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Abuse of tropicamide eye drops: review of clinical data

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Official websites use. Share sensitive information only on official, secure websites. E-mail: val. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Over the past 15 years, the increasing nonmedical use of tropicamide ophthalmic drops has been reported in Europe, coinciding with an increase in opioid addiction and drug-related mortality. Although tropicamide is generally known as a cheap alternative to heroin in Eastern Europe, it still appears to be a relatively new phenomenon that has arisen over the last decade. A narrative review was conducted of all the relevant sources published in more than five countries between January 1, and January 10, For bibliographic accuracy, the materials published in Russian and Italian were professionally translated to English. During the preparation of this report, we were able to interview five Russian-speaking patients who injected tropicamide in the past and we discuss another case of intravenous tropicamide use. This review was acknowledged by the institutional review board of the University of Missouri-Kansas City. All patients interviewed at the Unica Medical Center consented for their clinical information to be reported in a medical publication. The information provided in this article may help providers better detect tropicamide abuse and incorporate new rehabilitation strategies into the management of these patients. Tropicamide is a topical anticholinergic antagonist that is used in ophthalmic practice in the same way as many cycloplegic agents. For example, it is used for diagnostics in fundus examination, during surgical procedures, and as direct therapy for some inflammatory eye conditions. It has been hypothesized that the rise of tropicamide use in Russia is related to increased enforcement of policies targeting illicit drug use. The number of Western European tropicamide addicts has soared over the past decade. New scientific reviews of the research that fueled the trend suggest that drugs like tropicamide have been oversold in Italy 3 and France. For example, at least 17 falsified tropicamide prescriptions were identified in France in This report examines 1 the clinical aspects of tropicamide abuse in various countries and the characteristics of affected individuals, and 2 what is known about different therapies used during treatment to help those who are using tropicamide. In the spring of , during data collection for a review on tropicamide, we attempted to obtain information from former tropicamide users. The theoretical part of this study was acknowledged by the institutional review board of the University of Missouri-Kansas City. After obtaining informed consent and formal approval, we conducted five diagnostic semi-structured psychiatric interviews with a pre-designed blend of closed- and open-ended questions to ensure that each of the participants participated in a consistent and reliable interview session. The responses were analyzed accordingly. All respondents were in sustained remission at the time of the interview, having devoted months of their life to sobriety:. Patient 1, in remission for four years, seven-year history of tropicamide consumption with stimulants. Patient 2, in remission for five years, four-year history of tropicamide consumption with opiates and pregabalin. Patient 3, in remission for six years, two-year history of tropicamide consumption with opiates and stimulants. Patient 4, in remission for six years, six-year history of tropicamide consumption with opiates and stimulants. Patient 5, in remission for nine years, five-year history of tropicamide consumption with opiates. Table 1 provides additional information regarding the patients included in this study. After withdrawal, the urge to resume consumption is many times stronger than that of opiates alone. The urge is especially strong on an emotional level; it causes severe suffering. When taken together with stimulants, tropicamide also enhances their effect. The respondents reported that perceptive distortion stopped immediately after intoxication ended. Tropicamide is an anticholinergic ophthalmic solution that causes mydriasis and cycloplegia. When taken in large doses, however, tropicamide can produce stimulant, euphoric, and hallucinogenic effects. Tropicamide is misused because of its stimulating and euphoric properties, which are explained by the high affinity tropicamide has for cholinergic receptors. As a result, acetylcholine accumulates in the synaptic cleft — which means a significant part of the parasympathetic effect is blocked — and central nervous system activity shifts toward adrenergic system overactivity and various psychotomimetic and hallucinogenic effects. Muscarinic receptor activation in the cerebral cortex is involved in limiting discrete events in the stream of consciousness. In the absence of cortical acetylcholine, temporarily inadequate information from internal and external stimuli, which is always present on a parallel subconscious level, invades conscious processes. This partially explains the misuse of antimuscarinic drugs such as tropicamide, which can cause visual hallucinations. Older age, a scarcity of sensory impressions, and a noticeable weakening of cognitive function may contribute to the development of anticholinergic hallucinations with low doses of the drug. The prevalence rates of drug abuse in Eastern Europe, although decreasing according to official statistics, appear to be higher than those in Central and Western Europe. For example, the rate of heroin-related events in Eastern Europe has increased almost twofold, whereas the rate of tropicamide abuse remains unclear. Since , tropicamide use has steadily increased among individuals with substance use disorders. The first reported cases of recreational intravenous use of tropicamide eye drops were published in after large quantities of eye drop bottles began appearing around pharmacies. In the initial attempts to analyze this phenomenon, researchers had to turn to unofficial primary sources, such as thematic forums, social media communities, and news reports. Two other observational studies have described patients in Kazakhstan who were addicted to several psychoactive substances, 10 of whom were classified as addicted to tropicamide. Of the ophthalmic product requests by observed customers, 1 in 6 requests for ophthalmic products were associated with suspected abuse. From until July , 65 pharmacies reported more than 90 suspicious but unsuccessful attempts to obtain tropicamide eye drops. The misuse of anticholinergic eye drops has become widespread among people with intellectual disabilities and mental disorders. Tropicamide misuse should be suspected in patients who develop an unusual array of symptoms. One of the earliest cases of tropicamide solution misuse was reported in Tropicamide was prescribed, along with antimicrobial agents and cyclopentolate. After two years, the patient returned to the clinic with complaints of drug-induced keratitis. The patient was observed for four days, while all other medications were withdrawn. However, at the next visit, all symptoms remained, including mydriasis. The patient admitted that he continued instilling drops of tropicamide and cyclopentolate. These patients lost kg of weight two to three months after initiating tropicamide as part of their established heroin routines. Similar to other substances, such as arsenic, tropicamide accumulates in various organs, tissues, and body fluids, causing hepatic and renal failure. Tropicamide-abusing patients suffer from many psychiatric difficulties, leading some researchers to suggest that polysubstance use may be a syndrome associated with a pre-existing psychiatric disorder and with certain personality traits. In recent years, analysis of clinical cases published in the literature shows that the use of both pure tropicamide and its combination with opioids may be more common than originally thought. By blocking muscarinic receptors, tropicamide produces dilatation of the pupil, preventing the eye from accommodating for near vision. Bersani et al. All patients injected tropicamide and heroin in the same syringe. In most cases, immediate systematic combined use of heroin and tropicamide ensued. In addition, tropicamide was specifically credited with increasing the length of a heroin high, which resulted in a dramatic increase in the frequency of injections. In the early stages of tropicamide abuse, the dosage was 0. According to Mokhnachev et al. Ostler reported that discontinuing the eye drops led to a pronounced withdrawal syndrome characterized by anxiety, sweating, nausea and vomiting, muscle stiffness, and tremors. Opioid withdrawal symptoms were less pronounced in those who used them combined with tropicamide ie, these patients reported an improvement in opiate withdrawal symptoms. This is consistent with the findings on the benefits of atropine as a possible means of withdrawal treatment. Patients were burdened by their hospital stay, demanded immediate discharge, were rude, and expressed a conscious cravings for tropicamide. These cravings remained relevant for days after opioid withdrawal. In patients who used opiates with or without tropicamide, Kuliev found a significantly higher rate of psychopathological symptoms among those who used tropicamide, concluding that they appear to be a vulnerable population. Although polysubstance abuse often refers to the abuse of multiple illicit agents, it is also includes the use of prescription medications in nonmedical circumstances. Studies published from to reported that tropicamide was used in combination with various psychostimulants. Those who were admitted to the hospital also reported enhanced onset following amphetamine use. Many developed acute paranoia and persecutory delusions. The authors suggested that tropicamide antagonizes muscarinic receptors, thereby causing the onset of hallucinations and reducing the level of consciousness. Patients who used tropicamide alone described a feeling of extraordinary lightness, with difficulty staying on their feet. Other systemic symptoms of tropicamide use include hyperthermia, tremors, paralytic ileus, persistent mydriasis, 40 cardiovascular effects 41 , 42 and anaphylaxis. In theory, any anticholinergic drug use may result in cognitive impairment, but reports regarding the cognitive effect of tropicamide are limited. Tropicamide is a non-selective muscarinic antagonist that binds to all main subtypes of muscarinic receptors. Fortunately, it rarely causes systemic neurocognitive effects when used topically. Later, this patient developed acute psychosis and was admitted to a psychiatric ward. This review of the existing data shows that the abuse of ophthalmic drops is still under-researched worldwide. Our observations also confirm that risk factors occurring during early childhood further increase the risk of substance abuse. Moreover, these risk factors are common across multiple substance use disorders. Although tropicamide abuse is not common in the USA, optometrists and ophthalmologists may encounter many other illegal drugs. Familiarity with the local healthcare network is important for improving patient outcomes. Box 1 summarizes how abusing specific drugs can affect various ocular structures. While the tropicamide abuse epidemic is still predominantly fueled by intravenous drug users from the former Soviet Union, there are clear signs that the epidemic continues to spread around the world. Furthermore, the lack of effective coordination between law enforcement, state government and public health agencies has led to inadequate interagency preparation and response to drug-related threats, as well as other public health emergencies. In response to the addiction crisis, Russia and other countries should focus their efforts on improving access to treatment and recovery services. Yet, despite abundant evidence that addiction is a treatable medical condition, drug addiction continues to be criminalized. European data show that individuals with substance use disorders benefit more from a supportive approach than punishment. This system still limits access to evidence-based drug dependence treatment for injection drug users including tropicamide users. Moreover, some countries have encountered serious problems due to the use of prescription drugs with psychotropic effects for non-medical purposes. Today, anyone can buy agents like tropicamide online without ever showing proof of age or a prescription. We reviewed multiple protocols and treatment strategies available online but could not identify a unified approach in the treatment of these patients. Although neurotoxicity and behavioral changes can be caused by numerous anticholinergic agents, the main treatment for poisoning due to tropicamide abuse is terminating exposure to the substance. Some cholinergic agents, such as pilocarpine, are used off label to counter the effects of cycloplegics like tropicamide and diminish the other effects of anticholinergics, but their systemic use is questionable. Similarly, other adrenergic antagonists, such as dapiprazole or moxisylyte, can be used topically, 58 but no approved methods exist for reversing tropicamide-induced systemic effects. According to Bozkurt et al. Furthermore, the lack of effective coordination between law enforcement and social agencies and the lack of complex and multidisciplinary approaches, especially to drug demand reduction, treatment, and rehabilitation, must still be addressed in most countries. Finally, more high-quality, large-scale studies are needed to accurately characterize tropicamide misuse globally. JB's institution has received funding from Genzyme to support his work. The other authors report no conflicts of interest. This study would not have been possible without the academic and administrative support of the University of Missouri-Kansas City and Unica Medical Center. We are grateful to all those with whom we have had the pleasure to work during this and other related projects. Abuse of tropicamide eye drops: review of clinical data. Braz J Psychiatry. As a library, NLM provides access to scientific literature. Find articles by Val Bellman. Find articles by Anastasia Ukolova. Find articles by Elena Erovichenkova. Find articles by Sarah Lam. Find articles by Hirsch K Srivastava. Find articles by Jared Bruce. Find articles by Douglass M Burgess. PMC Copyright notice. Open in a new tab. Adapted from Kuliev. Substance Ocular changes and findings Alcohol Horizontal gaze-evoked nystagmus. Increased risk of cataracts, macular degeneration, optic neuropathy, impaired visual quality, and retinal vascular disease. Heroin Pupillary changes, talc retinopathy, endogenous infectious endophthalmitis and toxoplasmic chorioretinitis in intravenous users. Methamphetamine and other stimulants Pupillary dilation, decreased accommodation with blurry vision, intra-retinal hemorrhage or a non-ischemic optic neuropathy, episcleritis, scleritis and retinal vasculitis, cornea ulceration, and exposure keratopathy. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Multiple relapses shortly after inpatient hospitalizationsNo relapses after rehab. Multiple relapses shortly after inpatient hospitalizations No relapses after 2 rehabs. Horizontal gaze-evoked nystagmus. Pupillary changes, talc retinopathy, endogenous infectious endophthalmitis and toxoplasmic chorioretinitis in intravenous users. Pupillary dilation, decreased accommodation with blurry vision, intra-retinal hemorrhage or a non-ischemic optic neuropathy, episcleritis, scleritis and retinal vasculitis, cornea ulceration, and exposure keratopathy.

Kulob buying weed