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Teriflunomide is an oral agent that has long been used to treat relapsing-remitting multiple sclerosis. Teriflunomide inhibits the rapid proliferation of T and B lymphocytes by inhibiting the activity of dihydroorotate dehydrogenase. Common side effects include headache, alanine aminotransferase level elevation, hair thinning, and arthralgia. Cases of restless legs syndrome (RLS) associated with the use of teriflunomide have not been previously reported; however, RLS is more frequently observed in patients with multiple sclerosis (MS) than in healthy individuals. Herein, we present two patients with MS with low Expanded Disability Status Scale scores who developed RLS symptoms shortly after starting teriflunomide and whose complaints improved immediately after discontinuing the drug. These cases emphasize the need to consider RLS as a potential side effect of teriflunomide treatment in patients with MS, in whom RLS is more common., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects., Case Presentation: A 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge., Discussion and Conclusions: This case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation., (© 2024. The Author(s).)

Restless leg syndrome (RLS) is a common but underestimated sensorimotor disorder that significantly affects the quality of life (QoL) which can be induced by antidepressants. This study aims to investigate the frequency and potential risk factors of RLS and side effects in selective serotonin reuptake inhibitors/serotonin and noradrenaline reuptake inhibitors (SSRI/SNRI) users. This cross-sectional study included 198 outpatients who received SSRI/SNRI for 4-8 weeks. Clinical evaluation was performed using the International Restless Leg Syndrome Study Group rating scale for RLS, Udvalg for Kliniske Undersøgelser side effects rating scale, and a short form 36 (SF-36) questionnaire for QoL. The frequency of RLS was 25%. RLS significantly increased with smoking and habituality. Also, habituality increased neurologic side effects reporting. The use of antipsychotics and calcium channel blockers decreased reporting of autonomic side effects. QoL decreased with RLS, psychiatric, neurologic, autonomic, and other side effects in different domains of SF-36. These findings suggested that SSRI/SNRI use could be associated with a higher risk of RLS, especially in smokers. QoL could be influenced negatively by RLS and all side effects. However, further prospective studies are needed to confirm these associations in large samples., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To examine the association between long-term use of dopamine agonists (DAs) and the risk of lung cancer in patients with restless legs syndrome (RLS)., Methods: We conducted a retrospective cohort study using Optum Clinformatics® database. We included adults ≥40 years diagnosed with RLS during the study period (1/2006-12/2016). Follow-up started with the first RLS diagnosis and ended on the earliest of: incident diagnosis of lung cancer, end of enrollment in the database or end of the study period. The exposure of interest was cumulative duration of DAs use, measured in a time-varying manner. We constructed a multivariable Cox regression model to estimate HRs and 95% CIs for the association between lung cancer and cumulative durations of DA use, adjusting for potential confounding variables., Results: We identified 295 042 patients with a diagnosis of RLS. The mean age of the cohort was 62.9; 66.6% were women and 82.3% were white. The prevalence of any DA exposure was 40.3%. Compared to the reference group (no use and ≤1 year), the crude HRs for lung cancer were 1.16 (95% CI 0.99-1.36) and 1.14 (95% CI 0.86-1.51) for 1-3 years and >3 years of cumulative DA use, respectively. The adjusted HR for lung cancer was 1.05 (95% CI 0.88-1.25) for 1-3 years and 1.02 (95% CI 0.76-1.37) for >3 years of cumulative DA use, respectively., Conclusions: At typical doses for the clinical management of RLS, long-term DA use was not associated with risk of lung cancer., (© 2023 John Wiley & Sons Ltd.)

Background and Objectives: Restless legs syndrome (RLS) is a sensory-motor neurologic disorder. Low-dose opioids are prescribed for patients with refractory or augmented RLS. The long-term safety, dose stability, and efficacy of these medications for RLS treatment is still unclear. In this study, we report the 2-year longitudinal data in a sample of patients treated with opioids for RLS in the community., Methods: The National RLS Opioid Registry is an observational longitudinal study consisting of individuals taking a prescribed opioid for diagnosed and confirmed RLS, most of whom experienced augmented symptoms from dopamine agonists. Information on opioid dosages, side effects, past and current concomitant RLS treatments, RLS severity, psychiatric symptoms, and opioid abuse risk factors was collected at initial Registry entry and every 6 months thereafter by surveys on REDCap. No feedback or intervention was provided by the study staff to local providers., Results: Registry participants (n = 448) with 2-year longitudinal data available were mostly White, female, older than 60 years, and, at Registry entry, had been on opioids for a median of 1-3 years at a mean morphine milligram equivalent (MME) of 38.4 (SD = 43.5). No change in RLS severity in the overall cohort was observed over the 2-year follow-up period. The median change in daily opioid dose from baseline to 2 years was 0 MME (interquartile range = 0-10). While 41.1% of participants increased their dose during the follow-up period (median increase = 10 MME), 58.9% decreased their dose or saw no change. Only 8% and 4% saw increases of >25 MME and >50 MME, respectively. Ninety-five percent of those who increased opioid dose >25 or >50 MME had one of the following features: switching opioids, discontinuation of nonopioid RLS treatment medications, at least mild insomnia at baseline, a history of depression, male sex, younger than 45 years, and opioid use for comorbid pain., Discussion: Low-dose opioid medications continue to adequately control symptoms of refractory RLS over 2 years of follow-up in most of the participants. A minority of patients did see larger dose increases, which were invariably associated with a limited number of factors, most notably changes in opioid and nonopioid RLS medications and opioid use for a non-RLS condition. Continued longitudinal observations will provide insight into the long-term safety and efficacy of opioid treatment of severe, augmented RLS., Classification of Evidence: This study provides Class IV evidence that opioid doses increase in roughly 40% of patients, in most by small amounts, over a 2-year period when prescribed for adult refractory restless leg syndrome., (© 2023 American Academy of Neurology.)

Problematic gambling has been suggested to be a possible consequence of dopaminergic medications used mainly in neurological conditions, i.e. pramipexole and ropinirole, and possibly by one antipsychotic compound, aripiprazole. Patients with Parkinson's disease, restless legs syndrome and other conditions potentially treated with dopamine agonists, as well as patients treated for psychotic disorders, are vulnerable patient groups with theoretically increased risk of developing gambling disorder (GD), for example due to higher rates of mental ill-health in these groups. The aim of the present paper is to review the epidemiological, clinical, and neurobiological evidence of the association between dopaminergic medications and GD, and to describe risk groups and treatment options. The neurobiology of GD involves the reward and reinforcement system, based mainly on mesocorticolimbic dopamine projections, with the nucleus accumbens being a crucial area for developing addictions to substances and behaviors. The addictive properties of gambling can perhaps be explained by the reward uncertainty that activates dopamine signaling in a pathological manner. Since reward-related learning is mediated by dopamine, it can be altered by dopaminergic medications, possibly leading to increased gambling behavior and a decreased impulse control. A causal relationship between the medications and GD seems likely, but the molecular mechanisms behind this association have not been fully described yet. More research is needed in order to fully outline the clinical picture of GD developing in patient groups with dopaminergic medications, and data are needed on the differentiation of risk in different compounds. In addition, very few interventional studies are available on the management of GD induced by dopaminergic medications. While GD overall can be treated, there is need for treatment studies testing the effectiveness of tapering of the medication or other gambling-specific treatment modalities in these patient groups., (© 2023. The Author(s).)

Diabetes is a global health concern that has affected almost 415 million people globally. Bromocriptine is a dopamine D2 agonist, which is a Food and Drug Administration (FDA)-approved drug to treat type 2 diabetes mellitus (T2DM) patients. However, it is considered that a novel treatment therapy is required which can be used in the treatment of diabetes with or without other antidiabetic agents. Dopamine agonists are usually used in neurological disorders like Parkinson's disease (PD), restless leg syndrome, and hyperprolactinemia. However, dopamine agonists including bromocriptine and cabergoline are also effective in reducing the glycemic level in T2DM patients. Bromocriptine was formerly used for the treatment of PD, hyperprolactinemia, and restless leg syndrome, but now it is used for improving glycemic levels as well as reducing free fatty acids and triglycerides. In addition, cabergoline has been found to be effective in glycemic control, but this drug is yet to be approved by the FDA due to its limitations and lack of study. Findings of the clinical trials of bromocriptine have suggested that it reduces almost 0.4-0.8% glycated hemoglobin and cardiovascular risk by 40% in insulin-resistant patients. Moreover, the safe use of bromocriptine in obese T2DM patients makes it a more attractive option as it causes weight loss. Indeed, bromocriptine is a novel therapy for T2DM patients, as its mechanism of action is unique in T2DM patients with minimal adverse effects. This review summarizes the potential of dopamine agonists in the treatment of T2DM., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pathologic gambling is a rare but severe side effect of dopamine agonists (DA). Low dosage DA, as given when treating restless legs syndrome (RLS), has been thought only to have mild side effects. This case report describes two patients with low dosage pramipexole for RLS, who developed gambling addiction for a decade, highly affecting their quality of life. After stopping the treatment, the patients' gambling addiction ceased. Even though this is a very rare side effect, patients prescribed a DA should be informed of the risk of gambling addiction, independently of dosage.

Many case reports have demonstrated that using antidepressants and especially the selective serotonin reuptake inhibitors (SSRIs), and the noradrenergic and specific serotonergic antidepresants mirtazapine and mianserin can lead to restless legs syndrome (RLS). However, there are disagreements in the results of the limited number of investigations on the relationship of RLS with antidepressants. Trazodone is a frequently used antidepressant with complex agonistic/antagonistic effects on the serotonergic system and moderate blockage on the histamine receptor. This report dicusses the case of a 39-year old female patient who developed RLS after using trazodone (100mg/day) prescribed by her pscyhiatrist for treating her insomnia complaints. We have learned from the patient's statement that she felt burning, tingling and restlessness in her legs, that started from the first night of the treatment and caused an urge to move her legs. The effects were attributed to trazodone and the treatment was discontinued. The patient reported at her control examination the disappearance of RLS symptoms one day after discontinuing trazodone use and the complete improvement of her insomnia complaints.

Background: Patients with Restless Legs Syndrome (RLS) experience psychological distress and diminished quality of life. Antipsychotics and antidepressants are known to be linked to RLS., Aims: This study aims to investigate the presence of RLS in psychiatric patients who receive antipsychotic and antidepressant drugs and to determine potential risk factors for its occurrence., Methods: Two hundred patients who received antipsychotic and antidepressant drugs for more than 1 month were recruited from two tertiary psychiatric centers in Cairo, Egypt. One hundred apparently healthy volunteers were also included. All patients and controls were screened using the four-items questionnaire (Arabic version) for RLS. RLS severity was scored according to the validated Arabic version of International Restless Legs Syndrome Study Group rating scale (IRLS). Mimicking conditions were carefully investigated and excluded., Results: Forty-one percent of the patients who receive antipsychotic and antidepressant drugs were found to have RLS. Family history, past history and smoking are potential risk factors. Trazodone and haloperidol were less associated with RLS., Conclusions: Although limited by its cross-sectional design, these findings suggest that patients who receive antipsychotic and antidepressant are susceptible to RLS. However, these results need to be replicated on a wider scale., (© 2021 John Wiley & Sons Ltd.)

Background: One of the advantages of CGRP monoclonal antibodies is their excellent safety and tolerability. However, postmarketing surveillance, is essential to detect potential rare emergent adverse events., Objectives: To report two patients who developed restless legs syndrome symptoms after treatment with CGRP antibodies., Methods and Results: Two women with chronic refractory migraine, with no significant medical antecedents, developed typical restless legs syndrome symptoms 1.5 and 4 months after starting erenumab 140 mg, respectively. In case 1 symptoms resolved when erenumab was stopped for two months but reappeared on galcanezumab. In both patients migraine attacks had dramatically decreased and no iron deficiency was found., Conclusions: Even though caution is needed before establishing a causal relationship, these cases suggest that restless legs-like symptoms might be an emergent adverse event of CGRP antibodies, regardless of the mechanism of action. We propose that plastic changes in CGRP sensory fibers, which are very abundant in legs, induced by CGRP monoclonal antibodies could be the reason for restless legs syndrome development.

Background: Restless arms syndrome (RAS) is characterized by uncomfortable aching or burning sensations in the arms. RAS is regarded as an upper limb variant of restless legs syndrome (RLS). The lack of specific diagnostic criteria makes it difficult to recognize the RAS. Therefore, RAS is usually neglected in clinical practice. Moreover, when a patient was diagnosed with RAS, the adjustment of medications was the first choice for doctors, which may make the patient's condition unstable., Case Presentation: A 33-year-old woman was diagnosed with schizophrenia and major depressive disorder. Starting with 0.6 g/d amisulpride, 0.1 g/d quetiapine, 75 mg/d venlafaxine sustained-release tablets, the patient reported symptoms of RAS (itching arms) on the fourth day since the latest hospitalization. After ruling out other factors, her RAS was suspected to be induced by antidepressants or antipsychotics. Without medication adjustment, RAS spontaneously remitted., Conclusions: This case suggests that psychiatrists should pay attention to RAS when using antipsychotics and/or antidepressants. Moreover, RAS may be transitory. When a patient manifests RAS, observation may be one choice instead of an immediate medication adjustment., (© 2021. The Author(s).)

Background: Restless Legs Syndrome (RLS) is a sensorimotor disorder characterized by unpleasant and distressing sensations in the lower limbs that are more pronounced in the evening, commence or worsen at rest, and show partial or complete relief following movement. It can occur as a primary disorder, secondary to medical conditions or treatment with medications including but not limited to antidepressants or antipsychotics., Case Presentation: A 32-year old man with major depressive disorder showed partial response to Escitalopram 10 mg daily. Agomelatine 25 mg at night was added to Escitalopram to treat his residual depressive symptoms, namely insomnia and tiredness. Within two days he developed restlessness and unpleasant sensations in his legs which were worse at night. Symptom severity increased over the following days, prompting an urgent consultation a week later. The patient's presentation met the criteria for RLS. Agomelatine was discontinued leaving the patient on Escitalopram alone. The patient's symptoms improved within 24 h of stopping Agomelatine, with complete resolution four days later. There was no recurrence of RLS during follow-up. The patient scored 6 on Naranjo's adverse drug reaction probability scale, indicating a probable adverse drug reaction caused by Agomelatine., Conclusions: To the best of our knowledge, this is the first case report of suspected Agomelatine-induced RLS. Clinicians need to be aware of RLS to enable prompt diagnosis and management. We suggest adding Agomelatine to the list of agents that can potentially induce RLS.

Pramipexole is a dopaminergic pharmacologic agent with reported adverse effects that include hypersexuality, shift in sexual interests, pathological gambling, compulsive shopping, and binge eating. Pramipexole is indicated in the treatment of Parkinson's disease and restless leg syndrome and has been used as adjunctive or add-on treatment in major depressive disorder. This report describes the successful treatment of a series of 4 adult men who presented with concerns about problematic sexual interests and behaviors that began after treatment with pramipexole related to Parkinson's disease or restless leg syndrome., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

None: Restless legs syndrome is a common sensorimotor movement disorder affecting an estimated 15-20% of the general adult population in the United Sates. Several drugs and drug classes have been shown to either cause and/or exacerbate symptoms of restless legs syndrome. With the epidemic of obesity and the heightened awareness of the harmful effects of added sugars, the consumption of low and no-calorie sweeteners has substantially increased. We report a case where the patient developed restless legs syndrome symptoms with the use of a stevia extract-based no calorie sweetener. To our knowledge, this is the first case report of restless legs syndrome possibly associated with low or no-calorie sweetener use., (© 2020 American Academy of Sleep Medicine.)

Objective: To assess emotional processing and alexithymia in patients with restless legs syndrome (RLS) with augmentation versus those who never had augmentation., Methods: We recruited 26 patients who had a history of augmentation (AUG), either current or past, 27 RLS patients treated with dopamine agonists who never had augmentation (RLS controls), and 21 healthy controls (HC). All participants were screened for impulse control disorders (ICDs). Alexithymia was assessed by means of the Toronto Alexithymia Scale - 20 (TAS-20). Facial emotion recognition was tested through an eye-tracking task. Furthermore, all participants performed neuropsychological tests assessing global cognitive status, impulsivity, anxiety, and depression., Results: ICD symptoms occurred more frequently in AUG patients than in RLS controls (P = 0.047). Patients with AUG scored higher on the TAS-20 (P = 0.007) and the attentional subdomain of an impulsivity scale (BIS-11; P = 0.015) compared to HC. Patients with AUG also performed worse on the facial emotion recognition task relative to RLS controls (P = 0.009) and HC (P = 0.003). We found a group difference for the time to first fixation and the fixation count in the mouth region (P = 0.019 and P = 0.021, respectively). There were no other differences in the eye tracking examination., Interpretation: This study showed evidence of poorer emotional processing in patients who had augmentation compared to RLS patients without augmentation and healthy controls. The altered exploration pattern of faces and the higher alexithymia scores suggest abnormalities in emotion processing in patients with augmentation., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Topiramate (TPM) is a fructose derivative, which was originally developed as an antiepileptic. In this context, movement disorders (MDs) are possible adverse events secondary to TPM., Case Reports: Two patients (cases 1 and 2) developed myoclonus, and the other 2 had restless leg syndrome (RLS, cases 3 and 4). The mean age of the individuals (3 female patients) was 45.75 ± 21.28 years. All the individuals had a negative family history for movement and psychiatry disorders. Topiramate was started at 25 mg with a gradual increase of 25 mg every week. The mean time of onset and recovery of the MD were 1.37 ± 1.10 and 1.02 ± 0.77 months, respectively. The mean TPM dose was 87.5 ± 47.87 mg. Individual 1 presented with upper and lower limb jerks; individual 2 only with upper limb involvement. Individuals 3 and 4 experienced insomnia and nocturnal leg discomfort during inactivity with an urge to move the legs, which they denied having previously; the RLS symptoms occurred within approximately 1 to 3 hours of TPM evening dose. On neurological examination, no tremor or bradykinesia was observed; deep tendon reflexes, sensory examination, and strength were normal and preserved. Laboratory tests, neuroimaging, and electromyography were within normal. Topiramate was discontinued in all of the subjects. Full recovery was obtained in all cases., Conclusions: To the authors' knowledge, there are 6 cases of myoclonus, 5 RLS, 2 dystonia, 1 dyskinesia, and 1 periodic limb MD. The best management is probably the discontinuation of TPM, but in RLS patients, the addition of a dopaminergic agonist can be beneficial.

Purpose: Largely based on case series, several drugs have been implicated in drug-induced restless legs syndrome (RLS) including selective serotonin reuptake inhibitors (SSRI). We aimed to assess the association between initiation of SSRIs and RLS in a self-controlled design., Methods: We conducted a symmetry analysis, including Danish adults who filled in their first prescription of an SSRI in the period of 1997-2017 and initiated an RLS drug (quinine, ropinirole, pramipexole or rotigotine) 1 year prior to or after this date. A symmetrical distribution of prescriptions before and after SSRI initiation is expected if there is no association between SSRI and RLS (a sequence ratio (SR) of 1.0). The symmetry analysis design is robust to confounders that are stable over time. Subgroup analyses were conducted, restricting the population on sex, age, selected diagnoses and concurrent medication., Results: A total of 10,875 patients filled in their first-ever prescription of both an SSRI and an RLS drug within a 1-year interval; 5341 patients filled their prescription of SSRI prior to their prescription of an RLS drug, and 5534 patients redeemed their prescriptions in the opposite order (SR 0.97, 95% CI 0.93-1.00). Restricting the outcome to dopamine agonist initiation revealed a slightly increased sequence ratio (SR 1.34, 95% CI 1.24-1.46), which was reduced when adjusting for trends in prescription (adjusted SR 1.21, 95% CI 1.12-1.32). Restricting the outcome to quinine initiation showed no association., Conclusion: We found no association between the initiation of an SSRI and the development of RLS assessed by the prescription of an RLS drug.

Study Objectives: Restless legs syndrome (RLS) has been hypothesized to be generated by abnormal striatal dopamine transmission. Dopaminergic drugs are effective for the treatment of RLS. However, long-term use of dopaminergic drugs causes adverse effects. We used iron-deficient (ID) and iron-replacement (IR) rats to address the neuropathology of RLS and to determine if a histamine H3 receptor (H3R) antagonist might be a useful treatment. Histamine H3R antagonists have been shown to decrease motor activity., Methods: Control and ID rats were surgically implanted with electrodes for polysomnographic recording. After 3 days of baseline polysomnographic recordings, rats were systemically injected with the H3R agonist, α-methylhistamine, and antagonist, thioperamide. Recordings were continued after drug injection. Striatal H3R levels from control, ID, and IR rats were determined by western blots. Blood from control, ID, and IR rats was collected for the measurement of hematocrit levels., Results: α-Methylhistamine and thioperamide increased and decreased motor activity, respectively, in control rats. In ID rats, α-methylhistamine had no effect on motor activity, whereas thioperamide decreased periodic leg movement (PLM) in sleep. Sleep-wake states were not significantly altered under any conditions. Striatal H3R levels were highest in ID rats, moderate to low in IR rats, and lowest in control rats. Striatal H3R levels were also found to positively and negatively correlate with PLM in sleep and hematocrit levels, respectively., Conclusions: A striatal histamine mechanism may be involved in ID anemia-induced RLS. Histamine H3R antagonists may be useful for the treatment of RLS., (© Sleep Research Society 2019. Published by Oxford University Press [on behalf of the Sleep Research Society].)

Previous research has suggested an association between antidepressants use and clinical restless legs syndrome (RLS) in patients, but there has never been a single study investigating the risk of RLS in irritable bowel syndrome (IBS) patients treated with antidepressants. Hence, we aimed to explore the association between IBS and RLS and to examine the risk of RLS in IBS patients treated with antidepressants. With the use of the National Health Insurance Research Database of Taiwan, 27,437 adults aged ≥ 20 years with newly diagnosed IBS (ICD-9-CM Code 564.1) and gender- and age-matched 54,874 controls without IBS were enrolled between 2000 and 2012. All patients were followed-up until RLS diagnosis, withdrawal from the National Health Insurance program, or end of 2013. We used the Cox proportional hazards model to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of RLS. RLS was more prevalent in IBS patients than in the non-IBS group (7.57 versus 3.36 per 10,000 person-years), with an increased risk of RLS (adjusted HR [aHR], 1.91; 95% CI, 1.52-2.40). Multivariate Cox proportional hazards analysis identified older age (age, 51-65 years; aHR, 1.67; 95% CI, 1.09-2.56; and age > 65; aHR, 1.59; 95% CI, 1.02-2.48), hypothyroidism (aHR, 4.24; 95% CI, 1.92-9.37), CAD (aHR, 1.70; 95% CI, 1.17-2.48), and depression (aHR, 3.15; 95% CI, 2.14-4.64) as independent RLS risk factors in IBS patients. In addition, the male SSRIs users were associated with significantly higher risk of RLS (aHR, 3.05 95% CI, 1.34-6.92). Our study showed that the IBS group has higher risk of RLS. Moreover, SSRIs use may increase the risk of RLS in male IBS patients., Competing Interests: The authors have declared that no competing interests exist.

Abstract: Restless legs syndrome is a chronic disorder that is characterized by an urge to move the legs and unpleasant sensations in the lower extremities. Its symptoms develop slowly and a sudden onset is very unusual, which may be confusing for the emergency physician. We describe a case of an abrupt presentation of restless legs syndrome symptoms induced by infusion of metoclopramide during treatment of a migraine attack in settings of an emergency department. The patient shortly after infusion of metoclopramide started to experience rapid movements of the legs, claiming that it was the only way to relieve extremely unpleasant sensations in her legs. The symptoms subsided after saline infusion and did not appear again., (© 2019 American Academy of Sleep Medicine.)

Background: The link between restless legs syndrome (RLS) and the number of amalgam fillings in older people was investigated. Restless legs syndrome decreases the quality of life and impairs normal functioning. Mercury (in amalgam) may be toxic to nerve cells and may account for the incidence of RLS., Material and Methods: The relationship between RLS and the presence of amalgam in the teeth of 104 people aged 60-97 years old was determined. By using 4 questions, together with the diagnostic criteria from the internationally used questionnaire produced by the International Restless Legs Syndrome Study Group (IRLSSG), authors assessed the extent of the symptoms and occurrence of RLS. Careful medical history and medical examination were used for ascertaining each subject's type of restorative materials (i.e., amalgam or other metal) and the number of such fillings., Results: Subjects who answered "yes" (indicating presence of RLS) to the 4 subsequent questions had a significantly higher number of amalgam dental fillings as compared to the subjects without RLS symptoms. Presence of other metal dental restorative materials and the number of amalgam dental fillings reported in the past had no significant influence on RLS symptomatology., Conclusions: Authors conclude that while examining the correlates of the appearance of restless legs syndrome the use of amalgam in the dentition should be taken into account. Med Pr. 2019;70(1):9-16., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Restless Legs Syndrome (RLS) or Willis-Ekbom Disease is an under-diagnosed chronic and progressive primary sensory-motor disorder. It can lead to severe sleep disturbances, a usual cause of consultation. It is characterized by an urgent need to move the legs in resting situations, a cardinal symptom that is usually accompanied by an unpleasant sensation in legs. These symptoms appear or aggravate at the end of the day and in resting situations and are alleviated with movement. Based on these clinical characteristics, it has been defined as a quiescegenic focal akathisia. The diagnosis is essentially clinical. As a guide, there are five cardinal diagnostic criteria. The treatment consists of non-pharmacological measures and the use of medications such as dopamine agonists. Despite the treatment, the symptoms persist in 40% of patients. Psychiatrists should be aware of the syndrome since many drugs used by them such as antipsychotics, antidepressants and anxiolytics can worsen the symptoms. Moreover, the syndrome may be associated with depressive and anxiety diseases.

Meis homeobox 1 (Meis1) is a transcription factor functioning in the development of the nervous system and the cardiovascular system. Both common and rare variants within the gene have been associated with restless legs syndrome (RLS), while its association with symptoms of insomnia has also been discovered recently. RLS is associated with sleep disturbances, and while Meis1 haploinsufficiency is one of the most promising strategies for an RLS animal model, sleep phenotyping of Meis1 knockout mice has never been conducted. We report a detailed sleep analysis of heterozygous Meis1 knockout mice and challenge it with pramipexole, a dopamine agonist used in the treatment of RLS. At baseline, the Meis1-haploinsufficient mice had a trend towards lower delta power in the electroencephalogram (EEG) during sleep compared to the wild-type littermates, possibly indicating reduced sleep quality, but not sleep fragmentation. Pramipexole had a sleep disrupting effect in both genotype groups. In addition, it exerted differential effects on the EEG power spectra of the two mouse lines, remarkably elevating the theta power of the mutant mice during recovery more than that of the wild-types. In conclusion, Meis1 haploinsufficiency seems to have only a modest effect on sleep, but the gene may interact with the sleep-disrupting effect of dopamine agonists., (© 2017 European Sleep Research Society.)

Objective: To review the literature on drug-induced restless legs syndrome (DI-RLS)., Data Sources: The review included a search for English-language literature from 1966 to December 2017 in the MEDLINE, PubMed, and Ovid databases using the following search terms: restless legs syndrome (RLS), periodic limb movement, adverse effects, and drug-induced. In addition, background articles on the pathophysiology, etiology, and epidemiology of RLS were retrieved. Bibliographies of relevant articles were reviewed for additional citations., Study Selection and Data Extraction: All case reports, case series, and review articles of DI-RLS were identified and analyzed. There were only a small number of controlled clinical trials, and most data were from case reports and case series., Results: Several drugs and drug classes have been implicated in DI-RLS, with antidepressants, antipsychotics, and antiepileptics having the most evidence. In addition, RLS may be linked with a number of disorders or underlying predisposing factors as well., Conclusions: The prevalence of RLS is variable and ranges from 3% to 19% in the general population. There are many predisposing factors to RLS, but an emerging body of evidence suggests that there is an association between numerous drugs and RLS.

Objectives: Restless genital syndrome (RGS) includes discomfort, pain, numbness, vibration, restlessness, or a burning sensation involving the vagina, perineum, pelvis, penis, and proximal portion of the lower limbs in patients. The RGS has been sometimes reported in Parkinson disease. In patients without Parkinson disease, RGS is also known as persistent genital arousal disorder (PSAS), which includes uncontrollable genital arousal, with or without orgasm or genital engorgement, unrelated to sexual desire. Although withdrawal from selective serotonin reuptake inhibitors antidepressants is reported to induce PSAS, there is no report of RGS or PSAS induced by antidepressants., Methods: We obtained the consent for the presentation and have not identified individuals for ethical reasons., Results: We first report a woman patient with depression induced RGS by milnacipran (MLN)., Conclusions: We discuss the relationship with restless legs syndrome and the difference from akathisia. It is highly possible MLN affected her RGS because she experienced RGS for the first time after the dose of MLN was increased. A limitation of this report is that we stopped MLN and administered gabapentin enacarbil immediately. We should join MLN to the list of compounds suspected of inducing RGS.

Objective/background: Because restless legs syndrome (RLS) is a problematic syndrome, demonstrating an association between use of selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) and RLS may help direct patient care. The goals of this study were (1) to establish the incidence of RLS in mental health patients being treated with SSRIs or SNRIs in a local Veterans Affairs medical center and (2) to evaluate the frequency with which certain SSRIs or SNRIs are associated with RLS and the trend in frequency of the diagnosis since the revision of the criteria for RLS offered by the International Restless Leg Syndrome Study Group (IRLSSG), the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and the International Classification of Sleep Disorders, Revised (ICSD-3)., Methods: A retrospective chart review was used to evaluate the number of patients receiving SSRI/SNRI therapy with and without a diagnosis of RLS, with the date of the RLS diagnosis and initiation of SSRI/SNRI therapy noted. The frequency with which certain SSRIs/SNRIs were associated with RLS, and the frequency of RLS diagnoses since January 2012 were also noted. Descriptive statistics and logistic regression were used for data analysis., Results: A total of 254 charts were reviewed. A majority of the patients (89.8%) were male, and 14 (5.5%) were diagnosed with RLS. A logistic regression equation approached significance in predicting RLS (P=0.053). Age and sex emerged as significant predictors of RLS. The prevalence of any individual SSRI or SNRI being associated with RLS was indeterminable. No difference was seen in the number of RLS diagnoses since the refining of the IRLSSG, DSM-5, and ICSD-3 criteria., Conclusions: The use of SSRIs/SNRIs does not seem to be associated with a diagnosis of RLS. In addition, the diagnosis of RLS does not seem to have become more common since the revision of the diagnostic criteria for the disorder.

The authors report the cumulative incidence of Restless Legs Syndrome (RLS) over a 3 years follow-up period in 92 de novo Parkinson's disease patients under chronic dopaminergic therapy and the clinical course of the sensory-motor disorder over 12 months as from its onset. The overall cumulative incidence of RLS was found by 15.3%, i.e. 14 incident cases, and by 11.9%, i.e. 11 incident cases, after the exclusion of possible "secondary" forms of the disorder. These figures are higher than those reported in general population in Germany (Study of Health in Pomerania), confirming our previous findings of incidence rate of the disorder. At the end of the 3 years follow-up period the prevalence of "current" RLS was significantly higher than that previously found in drug naïve Parkinson's disease patients and in controls, supporting the view that RLS emerging in the course of chronic dopaminergic therapy is the main determinant of the co-morbid association with Parkinson's disease. During the 12 months period of observation the RLS showed a frequency of occurrence of 6.08 episodes per month on average and a remittent clinical course was prevailing in the 11 incident cases, with a significant frequency decrease in the second as compared to the first 6 months, i.e. 3.26 versus 8.9 episodes per month, and none of the patients developed augmentation in the same period. It is hypothesized that the remittent course could be due to long-term adaptation (downregulation) of the hypersensitive post-synaptic dopamine receptors in the spinal cord to a continuous dopaminergic stimulation, possibly coupled with compensatory up-regulation of pre-synaptic dopamine re-uptake mechanism, in the patients in which the hypothalamic A11 area, site of origin of the dopamine-mediated diencephalo-spinal pathway, is involved in the neurodegenerative process.

Restless legs syndrome is an underdiagnosed sensori-motor disorder and psychotropic drugs are one of the main secondary causes of the illness. The most common psychotropic agents that cause restless legs syndrome are antidepressants; however, antipsychotics have also been reported to induce restless legs syndrome. The prevalence, vulnerability factors and the underlying mechanism of antipsychotic-induced restless legs syndrome are unclear. A possible explanation is that dopaminergic blockade is the main precipitator of the syndrome. Quetiapine-induced restless legs syndrome is another point of interest because of its low binding to D2 receptors. We herein report the case of a restless legs syndrome that emerged after a single low dose quetiapine administration.

Purpose: Augmentation has been known as the major complication of long-term dopaminergic treatment of restless legs syndrome (RLS). However, there have been no reports on the prevalence of augmentation in Korea. Thus, we aimed to assess the rate of augmentation and evaluate related factors in Korean RLS patients., Methods: Ninety-four idiopathic RLS patients who have been treated over a period of at least 6 months were enrolled. Thirty subjects were treated with a dopamine agonist only, and 64 were treated with a dopamine agonist and alpha two delta ligands. We assessed the clinical characteristics of those RLS subjects and evaluated the rate of augmentation. Augmentation was assessed using the NIH criteria for augmentation by two RLS experts independently., Results: Eleven subjects (11.7%) were classified as having definitive or highly suggestive clinical indication of augmentation. In comparing the augmentation group with the non-augmentation group, there were no significant differences of baseline clinical characteristics. Four (13.3%) of the dopamine agonists monotherapy group and seven (10.9%) of the combination therapy group were categorized as augmentation. There was no significant difference in the augmentation rate between these two groups., Conclusions: We found an 11.7% augmentation rate in Korean RLS subjects. There was no difference in the rate of RLS augmentation between the dopaminergic monotherapy group and the combined treatment group. It may be related with using a similar dosage of dopaminergic drugs.

Restless leg syndrome (RLS) is a common disorder, frequently of unclear origin, which is often associated with significant distress. There are a few case reports of atypical antipsychotic agents (AAP) causing RLS. The pathophysiological mechanisms resulting in emergence of these movements suggest central dopaminergic dysfunction. Dopamine agonists and L-dopa reduce the symptoms of RLS, and some agents that block the dopaminergic system aggravate RLS. Genetic influences are implicated in RLS and an association between gene polymorphisms and antipyschotic-associated onset of RLS has been postulated. Greater awareness of potential causes of RLS, and its differentiation from akathisia and illness related agitation might help in reducing the distress associated with it and improving patient compliance in patients using atypical antipsychotic agents.

Akathisia and restless legs syndrome (RLS) share some common clinical features and a common relationship with dopamine dysfunction. However, the underlying causes and appropriate treatments for akathisia and RLS are different. Herein we describe a case of RLS that was precipitated by a single dose of asenapine, which is an atypical antipsychotic, and dissect the features that support the contention that this was indeed a case of RLS and not akathisia., (© 2014 American Academy of Sleep Medicine.)