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      Drug-Induced Peripheral Neuropathy: A Narrative Review

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          Abstract

          Background

          Peripheral neuropathy is a painful condition deriving from many and varied etiologies. Certain medications have been implicated in the iatrogenic development of Drug Induced Peripheral Neuropathy (DIPN) and include chemotherapeutic agents, antimicrobials, cardiovascular drugs, psychotropic, anticonvulsants, among others. This review synthesizes current clinical concepts regarding the mechanism, common inciting medications, and treatment options for drug-induced peripheral neuropathy.

          Methods

          The authors undertook a structured search of bibliographic databases for peer-reviewed research literature using a focused review question and inclusion/exclusion criteria. The most relevant and up to date research was included.

          Results

          Drug-induced peripheral neuropathy is a common and painful condition caused by many different and frequently prescribed medications. Most often, DIPN is seen in chemotherapeutic agents, antimicrobials, cardiovascular drugs, psychotropic, and anticonvulsant drugs. Certain drugs exhibit more consistent neuropathic side effects, such as the chemotherapeutic compounds, but others are more commonly prescribed by a larger proportion of providers, such as the statins. DIPN is more likely to occur in patients with concomitant risk factors such as preexisting neuropathy, diabetes, and associated genetically predisposing diseases. DIPN is often difficult to treat, however medications including duloxetine, and gabapentin are shown to reduce neuropathic pain. Advanced techniques of neuromodulation offer promise though further randomized and controlled studies are needed to confirm efficacy.

          Conclusion

          Awareness of the drugs covered in this review and their potential for adverse neuropathic effect is important for providers caring for patients who report new onset symptoms of pain, paresthesia, or weakness. Prevention of DIPN is especially important because treatment often proves challenging. While many pharmacologic therapies have demonstrated analgesic potential in the pain caused by DIPN, many patients remain refractive to treatment. More studies are needed to elucidate the effectiveness of interventional, neuromodulating therapies.

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          Most cited references57

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          Chemotherapy-Induced Peripheral Neuropathy: A Current Review.

          Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect experienced by patients receiving treatment for cancer. Approximately 30-40% of patients treated with neurotoxic chemotherapy will develop CIPN and there is considerable variability in its severity between patients. It is often sensory-predominant with pain and can lead to long-term morbidity in survivors. The prevalence and burden of CIPN late effects will likely increase as cancer survival rates continue to improve. In this review, we discuss the approach to peripheral neuropathy in patients with cancer and address the clinical phenotypes and pathomechanisms of specific neurotoxic chemotherapeutic agents. This article is protected by copyright. All rights reserved.
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            Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial.

            To evaluate the efficacy and safety of pregabalin in the treatment of postherpetic neuralgia (PHN). The authors conducted a multicenter, parallel-group, double-blind, placebo-controlled, 8-week, randomized clinical trial in PHN, defined as pain for 3 or more months following herpes zoster rash healing. Patients (n = 173) were randomized to treatment with pregabalin or placebo. Patients randomized to pregabalin received either 600 mg/day (creatinine clearance > 60 mL/min) or 300 mg/day (creatinine clearance 30 to 60 mL/min). The primary efficacy measure was the mean of the last seven daily pain ratings. Secondary endpoints included additional pain ratings, sleep interference, quality of life, mood, and patient and clinician ratings of global improvement. Pregabalin-treated patients had greater decreases in pain than patients treated with placebo (endpoint mean scores 3.60 vs 5.29, p = 0.0001). Pain was significantly reduced in the pregabalin-treated patients after the first full day of treatment and throughout the study, and significant improvement on the McGill Pain Questionnaire total, sensory, and affective pain scores was also found. The proportions of patients with >or=30% and >or=50% decreases in mean pain scores were greater in the pregabalin than in the placebo group (63% vs 25% and 50% vs 20%, p = 0.001). Sleep also improved in patients treated with pregabalin compared to placebo (p = 0.0001). Both patients and clinicians were more likely to report global improvement with pregabalin than placebo (p = 0.001). Given the maximal dosage studied, pregabalin had acceptable tolerability compared to placebo despite a greater incidence of side effects, which were generally mild to moderate in intensity. Treatment of PHN with pregabalin is safe, efficacious in relieving pain and sleep interference, and associated with greater global improvement than treatment with placebo.
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              Long-term chemotherapy-induced peripheral neuropathy among breast cancer survivors: prevalence, risk factors, and fall risk.

              Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity associated with chemotherapy, but researchers rarely study its risk factors, fall risk, and prevalence in long-term breast cancer survivors. We aimed to determine CIPN prevalence, risk factors, and association with psychological distress and falls among long-term breast cancer survivors. We conducted Cross-sectional analyses among postmenopausal women with a history of stage I-III breast cancer who received taxane-based chemotherapy. Participants reported neuropathic symptoms of tingling/numbness in hands and/or feet on a 0-10 numerical rating scale. We conducted multivariate logistic regression analyses to evaluate risk factors associated with the presence of CIPN and the relationship between CIPN and anxiety, depression, insomnia, and patient-reported falls. Among 296 participants, 173 (58.4 %) reported CIPN symptoms, 91 (30.7 %) rated their symptoms as mild, and 82 (27.7 %) rated them moderate to severe. Compared with women of normal weight, being obese was associated with increased risk of CIPN (adjusted OR 1.94, 95 % CI: 1.03-3.65). Patients with CIPN reported greater insomnia severity, anxiety, and depression than those without (all p < 0.05). Severity of CIPN was associated with higher rates of falls, with 23.8, 31.9, and 41.5 % in the "no CIPN," "mild," and "moderate-to-severe" groups, respectively, experiencing falls (p = 0.028). The majority of long-term breast cancer survivors who received taxane-based chemotherapy reported CIPN symptoms; obesity was a significant risk factor. Those with CIPN also reported increased psychological distress and falls. Interventions need to target CIPN and comorbid psychological symptoms, and incorporate fall prevention strategies for aging breast cancer survivors.
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                Author and article information

                Journal
                Curr Clin Pharmacol
                Curr Clin Pharmacol
                CCP
                Current Clinical Pharmacology
                Bentham Science Publishers
                1574-8847
                2212-3938
                April 2020
                April 2020
                : 15
                : 1
                : 38-48
                Affiliations
                Harvard Medical School, Beth Israel Deaconess Medical Center, Department of Anesthesia, Critical Care, and Pain Medicine, Boston, , MA, , 02118 , United States; Creighton University School of Medicine-Phoenix Regional Campus, St. Joseph’s Hospital and Medical Center , Phoenix, , AZ, 85013 , United States; Valley Anesthesiology and Pain Consultants, Phoenix, AZ, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, Creighton University School of Medicine , Omaha, , NE , United States
                Author notes
                [* ]Address correspondence to this author at the Beth Israel Deaconess Medical Center, Department of Anesthesiology, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215; Tel: 617-278-8000; E-mail: mjones13@ 123456bidmc.harvard.edu
                Article
                CCP-15-38
                10.2174/1574884714666190121154813
                7365998
                30666914
                44b9a54a-91ff-400b-89eb-e61c2c66c848
                © 2020 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 23 October 2018
                : 03 December 2018
                : 11 January 2019
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                drug induced peripheral neuropathy,chemotherapy,statins,gabapentinoids,pain,paresthesia,weakness

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