Discontinuation Of Pregabalin Research Articles

Pregabalin-Induced Parkinsonism: Case Report and Review of the Literature.

Pregabalin is an anti-epileptic drug approved for the treatment of neuropathic pain and focal-onset seizures. In a few cases, pregabalin was associated with parkinsonism. We present a case of a 48-year-old female who had hypertension and was on losartan 50mg/daily. Her general practitioner prescribed pregabalin 150mg/daily for fibromyalgia-related pain. The subject doubled the dosage without medical advice. After 5 days of the increased dosage, she started to experience difficulty and slowness in movement associated with resting tremors. Neuroimaging, electrodiagnostic studies, and laboratory exams were unremarkable. Secondary parkinsonism was suspected, so pregabalin was discontinued. The subject fully recovered within 7days. To the authors' knowledge, only 6 cases of pregabalin-induced parkinsonism were reported in the literature. Pregabalin discontinuation was the most common management. All individuals fully recovered after pregabalin withdrawal. The mechanism of pregabalin-induced parkinsonism is not fully understood.

Literature review on pregabalin and the risk of addiction

Pregabalin is a gamma-aminobutyric acid (GABA) analogue used in the treatment of epilepsy, neuropathic pain, generalized anxiety disorder and currently being studied for other indications, there is an ongoing debate about the addictive potential of pregabalin. The aim of this study was to identify the number of cases of abuse or addiction to pregabalin published in the literature. The study consists of a census of the number of published cases of pregabalin abuse or dependence on PubMed and Science Direct up to the year 2021. A total of 130 cases of pregabalin abuse or dependence have been identified (mean age of 30 years, 73% male). The average daily dose of pregabalin was 3.1 g. Psychiatric diagnoses other than substance-related disorders were reported in the largest number of patients, and almost all of the patients exhibited withdrawal symptoms after discontinuation of pregabalin. Current literature suggests a significant and growing concern for pregabalin abuse. The sociodemographic level, the availability of the drug as well as the legal vacuum can be possible risk factors for the hyperconsumption of pregabalin as well as the development of addictive behaviors related to this molecule.

Pregabalin withdrawal in patients without psychiatric disorders taking a regular dose of pregabalin: A case series and literature review

Pregabalin is a drug that can cause psychiatric symptoms via pregabalin withdrawal. Prior reports on pregabalin withdrawal have mainly focused on cases with pregabalin dependence or abuse, and little attention has been paid to patients who are prescribed regular doses of pregabalin. Herein, we report three cases of pregabalin withdrawal in patients without psychiatric disorders, taking regular doses of pregabalin, who developed psychiatric symptoms such as insomnia and anxiety after abrupt discontinuation of pregabalin. In addition, we conducted a systematic review of six case reports (previous studies) of pregabalin withdrawal under regular doses of pregabalin. Among the six cases, three patients had no comorbid mental or substance use disorders, the dose of pregabalin ranged from 150 to 600 mg/d, and the duration of pregabalin use ranged from a few weeks to many years. Of these six cases of pregabalin withdrawal, five had psychopathological symptoms, three had vegetative symptoms, and three had neurologic and physical complications. We concluded that since pregabalin withdrawal can occur even with regular doses and short‐term use, clinicians must carefully reduce pregabalin doses when reducing or discontinuing treatment, paying close attention to withdrawal symptoms. Our case series sheds light on the scant evidence from previous research on physical dependence in patients who are taking regular doses of pregabalin. Furthermore, our cases were also valuable in demonstrating that pregabalin withdrawal can occur even after a relatively short period of 2 months.

Depression with psychosis following pregabalin discontinuation

There has been controversy about the efficacy of pregabalin for some indications, as well as the potential for misuse and adverse effects. Here, the authors discuss a female who was admitted with symptoms of severe depression and psychotic features with a potential causation of discontinuation of pregabalin that had been used for several years. due to chronic back pain.

Pregabalin-induced focal myositis: A report of two cases and review of literature

Background: Drug-induced myopathy should be on the differential diagnosis in patients with non-traumatic muscle pain. It is important to consider the diagnosis as symptoms typically abate with removal of the offending agent. Case: Two elderly females presented separately with complaint of lower extremity pain and swelling. There was no elevation in inflammatory markers or muscle enzymes in either case. MRI revealed inflammatory changes on T2-weighted sequences. Both patients experienced rapid improvement of symptoms with discontinuation of pregabalin. Discussion: Medication-induced myositis should be considered in patients presenting with muscle complaints. Due to the overall high prevalence of pregabalin in the management of chronic pain, it is important to consider its role in the pathogenesis of focal myositis.

Following unilateral spinal contusion pregabalin has an at‐time effect on pruritus and a protective effect on mechanosensory nociception, but does not improve ipsilateral motor outcomes with early administration in rats

Anticonvulsants like pregabalin (PGB) are the first‐line treatment for neuropathic pain caused by traumatic injury and non‐traumatic diseases of the central nervous system. Recent evidence from a human cohort study suggests that early use of pregabalin after spinal cord injury (SCI) may result in improved motor scores, however, it is unknown to what extent changes in spinal neural circuitry are involved. Using a rat model of unilateral cervical contusion, we examined the effect of pregabalin treatment on both motor and sensory function. For four weeks post‐injury, rats were given daily pregabalin or filtered water via oral gavage. Motor function was scored using the Montoya staircase assessment for food pellet retrieval (MSA). Additionally, pruritus and noxious mechosensation were assessed through behavioural evidence of scratching and the Randall‐Selitto analgesiometre, respectively. Finally, we used immunohistochemistry to characterize the primary afferent axons responsible for conveying signals related to nociception and itch. We found no significant relationship between the early administration of pregabalin and improved motor scores in the affected forelimb following MSA analysis. However, rats receiving pregabalin had improved performance on the MSA using their contralateral paw, suggesting alleviation of ongoing pain. Additionally, we found that self‐injurious scratching, often displayed by animals with this type of injury, was greatly reduced in those treated with PGB. However, following a two‐month sham injury experiment without PGB treatment, it was found that the scratching was not necessarily due to SCI, except for a small number of cases in which scratching included the territory of the greater auricular nerve. Furthermore, results of the Randall‐Selitto analgesiometre indicate a protective effect that lasted after discontinuation of PGB. Finally, we saw no changes in the density of pruritic and nociceptive primary afferents just rostral to the site of injury. Our findings suggest that in rats with a unilateral SCI, PGB treatment has a possible protective effect on mechanosensory nociception, aids in diminishing pain and itch during use, and contrary to the human cohort study, does not improve motor outcomes with early administration.Support or Funding InformationWings for Life; Natural Sciences and Engineering Research Council (NSERC)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Crying spells triggered by thumb-index rubbing after thalamic stroke: a case report

BackgroundPathologic crying, devoid of any emotional counterpart, is known to occur as a consequence of various brain stem, cortical hemispheric and cerebellar lesions or, quite exceptionally, of “dacrystic” epilepsy. The case reported here suggests that thalamic lesions may also cause crying spells, under the special circumstances described below.Case presentationAfter a mild left thalamic stroke a caucasian 77 years old man presented with crying spells with no emotional counterpart, triggered by thumb-index rubbing of his right hand. Only a modest sensation loss on right infra-orbital and nose-labial areas and the first three right fingers could be detected at clinical examination. The circumstances and processes leading to the crying spells were investigated, together with their neural substrate. Brain computerized tomography (CT), magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) were conducted. Neurophysiologic studies included Video-Electroencephalography, Electromyography, motor and sensory Evoked potentials. Active thumb-index rubbing, passive fingertips stimulation and interaction of sensory-motor stimulation with cognitive/speech activities were tested under different paradigms. A treatment with pregabalin (75 mg twice a day) was attempted. CT and MRI showed a small ischemic infarct in the left ventral postero-lateral thalamus, while fMRI led to the expected findings, i.e. a bilateral activation of the hand motor representation during the crying-triggering right-hand finger rubbing activity. Sensory potentials evoked from stimulation of the right upper limb were the only abnormal neurophysiologic test. Crying spells could be invariably evoked by both real and imagined active finger rubbing, in either the left of right hemi-space. Rubbing by an examiner was ineffective. Immersion in water (18 °C) but not oiling of the fingertips prevented the symptom. Administration and discontinuation of pregabalin 75 mg daily could be associated with suppression and reappearance of the symptom, respectively.ConclusionsIn this patient loss of sensation seemed to generate crying spells rather than the more common allodynia. As a matter of speculation, both symptoms might represent responses to a sensory loss, but in this case the pathway might have been selectively affected providing inhibition from the lateral to the medial segment of the VPLT, which is linked to the anterior cingulate (limbic) cortex engaged in emotional behaviour.

Effect of duloxetine on neuropathic pain in patients intolerant to continuous administration of pregabalin.

Purpose: We examined duloxetine's effectiveness in the treatment of neuropathic pain in patients who were intolerant to continuous pregabalin administration. Materials and Methods: The present study is a retrospective study of patients diagnosed with neuropathic pain with neuropathic leg pain as the chief complaint. We analyzed 20 cases in which pregabalin was changed to duloxetine because of adverse effects (16 cases) or treatment failure (4 cases). The incidence of adverse events after duloxetine administration was used as the primary endpoint, with the secondary endpoint being the leg pain level based on a numerical rating scale (NRS). Results: The incidence of adverse events after starting duloxetine was 40%. Average leg pain scores measured on the NRS were 8.4±1.4, 6.4±1.4, and 4.1±2.0 at the time of the patients' first visit, pregabalin discontinuation, and after switching to duloxetine, respectively. A significant difference in NRS scores was found between the first visit and pregabalin discontinuation and also between pregabalin discontinuation and after the switch to duloxetine (p<0.05), indicating that pain decreases over time. Furthermore, NRS scores significantly declined between the patients' first visit and after the switch to duloxetine (p<0.05). The improvement in NRS score was 20±12.8% after pregabalin administration and 23±12.0% after duloxetine administration compared with baseline scores (no significant difference between pregabalin and duloxetine; p>0.05). Conclusion: When patients with neuropathic pain are unable to tolerate pregabalin because of adverse effects, changing the medication to duloxetine may be an option.

Pregabalin prescription for terminally ill cancer patients receiving specialist palliative care in an acute hospital.

BackgroundPregabalin is recommended as an adjuvant analgesic for neuropathic cancer-related pain, and may be taken at all steps of the World Health Organization analgesic ladder. However, unlike opioids, pregabalin treatments are limited to an oral administration route. If patients have oral feeding difficulties, it is not possible to administer any drug as an adjuvant analgesic for neuropathic cancer-related pain. Therefore, the aim of the present study was to clarify the problems of pain control after pregabalin discontinuation in terminally ill cancer patients.MethodsOur subjects comprised cancer patients who died during their hospital stay and were referred between April 2013 and October 2015 to the palliative care team of the 899-bed Cancer Hospital at the Nippon Medical School Hospital in Japan. The medical records of each patient were retrospectively reviewed, and patient characteristics were recorded.ResultsWe obtained data on 183 patients during the study period. Thirty-eight (20.8 %) patients were treated with pregabalin. Thirty-three (86.8 %) out of 38 patients were prescribed pregabalin for neuropathic cancer-related pain. The incidence of bony metastases was significantly higher in patients administered pregabalin than in those not taking the drug (non-pregabalin group 32.4 % vs pregabalin group 57.9 %). Pregabalin was ultimately discontinued in all patients, with the main reason being oral feeding difficulties (81.6 %). After the discontinuation of pregabalin, the amount of opioid drugs administered was increased in 56.5 % of patients with oral feeding difficulties.ConclusionOur results demonstrated that the amount of opioid drugs administered was increased in more than 50 % of patients following the discontinuation of pregabalin, and was repeatedly increased for some patients. A new administration route is required for cancer patients unable to take oral medication.Trial registration UMIN000022507. May 28, 2016 retrospectively registered.

Conversion from thrice- to twice-daily pregabalin dosing for pain: Economic and clinical outcomes in a veteran population.

Results of a study analyzing economic and clinical outcomes one year after conversion from thrice- to twice-daily pregabalin dosing for pain are presented. A retrospective chart review was conducted at two Veterans Affairs facilities. The analyzed population included all patients receiving pregabalin for pain whose dosing was converted from thrice- to twice-daily pregabalin dosing during a one-year period. The primary endpoint was the economic impact of the conversion. Secondary endpoints included reversion to thrice-daily pregabalin dosing, pregabalin discontinuation, addition of medications for pain, and unscheduled neuropathy-related visits. Among the 57 patients included in the data analysis, 41 continued to take pregabalin twice daily, 10 had pregabalin discontinued, and 6 had dosing reverted to thrice daily. The mean age of patients and the distribution of add-on pain medications did not differ significantly between patients whose pregabalin dosing frequency remained at twice daily and patients whose frequency reverted to thrice daily. The costs associated with pregabalin therapy differed significantly between the preconversion and postconversion periods. A savings of $115,867 was realized from this conversion for both facilities combined over the course of one year. In patients receiving pregabalin for pain, conversion from thrice- to twice-daily pregabalin dosing-while maintaining the same daily dose-resulted in substantial cost savings while having little effect on clinical outcomes.

Somatoform Disorders-a New Target for Pregabalin

Somatoform Disorders (SD) represent a big clinical challenge regarding frequent medical assistance demand, functional impairment and partial pharmacotherapy response. The study objective was to ascertain the efficacy and tolerability of pregabalin (PG) in patients with SD and patients with comorbid diagnoses as follows: F41.1, F32, F33 or F34 and F45 with partial response to antidepressant therapy (SSRI, SNRI, MAOI, TCAs, SARIs, SNDIs) after long-term treatment. This was prospective, nine months, open-label study. The sample consisted of 31 patients with SD diagnosed as F45 according to ICD-10 criteria by standard clinical interview. The assessment was made by the following instruments: 100 mm visual analogue scale (VAS) which assessed physical symptom severity and Clinical Global Impression Scale (CGI). The baseline assessment was done, while follow up was made after seventh day, one, two and nine months. Patients were treated with PG (dose ranged from 150 to 300 mg per day), as monotherapy or in combination with antidepressant and/or benzodiazepines (BZD) which were previously taken. At the end of the study 18 patients (58.06%) self-rated their severity as no pain, while 8 (25.81%) rated as mild pain using VAS. After nine months 26 patients (83.87%) showed an overall improvement (CGI). Five patients (16.13%) had side effects (feeling of dizziness in initial PG treatment phase), which was the reason for the PG discontinuation in three patients (9.67%). High efficiency, absence of serious side effects and good tolerability of pregabalin opens a new opportunity for the successful treatment of patients with SD.

Pregabalin-Associated Heart Failure Decompensation in a Patient With a History of Stage I Heart Failure.

To describe an elderly male patient with a prior history of New York Heart Association (NYHA) class I heart failure (HF) who presented with cardiac decompensation related to pregabalin therapy and to review the literature involving the effects of pregabalin in HF patients. An 84-year-old man with NYHA class I HF (left-ventricular ejection fraction between 45% and 50%) presented to the emergency department with acute HF decompensation approximately 10 days after initiation of pregabalin for the management of peripheral neuropathy. Discontinuation of pregabalin and administration of furosemide resulted in resolution of symptoms. Shortness of breath; facial, neck, and peripheral edema; and weight gain all improved within 2 days. Three months following discontinuation of furosemide and pregabalin, the patient remained stable without any recurring symptoms or progression in HF. Pregabalin is associated with a 10% to 15% prevalence of peripheral edema and weight gain, with cases reported in patients both with and without HF. Whereas most reported HF exacerbations have occurred in patients with NYHA class II to IV HF, this case is one of the first to be reported in a patient with NYHA class I. According to the Naranjo probability scale (score of 4), it was possible that the patient's HF symptoms were related to pregabalin. The mechanism of action of pregabalin-induced HF is unknown, but pregabalin has been shown to act as a calcium channel antagonist. Although further studies are needed, this case suggests that close monitoring of patients with NYHA class I HF should be considered when initiating pregabalin therapy.

Incomplete atrioventricular block in a patient on pregabalin therapy

The authors report on a case of incomplete atrio-ventricular block in a patient on pregabalin therapy. Pregabalin was not overdosed; renal function of the patient was normal. The effect reverted after pregabalin discontinuation.

Patient with insidious hypoactive delirium associated with pregabalin

AbstractPregabalin has favorable effects on several types of neurological pain, but can cause side‐effects including dizziness, somnolence and delirium. Delirium presents as two variants in terms of psychomotor disturbance: the hyperactive type, showing agitation and vigilance; and the hypoactive type, showing lethargy and decreased motor activity. Patients with delirium associated with pregabalin therapy have been reported to experience hyperactive delirium. Here, we report the case of a 68‐year‐old patient with insidious hypoactive delirium caused by pregabalin therapy for postherpetic neuralgia. Delirium improved after discontinuation of pregabalin. Hypoactive delirium is considered to be more common than the hyperactive type in older adults, and is likely to be overlooked. Attention should thus be paid to latent cases of hypoactive delirium associated with pregabalin therapy in elderly individuals.

1019 – Safety of discontinuation of pregabalin after long-term treatment in subjects with generalised anxiety disorder (GAD)

Pregabalin is indicated for the treatment of generalised anxiety disorder (GAD) in adults in Europe. When pregabalin is discontinued, a 1-week (minimum) taper is recommended to prevent potential discontinuation symptoms. To evaluate whether a 1-week pregabalin taper, after 3 or 6 months of treatment, is associated with the development of discontinuation symptoms (including rebound anxiety) in subjects with GAD. Subjects were randomised to double-blind treatment with low- (150-300 mg/d) or high-dose pregabalin (450-600 mg/d) or lorazepam (3-4 mg/d) for 3 months. After 3 months ~25% of subjects in each group (per the original randomisation) underwent a double-blind, 1-week taper, with substitution of placebo. The remaining subjects continued on active treatment for another 3 months and underwent the 1-week taper at 6 months. Discontinuation after 3 months was associated with low mean changes in Physician Withdrawal Checklist (PWC) scores (range: +1.4 to +2.3) and Hamilton Anxiety Rating Scale (HAM A) scores (range: +0.9 to +2.3) for each pregabalin dose and lorazepam. Discontinuation after 6 months was associated with low mean changes in PWC scores (range: -1.0 to +3.0) and HAM A scores (range: -0.8 to +3.0) for all active drugs and placebo. Incidence of rebound anxiety during pregabalin taper was low and did not appear related to treatment dose or duration. A 1-week taper following 3 or 6 months of pregabalin treatment was not associated with clinically meaningful discontinuation symptoms as evaluated by changes in the PWC and HAM A rating scales. This study was funded by Pfizer Inc.

Pregabalin intoxication-induced encephalopathy with triphasic waves

This report documents the case of a 79-year-old woman presenting with encephalopathy and triphasic waves (TWs) due to pregabalin (PGB) intoxication. For the two years prior to admission, she had taken PGB to treat post-herpetic neuralgia. Brain MRI revealed mild leukoaraiosis and cortical atrophy. Electroencephalography showed continuous frontal-dominant TWs. These TWs were suppressed by intravenous lorazepam, but mental function was not improved. Laboratory tests revealed prerenal azotemia, which may elevate serum PGB and cause toxic encephalopathy with TWs. After fluid therapy and discontinuation of PGB, mental status recovered completely and TWs disappeared. I conclude that PGB intoxication due to deficient renal clearance can cause a reversible encephalopathy with TWs.

Pregabalin-associated acute psychosis and epileptiform EEG-changes

Pregabalin is a novel anticonvulsive and analgesic drug that has been marketed in Europe for more than a year. The typical side effects are dizziness, somnolence and weight gain. We present a patient who, after unintended rapid up-titration of pregabalin, experienced psychotic symptoms associated with rhythmic EEG-changes resolving completely after discontinuation of pregabalin and benzodiazepine administration.