Exploring the limited use of transdermal medications in psychiatry: Challenges and potential solutions

Abstract

Transdermal medications are an useful yet underutilized tool in the field of psychiatry. Despite numerous advantages of using this route of medication delivery, transdermal medications remain less popular compared to other routes of medication administration such as oral and intramuscular routes in the management of various psychiatric conditions. In this editorial, we examine the advantages of transdermal medications with a brief overview of transdermal being used in psychiatry and other medical specialties. We discuss the factors that play a role in their limited usage in psychiatry. We highlight certain patient categories who can specifically benefit from them and discuss potential solutions that can broaden the perspective of treating clinicians making this an intriguing avenue in the field of psychiatry.

Key Words: Transdermal medications; Psychiatric medications; Psychopharmacology; Treatment options; Potential solutions

Core Tip: The field of psychiatry is advancing at an exponential rate. The advancements made in the diagnostic and treatment modalities for various psychiatric conditions is exemplary. Transdermal route of medication delivery has been around for past few decades, however, this route has not been a favorable route in psychiatry practices due to various biochemical, patient as well as clinician preferences. In this editorial article we discuss this issue and bring forward some potential solutions to make transdermal medication delivery as a viable option in the area of psychiatry.

INTRODUCTION

In today’s ‘instant and QR code culture’ anything that can help to save time and effort is usually well-received. With skin being the largest organ of our body, the use of transdermal creams, ointments, and patches is a convenient route for delivery of medications. The need for further innovative methods and routes of delivery of mostly non-medicinal agents has been a driving force for scientific and pharmaceutical fraternities to do more groundbreaking research in this arena. The discovery that extent of absorption could be controlled by modifying the diffusion area of the cell and controlling the level of skin hydration was the key point for the development of transdermal patches[1]. In this review article, we explore why transdermal medications are still not considered to be a popular route of medicine delivery in clinical psychiatric practices. We also discuss the type of patients are more likely to benefit from transdermal route of medication delivery in psychiatry.

USE OF TRANSDERMAL MEDICATIONS IN OTHER MEDICAL SPECIALTIES

Before discussing the limited use of transdermal medications in psychiatry we review some of the factors that make this route of medication administration more acceptable and prevalent in other medical specialties. In addition to being convenient this route of medication administration is minimally invasive[2,3]. Pharmacokinetically, the frequent dosing of the medications is not necessary especially for the medications with a short half-life due to sustained steady-state blood levels[2]. It is a safer option for patients with hepatic impairment due to the avoidance of hepatic first-pass metabolism[2,3]. The gastrointestinal side effects are reduced and the concerns for potential gastrointestinal drug-drug interactions and effects of food on absorption of medications are lower[3]. The delivery method is cost-effective when compared with other medication forms, as transdermal patches can deliver medications from 1 to 7 days[2,3].

Over the last few decades with further advancements in technology, the use of transdermal medications has come a way long ranging from the novel transdermal patch of scopolamine to treat motion sickness to the smart technology utilizing insulin patch that delivers insulin least invasively via the subcutaneous route with high accuracy for treatment of diabetes mellitus[4]. Similarly, transdermal estrogen and progesterone patch has been used for contraception and the management of menopausal symptoms in women such as hot flashes and night sweats since the 1980s. Transdermal estrogen products including patch and gel products have been approved for the prevention of postmenopausal osteoporosis by producing physiological estradiol levels[5]. The advantages include decreased side effects compared to the oral formulations, improved compliance and convenience of use.

CURRENT TRANSDERMAL MEDICATIONS USED IN PSYCHIATRY

Though limited, psychiatric transdermal medications have been utilized in management of some conditions in psychiatry[3,6]. One of the first available transdermal patch Scopolamine patch is used to treat sialorrhea, a side effect of psychotropic medications. The alpha-adrenergic Clonidine patch is utilized for control of impulsivity and hyperactivity in attention-deficit hyperactivity disorder (ADHD), Autism spectrum disorder, and Oppositional Defiant Disorder. Additionally, the clonidine patch is used to assist with sleep disorders, anxiety related to post-traumatic stress disorder, tics in Tourette syndrome and management of opioid withdrawal. For management of ADHD, the methylphenidate-based patch Daytrana allows for ease of use in children during the school hours. Xelstrym is an amphetamine-based transdermal patch more recently approved by the US Food and Drug Administration (FDA) in 2022 for management of ADHD.

Monoamine oxidase inhibitor Selegiline in patch form is effective with less side effects in the treatment of major depressive disorder and Parkinson’s disease due to avoidance of first pass metabolism and helps to evade the associated dietary restrictions[3,6]. Estrogen and Testosterone patches have been shown to be effective in the treatment of depression, specifically in the elderly males and in women suffering from premenstrual dysphoric disorder and postpartum depressive disorder. Partial opioid agonist Buprenorphine transdermal patch is used for management of chronic pain. Rotigotine, a dopamine agonist, is used for management of Parkinson’s disease.

Antipsychotics available in transdermal formulation include Asenapine patch that was approved by the FDA in 2019 for the treatment of schizophrenia. Several short and long-term trials have established the efficacy and tolerability of Asenapine patch, with its tolerability being similar to the more metabolically favorable second-generation antipsychotics[7]. Cholinesterase inhibitor Rivastigmine patch has shown benefits of convenient administration by the care givers of patients suffering with dementia. The new transdermal formulation of Donepezil has benefited Alzheimer’s dementia patients with the advantage of decreasing the medication’s gastrointestinal side effect profile[8].

One notable factor is that the pharmacokinetics of certain medications differ significantly when taken by another route as opposed to transdermal use. One example of this is Asenapine which when taken by the sublingual route escapes rapid hepatic metabolism with the advantage of rapid onset of action but still has limited bioavailability of only 35% by this route[9]. The transdermal route of delivery of Asenapine not only allows the by-pass of first pass metabolism it also results in steady and sustained release over a long period of time thus increasing its bioavailability. Similarly, Blonanserin is a second-generation antipsychotic used in Asian countries such as Japan and Korea. The Blonanserin transdermal patch was developed in Japan and launched in 2019. As compared to oral route, when the medication is delivered transdermally, steadier release of medication allows for stable plasma levels of the medication and lowers the risks for side effects such as extrapyramidal side effects[10].

WHY ARE TRANSDERMAL MEDICATIONS UNDER-UTILIZED IN PSYCHIATRY?

Transdermal medications remain less popular compared to other routes of medication administration such as oral and intramuscular routes in the management of various psychiatric conditions.

The variability in absorption resulting in questionable outcomes is a critical factor in the clinical use of medications via this route. The absorption rates of medications depend on skin permeability, area, temperature and the metabolic activity of the skin[6,11]. The development of an effective transdermal delivery system directly co-relates with the biochemical properties of each drug molecule being targeted[6,12]. In order to adequately penetrate through the skin barrier the drug molecule has to be non-ionic and lipophilic in nature[6]. The medications with lower molecular weight and lower melting points can be easily formulated into a transdermal patch as they permeate the skin more efficiently[11].

Another factor playing a role in their low popularity is the slower onset of action compared to intramuscular or intravenous routes which makes them less efficient for rapid symptom control such as a panic attack or episode of acute agitation[11]. Therefore, the use of transdermal medications are not utilized in emergency department and acute inpatient settings.

Limited psychoeducation of patients and caregivers is another crucial reason resulting in lower use of transdermal medications in routine clinical practices. Hot temperatures can impact the efficacy of the transdermal medication delivery[11]. The discussion and education of patients regarding choosing the appropriate site of application and maintaining skin temperature is important. Avoiding hot showers or baths needs to be discussed.

Medication errors and misuse is another concern[11]. Case reports of fentanyl patch overdoses due to chewing and transmucosal absorption have been documented. Most common medication error associated with transdermal medications reported has been application of more than one Rivastigmine patch at one time without removal of the previous one in patients with dementia. There is always the potential for development of localized skin irritation or in rare cases development of contact dermatitis.

Patients with sensory sensitivities in conditions such as autism spectrum disorder may find the sensation of wearing transdermal medications to be uncomfortable. The adhesive or texture of the patch could be overwhelming and could cause distress in this patient population.

PATIENTS WHO CAN BENEFIT FROM TRANSDERMAL MEDICATIONS

Pediatric population

Adherence to treatment for chronic conditions is challenging and ADHD in pediatric age range is not any different in that regard. The Daytrana patch was the first long-acting methylphenidate transdermal delivery system that was introduced into the market in May 2006. Since its launch it has been utilized in younger pediatric patients due to their challenges of taking oral medications such as difficulty in swallowing pills or resistance to comply[13]. A review of clinical trials evaluating the use of a methylphenidate patch in the treatment of ADHD in children and adolescents found this route of medication delivery to be safe and showed improved adherence to treatment[14]. This route was found to offer additional practical advantages to the patients and caregivers including once-daily dosing and flexible wear times with visual confirmation of compliance. The review noted that this medication delivery system had a side-effect profile similar to that of other stimulants.

Interestingly, a gap of 16 years was noted in the development of another transdermal patch for the management of ADHD in pediatric populations. Xelstrym is an amphetamine-based transdermal medication and a recently available treatment option for ADHD. The availability of an amphetamine-based transdermal medication option is helpful for patients who respond better to amphetamine-based medications as compared to methylphenidate-based medications.

Geriatric population

Controlled use of transdermal psychotropic medications exists in general clinical practice for geriatric populations to date. Of the available transdermal treatment options, several exist for treating psychiatric and neurologic disorders including dementia, depression, and pain associated with post-herpetic neuralgia[15]. In the geriatric population, where cognitive reserves are frequently limited and adherence to oral medication regimens is often unlikely given resistance, misunderstanding, or other deficits, a patch option can be simpler for patients and/or caregivers to manage regularly. The involvement of caregivers in this population is a unique consideration, and having a visual indicator of medication compliance in the form of a patch can serve as an immense benefit.

Rivastigmine transdermal patch has been approved for utilization since 2007 to treat mild to severe Alzheimer’s dementia and mild to moderate Parkinson’s dementia[16]. The rivastigmine patch has shown reasonable tolerance and efficacy while eliminating some adverse side effects of its capsule counterpart such as gastrointestinal side effects[17]. Notably, in the IDEAL RCT study examining safety, tolerability, and efficacy of the rivastigmine patch compared to the capsule and placebo treatments, more than 70% of caregivers reported preference of patches for reasons of ease of scheduling, self-sufficiency, and minimal side effects[17,18].

Rotigotine is a dopamine agonist which aids in Parkinson’s treatment. However, it is only available in transdermal format due to poor oral bioavailability and extensive first pass metabolism, highlighting a unique advantage of the transdermal delivery system[15]. Transdermal administration avoids the more pulsatile dopaminergic stimulation of repeated oral dosing that predisposes to dyskinetic complications; this transdermal medication has utility in a perioperative setting when oral agents cannot be administered. Additionally, it can also treat restless leg syndrome making it a versatile treatment option for geriatric patients[15].

POTENTIAL SOLUTIONS

Ongoing research and publications on the safety and effectiveness of transdermal psychotropic medications will help to build further credibility. Increasing awareness among healthcare professionals as well as patients is crucial. Continuing educational programs, highlighting benefits such as improved treatment adherence with lower associated side effects and collaboration with mental health organizations can contribute to widespread acceptance. Emphasizing the convenient and consistent release of medication will help to promote transdermal medication options as viable alternatives in management of psychiatric conditions. Partnering with pharmaceutical companies to invest in developing transdermal medications for various psychiatric conditions will broaden the available choices. Incorporating patient testimonials and success stories into promotional materials will provide real-world perspectives and help to alleviate concerns about the use of transdermal medications in the field of psychiatry.

CONCLUSION

Transdermal medications have shown to be a useful, yet underutilized tool in the field of psychiatric disorders. Despite biochemical limitations, there are several psychiatric medications that could be beneficial in this administrative form. Certain patient population subsets have proven benefit from transdermal patches and more could likely benefit with the further education, awareness, and collaborative care.