pregabalin and Weight-Gain

Weight gain caused by antiepileptic drugs (AEDs) constitutes a serious problem in the management of people with epilepsy. AEDs associated with weight gain include sodium valproate, pregabalin and vigabatrin. Excessive weight gain can lead to non-compliance with treatment and to an exacerbation of obesity-related conditions. The mechanisms by which AEDs cause weight gain are not fully understood. It is likely that weight change induced by some AEDs has a genetic underpinning, and recent developments in DNA sequencing technology should speed the understanding, prediction and thus prevention of serious weight change associated with AEDs. This review focuses on the biology of obesity in the context of AEDs. Future directions in the investigations of the mechanism of weight change associated with these drugs and the use of such knowledge in tailoring the treatment of specific patient groups are explored.

Topics: Animals; Anticonvulsants; Epilepsy; gamma-Aminobutyric Acid; Genetic Predisposition to Disease; Humans; Medication Adherence; Obesity; Pregabalin; Sequence Analysis, DNA; Valproic Acid; Vigabatrin; Weight Gain

Pregabalin is used in the treatment of postherpetic neuralgia, diabetic neuropathic pain, partial seizures, anxiety disorders and fibromyalgia. Recognized adverse effects associated with its use include cognitive impairment, somnolence and dizziness. Heart failure associated with pregabalin has been described, however the strength of this association has not been well characterized. To examine this further, we will conduct a systematic review of the risk of heart failure and edema associated with use of pregabalin.. We will include all studies (experimental, quasi-experimental, observational, case series/reports, drug regulatory reports) that examine the use of pregabalin compared to placebo, gabapentin or conventional care. Our primary outcome is heart failure and the secondary outcomes include edema and weight gain. We will search electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials), and grey literature sources (trial registries, conference abstracts) to identify relevant studies. To ensure literature saturation, we will contact drug manufacturers, conduct forward citation searching, and scan the reference lists of key articles and included studies. We will not restrict inclusion by language or publication status.Two reviewers will screen citations (titles and abstracts) and full-text articles, conduct data abstraction, and appraise risk of bias. Random-effects meta-analysis will be conducted if the studies are deemed heterogeneous in terms of clinical, statistical and methodological factors but still suitable for meta-analysis.. The results of this review will assist physicians to better appreciate pregabalin's risk for edema or congestive heart failure and will be pertinent to the thousands of patients worldwide who are administered this medication.Our protocol was registered in the PROSPERO database (CRD42012002948).

Topics: Edema; gamma-Aminobutyric Acid; Heart Failure; Humans; Outcome Assessment, Health Care; Pregabalin; Research Design; Review Literature as Topic; Risk; Weight Gain

We examined patterns of weight change among patients treated with pregabalin for up to 1 year.. Patients with ≥1 pre-treatment weight measurement, ≥2 measurements in Period 1 (day 2-56), and ≥2 during Period 2 (day 57-356) were identified from pooled data of 106 studies including 43,525 patients. Seven patterns were developed and used for exploratory 'change point' analyses (day on-treatment when weight-change trend changed from initial trajectory) and to assess patterns of weight change by baseline weight/body mass index (BMI).. A total of 3187 patients (from 41 studies) were eligible. 98.9% of patients were described by three of the seven patterns. The majority of patients (2607/3187 [81.8%]) remained within ±7% of baseline weight ('Pattern 4'). Fewer patients (463/3187 [14.5%]) were 'delayed weight gainers' (exceeded 7% weight gain in Period 2 but not Period 1 ['Pattern 6']), fewer still (82/3187 [2.6%]) were 'early weight gainers' (exceeded ≥7% baseline weight in Period 1 and remained above 7% or continued to gain weight in Period 2 ['Pattern 7']). Overall weight gainers (Patterns 6, 7) experienced 1-year weight gain (median [% change]) of +6.20 kg [+9.12%] and 5.46 kg [+13.9%] vs. 2.22 kg [+2.10%] for non-weight gainers (Pattern 4). Average baseline weight/BMI was lower for weight gainers (Patterns 6, 7) versus other patterns. Early weight gainers (Pattern 7) had change point day at day 40 versus day 54 for Pattern 4 and day 69 for Pattern 6. Use of concomitant medications and influence of comorbid conditions on weight should be considered as inherent variables when interpreting the study.. The majority of patients treated with pregabalin (150-600 mg/day) for 1 year maintained weight within ±7% baseline weight. One in six patients gained ≥7% weight from baseline, and generally exceeded 7%, 2-12 months after treatment onset.

Topics: Adult; Aged; Anticonvulsants; Body Weight; Comprehension; Diabetic Neuropathies; Epilepsies, Partial; Female; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Neuralgia, Postherpetic; Pregabalin; Weight Gain

This study assessed the comparative efficacy of pregabalin for refractory partial seizures.. Four-hundred and thirty-four patients with partial seizures were randomized to pregabalin, lamotrigine, or placebo as adjunctive therapy for 17 weeks of double-blind treatment. In phase I (11 weeks), pregabalin was titrated over 1 week and lamotrigine over 5 weeks to fixed dosages of 300mg/day for both. In phase II (6 weeks), patients not yet seizure-free were increased to pregabalin 600mg/day or lamotrigine 400mg/day.. During phase I, there was a nonsignificant trend toward a greater reduction in seizures with pregabalin versus placebo and lamotrigine. Across the 17 weeks of treatment, pregabalin showed a median percentage reduction from baseline in seizure frequency of -20.0% (p=.001) versus placebo, and -9.7% (p=.080) versus lamotrigine. The responder rate (> or =50% reduction in seizure frequency) for pregabalin exceeded that of placebo (36% vs 21%; p=.007) and lamotrigine (36% vs 24%; p=.04). Adverse events were consistent with the known safety profiles of pregabalin and lamotrigine.. Pregabalin was demonstrated to be noninferior to lamotrigine in the treatment of refractory partial seizures. Overall conclusions were complicated by an unusually large and heterogeneous placebo response.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Dizziness; Double-Blind Method; Epilepsies, Partial; Female; gamma-Aminobutyric Acid; Humans; Lamotrigine; Male; Middle Aged; Placebo Effect; Pregabalin; Seizures; Triazines; Weight Gain; Young Adult

To evaluate bodyweight gain during pregabalin therapy for epilepsy and the utility of a short counseling program to prevent this side effect.. Randomized controlled trial on the effects of extended versus standard patient counseling on the risk of bodyweight gain with 3- and 6-month follow-up including a consecutive sample of adult outpatients with epilepsy eligible for pregabalin add-on treatment (N=98).. The seizure response rate was about 30%, the seizure freedom rate was 5% at the 6-month follow-up (intent-to-treat sample, N=98). The median bodyweight gain for the according-to-protocol sample (N=62) was 4.0 kg with no effect of extended counseling. Bodyweight gain was correlated with number of anticonvulsant drugs (r=.32, p<.05).. Pregabalin treatment is associated with a high risk for bodyweight gain which in part depends on total anticonvulsant drug load. This side effect cannot be prevented by extended patient counseling within a standard clinical setting.

Topics: Adult; Anticonvulsants; Body Mass Index; Counseling; Diet; Epilepsy; Exercise; Female; Follow-Up Studies; gamma-Aminobutyric Acid; Humans; Male; Pregabalin; Risk; Seizures; Surveys and Questionnaires; Treatment Outcome; Weight Gain

We assessed the efficacy and safety of a flexible-dose pregabalin regimen in patients with diabetic peripheral neuropathy (DPN) or postherpetic neuralgia (PHN) under clinical practice conditions. Further, the trial investigated the correlation of unspecific measures of change (patient and physician global impression of change, PGIC and CGIC) and specific measures of morbidity. The primary outcomes of this prospective, open-label, non-controlled study were the correlation between global status (PGIC and CGIC) and changes in pain, sleep, and anxiety scores as assessed on numerical or visual rating scales. A total of 217 outpatients were included in 53 centres. The most frequently used dosing regimen involved a starting dose of 150mg/d and dose escalation to 300mg/d after one week (mean: 301mg/d, administered in two doses). The significant changes on pain, sleep and anxiety scales (-40%, -43%, -42%) between baseline and study end after 4-week pregabalin treatment were paralleled by the changes in ratings in both the PGIC and CGIC. The correlation with both PGIC and CGIC was 0.60 for pain, 0.51 for sleep and 0.20 or 0.13 for the correlation of anxiety with PGIC and CGIC, respectively. All correlations with exception of the pair CGIC/anxiety reached statistical significance. In conclusion, pregabalin in a flexible-dose regimen improved pain, sleep, anxiety and general state, and was well tolerated. The efficacy and safety profile of pregabalin was consistent with the data from the controlled clinical trials. The PGIC and CGIC and the specific pain and sleep scores, but not the anxiety score were generally well correlated but not synonymous.

Topics: Adolescent; Adult; Aged; Anxiety; Diabetic Neuropathies; Dizziness; Dose-Response Relationship, Drug; Drug Administration Schedule; Edema; Fatigue; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Neuralgia; Neuralgia, Postherpetic; Pain Measurement; Patient Satisfaction; Pregabalin; Prospective Studies; Sleep Disorders, Intrinsic; Weight Gain

Pregabalin is a novel compound in development for the treatment of anxiety disorders. The safety and efficacy of pregabalin for the treatment of social anxiety disorder was evaluated in a double-blind, multicenter clinical trial in which 135 patients were randomized to 10 weeks of double-blind treatment with either pregabalin 150 mg/d. pregabalin 600 mg/d, or placebo. The primary efficacy parameter was change from baseline to end point in the Liebowitz Social Anxiety Scale (LSAS) total score. Safety was assessed through clinical and laboratory monitoring, and recording spontaneously reported adverse events. Ninety-four patients (70%) completed the 11-week double-blind treatment phase. LSAS total score was significantly decreased by pregabalin 600 mg/d treatment compared with placebo (P = 0.024, analysis of covariance). Significant differences (P < or = 0.05) between pregabalin 600 mg/d and placebo were seen on several secondary measures including the LSAS subscales of total fear, total avoidance, social fear, and social avoidance, and the Brief Social Phobia Scale fear subscale. Pregabalin 150 mg/d was not significantly better than placebo on any measures. Somnolence and dizziness were the most frequently occurring adverse events among patients receiving pregabalin 600 mg/d. In conclusion, pregabalin 600 mg/d was an effective and well-tolerated treatment of social anxiety disorder.

Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Anxiety; Double-Blind Method; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pregabalin; Psychiatric Status Rating Scales; Social Behavior Disorders; Weight Gain

Medication-induced weight gain can be frustrating to patients and health care providers. Drug-induced weight gain is a profound side effect of numerous commonly used medications. The present study aimed to investigate FAERS reports about drug-induced weight gain in the last ten years. Using the US FDA Adverse Event Reporting System (FAERS) between 2012 and 2021, a retrospective, descriptive analysis was conducted to analyze the major reported Adverse Events about weight gain. During the last ten years, 137370 reports were submitted to FAERS about drug-induced weight gain. The most common drugs that are reported by the patients and that are associated with weight gain were risperidone (11.55%), adalimumab (3.94%), pregabalin (3.86%), aripiprazole (3.1%), etanercept (2.72%), and prednisone (2.70%). In conclusion, the present study showed that drug-induced weight gain is a common side effect of several medications frequently used to treat chronic diseases. Healthcare providers should educate their patients about the medicines that may cause weight gain.

Topics: Adalimumab; Adverse Drug Reaction Reporting Systems; Aripiprazole; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Etanercept; Humans; Prednisone; Pregabalin; Retrospective Studies; Risperidone; United States; Weight Gain

Pregabalin is a commonly used therapy currently recommended as first-line treatment for a number of neuropathic pain (NeP) conditions. Since licensure, a number of clinical trials of pregabalin in different NeP conditions have been completed from which additional data on safety and tolerability can be drawn. In this analysis, patient-level data from 31 randomized clinical trials of pregabalin in peripheral NeP sponsored by Pfizer were pooled and assessed for incidence of adverse events (AEs). Incidence by age, disease condition, and race, together with risk differences and time to onset and resolution of AEs, was assessed. In total, 7,510 patients were included: 4,884 on pregabalin (representing 805 patient-years treatment) and 2,626 on placebo. Pregabalin vs. placebo risk analysis identified 9 AEs with a risk difference, for which the lower limit of the 95% confidence interval (CI) was > 1%: dizziness (risk difference [95% CI]: (17.0 [15.4 to 18.6]), somnolence (10.8 [9.5 to 12.1]), peripheral edema (5.4 [4.3 to 6.4]), weight increase (4.7 [3.9 to 5.5]), dry mouth (2.9 [2.1 to 3.8]), constipation (2.3 [1.5 to 3.2]), blurred vision (2.2 [1.6 to 2.9]), balance disorder (2.0 [1.5 to 2.5]), and euphoric mood (1.6 [1.2 to 2.0]). The most common AEs, dizziness and somnolence, typically emerged within the first 1 to 2 weeks of treatment and resolved 1 to 2 weeks later, without resulting in cessation of treatment. The data from this review provide information, indicating which AEs may be expected in patients treated with pregabalin, and suggest that careful dose titration to the highest tolerable dose is the most appropriate approach in clinical practice.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics; Case-Control Studies; Constipation; Disorders of Excessive Somnolence; Dizziness; Edema; Female; Humans; Male; Middle Aged; Mood Disorders; Neuralgia; Postural Balance; Pregabalin; Sensation Disorders; Vision Disorders; Weight Gain; Young Adult

Cosmetic side effects (CSEs) such as weight gain and alopecia are common, undesirable effects associated with several AEDs. The objective of the study was to compare the CSE profiles in a large specialty practice-based sample of patients taking both older and newer AEDs.. As part of the Columbia and Yale AED Database Project, we reviewed patient records including demographics, medical history, AED use, and side effects for 1903 adult patients (≥16years of age) newly started on an AED. Cosmetic side effects were determined by patient or physician report in the medical record and included acne, gingival hyperplasia, hair loss, hirsutism, and weight gain. We compared the overall rate of CSEs and intolerable CSEs (ICSEs-CSEs that led to dosage reduction or discontinuation) between different AEDs in both monotherapy and polytherapy.. Overall, CSEs occurred in 110/1903 (5.8%) patients and led to intolerability in 70/1903 (3.7%) patients. Weight gain was the most commonly reported CSE (68/1903, 3.6%) and led to intolerability in 63 (3.3%) patients. Alopecia was the second most common patient-reported CSE (36/1903, 1.9%) and was intolerable in 33/1903 (1.7%) patients. Risk factors for CSEs included female sex (7.0% vs. 4.3% in males; p<0.05) and any prior CSE (37% vs. 2.9% in patients without prior CSE; p<0.001). Significantly more CSEs were attributed to valproic acid (59/270; 21.9%; p<0.001) and pregabalin (14/143; 9.8%; p<0.001) than to all other AEDs. Significantly less CSEs were attributed to levetiracetam (7/524; 1.3%; p=0.002). Weight gain was most frequently associated with valproic acid (35/270; 13.0%; p<0.001) and pregabalin (12/143; 8.4%; p<0.001). Hair loss was most commonly reported among patients taking valproic acid (24/270; 8.9%; p<0.001). Finally, gingival hyperplasia was most commonly reported in patients taking phenytoin (10/404; 2.5%; p<0.001). Cosmetic side effects leading to dosage change or discontinuation occurred most frequently with pregabalin and valproic acid compared with all other AEDs (13.3 and 5.6% vs. 2.3%; p<0.001). For patients who had been on an AED in monotherapy (n=677), CSEs and ICSEs were still more likely to be attributed to valproic acid (30.2% and 17.1%, respectively) than to any other AED (both p<0.001).. Weight gain and alopecia were the most common patient-reported CSEs in this study, and weight gain was the most likely cosmetic side effect to result in dosage adjustment or medication discontinuation. Particular attention should be paid to pregabalin, phenytoin, and valproic acid when considering cosmetic side effects. Female patients and patients who have had prior CSE(s) to AED(s) were more likely to report CSEs. Knowledge of specific CSE rates for each AED found in this study may be useful in clinical practice.

Topics: Acne Vulgaris; Adult; Alopecia; Anticonvulsants; Epilepsy; Female; gamma-Aminobutyric Acid; Gingival Diseases; Hirsutism; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Pregabalin; Risk Factors; Sex Factors; Valproic Acid; Weight Gain

Topics: Analgesics; Anti-Anxiety Agents; Anticonvulsants; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pregabalin; Weight Gain

Topics: Adult; Alprazolam; Anti-Anxiety Agents; Anticonvulsants; Anxiety Disorders; Benzodiazepines; Comorbidity; Female; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pregabalin; Selective Serotonin Reuptake Inhibitors; Weight Gain

Topics: Aged; Anticonvulsants; Bumetanide; Chronic Disease; gamma-Aminobutyric Acid; Heart Failure; Herpes Zoster; Humans; Male; Neuralgia, Postherpetic; Pregabalin; Treatment Outcome; Weight Gain