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The Cochrane Database of Systematic... Jun 2018This is an update of the original Cochrane Review published in Issue 4, 2011.Attention deficit hyperactivity disorder (ADHD) is the most prevalent of the comorbid... (Review)
Review
BACKGROUND
This is an update of the original Cochrane Review published in Issue 4, 2011.Attention deficit hyperactivity disorder (ADHD) is the most prevalent of the comorbid psychiatric disorders that complicate tic disorders. Medications commonly used to treat ADHD symptoms include stimulants such as methylphenidate and amphetamine; non-stimulants, such as atomoxetine; tricyclic antidepressants; and alpha agonists. Alpha agonists are also used as a treatment for tics. Due to the impact of ADHD symptoms on the child with tic disorder, treatment of ADHD is often of greater priority than the medical management of tics. However, for many decades, clinicians have been reluctant to use stimulants to treat children with ADHD and tics for fear of worsening their tics. OBJECTIVES: To assess the effects of pharmacological treatments for ADHD in children with comorbid tic disorders on symptoms of ADHD and tics.
SEARCH METHODS
In September 2017, we searched CENTRAL, MEDLINE, Embase, and 12 other databases. We also searched two trial registers and contacted experts in the field for any ongoing or unpublished studies.
SELECTION CRITERIA
We included randomized, double-blind, controlled trials of any pharmacological treatment for ADHD used specifically in children with comorbid tic disorders. We included both parallel-group and cross-over study designs.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures of Cochrane, in that two review authors independently selected studies, extracted data using standardized forms, assessed risk of bias, and graded the overall quality of the evidence by using the GRADE approach.
MAIN RESULTS
We included eight randomized controlled trials (four of which were cross-over trials) with 510 participants (443 boys, 67 girls) in this review. Participants in these studies were children with both ADHD and a chronic tic disorder. All studies took place in the USA and ranged from three to 22 weeks in duration. Five of the eight studies were funded by charitable organizations or government agencies, or both. One study was funded by the drug manufacturer. The other two studies did not specify the source of funding. Risk of bias of included studies was low for blinding; low or unclear for random sequence generation, allocation concealment, and attrition bias; and low or high for selective outcome reporting. We were unable to combine any of the studies in a meta-analysis due to important clinical heterogeneity and unit-of-analysis issues.Several of the trials assessed multiple agents. Medications assessed included methylphenidate, clonidine, desipramine, dextroamphetamine, guanfacine, atomoxetine, and deprenyl. There was low-quality evidence for methylphenidate, atomoxetine, and clonidine, and very low-quality evidence for desipramine, dextroamphetamine, guanfacine and deprenyl in the treatment of ADHD in children with tics. All studies, with the exception of a study using deprenyl, reported improvement in symptoms of ADHD. Tic symptoms also improved in children treated with guanfacine, desipramine, methylphenidate, clonidine, and a combination of methylphenidate and clonidine. In one study, tics limited further dosage increases of methylphenidate. High-dose dextroamphetamine appeared to worsen tics in one study, although the length of this study was limited to three weeks. There was appetite suppression or weight loss in association with methylphenidate, dextroamphetamine, atomoxetine, and desipramine. There was insomnia associated with methylphenidate and dextroamphetamine, and sedation associated with clonidine.
AUTHORS' CONCLUSIONS
Following an updated search of potentially relevant studies, we found no new studies that matched our inclusion criteria and thus our conclusions have not changed.Methylphenidate, clonidine, guanfacine, desipramine, and atomoxetine appear to reduce ADHD symptoms in children with tics though the quality of the available evidence was low to very low. Although stimulants have not been shown to worsen tics in most people with tic disorders, they may, nonetheless, exacerbate tics in individual cases. In these instances, treatment with alpha agonists or atomoxetine may be an alternative. Although there is evidence that desipramine may improve tics and ADHD in children, safety concerns will likely continue to limit its use in this population.
Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child, Preschool; Clonidine; Desipramine; Dextroamphetamine; Female; Guanfacine; Humans; Male; Methylphenidate; Randomized Controlled Trials as Topic; Selegiline; Tic Disorders
PubMed: 29944175
DOI: 10.1002/14651858.CD007990.pub3 -
Critical Care (London, England) Jun 2023To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI). (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI).
BACKGROUND
Administration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit.
METHODS
This phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16-64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study.
RESULTS
Dose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups [0.3 days, 95% CI (- 5.4, 5.8), p = 1.0]. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p = 0.012), there were no between-group differences in the secondary outcomes.
CONCLUSION
Despite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI. Trial Registration Number NCT01322048.
Topics: Humans; Propranolol; Clonidine; Pilot Projects; Treatment Outcome; Brain Injuries, Traumatic; Adrenergic Agents
PubMed: 37296432
DOI: 10.1186/s13054-023-04479-6 -
American Journal of Hypertension May 2022There are limited and nonconcordant data on the rapidity and safety of blood pressure response to clonidine in the setting of asymptomatic severe hypertension. We... (Review)
Review
BACKGROUND
There are limited and nonconcordant data on the rapidity and safety of blood pressure response to clonidine in the setting of asymptomatic severe hypertension. We evaluated the blood pressure response to clonidine in hospitalized patients with asymptomatic severe hypertension.
METHODS
We performed a review of hospitalized, noncritically ill patients receiving clonidine within 6 hours of developing asymptomatic severe hypertension (systolic blood pressure [SBP] >180 or diastolic blood pressure [DBP] >110 mm Hg in the absence of acute hypertension-mediated target organ damage). The incidence of mean arterial pressure (MAP) reduction by ≥30% at 4 hours after clonidine was the primary endpoint.
RESULTS
We identified 200 relevant patient encounters (median age 63 years, 48.5% women). Median time to clonidine following asymptomatic severe hypertension was 2.8 hours. A total of 20 (10%) patients had ≥30% MAP reduction within 4 hours after clonidine, and 32 (16%) patients had ≥30% reduction in either SBP, DBP, or MAP. Older age, female sex, and preexisting vascular disease were associated with ≥30% MAP reductions (P < 0.05). Only patient sex and clonidine dose of 0.3 mg were significant in multivariable models. There were 14 adverse events observed within 24 hours of administration of clonidine; most (9) were acute kidney injury. There were no ischemic (myocardial, cerebrovascular) events.
CONCLUSIONS
A substantial minority of hospitalized patients with asymptomatic severe hypertension experience precipitous blood pressure decline with clonidine, and though blood pressure declines more precipitously in women and those receiving higher doses (0.3 mg specifically), the response to clonidine is generally not predictable on clinical grounds.
Topics: Blood Pressure; Clonidine; Female; Humans; Hypertension; Incidence; Male; Middle Aged
PubMed: 35038322
DOI: 10.1093/ajh/hpac004 -
Pharmacology 2016Clonidine, an alpha agonist, formally prescribed in clinical medicine as antihypertensive medication, is currently being used more frequently to address a multitude of... (Review)
Review
Clonidine, an alpha agonist, formally prescribed in clinical medicine as antihypertensive medication, is currently being used more frequently to address a multitude of psychiatric entities. The long-acting formulation is approved by the Food and Drug Administration for use in treating the attention-deficit/hyperactivity disorder. In addition to this only legitimate indication, it has long been used successfully for opiate detoxification, post-traumatic stress disorder and de la Tourette syndrome. Moreover, clonidine helps in the treatment of neuroleptic-induced akathisia, stimulant-induced insomnia and clozapine-induced sialorrhea. It has been tried in treating menopausal syndrome and psychogenic polydipsia. Although the strength of evidence supporting the use of clonidine in such clinical scenarios is highly variable and oscillating, from strong to only flimsy, this overview is intended to shed some light on the clonidine portfolio as a potential and attractive addition to the psychopharmacologic armamentarium.
Topics: Animals; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Clonidine; Humans; Menopause; Opioid-Related Disorders; Psychomotor Agitation; Sialorrhea; Stress Disorders, Post-Traumatic; Tics
PubMed: 27161101
DOI: 10.1159/000446441 -
Critical Care (London, England) Feb 2017This systematic review and meta-analysis investigates the efficacy and safety of clonidine as a sedative in critically ill patients requiring invasive mechanical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This systematic review and meta-analysis investigates the efficacy and safety of clonidine as a sedative in critically ill patients requiring invasive mechanical ventilation.
METHODS
We performed a comprehensive search of MEDLINE, EMBASE, CINAHL and the Cochrane trial registry. We identified RCTs that compared clonidine to any non-clonidine regimen in critically ill patients, excluding neonates, requiring mechanical ventilation. The GRADE method was used to assess certainty of evidence.
RESULTS
We included eight RCTs (n = 642 patients). In seven of the trials clonidine was used for adjunctive rather than stand-alone sedation. There was no difference in the duration of mechanical ventilation (mean difference (MD) 0.05 days, 95% confidence interval (CI) = -0.65 to 0.75, I = 86%, moderate certainty), ICU mortality (relative risk (RR) 0.98, 95% CI = 0.51 to 1.90, I = 0%, low certainty), or ICU length of stay (MD 0.04 days, 95% CI = -0.46 to 0.53, I = 16%, moderate certainty), with clonidine. There was a significant reduction in the total dose of narcotics (standard mean difference (SMD) -0.26, 95% CI = -0.50 to -0.02, I = 0%, moderate certainty) with clonidine use. Clonidine was associated with increased incidence of clinically significant hypotension (RR 3.11, 95% CI = 1.64 to 5.87, I = 0%, moderate certainty).
CONCLUSIONS
Until further RCTs are performed, data remains insufficient to support the routine use of clonidine as a sedative in the mechanically ventilated population. Clonidine may act as a narcotic-sparing agent, albeit with an increased risk of clinically significant hypotension.
Topics: Clonidine; Critical Illness; Humans; Hypnotics and Sedatives; Hypotension; Intensive Care Units; Length of Stay; Respiration, Artificial
PubMed: 28330506
DOI: 10.1186/s13054-017-1610-8 -
The Cochrane Database of Systematic... May 2016Withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment.
OBJECTIVES
To assess the effectiveness of interventions involving the use of alpha2-adrenergic agonists compared with placebo, reducing doses of methadone, symptomatic medications, or an alpha2-adrenergic agonist regimen different to the experimental intervention, for the management of the acute phase of opioid withdrawal. Outcomes included the withdrawal syndrome experienced, duration of treatment, occurrence of adverse effects, and completion of treatment.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1946 to November week 2, 2015), EMBASE (January 1985 to November week 2, 2015), PsycINFO (1806 to November week 2, 2015), Web of Science, and reference lists of articles.
SELECTION CRITERIA
Randomised controlled trials comparing alpha2-adrenergic agonists (clonidine, lofexidine, guanfacine, tizanidine) with reducing doses of methadone, symptomatic medications or placebo, or comparing different alpha2-adrenergic agonists to modify the signs and symptoms of withdrawal in participants who were opioid dependent.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We included 26 randomised controlled trials involving 1728 participants. Six studies compared an alpha2-adrenergic agonist with placebo, 12 with reducing doses of methadone, four with symptomatic medications, and five compared different alpha2-adrenergic agonists. We assessed 10 studies as having a high risk of bias in at least one of the methodological domains that were considered.We found moderate-quality evidence that alpha2-adrenergic agonists were more effective than placebo in ameliorating withdrawal in terms of the likelihood of severe withdrawal (risk ratio (RR) 0.32, 95% confidence interval (CI) 0.18 to 0.57; 3 studies; 148 participants). We found moderate-quality evidence that completion of treatment was significantly more likely with alpha2-adrenergic agonists compared with placebo (RR 1.95, 95% CI 1.34 to 2.84; 3 studies; 148 participants).Peak withdrawal severity may be greater with alpha2-adrenergic agonists than with reducing doses of methadone, as measured by the likelihood of severe withdrawal (RR 1.18, 95% CI 0.81 to 1.73; 5 studies; 340 participants; low quality), and peak withdrawal score (standardised mean difference (SMD) 0.22, 95% CI -0.02 to 0.46; 2 studies; 263 participants; moderate quality), but these differences were not significant and there is no significant difference in severity when considered over the entire duration of the withdrawal episode (SMD 0.13, 95% CI -0.24 to 0.49; 3 studies; 119 participants; moderate quality). The signs and symptoms of withdrawal occurred and resolved earlier with alpha2-adrenergic agonists. The duration of treatment was significantly longer with reducing doses of methadone (SMD -1.07, 95% CI -1.31 to -0.83; 3 studies; 310 participants; low quality). Hypotensive or other adverse effects were significantly more likely with alpha2-adrenergic agonists (RR 1.92, 95% CI 1.19 to 3.10; 6 studies; 464 participants; low quality), but there was no significant difference in rates of completion of withdrawal treatment (RR 0.85, 95% CI 0.69 to 1.05; 9 studies; 659 participants; low quality).There were insufficient data for quantitative comparison of different alpha2-adrenergic agonists. Available data suggest that lofexidine does not reduce blood pressure to the same extent as clonidine, but is otherwise similar to clonidine.
AUTHORS' CONCLUSIONS
Clonidine and lofexidine are more effective than placebo for the management of withdrawal from heroin or methadone. We detected no significant difference in efficacy between treatment regimens based on clonidine or lofexidine and those based on reducing doses of methadone over a period of around 10 days, but methadone was associated with fewer adverse effects than clonidine, and lofexidine has a better safety profile than clonidine.
Topics: Acute Disease; Adrenergic alpha-2 Receptor Agonists; Clonidine; Controlled Clinical Trials as Topic; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome
PubMed: 27140827
DOI: 10.1002/14651858.CD002024.pub5 -
European Journal of Hospital Pharmacy :... Mar 2023Clonidine is an alpha-2 adrenoreceptor agonist and is frequently combined with opioids (ie, morphine hydrochloride (HCl)) for the management of chronic pain. In...
OBJECTIVES
Clonidine is an alpha-2 adrenoreceptor agonist and is frequently combined with opioids (ie, morphine hydrochloride (HCl)) for the management of chronic pain. In palliative care, the administration of clonidine and morphine HCl is recommended in case of tolerance effect. This study aimed to evaluate the physical and chemical stability of this admixture at high and low concentrations in 14 and 48 mL polypropylene syringes.
METHODS
The stability of a low concentration admixture of clonidine (Catapressan 0.15 mg/mL, Boehringer Ingelheim, Germany) and morphine (morphine HCl 40 mg/mL, Sterop, Belgium) at 0.003 and 0.417 mg/mL, respectively, was evaluated by using five polypropylene syringes of 48 mL. The high concentration admixture consisted of 0.032 mg/mL clonidine and 4.286 mg/mL morphine HCl and was evaluated by using five polypropylene syringes of 14 mL. All syringes were stored for 30 days at 5°C±3°C. Periodic samples were visually and microscopically examined to observe any particle appearance or colour change. pH and absorbance at three wavelengths (350, 410 and 550 nm) were monitored. The concentrations were measured by ultra-high performance liquid chromatography-photodiode array detection.
RESULTS
During the 30 days, there was no change in colour or appearance of opacity, turbidity or precipitation, and pH remained stable. The low and high concentration admixtures were considered chemically stable since the lower limit of the 90% CI remained superior to 90% of the initial concentration. Concentration measurements showed that the degradation rate was less than 1% over 10 days for each component in both admixtures.
CONCLUSIONS
The admixture of clonidine and morphine HCl at low and high concentrations in polypropylene syringes appeared to be physically and chemically stable throughout the study period of 30 days at 5°C±3°C. In conclusion, the admixture can be prepared in advance under aseptic conditions by a centralised intravenous additive service in the pharmacy department.
Topics: Humans; Clonidine; Polypropylenes; Syringes; Analgesics, Opioid; Morphine Derivatives; Drug Stability
PubMed: 34758972
DOI: 10.1136/ejhpharm-2021-002940 -
BMC Research Notes May 2021The naked mole rat (NMR) (Heterocephalus glaber) is increasingly considered an important biomedical research model for various conditions like hypoxic brain injury,...
OBJECTIVE
The naked mole rat (NMR) (Heterocephalus glaber) is increasingly considered an important biomedical research model for various conditions like hypoxic brain injury, cancer and nociception. This study was designed to investigate the effects of clonidine and yohimbine, an alpha-2 (α) adrenoceptor agonist and antagonist respectively in the tail flick and hot plate tests.
RESULTS
A significant difference in tail flick latency was noted between saline control and 30 µg/kg clonidine, which was reduced after administration of 30 µg/kg yohimbine. A significant difference in hot plate latency was also noted between saline control and 30 µg/kg clodinine during the periods 30, 45, 60, 75 and 90 min after administration, and between saline control and 10 µg/kg clonidine during 30 min after administration. The hot plate latency by 30 µg/kg clonidine was also reduced by 30 µg/kg yohimbine during 30 min after administration. Since the tail-flick and hot plate tests mediate the effects at spinal and supraspinal levels respectively, the present study indicates the presence and involvement of noradrenergic receptors in thermal antinociception at spinal and supraspinal levels of the NMR, similar to what has been found in other mammals.
Topics: Analgesics; Animals; Clonidine; Mole Rats; Yohimbine
PubMed: 34001271
DOI: 10.1186/s13104-021-05607-7 -
The Primary Care Companion For CNS... Aug 2016To review currently available formulations and emphasize unmet needs in the pharmacologic management of attention-deficit/hyperactivity disorder (ADHD). (Review)
Review
OBJECTIVE
To review currently available formulations and emphasize unmet needs in the pharmacologic management of attention-deficit/hyperactivity disorder (ADHD).
DATA SOURCES
Publications and clinical trials were identified through PubMed and ClinicalTrials.gov, respectively. A Web-based search identified prescribing information for approved agents for treating ADHD, along with relevant guidelines and diagnostic criteria.
STUDY SELECTION
The following search terms were used: (1) ADHD or attention-deficit/hyperactivity disorder or ADD or attention deficit hyperactivity disorder and/or (2) amphetamine or methylphenidate or atomoxetine or guanfacine or clonidine. Additional searches were performed using product brand names, and clinical trial was applied as a filter. Relevant studies were only included if published in English-language peer-reviewed journals and if involved agents were currently available (or pursuing approval) in the United States. Reviews of literature prior to 2005 and from 2005 to 2008 have been published previously; therefore, the present search focused on studies published from January 2009 through May 2016. In addition, reference lists of review articles and relevant studies were also examined to help identify additional studies.
DATA EXTRACTION
A total of 578 publications were identified from the PubMed search, from which 426 publications were initially excluded based on review of the title and abstract. Reasons for exclusion included a focus on comorbid disorders, specific subpopulations, endpoints unrelated to improving ADHD symptomatology (eg, executive function, cognition, substance use), or quality of life measures. A more thorough assessment of the remaining citations, including publications and prescribing information, produced the final 219.
RESULTS
Pharmacotherapy with stimulant and nonstimulant options is the most common approach for treating ADHD in adults and children. Stimulants are mostly formulated as either tablets or capsules; however, the newer generation includes transdermal patches, oral suspensions (liquids), chewable tablets, and orally disintegrating tablets. Nonstimulants are available in oral capsule (atomoxetine) and tablet (guanfacine and clonidine) formulations.
CONCLUSIONS
Despite the broad range of treatment options currently available, nonadherence remains a significant problem in ADHD. While evidence is currently lacking, the availability of new formulations may improve adherence.
Topics: Adrenergic Agents; Amphetamines; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Clinical Trials as Topic; Clonidine; Guanfacine; Humans; Methylphenidate; Treatment Outcome
PubMed: 27828696
DOI: 10.4088/PCC.16r01979 -
Revista Da Associacao Medica Brasileira... Jul 2022This study aimed to assess the clonidine infusion rate in the first 6 h, as maintenance dose (first 24 h), and in the pre-extubation period (last 24 h), as well as the...
OBJECTIVE
This study aimed to assess the clonidine infusion rate in the first 6 h, as maintenance dose (first 24 h), and in the pre-extubation period (last 24 h), as well as the cumulative dose of other sedatives and the hemodynamic response.
METHODS
This is a retrospective cohort study.
RESULTS
Children up to the age of 2 years who were admitted to the pediatric intensive care unit of a tertiary referral hospital in the south region of Brazil, between January 2017 and December 2018, were submitted to mechanical ventilation, and received continuous clonidine infusions were included in the study. The initial, maintenance, and pre-extubation doses of clonidine; the vasoactive-inotropic score; heart rate; and systolic and diastolic blood pressure of the study participants were assessed. A total of 66 patients with a median age of 4 months who were receiving clonidine infusions were included. The main indications for mechanical ventilation were acute viral bronchiolitis (56%) and pneumonia associated with acute respiratory distress syndrome (15%). The median of clonidine infusion in the first 6 h (66 patients) was 0.53 μg/kg/h (IQR 0.49-0.88), followed by 0.85 μg/kg/h (IQR 0.53-1.03) during maintenance (57 patients) and 0.63 μg/kg/h (IQR 0.54-1.01) during extubation period (42 patients) (p=0.03). No differences were observed in the doses regarding the indication for mechanical ventilation. Clonidine infusion was not associated with hemodynamic changes and showed no differences when associated with adjuvants.
CONCLUSION
Clonidine demonstrated to be a well-tolerated sedation option in pediatric patients submitted to mechanical ventilation, without relevant influence in hemodynamic variables.
Topics: Child; Child, Preschool; Clonidine; Humans; Hypnotics and Sedatives; Infant; Intensive Care Units, Pediatric; Respiration, Artificial; Retrospective Studies
PubMed: 35830018
DOI: 10.1590/1806-9282.20220166