Choosing the appropriate pharmacotherapy for Morgellons disease: an expert perspective

KEYWORDS:

• Aripiprazole
• delusional infestation
• delusional parasitosis
• first-generation antipsychotic
• morgellons disease
• olanzapine
• pimozide
• risperidone
• second generation antipsychotic
• somatic symptom disorder

1. Introduction

Morgellons disease (MD) is a cutaneous condition with a controversial etiology in which affected patients report embedding of fibers, strands, hairs, or other inanimate materials in the skin. Clinically, this condition presents as multiple nonhealing lesions that can be ulcerated and superficially infected; affected patients claim the lesions appear spontaneously. Classically, lesions often spare the hard-to-reach areas such as the mid-back, and patients often bring in a collection of specimens which they claim to have removed from their skin (so-called ‘matchbox sign’).[1,2] The typical patient with MD is a middle-aged Caucasian woman: 77% of MD patients studied in an extensive descriptive study by the Centers for Disease Control (CDC) were female and Caucasian and had a median age of 52 years [2].

MD has a controversial etiology, with some researchers purporting a link between the condition and infection with tickborne bacteria such as Borrelia species [3]. However, a sizable descriptive study of patients with MD by the CDC from 2006 to 2008 was unable to confirm a link between the dermopathy and any infectious agent and was also unable to corroborate visible protrusion of fibers from within the skin in these patients [2]. As a result, MD is currently regarded by the larger medical community as a psychiatric diagnosis, more specifically as a subtype of delusional infestation (DI) in which patients perceive infestation with fibers as opposed to insects. Although the authors refer to MD throughout this text as a distinct clinical subtype of DI (i.e. perception of infestation with fibers as opposed to insects/parasites), the authors do not consider MD to have standalone validity as a diagnostic entity separate from DI.

Regardless of etiology, MD causes marked morbidity, with affected patients suffering greatly and experiencing decreased quality of life due to their symptoms [4]. Due to the lack of standardized management guidelines for MD and a dearth of randomized controlled trials (RCTs) on first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) for the treatment of DI, most data on the treatment of this condition currently stem from case reports/series[5]. MD is also made exceptionally difficult to manage due to the fact that patients suffering from MD tend to have very little illness insight. Therefore, they are often extremely wary of or downright refuse psychiatric interventions such as psychiatric consultation and/or initiation of and adherence to antipsychotic pharmacotherapy [6]. In this paper, we will discuss the pharmacotherapeutic options available for the treatment of MD in various scenarios, as well as strategies for discussing pharmacotherapy and management with patients with MD. These strategies are designed to improve patient-physician relationships and in turn improve medication adherence in a notoriously nonadherent and difficult-to-treat patient population.

2. Pharmacotherapy for Morgellons disease

2.1. Tailoring treatment according to etiology

Due to a lack of RCT data on the treatment of MD, physicians treating this condition rely mostly on evidence from case reports/case series to make treatment decisions. An overview of the most important options available for the treatment of this condition will be discussed in the upcoming sections (Table 1). Though MD is widely regarded by the medical community as a delusional disorder and antipsychotic medications (FGAs and SGAs) are the only drugs known to alter the disease course and offer remission, it is important to consider any other potential psychiatric comorbidities in patients with MD before initiating pharmacotherapy [6,7].

Table 1. Dosing, efficacy, and safety of psychopharmacotherapy options for the management of Morgellons disease (subtype of delusional infestation)

Drug	Dosage for MD	Efficacy Data	Potential Adverse Events
Pimozide (FGA)	1–5 mg QD [5]	Double-blind placebo-controlled crossover study: 10/11 patients improved significantly with 1–5 mg daily pimozide treatment [5] Case series of 33 patients (18 patients on 1–5 mg daily pimozide): 6/18 achieved full remission; 5/18 patients less symptomatic; 7/18 experienced no change [5]	QTc prolongation, EPS, drug-drug interactions, depression [5]
Trifluoperazine (FGA)	1 mg QD, with uptitration each month by 1 mg depending on clinical picture (average doses for 50% to 90% improvement and at least 90% improvement were 1.9 mg/day and 2.3 mg/day respectively) [15]	Retrospective review: 24 patients treated with 1 mg daily (uptitrated by 1 mg monthly as needed): 7/24 returned to baseline function; 15/24 achieved at least 50% improvement [15]	Drowsiness [15]
Risperidone (SGA)	0.25–8 mg QD[8]	Case-based analysis: at 6 weeks, partial or full remission was achieved in 69% of cases (24/35) [8]	Risk of metabolic syndrome [8]
Olanzapine (SGA)	2.5–20 mg QD [8]	Case-based analysis: at 6 weeks, partial or full remission was achieved in 72% of cases (13/18) [8]	Risk of metabolic syndrome [8]
Aripiprazole (SGA)	5–30 mg QD [9]	Case report: belief of parasitic infestation lessening after 2 weeks of treatment with 3.75 mg QD; no more formication or scratching after 1 month of final dose (7.5 mg QD) [9]	Risk of metabolic syndrome potentially lower than with other SGA drugs [9]
Amisulpride (SGA)	200–1200 mg nightly for adults; 50–400 mg nightly for elderly patients [10]	Retrospective review of 7 patients treated with amisulpride: 3/7 cases showed complete remission, 3/7 showed partial remission, and 1/7 cases showed no response [11]	Risk of metabolic syndrome; prolonged QT interval

Key: EPS = extrapyramidal side effects; FGA = first-generation antipsychotic; QD = daily; QTc = corrected QT; SGA = second-generation antipsychotic

In the case of comorbid psychiatric disorders such as anxiety, depressive disorders, schizophrenia, and underlying substance abuse (e.g. stimulant abuse) or underlying general medical conditions such as renal or hepatic disease which can lead to pruritus, it is important to treat the underlying condition before initiating therapy specifically for MD [7]. In the case of primary MD which does not stem from any underlying psychiatric or medical conditions or substance abuse, low doses of FGAs and SGAs are successful in reducing or eliminating symptoms and improving quality of life in MD patients, and are the only drugs known to alter the disease course and offer a cure [6].

2.2. First-generation antipsychotics

The FGA drug pimozide was historically favored for management of MD due to the early success of the drug in a small RCT in the 1980s. In multiple case studies and series, low-dose pimozide treatment for several months yielded significant improvement to complete resolution of MD lesions [12,13]. However, pimozide is no longer considered the drug of choice due to adverse events (AEs) such as QT interval prolongation, extrapyramidal side effects, drug–drug interactions, and depression [1,5].

Pimozide has been largely replaced by SGAs for the treatment of MD and other psychiatric conditions due to superior safety profiles of the latter drugs. However, pimozide remains uniquely suited to manage patients with MD who are averse to psychiatric interventions/antipsychotic medications, as the drug no longer has a psychiatric indication in the US [6,14]. In patients such as this, pimozide can still be considered at low doses that limit the potential for extrapyramidal and cardiotoxic AEs. Trifluoperazine is another FGA that has been shown to be effective for the treatment of MD, although similar safety concerns exist [15].

2.3. Second-generation antipsychotics

SGAs such as risperidone, amisulpride, olanzapine, aripiprazole, and quetiapine are considered the drugs of choice for the treatment of MD [1]. These newer drugs have more favorable AE profiles when compared to FGAs such as pimozide, which may contribute to improved adherence to this drug class [16]. In the management of MD, SGAs are used at much lower doses than used to treat other psychiatric conditions such as schizophrenia: a dose range of 0.5–2.0 mg/day of risperidone or olanzapine is typical for MD, whereas the typical dose range for schizophrenia is much higher at 2–16 mg/day [1,6]. In certain MD patients who are particularly averse to antipsychotic therapy, mentioning this dosing difference may help alleviate concern. In one retrospective study of 35 patients, risperidone was the drug most often prescribed for MD followed by olanzapine, both used at the aforementioned low doses, and represented key components of effective treatment regimens [1,6,17]. In a review of 63 cases reported in the literature, risperidone and olanzapine were the most often prescribed for MD (72% of the cases), and full or partial remission occurred in 69% and 72% of the cases, respectively [1]. Based on case reports, amisulpride may be another feasible SGA option for MD treatment, as its selective D2 and D3 dopaminergic activity makes its mechanism of action similar to that of FGAs, without the increased risk for adverse effects. Additionally, the lack of anticholinergic and adrenolytic adverse effects seen with this drug may be particularly useful in older patients with cardiovascular risk factors.¹⁴ Second-generation antipsychotics seem to be extremely effective for the treatment of MD, but further systematic clinical trials are needed to solidify the management guidelines for this condition.

2.4. Adjunctive psychotropic medications

Although antipsychotic medications are the framework for pharmacologic management of MD, certain other psychotropic medications such as antidepressants may also have utility as adjunct therapies in this patient population. For example, a patient with major depression and coexisting MD symptoms may respond to antidepressant therapy alone, without the need for antipsychotics. In the first formal study of a mixed patient sample investigating different treatment approaches, all patients with depressive disorder responded to antidepressants such as amitriptyline, doxepin, and maprotiline (75% remission and 25% response) [7]. Doxepin in particular may be useful for MD patients complaining of pruritus due to its H1 and H2 histamine-blocking activity [18].

2.5. Local therapies

Local treatment of skin lesions in MD may be an important component of the management algorithm. As MD patients tend to be convinced that their issue is purely a dermatologic one without a psychiatric component, some MD patients may become upset if they feel the cutaneous manifestations of their condition are overlooked by their physician; therefore, it may be beneficial to incorporate certain topical and local therapies into the therapeutic regimen as adjuncts to psychotropic medications. Some topical therapies that can be considered in certain patients include antiseptic-containing emollients (which are generally well-liked and tolerated by patients), emollient spray, topical doxepin, and 2% ketoconazole shampoo [17].

3. Non-pharmacological management of Morgellons disease

A major reason for the difficulty in managing MD is that patients with MD often have low illness insight and are extremely wary of psychiatric interventions and antipsychotic pharmacotherapy, which can lead to poor adherence to proper treatment. This poor adherence can be further magnified by perceptions of rejection or dismissal by the medical community [19]. The importance of acknowledging patient distress, adopting a non-confrontational approach, and forming a strong patient–physician relationship cannot be overstated in this patient population [17]. Frequent follow-ups with patients with MD–through once weekly phone calls, office visits every two to four weeks, and other checks of medication adherence – may also help foster trust. For known nonadherent patients, long-acting injectable antipsychotics may be considered. Though antipsychotics are extremely effective for the treatment of MD, they will only work if the patient takes them, and patients who trust their physician and feel that they have their best interest in mind are more likely to be adherent.

4. Conclusion

Although the successful management of patients with MD is difficult due to low levels of illness insight and adherence in this patient population, antipsychotic medications–especially SGAs such as risperidone and olanzapine–are extremely effective for this condition. It is the treating physician’s responsibility to present these treatment options in a way that fosters a trusting relationship with the patient and encourages medication adherence, which, when successfully done, can lead to improved treatment outcomes in this difficult-to-manage condition.

5. Expert opinion

There are several possible approaches for managing patients with MD. The first is to explain to the patient that their condition involves a delusion, and a psychiatrist is best suited to manage their condition. However, because many patients with MD are averse to psychiatric intervention or consultation and are convinced that their issue is a dermatologic one, this strategy is often unsuccessful, causing sometimes irreparable damage to the patient–physician relationship and causing the patient to seek out an alternate health-care provider.

In our experience, a more successful approach involves validating the patient’s distress and explaining to them that though we cannot give a clear answer as to why they feel they are infested, certain medications also used in psychiatry, such as risperidone, have helped many patients with a similar problem. In the case of a patient who may be hesitant to allow the involvement of a psychiatrist in their care, it can be mentioned that psychiatrists have more experience than dermatologists in monitoring the dosing for these types of drugs and that the antipsychotic doses used for their condition are much lower than the doses used to manage psychiatric conditions, such as schizophrenia.

However, the ethics of managing patients with MD may be complicated. Knowing that patients with MD are generally very wary of psychiatric medications and intervention and in an attempt to make patients more likely to agree to antipsychotic therapy, some physicians treating patients with MD tend to gloss over or speak vaguely or euphemistically about the therapy that they are prescribing or the reasons for prescribing it, which may utilize therapeutic privilege and withhold information from the patient. It is possible that this approach could erode the patient–physician relationship in the long term, though it is also possible that this approach will help build and maintain a successful therapeutic partnership in patients with DI. Strategies such as claiming that antipsychotics are needed for the psychological impacts from the skin lesions (as opposed to disclosing that antipsychotics are the primary treatment for the patient’s delusions), stating that antipsychotics have successfully treated similar patients in the past without explaining why, or euphemistically suggesting a psychiatric cause of their condition without mentioning the delusions directly are all varying degrees of deception. Whether deception is appropriate in this situation has been questioned [20]. The benefit of deception for beneficence must be weighed against the risk of deception to patient autonomy. Those who advocate for full disclosure of the diagnosis of DI, its psychiatric basis, and the evidence-based need for psychopharmacotherapy to treat DI admit that this method may lead the patient to refuse a therapy that could help alleviate their symptoms [20].

Because many prescription drugs and illicit substances, such as stimulants used in ADHD management and cocaine, can cause or worsen feelings of formication, physicians should consider screening for and encourage reduction of stimulants and other psychoactive substances in their MD patients. In a study of 147 patients with DI by the Mayo Clinic, 24% of the patients had a history of illicit drug use, while 8 patients were taking prescribed medications that may bring about delusional states such as amphetamine and dextroamphetamine, methylphenidate, ciprofloxacin, and levodopa [21]. In the CDC’s pivotal 2012 study on MD’s etiology, in a case series of 41 patients, 24% had a past history of drug or alcohol abuse, and 50% of the patients had at least one drug (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates, or propoxyphene) detected through hair sampling. High rates of drug abuse in this patient population have also been our clinical experience [2]. Because discussion of the use of illicit substances with patients and its potential contribution to their delusional disorder can be a sensitive topic, one potential route for discussion could emphasize that certain drugs make some patients a ‘petri dish’ for infestation and that reducing the use of these drugs may be necessary to ‘get the infestation under control.’ The complexity of managing patients who are on multiple drugs with psychoactive effects may be another reason to involve a psychiatrist in the management of these patients and their treatment regimens.

Declaration of Interest

S Feldman has received research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen Inc, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, Leo Pharma, Mylan, Celgene, Valeant, Menlo, Merck & Co, Qurient Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Advance Medical, Suncare Research, Informa, UpToDate, and the National Psoriasis Foundation. He is also the founder and majority owner of www.DrScore.com and founder and part owner of Causa Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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