NAC group (32/35 completed the study) showed significant improvements in NE-YBOCS, Clinical Global Impression (CGI) Severity scales, but no difference in psychosocial functioning. No imputation was undertaken for missing data in the data analysis. The treatment was well-tolerated.

Delusional Parasitosis

Pimozide

One double-blinded crossover study assessed the efficacy of pimozide (2, 7 mg/d) among 11 patients (90.9% females) with delusional parasitosis. ³⁵ Of the patients, 90.9% improved during the pimozide phase with relief of itch (P = .04) and reduced delusions (P = .03). Additionally, Brief Psychiatric Rating Scale (BPRS) scores decreased significantly with pimozide treatment (P = .01). Two patients did not complete crossover investigation. Increased insomnia, drowsiness, akathisia, parkinsonism, and depressive reaction were reported during the pimozide period.

Nail Biting

Clomipramine vs desipramine

One study recruited 25 patients with severe nail biting (76.0% females). ³¹ Among 14 students who completed the study, clomipramine (120 ± 48 mg/d) was shown to be superior to desipramine (135 ± 53 mg/d) in decreasing nail biting as measured by Nail Biting Severity Scale, Nail Biting Impairment Scale, and a number of clinical progress scales.

N-acetylcysteine (NAC)

One double-blinded randomized control trial recruited 42 children and adolescents (66.7% females) with chronic nail biting. ³⁷ A total of 25 patients completed the study. The NAC group (n = 14) had significantly increased nail length after the first month than the placebo group (n = 11) (P < .04) but showed no difference after 2 months (P = .59) with intent-to-treat analysis.

Dermatitis From Compulsive Hand Washing

Clomipramine

38 patients (78.9% females) with dermatitis from compulsive hand washing were randomized into a clomipramine group (n = 17) or a placebo group (n = 21). ³² At the end of the 10 week treatment with oral clomipramine (dosage was not provided), 65.0% of the patients in the clomipramine group had improvement in their dermatitis assessed by physicians, which is significantly higher than those receiving placebo (29.0%) (P < .001). Independent of dermatological improvement, clomipramine also significantly improved the scores in YBOCS (P < .001).

Quality Assessment

Quality assessment with the Cochrane Risk-of-Bias Tool and a scheme modified from the Oxford Centre of Evidence-based Medicine was completed and it showed overall low risk with various aspects of the included studies (Supplemental Table 2). The percentages of low-risk studies among all included studies were 85.7% and 76.2% for random sequence generation and allocation concealment, respectively. For other aspects of study quality, including blinding of outcome assessment, incomplete outcome data, and selective reporting, the percentage of low-risk studies was 90.5%.

Discussion

Evidence based on RCTs of pharmacological management of primary psychodermatologic disorders is still limited. This may explain the lack of therapeutic guidelines in general and clear recommendations of pharmacological interventions for PPDs. However, the British Association of Dermatologists recently published guidelines for the management of adults with delusional parasitosis which suggested the first-line recommendations for pharmacological interventions include amisulpride, olanzapine, and risperidone based on the most available evidence for efficacy and a better side-effect profile than first-generation antipsychotics. ³⁸ Our review identified only one RCT on the use of pimozide from 1982. It highlighted the challenges of evaluating pharmacological interventions in RCTs. It also emphasized the need for more studies to establish evidence-based recommendations that can help guide clinicians who are managing these conditions, whether they are dermatologists, psychiatrists, or family doctors.

The review highlights that current pharmacological management of PPDs is largely condition-specific and depends on understanding each diagnosis and its underlying pathophysiology. For instance, TTM has been classified under the class of obsessive-compulsive and related disorders in the current DSM-5. However, this classification has been questioned given the differences between the two conditions and the lack of treatment response in trichotillomania patients when managed with OCD first-line therapies (i.e., SSRIs). ^39,40 In a study comparing 278 OCD patients and 54 TTM patients, it was found that OCD patients reported higher rates of comorbidities, more harm avoidance and more maladaptive beliefs compared to patients with TTM. ³⁹ These differences emphasize the need to compare different therapeutic approaches utilized. Recognition of DP as a part of somatic-type delusional disorders may help clinicians to explore relevant therapies utilized in the psychiatry literature. Condition-specific factors that may affect the conditions’ characteristics also include several genes that were identified to characterize specific primary psychodermatologic disorders such as the SAP90/PSD9-associated protein (SAPAP3) gene for PSP and TTM, the Slit and Trk-like 1 (SLITRK1) for TTM, and the genes encoding Dopamine Receptor 1 (DRD1) and Serotonin Receptors (5-HTTLPR and 5-HT2A) for body-focused repetitive behaviors (BFRBs). ^{41 -43} Whether these genes affect treatment response or not is yet to be determined. Therefore, the gap of knowledge related to the underlying etiologies of PPDs and factors that affect disease development, severity and progression might be contributing to the fact that we still have no standardized recommendations on pharmacological therapy. In addition, the results emphasized that medications from the same class may work differently for the same condition. For example, fluoxetine utilized in three trials did not show efficacy for TTM, but sertraline which in the same class of SSRI did show efficacy. Same medication may have variable efficacy among different PPDs as fluoxetine was effective for skin picking but not TTM. In the pediatric population studied in the trials, NAC was shown to be effective for nail biting but not TTM while Grant et al. reported efficacy of TTM in the trial composed of adult population. ^20,21,37

Among pharmacological interventions with efficacies identified in the review, most of them are primary psychiatric medications including SSRIs (fluoxetine, sertraline), tricyclic antidepressants (clomipramine, desipramine), and antipsychotics (pimozide, and olanzapine). The only non-psychiatric medication was NAC. Serotonin, dopamine, noradrenaline, and glutamate are shown to be involved in the pathophysiology of OCD and its related disorders, and different medications target different neurotransmitters. ⁴⁴ Both SSRIs and tricyclic antidepressants have serotonin reuptake inhibitor activity to increase the level of serotonin, hence improving the symptoms of OCDs. ⁴⁴ On the other hand, antipsychotics inhibits dopaminergic neurotransmission. ⁴⁵ NAC indirectly elicits an inhibitory effect on synaptic release of glutamate and restoration of extracellular glutamate levels in the nucleus accumbens to improve impulse control. ⁴⁶ Overall, the specific mechanisms of these pharmacological interventions for PPDs are still unclear.

Psychiatric conditions are not always managed pharmacologically. In fact, some argue that pharmacological interventions have failed to show long-term clinical benefits (e.g., relapse prevention, quality of life improvement, suicide prevention) that outweigh harms (e.g., side effects). ⁴⁷ A Cochrane meta-analysis on compared tricyclic antidepressants and active placebos (placebos containing substances that mimic the side effects of TCAs) in depression and reported that the difference is small as well as that the effect of TCAs on mood improvement might be overestimated. ⁴⁸ In addition, longer-term outcomes for schizophrenia patients were found to be better in developing countries compared to the United States . This unexpected finding implied a possible difference in use of antipsychotics in more acute stages of schizophrenia in developing countries compared to additional long-term antipsychotic treatment in developed countries and raised an argument on potential harm caused by maintenance use (e.g., metabolic complications). ⁴⁹ Therefore, for PPDs, adjunctive or alternate therapies such as psychotherapy are important to consider when establishing treatment guidelines. For example, Daughtry et al. reported TTM patients on sertraline showed improvement in symptoms severity, but dual therapy with sertraline and habit reversal therapy (HRT) was significantly superior to mono-therapy. ¹⁹ Pharmacological interventions should therefore be investigated in the short- and long-term, with a meticulous weighing of benefits against harms, and consideration of other treatment modalities that can substitute or support them.

There are several PPDs that had no identified RCTs, including psychogenic pruritus, tanning dependence and dermatitis artefacta. Diagnosing and treating these conditions is challenging, especially with the lack of controlled trials which contributes to inadequate evidence and lack of guidance for approaching these conditions. As an example of inadequate evidence, several reports suggest TCAs, particularly doxepin and amitriptyline, for treatment of psychogenic pruritus. ⁵⁰ However, this seems to be mainly based on case reports, expert opinions and reviews, with no controlled trials or meta-analyses to validate the use of these medications for psychogenic pruritus. ⁵¹ As PPD patients tend to present to dermatologists first, interpreting their symptoms as skin-related, capturing these conditions in general dermatology clinics is important. However, it is challenging given patients’ limited insight into their conditions. Therefore, in order to better approach, capture and investigate more PPDs, especially the rarer ones that seem to be missing in the pool of studies we identified, multidisciplinary psychodermatology clinics are crucial, which were reported to be an optimal model for enhancing psychodermatologic care and research. ⁴ For example, Sears et al. reported their experience of establishing a pediatric psychodermatologic clinic composed of a consultant dermatologist and a clinical psychologist for establishment of a collaborative treatment plan during the COVID-19 pandemic, and patients and their families found this clinic to be helpful and effective. ⁵²

This review is focused on pharmacological interventions, which limits the ability to compare non-pharmacological approaches to PPDs such as cognitive behavioral therapy and stress reduction techniques (e.g., meditation), and even some physical modality has shown benefits. For example, Christensen et al. reported cases of using microneedling a novel treatment option for patients with trichotillomania. ⁵³ Another limitation of the review is that non-RCTs were excluded. RCTs have the highest level of evidence but the included RCTs have low number of participants. Open label studies may allow pooling of data from larger numbers of studies and patients. For example, a recent review included a total of 19 studies (126 patients) and highlighted the use of NAC as a safe and effective treatment for patients with TTM, SPD and onychophagia. ⁴⁶

This review provided a comprehensive understanding of high-level evidence regarding the pharmacological treatment options for various PPDs. Meanwhile, it is crucial for clinicians to understand the challenges of studying PPDs in RCTs and be familiar with other treatment options identified in other studies. A systematic reviewed from 2014 described both RCTs and open-label trials of pharmacotherapy for TTM which identified additional efficacious interventions including dronabinol, pimozide, and haloperidol. ⁵⁴ In addition, behavioral therapy with habit-reversal training components demonstrated a large benefit in improving TTM symptoms with strong evidence. ⁹ Similarly, a systematic review with meta-analysis on treatment for PSP showed significant benefit of behavioral therapies including cognitive behavioral therapy and habit reversal therapy in comparison with control groups. ⁵⁵ Its meta-analysis also suggested uncontrolled trials have limited utility for evaluating the efficacy of treatments for PSP because patients demonstrated significant improvement during short-term trials regardless of the efficacy of the intervention being investigated. ⁵⁵ In a systematic review of antipsychotic agents for DP conducted by McPhie et al., 51 studies were included in the analysis. ⁵⁶ Pimozide (1, 16 mg/day with 109 patients) and risperidone (0.5, 8 mg/day with 43 patients) were the most commonly studied antipsychotics, and heterogeneity in reporting of treatment outcomes and study designs limited the overall evolution of the data. ⁵⁶

More research is warranted to bridge the gaps in knowledge highlighted in this review. In the meantime, this evidence mapping paper can serve as a roadmap for clinicians to assess available trials and choose evidence-based interventions when they include pharmacotherapy in their management plans. This review can also guide researchers to fill in the identified gaps and choose future interventions to investigate based on previous outcomes.

Conclusion

Limited RCT-derived evidence supports the use of antidepressants in TTM, PSP, pathologic nail biting, and dermatitis from compulsive hand washing; antipsychotics in TTM and DP; and NAC in TTM and PSP. The evidence was inadequate to establish informed guidelines on the use of pharmacological interventions for the treatment of PPDs, especially considering the lack of controlled trials for several PPDs.

Supplemental Material

Table S1 - Supplemental material for Pharmacological Interventions for Primary Psychodermatologic Disorders: An Evidence Mapping and Appraisal of Randomized Controlled Trials

Supplemental material, Table S1, for Pharmacological Interventions for Primary Psychodermatologic Disorders: An Evidence Mapping and Appraisal of Randomized Controlled Trials by Tarek Turk, Chaocheng Liu, Esther Fujiwara, Sebastian Straube, Reidar Hagtvedt, Liz Dennett, Adam Abba-Aji and Marlene Dytoc in Journal of Cutaneous Medicine and Surgery

Supplemental Material

Appendix - Supplemental material for Pharmacological Interventions for Primary Psychodermatologic Disorders: An Evidence Mapping and Appraisal of Randomized Controlled Trials

Supplemental material, Appendix, for Pharmacological Interventions for Primary Psychodermatologic Disorders: An Evidence Mapping and Appraisal of Randomized Controlled Trials by Tarek Turk, Chaocheng Liu, Esther Fujiwara, Sebastian Straube, Reidar Hagtvedt, Liz Dennett, Adam Abba-Aji and Marlene Dytoc in Journal of Cutaneous Medicine and Surgery