pregabalin and Polyneuropathies

The treatment of polyneuropathy includes symptomatic therapy of sensory, motor and autonomic dysfunctions.. This article provides an overview of the current treatment recommendations for polyneuropathy, focusing on pain.. Current treatment guidelines will be discussed based on a literature research.. Calcium-channel anticonvulsants gabapentin/pregabalin as well as antidepressants duloxetine and amitriptyline are recommended as first line therapeutics. Alternatively, topical therapeutics can be used in the case of localized disorders. In individual cases, opioids or other antidepressants/anticonvulsants may be effective. Pharmacological treatment is often limited due to adverse events, which affect the central nervous system in particular.. In general, treatment for polyneuropathy should follow a multimodal concept and include the treatment of other symptoms. When choosing pain medication, comorbidities, patient's age and adverse events need to be taken into consideration. Phenotype-based stratification may support specialized pain therapy and achieve the best medical treatment.. HINTERGRUND: Die Therapie der Polyneuropathie beinhaltet die symptomatische Behandlung sensibler, motorischer und autonomer Funktionsstörungen. ZIEL: Der Beitrag soll einen Überblick über aktuelle Therapieempfehlungen bei Polyneuropathie geben. Der Fokus liegt dabei auf der Schmerztherapie.. Basierend auf einer Literaturrecherche werden die aktuellen Empfehlungen zur Therapie diskutiert.. Mittel der ersten Wahl zur Therapie von Schmerzen bei Polyneuropathie sind die an Kalziumkanälen ansetzenden Antikonvulsiva Gabapentin und Pregabalin sowie die Antidepressiva Amitriptylin und Duloxetin. Alternativ können bei lokalisierten Beschwerden topische Therapeutika eingesetzt werden. In Einzelfällen kann der Einsatz von Opioiden sowie anderen Antidepressiva und Antikonvulsiva erwogen werden. Limitiert wird die Therapie im Allgemeinen durch Nebenwirkungen vor allem zentralnervöser Art.. Generell sollte die Therapie multimodal erfolgen und die Behandlung weiterer Beschwerden umfassen. Bei der Auswahl der Schmerzmedikation sollten Komorbiditäten, Patientenalter und Nebenwirkungen berücksichtigt werden. Eine Stratifizierung der Patienten anhand des Phänotyps könnte dabei helfen, das bestmögliche Therapieansprechen zu erzielen.

Topics: Amitriptyline; Analgesics; Anticonvulsants; Antidepressive Agents; Calcium Channel Blockers; Humans; Neuralgia; Polyneuropathies; Pregabalin

Cryptogenic sensory polyneuropathy (CSPN) is a common generalized slowly progressive neuropathy, second in prevalence only to diabetic neuropathy. Most patients with CSPN have significant pain. Many medications have been tried for pain reduction in CSPN, including antiepileptics, antidepressants, and sodium channel blockers. There are no comparative studies that identify the most effective medication for pain reduction in CSPN.. To determine which medication (pregabalin, duloxetine, nortriptyline, or mexiletine) is most effective for reducing neuropathic pain and best tolerated in patients with CSPN.. From December 1, 2014, through October 20, 2017, a bayesian adaptive, open-label randomized clinical comparative effectiveness study of pain in 402 participants with CSPN was conducted at 40 neurology care clinics. The trial included response adaptive randomization. Participants were patients with CSPN who were 30 years or older, with a pain score of 4 or greater on a numerical rating scale (range, 0-10, with higher scores indicating a higher level of pain). Participant allocation to 1 of 4 drug groups used the utility function and treatment's sample size for response adaptation randomization. At each interim analysis, a decision was made to continue enrolling (up to 400 participants) or stop the whole trial for success (80% power). Patient engagement was maintained throughout the trial, which helped guide the study and identify ways to communicate and disseminate information. Analysis was performed from December 11, 2015, to January 19, 2018.. Participants were randomized to receive nortriptyline (n = 134), duloxetine (n = 126), pregabalin (n = 73), or mexiletine (n = 69).. The primary outcome was a utility function that was a composite of the efficacy (participant reported pain reduction of ≥50% from baseline to week 12) and quit (participants who discontinued medication) rates.. Among the 402 participants (213 men [53.0%]; mean [SD] age, 60.1 [13.4] years; 343 White [85.3%]), the utility function of nortriptyline was 0.81 (95% bayesian credible interval [CrI], 0.69-0.93; 34 of 134 [25.4%] efficacious; and 51 of 134 [38.1%] quit), of duloxetine was 0.80 (95% CrI, 0.68-0.92; 29 of 126 [23.0%] efficacious; and 47 of 126 [37.3%] quit), pregabalin was 0.69 (95% CrI, 0.55-0.84; 11 of 73 [15.1%] efficacious; and 31 of 73 [42.5%] quit), and mexiletine was 0.58 (95% CrI, 0.42-0.75; 14 of 69 [20.3%] efficacious; and 40 of 69 [58.0%] quit). The probability each medication yielded the highest utility was 0.52 for nortriptyline, 0.43 for duloxetine, 0.05 for pregabalin, and 0.00 for mexiletine.. This study found that, although there was no clearly superior medication, nortriptyline and duloxetine outperformed pregabalin and mexiletine when pain reduction and undesirable adverse effects are combined to a single end point.. ClinicalTrials.gov Identifier: NCT02260388.

Topics: Adult; Aged; Analgesics; Bayes Theorem; Comparative Effectiveness Research; Duloxetine Hydrochloride; Female; Humans; Male; Mexiletine; Middle Aged; Neuralgia; Nortriptyline; Pain Management; Polyneuropathies; Pregabalin; Treatment Outcome

The pharmacological treatments for painful polyneuropathy have not changed much for more than a decade, and less than half of the patients obtain adequate pain relief with first line treatments. Therefore, patient-specific factors which could predict drug response are searched for.. We analysed data from four published, randomized, controlled trials of drugs in painful polyneuropathy to see if diabetic etiology and duration of neuropathic pain had an impact on drug efficacy. The studies had a cross-over design, and had nearly similar outcome recordings as well as a thorough baseline registration of symptoms, signs and quantitative sensory testing. 244 patient records of drug effect distributed over treatments with three antidepressants (imipramine, venlafaxine, escitalopram) and two anticonvulsants (pregabalin, oxcarbazepine) were analysed.. Diabetes as etiology of polyneuropathy had no impact on the effect of antidepressants (imipramine, venlafaxine, escitalopram), but there was a significant interaction with treatment effect on anticonvulsants with better effects in diabetics (0.86 NRS points, p = 0.021) with most pronounced interaction for oxcarbazepine (1.47 NRS points, p = 0.032). There was an interaction between duration of neuropathic pain and treatment with antidepressants with better effect with duration less than 3 years (0.62 NRS points, p = 0.036), whereas anticonvulsants tended to work best with duration of pain for more than 3 years.. Despite the small sample size and limited number of drugs included this study suggests that diabetic etiology of polyneuropathy may impact on the efficacy of anticonvulsants, and duration of neuropathic pain may impact on the efficacy of antidepressants.. This study found that duration of pain appears to have an impact on the effect of antidepressants in neuropathic pain and that diabetes as etiology for painful polyneuropathy appears to influence pain relief obtained with anticonvulsants.

Topics: Adult; Aged; Anticonvulsants; Antidepressive Agents; Carbamazepine; Diabetic Neuropathies; Female; Humans; Imipramine; Male; Middle Aged; Neuralgia; Oxcarbazepine; Polyneuropathies; Pregabalin; Retrospective Studies; Time Factors; Venlafaxine Hydrochloride

The aim of this study was to explore the serum concentration-effect relation for first-line drugs in neuropathic pain and to determine if efficacy could be increased.. Data from a randomized, placebo-controlled, cross-over trial on imipramine, pregabalin, and their combination in painful polyneuropathy were used. Treatment periods were of 4 weeks' duration, outcome was the weekly median of daily pain rated by a 0 to 10 numeric scale, and drug concentrations were determined by high-performance liquid chromatography.. In 47 patients, pain was reduced -1.0 (95% confidence interval [CI], -1.5 to -0.6) by imipramine, -0.4 (95% CI, -0.9 to 0.1) by pregabalin, and -1.6 (95% CI, -2.1 to -1.1) by combination therapy. On monotherapy, there was no difference between responders and nonresponders with respect to concentrations of imipramine (mean, 161 vs. 229 nmol/L, P=0.129) and pregabalin (mean, 9.8 vs. 11.7 μmol/L, P=0.178). There was no correlation between drug concentration and pain reduction for imipramine (r=0.17, P=0.247), whereas there was a marginally, positive correlation for pregabalin (r=0.28, P=0.057). There was no interaction between treatment and concentration classes (imipramine < or ≥100 nmol/L, pregabalin < or ≥10 μmol/L) either for monotherapy or for combination therapy (P=0.161 to 0.797). Isobolographic presentations of reponders with imipramine and pregabalin concentrations during combination therapy did not indicate synergistic interaction.. There were no important relations between drug concentrations and efficacy, or indication of synergistic interaction between the drugs. It was not concluded that treatment can be improved by measurement of drug concentration of pregabalin.

Topics: Adrenergic Uptake Inhibitors; Adult; Aged; Aged, 80 and over; Analgesics; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Female; Humans; Imipramine; Male; Middle Aged; Neuralgia; Pain Measurement; Peripheral Nervous System Agents; Polyneuropathies; Pregabalin; Treatment Outcome

The objective of these studies was to assess the efficacy and safety of pregabalin in the treatment of human immunodeficiency virus (HIV)-associated neuropathic pain. Patients with HIV-associated distal sensory polyneuropathy (DSP) were randomized to treatment with flexible-dose pregabalin (150-600 mg/day) or placebo for 17 weeks in a single-blind, placebo lead-in, randomized, double-blind, parallel-group, placebo-controlled multinational trial. The primary efficacy outcome was the change in mean pain score on an 11-point numeric rating scale (NRS) from baseline to study endpoint. Participants who completed this trial were invited to participate in a 6-month open-label extension study with pregabalin. Of the 377 patients enrolled in the randomized controlled trial (pregabalin, n=183; placebo, n=194), 68.4% completed treatment. In the open-label extension, 217 patients were treated and 59.4% completed treatment. Both studies were terminated by the sponsor after a preplanned interim analysis indicated trial futility. At endpoint, the change from baseline in least-squares mean NRS pain scores in the intent-to-treat population was -2.04 for pregabalin versus -2.11 for placebo (P=.709). There were no significant differences between the pregabalin and placebo groups in the secondary efficacy measures. Incidence of adverse events was lower than seen in previous pregabalin studies. Overall, this trial did not show pregabalin to be more efficacious than placebo in treating HIV-associated DSP. Studies such as these, which fail to support their primary hypotheses, may be important in informing the methodology of future trials, especially when novel approaches to limit variability in the control group are included. ClinicalTrials.gov identifiers: NCT01049217 and NCT01145417.

Topics: Adult; Aged; Analgesics; Double-Blind Method; Female; HIV Infections; Humans; Male; Middle Aged; Neuralgia; Pain Measurement; Polyneuropathies; Pregabalin; Single-Blind Method; Treatment Outcome; Young Adult

Entecavir (Baraclude

Topics: Administration, Oral; Antiviral Agents; Brain; Drug Therapy, Combination; Duloxetine Hydrochloride; Glucocorticoids; Guanine; Hepatitis B, Chronic; Humans; Male; Middle Aged; Polyneuropathies; Prednisolone; Pregabalin; Tomography, X-Ray Computed

Topics: Analgesics; Female; HIV Infections; Humans; Male; Neuralgia; Polyneuropathies; Pregabalin

Topics: Adjuvants, Immunologic; Adrenergic Uptake Inhibitors; Amines; Analgesics; Antioxidants; Capsaicin; Cyclohexanecarboxylic Acids; Diabetic Neuropathies; Duloxetine Hydrochloride; Gabapentin; gamma-Aminobutyric Acid; Humans; Polyneuropathies; Pregabalin; Sensory System Agents; Thiamine; Thioctic Acid; Thiophenes