scholarly journals Use of clonidine in the management of opiate withdrawal in community patients

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S200-S200
Author(s):  
David Kelsey ◽  
Pierre Hoezoo ◽  
Pardeep Grewal

AimsClonidine has been used to alleviate symptoms of opiate withdrawal. No validated prescribing schedules exist for the use of Clonidine in opiate detoxification in community patients. We have devised a Clonidine prescribing schedule for adult outpatients seeking opiate detoxification.BackgroundOpiate cessation following prolonged use produces a central noradrenergic (NA) response in the locus coeruleus (LC), causing symptoms that can result in reinstatement of use. Pharmacotherapies for withdrawal are thought to work through decreased NA release in the LC by agonising pre-synaptic alpha-2 adrenoceptors. Clonidine has been used since the 1970s. However, it is off-license in the UK, and superseded by Lofexidine. Though both cause hypotension, this is less marked with Lofexidine, which may be anxiolytic and considered better tolerated. Lofexidine is no longer available in the UK. Specialists may need to resort to Clonidine for those seeking opiate detoxification.MethodWe performed a feasibility study with the primary outcome being tolerability of an outpatient clonidine schedule. Patients (n = 7) were aged between 18 and 65 years (mean 32). Six were prescribed buprenorphine as opiate substitution (OST), and one methadone.Exclusion criteria were in keeping with BNF contraindications.An ECG was obtained for each patient before treatment. A urine drug screen and Clinical Opiate Withdrawal Scale were taken to confirm opiate dependence and withdrawal. Patients self-monitored withdrawal using the Subjective Opiate Withdrawal Scale and daily blood pressure measurements. Standard adjuvants for withdrawal were prescribed.A test dose of 100mcg Clonidine was given to assess for hypotension. If tolerant they received 100mcg QDS, reducing over eight days.Patients were contacted by their recovery worker twice during the period.ResultFive of the seven completed the course, two dropped out due to hypotension. No other adverse effects warranting discontinuation were encountered. Patients reported fatigue and light-headedness as their most troublesome side-effects. Of 3 patients who returned SOWS scores, 2 reported decline by 21/64 and 14/64 respectively. One reported an increase of 49/64 over 8 days. 3 of the 5 subjects who completed the course were not abstinent at completion, citing opiate withdrawal symptoms as causative.ConclusionThere is scope for the safe use of clonidine in the community for motivated individuals. Adequate monitoring of heart rate and blood pressure is required. Starting doses at 100mcg QDS appear well tolerated. Prescribers may wish to reduce this over a longer period to encourage completion and improve tolerability. Further research is needed.

Author(s):  
Frederick D. Richard Hobbs ◽  
Gianfranco Gensini ◽  
Giovanni B. John Mancini ◽  
Athanasios J. Manolis ◽  
Beverly Bauer ◽  
...  

Background Single-pill amlodipine/atorvastatin targets the two most common modifiable cardiovascular risk factors, hypertension and dyslipidaemia. We evaluated the clinical utility of this single pill to help patients across Europe and Canada achieve country-specific targets for blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C). Design Two 16-week, open-label studies conducted in 122 study centres across the United Kingdom and Canada (JEWEL 1) and 113 centres across 11 European countries (JEWEL 2). Methods Patients with uncontrolled BP and controlled/uncontrolled LDL-C qualifying for treatment according to local governing guidelines were administered single-pill amlodipine/atorvastatin with appropriate lifestyle modification. Eight dosages of amlodipine/atorvastatin (5/10–10/80 mg) were titrated to achieve country-specific BP and LDL-C targets. The primary outcome was the percentage of patients reaching country-specific BP and LDL-C targets in 16 weeks. Results Among 2245 patients enrolled in the studies (JEWEL 1, n = 1138; JEWEL 2, n = 1107), 62.9% in JEWEL 1 and 50.6% in JEWEL 2 achieved both country-specific BP and LDL-C goals. BP was reduced by 20.4/10.7 and 21.8/12.6 mmHg in JEWEL 1 and JEWEL 2, respectively, and reductions in LDL-C were 0.90 mmol/l (34.8 mg/dl) and 1.09 mmol/l (42.2 mg/dl), respectively. The most common adverse events were peripheral oedema (11.0%), joint swelling (2.9%) and headache (2.9%), of which, only oedema was linked to study treatment. Conclusion Single-pill amlodipine/atorvastatin is an effective and well-tolerated treatment, which in a real-world setting helped more than half of the patients achieve both BP and LDL-C targets as recommended by local guidelines. Although fewer patients met their goals in JEWEL 2 than JEWEL 1, reductions in BP and LDL-C were slightly greater in JEWEL 2, suggesting that the observed differences are likely because of more stringent targets in Europe than in the UK/Canada.


2017 ◽  
Vol 31 (8) ◽  
pp. 1046-1055 ◽  
Author(s):  
Fergus D Law ◽  
Alison M Diaper ◽  
Jan K Melichar ◽  
Simon Coulton ◽  
David J Nutt ◽  
...  

Buprenorphine/naloxone, methadone and lofexidine are medications with utility in the treatment of opiate withdrawal. We report the first randomised controlled trial to compare the effects of these two medications on withdrawal symptoms and outcome during opiate induction/stabilisation and detoxification. A double-blind randomised controlled trial was conducted in an outpatient satellite clinic of a specialist drug service. Eighty opiate dependent individuals meeting DSM-IV criteria for opiate dependence, using ⩽ ½ g heroin smoked/chased or ¼ g heroin injected or ⩽ 30mg methadone, with ⩽ 3 years of opioid dependency, underwent a short-term opiate treatment programme involving induction/stabilisation on methadone 30mg or buprenorphine/naloxone 4mg/1mg, followed by detoxification (where the methadone group was assisted by lofexidine). The main outcome measures were urine drug screens for opiates and withdrawal and craving questionnaires. There were no overall differences in positive urine drug screens and drop-outs during any phase of the study. During induction/stabilisation, withdrawal symptoms subsided more slowly for buprenorphine/naloxone than for methadone, and craving was significantly higher in the buprenorphine/naloxone group ( p<0.05, 95% confidence interval −3.5, −0.38). During detoxification, withdrawal symptoms were significantly greater and the peak of withdrawal was earlier for the methadone/lofexidine group than the buprenorphine/naloxone group ( p<0.01, 95% confidence interval 3.0, 8.3). Methadone/lofexidine and buprenorphine/naloxone had comparable outcomes during rapid outpatient stabilisation and detoxification in low dose opiate users.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jessica Gong ◽  
Katie Harris ◽  
Sanne A. E. Peters ◽  
Mark Woodward

Abstract Background Sex differences in major cardiovascular risk factors for incident (fatal or non-fatal) all-cause dementia were assessed in the UK Biobank. The effects of these risk factors on all-cause dementia were explored by age and socioeconomic status (SES). Methods Cox proportional hazards models were used to estimate hazard ratios (HRs) and women-to-men ratio of HRs (RHR) with 95% confidence intervals (CIs) for systolic blood pressure (SBP) and diastolic blood pressure (DBP), smoking, diabetes, adiposity, stroke, SES and lipids with dementia. Poisson regression was used to estimate the sex-specific incidence rate of dementia for these risk factors. Results 502,226 individuals in midlife (54.4% women, mean age 56.5 years) with no prevalent dementia were included in the analyses. Over 11.8 years (median), 4068 participants (45.9% women) developed dementia. The crude incidence rates were 5.88 [95% CI 5.62–6.16] for women and 8.42 [8.07–8.78] for men, per 10,000 person-years. Sex was associated with the risk of dementia, where the risk was lower in women than men (HR = 0.83 [0.77–0.89]). Current smoking, diabetes, high adiposity, prior stroke and low SES were associated with a greater risk of dementia, similarly in women and men. The relationship between blood pressure (BP) and dementia was U-shaped in men but had a dose-response relationship in women: the HR for SBP per 20 mmHg was 1.08 [1.02–1.13] in women and 0.98 [0.93–1.03] in men. This sex difference was not affected by the use of antihypertensive medication at baseline. The sex difference in the effect of raised BP was consistent for dementia subtypes (vascular dementia and Alzheimer’s disease). Conclusions Several mid-life cardiovascular risk factors were associated with dementia similarly in women and men, but not raised BP. Future bespoke BP-lowering trials are necessary to understand its role in restricting cognitive decline and to clarify any sex difference.


Author(s):  
Tessa Rife ◽  
Christina Tat ◽  
Mahsa Malakootian

Abstract Purpose Guidelines recommend evaluating the risk of opioid-related adverse events prior to initiating opioid therapy. The orthopedic service at San Francisco Veterans Affairs Health Care System (SFVHCS) has not routinely used risk assessment tools such as the Stratification Tool for Opioid Risk Mitigation, prescription drug monitoring program data, and urine drug screening prior to opioid prescribing. A quality improvement project was conducted to evaluate the number of pharmacist-provided opioid risk mitigation recommendations implemented by orthopedic providers for patients who underwent total hip or knee arthroplasty at SFVHCS. Summary A pharmacist-led workflow for completing risk mitigation reviews was developed in collaboration with orthopedic providers, and urine drug screening was added to the preoperative laboratory testing protocol. The following recommendations were communicated via electronic medical record: limit postoperative opioids to a 7- or 14-day supply based on risk of suicide and/or overdose, offer naloxone and a medication disposal bag, and order a urine drug screen if not already completed. Risk reviews were completed for 75 patients. Among 64 patients with 2-month postdischarge data available, 88% (7 of 8) of 7-day and 79% (44 of 56) of 14-day opioid supply recommendations were implemented; 41% (26 of 59) of recommendations to issue a medication disposal bag, 17% (2 of 12) recommendations to order a missing urine drug screen, and 9% (5 of 55) of recommendations to offer naloxone were implemented. Conclusion Pharmacist-performed risk mitigation reviews paired with individualized recommendations led to high rates of orthopedic provider acceptance of limiting postdischarge opioid day supplies for patients who had total hip or knee arthroplasty. Alternative strategies may increase access to naloxone. Future research should examine the impact of risk mitigation tools in reducing prescribing of long-term opioid therapy and adverse events among orthopedic surgical patients.


2006 ◽  
Vol 26 (3) ◽  
pp. 435-439 ◽  
Author(s):  
Craig M Straley ◽  
Eric J Cecil ◽  
Mark P Herriman

Author(s):  
Makoto Hibino ◽  
Yoichiro Otaki ◽  
Elsa Kobeissi ◽  
Han Pan ◽  
Hiromi Hibino ◽  
...  

Background: Hypertension or elevated blood pressure (BP) is an important risk factor for aortic dissection (AD); however, few prospective studies concerning this topic have been published. We investigated the association between hypertension/elevated BP and AD in two cohorts and conducted a meta-analysis of published prospective studies, including these two studies. Methods: We analyzed data from the Japan Specific Health Checkups (J-SHC) Study and UK Biobank, which prospectively followed 534,378 and 502,424 participants, respectively. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association of hypertension/elevated BP with AD incidence in the UK Biobank and AD mortality in the J-SHC Study. In the meta-analysis, summary relative risks (RRs) were calculated using random effects models. A potential nonlinear dose-response relationship between BP and AD was tested using fractional polynomial models, and the best-fitting second-order fractional polynomial regression model was determined. Results: In the J-SHC Study and UK Biobank, there were 84 and 182 ADs during 4- and 9-year follow-up, and the adjusted HRs of AD were 3.57 (95% CI, 2.17-6.11) and 2.68 (95% CI: 1.78-4.04) in hypertensive individuals, 1.33 (95% CI: 1.05-1.68) and 1.27 (95% CI: 1.11-1.48) per 20-mmHg increase in systolic BP (SBP), and 1.67 (95% CI: 1.40-2.00) and 1.66 (95% CI: 1.46-1.89) per 10-mmHg increase in diastolic BP (DBP), respectively. In the meta-analysis, the summary RRs were 3.07 (95% CI 2.15-4.38, I2=76.7%, n=7 studies, 2,818 ADs, 4,563,501 participants) for hypertension and 1.39 (95% CI: 1.16-1.66, I2=47.7%, n=3) and 1.79 (95% CI: 1.51-2.12, I2=57.0%, n=3) per 20-mmHg increase in SBP and per 10-mmHg in DBP, respectively. The AD risk showed a strong, positive dose-response relationship with SBP and even more so with DBP. The risk of AD in the nonlinear dose-response analysis was significant at SBP >132 mmHg and DBP >75 mmHg. Conclusions: Hypertension and elevated SBP and DBP are associated with a high risk of AD. The risk of AD was positively dose-dependent, even within the normal BP range. These findings provide further evidence for the optimization of BP to prevent AD.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Joseph H Breeyear ◽  
Megan M Shuey ◽  
Todd L Edwards ◽  
Jacklyn Hellwege

Hypertension is estimated to affect more than 49.6% of US adults 20 years and older. Of those individuals with hypertension, more than ten million are classified as apparent treatment resistant hypertensive (aTRH). The attributable risk of uncontrolled hypertension was estimated to be 49% for cardiovascular disease and 62% for stroke. We developed a polygenic risk score (PRS) for systolic (SBP) and diastolic (DBP) blood pressure to examine the association between the genetic determinants of blood pressure and aTRH with the goal of identifying high risk individuals. The meta-analyzed transethnic results of Giri et al., Biobank Japan, and Liang et al. were used to generate a PRS with PRS-CS followed by p -value thresholding, and validation in the UK Biobank (n max =341,930). Associations were modeled with logistic regression adjusted for age, age-squared, BMI, sex, and ten principal components of ancestry in BioVU’s transethnic population (n max =37,978), as well as non-Hispanic Black (n max =5,026) and non-Hispanic White (n max =28,545) subsets. The SBP PRS was significantly associated with an increased aTRH risk in the non-Hispanic White subset (1.08 (1.04 - 1.12), p = 0.00037) and transethnic (1.08 (1.04 - 1.13), p = 0.00020) populations, but not the non-Hispanic Black subset. The DBP PRS was not associated with aTRH in any population. Our findings present evidence that individuals with a higher genetic predisposition towards hypertension are at higher risk of aTRH. By integrating polygenic risk scores and clinical covariates in prediction of aTRH, individuals’ therapeutic regimens may be tailored to help maintain stable blood pressures, therefore reducing their risk of comorbidities.


Author(s):  
Young Su Joo ◽  
Hyung Woo Kim ◽  
Ki Heon Nam ◽  
Jee Young Lee ◽  
Tae Ik Chang ◽  
...  

Studies on the longitudinal temporal trend of blood pressure (BP) and its impact on kidney function are scarce. Here, we evaluated the association of dynamic changes in systolic blood pressure (SBP) over time with adverse kidney outcomes. We analyzed 1837 participants from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease). The main exposure was 3 distinct SBP trajectories determined by the latent class mixed model (decreasing, stable, and increasing) using 3 SBP measurements at 0, 6, and 12 months. The primary outcome was CKD progression, defined as a composite of halving estimated glomerular filtration rate from baseline value or onset of end-stage kidney disease. SBP declined from 144 to 120 mm Hg in the decreasing SBP trajectory group and rose from 114 to 136 mm Hg in the increasing trajectory group within 1 year. During 6576 person-years of follow-up (median, 3.7 years), the composite outcome occurred in 521 (28.4%) participants. There were fewer primary outcome events in the decreasing (30.6%) and stable (26.5%) SBP trajectory groups than in the increasing trajectory group (33.0%). In the multivariable-adjusted cause-specific hazards model, increasing SBP trajectory was associated with a 1.28-fold higher risk for adverse kidney outcome compared with stable SBP trajectory. However, the risk for the primary outcome did not differ between the decreasing and stable SBP trajectory groups. In this longitudinal CKD cohort study, compared with stable SBP trajectory, increasing SBP trajectory was associated with higher risk for adverse kidney outcome, whereas decreasing SBP trajectory showed similar risk.


2019 ◽  
Vol 15 (4) ◽  
pp. 255-261 ◽  
Author(s):  
Eungjae Kim ◽  
Brian Patrick Murray ◽  
Maryam Salehi ◽  
Tim P. Moran ◽  
Joseph E. Carpenter ◽  
...  

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