buprenorphine and Weight-Gain

Side effects of medications for opioid use disorder (MOUD) such as weight gain contribute to their stigma. Substantial evidence suggests that women have a more severe side effect profile to MOUD than men, and concerns about weight gain during treatment are prevalent. However, the few studies reporting sex differences in weight gain during treatment show conflicting results and are restricted to methadone. In addition, little is known about possible sex differences in weight gain to buprenorphine, which is the most commonly prescribed MOUD in the United States.. To address these issues, we performed a systematic review and meta-analysis on the few studies reporting longitudinal data on sex differences in body mass index (BMI) gain during methadone treatment (Study 1). In a separate study, we also re-analyzed data from trial CTN-0030 of the National Institute on Drug Abuse Clinical Trial Network (NIDA CTN), which involved a 12-week buprenorphine treatment regimen (Study 2; n = 360; 209 Male, 151 Female).. For Study 1, across all papers reporting longitudinal data (k = 4, n = 362 OUD patients), there were BMI increases that ranged from 2.2 to 5.4 BMI after at least one year of methadone treatment, but there were no significant sex differences in BMI increases (Standardized Mean Difference, Female > Male = 0.352, SE =0.270; 95 % CI = [-0.18 0.88]; p = .193). Study 2 showed no significant differences in weight before and after 12 weeks of buprenorphine treatment nor did it show sex differences in weight change with treatment (β = 2.34, p = .511).. These analyses corroborate evidence of weight gain with methadone treatment but did not observe a sex-based disparity in weight gain with methadone or buprenorphine treatment for OUD.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies; Sex Characteristics; United States; Weight Gain

Buprenorphine is commonly used as (part of) postoperative analgesic treatment with dosage dependent side-effects such as pica behaviour. No strict consensus exists about the optimal dosing interval of buprenorphine, as its duration of action has been described as being in the range of 6-12 h. In this study, dosing intervals of 8 h (thrice-a-day) and 12 h (twice-a-day) for buprenorphine in a multimodal analgesic strategy (concurrent administration of a non-steroidal anti-inflammatory drug) were compared on food intake, weight and side-effects (gnawing on plastic Petri dishes and growth rate, indicative of pica behaviour) in rats. The food intake and weight of both intervals were comparable, as the animals from the twice-a-day group did not lose more weight or consumed less food during the analgesic period. The rats from the thrice-a-day group suffered from more side-effects, as the growth rate was decreased and more plastic was gnawed on. It is recommended to carefully evaluate analgesic and side-effects when using buprenorphine. When side-effects are observed, the possibility of increasing the dosing interval of buprenorphine should be explored. In this study, increasing the dosing interval of buprenorphine in a multimodal analgesic regimen resulted in reduced unwanted side-effects, without increasing weight loss or decreasing food intake. Although this is suggestive of provision of comparable analgesia, future studies including more pain-related readout parameters to assess the effect of the dosing interval on analgesic efficacy are recommended.

Topics: Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Buprenorphine; Drug Therapy, Combination; Electrodes, Implanted; Feeding Behavior; Injections, Subcutaneous; Male; Meloxicam; Neurosurgical Procedures; Pain, Postoperative; Pica; Postoperative Care; Rats; Rats, Wistar; Thiazines; Thiazoles; Time Factors; Weight Gain

Satisfactory pain relief with postoperative extradural bupivacaine increases the amount of breast feeding after Caesarean section. To investigate the effect of extradural buprenorphine, we have evaluated the amount of breast feeding and the gain in infant weight for 11 days after Caesarean section in patients who received continuous extradural bupivacaine with or without buprenorphine. Extradural buprenorphine significantly decreased both measures although there was no significant difference in pain intensity. We suggest that extradural buprenorphine suppressed breast feeding after Caesarean section.

Topics: Analgesia, Epidural; Analgesics, Opioid; Breast Feeding; Bupivacaine; Buprenorphine; Cesarean Section; Feeding Behavior; Female; Humans; Infant, Newborn; Pain, Postoperative; Pregnancy; Weight Gain

Medication treatments for opioid use disorder (MOUD) save lives and improve outcomes for countless individuals. However, data suggest the potential for significant weight gain during methadone treatment and little is known about weight change during buprenorphine treatment. Using Veteran Health Administration administrative data from fiscal year 2017 to fiscal year 2019, two cohorts were created: 1) Veterans diagnosed with opioid use disorder (OUD) taking methadone (N = 1425); and 2) Veterans diagnosed with OUD taking buprenorphine (N = 3756). Linear mixed models were used to analyze weight change during the first MOUD treatment episode in the observation period. Random slopes and intercepts were included in the model to estimate variation in BMI across individuals and time. The data revealed a slight upward trend in BMI over the course of treatment. Specifically, a daily increase of 0.004 for Veterans in methadone treatment and 0.002 for Veterans in buprenorphine treatment was observed. This translates to a gain of about 10 pounds over the course of 1 year of methadone treatment and 5 pounds for 1 year of buprenorphine treatment for a Veteran of average height and weight. The amount of weight gain in methadone treatment is significantly less than other published findings, but nonetheless indicates that assessment and discussions between patients and providers related to weight may be warranted.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; United States; United States Department of Veterans Affairs; Veterans; Weight Gain

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Naloxone; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Weight Gain; Young Adult

It is essential to identify objective and efficient methods of evaluating postoperative pain in rodents. The authors investigated whether postoperative changes in rates of body weight gain could serve as a measure of the efficacy of meloxicam or buprenorphine analgesia in growing rats. Young adult male Lewis rats underwent general endotracheal anesthesia and thoracotomy and were treated postoperatively for 3 d with saline (no analgesia), buprenorphine (six doses of 0.1 mg per kg) or meloxicam (three doses of 1 mg per kg). The authors evaluated rats' daily growth rates for 5 d after surgery and compared them with baseline (preoperative) growth rates. To discriminate between the effects of postoperative pain and other concurrent physiologic effects associated with anesthesia, thoracotomy or analgesia, the authors evaluated weight changes in multiple control groups. Treatment with buprenorphine in the absence of any other procedure or with anesthesia alone significantly affected rats' body weight. Notably, growth rate was maintained at near normal levels in rats treated postoperatively with meloxicam. These findings suggest that growth rate might serve as an efficient index of postoperative pain after major surgical procedures in young adult rats treated with meloxicam but not in rats treated with buprenorphine.

Topics: Analgesia; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Buprenorphine; Intubation, Intratracheal; Meloxicam; Pain, Postoperative; Rats; Rats, Inbred Lew; Thiazines; Thiazoles; Thoracotomy; Weight Gain

Effective postoperative analgesia is essential for improving patient well-being and decreasing morbidity. Historical recommendations of postoperative analgesics have been based on their effectiveness in attenuating a nociceptive response in animals that have not undergone a surgical procedure, potentially leading to over- or underestimation of postoperative analgesia requirements. This study was designed to evaluate the efficacy of four analgesics in a model of postsurgical pain, which involves surgical incision of the plantar aspect of the hindpaw in halothane-anesthetized rats. The hindpaw was selected as the injury site because it permits quantitative assessment of mechanical sensitivity, which increases as a consequence of tissue damage. As the primary endpoints for postoperative recovery, mechanical sensitivity and weight gain were determined for 5 days. Analgesic regimens included buprenorphine (0.025, 0.05, and 0.1 mg/kg subcutaneously [s.c.]; 1 ml/kg), fentanyl (0.01 and 0.1 mg/kg intraperitoneally [i.p.]; 1 ml/kg), flunixin meglumine (1.1 and 2.5 mg/kg, s.c.; 1 ml/kg) and acetaminophen (100 and 300 mg/kg orally; approximately 3 & 10 ml/kg). Drugs were administered once daily on days 0, 1, and 2 postoperatively. Buprenorphine, fentanyl, and flunixin all significantly decreased mechanical sensitivity, but buprenorphine provided the highest degree of analgesia during the postoperative treatment period. However, rats treated with buprenorphine exhibited heightened mechanical sensitivity once treatment was discontinued on day 2. Moreover, buprenorphine also compromised weight gain as compared to that of vehicle-treated animals. These findings suggest that potent nonsteroidal anti-inflammatory agents, such as flunixin, may be useful alternatives to opioid-based agents for the control of acute postoperative pain associated with a minor surgical procedure and highlight the importance of assessing the risk-benefit ratio when selecting analgesics and dosing regimens.

Topics: Acetaminophen; Analgesia; Analgesics; Animals; Biomechanical Phenomena; Buprenorphine; Clonixin; Fentanyl; Hindlimb; Kinetics; Male; Models, Animal; Pain Measurement; Pain, Postoperative; Rats; Rats, Sprague-Dawley; Weight Gain

The developmental effects of exposure to various doses of buprenorphine, methadone, or water during the perinatal period were studied in the rat. Rats were exposed to buprenorphine (0.3, 1.0, or 3.0 mg/kg/day), methadone (9 mg/kg/day), and/or water prenatally, postnatally, or both pre- and postnatally, via maternally implanted osmotic minipumps. Fetal and maternal mortality and morbidity were assessed, as well as the acquisition of several developmental milestones, pup weight gain, precipitated withdrawal, and the antinociceptive effect of morphine. Although perinatal exposure to buprenorphine failed to produce severe maternal and fetal or neonatal mortality, it was associated with a significant amount of perinatal mortality and perturbations of pup development. Pups developed physical dependence to both drugs, as evidenced by the ability of naloxone challenge to precipitate withdrawal. Both drugs induced tolerance to the antinociceptive effects of morphine in the tail-flick test. The effects of buprenorphine varied with the dose used, and the highest dose did not always produce the greatest effect. There were some similarities between the effects of perinatal buprenorphine and perinatal methadone; however, differences were also observed between the effects of the two drugs, which may be related to the different affinities and efficacies of the drugs at different opioid receptor subtypes.

Topics: Animals; Animals, Newborn; Buprenorphine; Drinking; Eating; Female; Growth; Litter Size; Methadone; Narcotics; Pain Measurement; Rats; Rats, Sprague-Dawley; Substance Withdrawal Syndrome; Weight Gain

Severe burns induce a state of immunosuppression, and the inflammatory response after burn injury may play a role in this phenomenon. This study examined the effect of the inflammatory response to endotoxin on burn-induced immunosuppression and oxidative stress. An endotoxin-resistant mouse strain (C3H/HeJ) and a normally responding mouse strain (C3H/HeN) were compared. The mice were separated into three groups of five animals for each experimental day: (1) saline, (2) buprenorphine, and (3) buprenorphine and 20% total body surface area burn. All animals were fed ad libitum. The inflammatory response was studied at 1, 4, 7, 10, and 14 days postburn. Proliferation of activated splenocytes in burn mice was significantly lower on days 7, 10, and 14 for the C3H/HeJ strain and on days 4 and 10 for the C3H/HeN strain. Globally, C3H/HeJ presented stronger immune suppression than C3H/HeN. Oxidative stress parameters (liver malonaldehyde, spleen metabolic activity, and thiol concentrations) were higher in endotoxin-resistant mice than in the control strain. Impairment of the inflammatory response was more pronounced and oxidative stress was greater in endotoxin-resistant burn mice than in normal burn controls. Buprenorphine administration was not related to depression of these immune parameters. The inflammatory response following burn injury may be beneficial to the immune system.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Burns; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Division; Cells, Cultured; Drug Resistance; Eating; Female; Immunophenotyping; Lipopolysaccharides; Malondialdehyde; Mice; Mice, Inbred C3H; Oxidative Stress; Spleen; Sulfhydryl Compounds; Weight Gain

As a routine postoperative treatment, a single dose of buprenorphine was given to rats at a dose of 0.05 mg/kg subcutaneously. However, some rats developed abnormal secretions around the nose and mouth and some animals died 3-5 days after surgery and analgesic treatment. At autopsy a yellow fibrous mass was found in the stomach and intestines. Observations of animals given buprenorphine revealed an abnormal ingestion of bedding material. This caused a disturbance to normal digestion, with gastric distension, weight loss or decreased growth rate, constipation and occasionally death. In this study rats were monitored for 6 days following surgery and analgesic treatment. A comparison of growth rates was made between rats given saline and buprenorphine or nalbuphine and between animals kept on bedding or grid floors for the first 24h after treatment. Of the animals held on bedding, the buprenorphine-treated animals did not lose weight as the other animals did, but had on the other hand a decreased growth rate during the measuring period of 6 days after surgery. When denied access to bedding for the first 24 h after surgery, rats given saline or nalbuphine had a reduced weight gain over the first 24 h, similar to the groups held on bedding. Rats held on grid floors and given buprenorphine continued to gain weight for the first 24 h. From day 3, there was no significant difference between the groups, which all gained weight.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Growth Disorders; Male; Rats; Rats, Sprague-Dawley; Rodent Diseases; Weight Gain

Three doses of buprenorphine (BUP) were administered by osmotic minipump from day 8 of gestation through parturition. In addition to 0.3, 1.0, and 3.0 mg/kg/day of BUP, a vehicle control group received sterile water via minipump and a nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. BUP produced a dose response reduction in maternal water intake and reduced maternal weight gain among the two high dose groups; resorptions and birthweight were unaffected. BUP increased perinatal mortality in the two high dose groups compared with the vehicle controls and produced inconsistent effects on postnatal growth. To examine the effects of BUP on the rest-activity cycle of the offspring, groups of 3 littermates from each of the treated and control groups were tested for an 8 h observation period on electronic activity monitors at 22 and 30 days of age. Unlike previous effects described for prenatally administered methadone, a disruption in the rest-activity cycle was not observed for any of the BUP treated groups.

Topics: Activity Cycles; Animals; Buprenorphine; Dose-Response Relationship, Drug; Drinking; Eating; Female; Maternal Behavior; Motor Activity; Narcotics; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Weight Gain