Clonidine
Trials found clonidine lowered blood pressure, with half of men reaching goal against a quarter on placebo, and network meta-analyses found clonidine and guanfacine reduced ADHD symptoms in children. Meta-analyses also found benefits for quitting smoking, opioid withdrawal and hot flashes. Drowsiness was very common. Stopping abruptly can cause rebound high blood pressure.
Add to Bio HackChecked 2026-11-13
- Status
- Prescription drugs in the US. Immediate-release clonidine tablets and the clonidine patch are FDA-approved for high blood pressure. Extended-release clonidine and extended-release guanfacine (Intuniv) are FDA-approved for ADHD, alone or added to stimulants. Use for quitting smoking, opioid withdrawal, hot flashes, sleep and anxiety is off-label.
- Also called
- clonidine, Catapres, Catapres-TTS, Kapvay, Onyda XR, clonidine patch, guanfacine, Intuniv, Tenex, alpha-2 agonist
- Taken for
- high blood pressure, ADHD, focus, hyperactivity, opioid withdrawal, quitting smoking, hot flashes, anxiety, PTSD, sleep
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Shown to help5
- StrongShown to reduce ADHD symptoms in children and teenagers against placebo, by a standardized difference of about 0.6 to 0.7 for clonidine and guanfacine.
- ModerateShown to lower blood pressure: in one trial 50% of men on clonidine reached goal against 25% on placebo, similar to other drug classes, with more stopping for intolerance.Very common
- ModerateShown to raise quit rates against placebo, with about 1.9 times the odds, in a Cochrane review of six small trials, with frequent dry mouth and sedation.
- ModerateShown to make severe opioid withdrawal less likely and completing withdrawal more likely than placebo, with results similar to a methadone taper but more low blood pressure.
- ModerateShown to reduce hot flashes in menopausal women by about one a day against placebo, an effect smaller than estrogen.
Reported risks9
- ModerateShown to raise drowsiness, in 38% on guanfacine against 11% on placebo and 31% to 38% on extended-release clonidine against 4%, with about 4 treated for one extra case.Very common
- LimitedThe clonidine tablet label reports dry mouth in about 40 of 100 people, dizziness in 16 and constipation in 10, mostly dose-related and easing over time.Very common
- ModerateShown to lower blood pressure and heart rate in ADHD trials, with low blood pressure in 7% on guanfacine against 3%, and reports of severe slow heart rhythms.Common
- ModerateShown in children's ADHD trials to raise nightmares, 9% at 0.4 mg against 0% on placebo, along with irritability and insomnia.Common
- LimitedThe labels warn that stopping clonidine or guanfacine suddenly can cause a rapid rise in blood pressure, with rare reports of brain swelling from hypertension, stroke and death.How often is not known
- LimitedThe label reports severe slow heart rate needing a pacemaker with diltiazem or verapamil, and a greater rebound risk when beta-blockers continue after clonidine is stopped.How often is not known
- LimitedThe labels warn that clonidine and guanfacine may add to the sedation of alcohol, barbiturates, benzodiazepines and other sedating drugs.How often is not known
- LimitedThe labels state tricyclic antidepressants can blunt clonidine's blood pressure effect, and drugs that block or speed the liver enzyme CYP3A4 change guanfacine levels.How often is not known
- LimitedThe labels report that people sensitized to the clonidine patch may develop a widespread rash, hives or swelling when switched to clonidine tablets. They give no rate.How often is not known
What people take it for, and what was found
Shown to help5
High blood pressure
Shown to lower blood pressure: in one trial 50% of men on clonidine reached goal against 25% on placebo, similar to other drug classes, with more stopping for intolerance.
Compared with placebo [1][2]; hydrochlorothiazide, atenolol, captopril, diltiazem and prazosin [1]; spironolactone as a fourth drug [3]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In a trial of six drugs, 50% on clonidine reached and kept the diastolic goal at one year, against 25% on placebo, 59% on diltiazem, 51% on atenolol, 46% on hydrochlorothiazide and 42% on captopril or prazosin. Drug intolerance was more frequent with clonidine (14%) [1]. With a clonidine patch, blood pressure was controlled in 11 of 15 people against 4 of 15 on placebo [2]. In resistant hypertension, office blood pressure control was similar with clonidine (29.3%) and spironolactone (33.3%), while spironolactone lowered 24-hour blood pressure more [3].
- Population
- 1,292 men with diastolic pressure 95 to 109 mm Hg, 48% Black, followed at least one year [1]; 30 adults with mild hypertension over 5 weeks [2]; adults with resistant hypertension on three drugs [3].
- Sources
- [1], [2], [3]
- Caveats
- No meta-analysis of clonidine for blood pressure was located. The six-drug trial enrolled men only [1]. These trials measured blood pressure, not heart attacks or strokes.
ADHD in children and teenagers
Shown to reduce ADHD symptoms in children and teenagers against placebo, by a standardized difference of about 0.6 to 0.7 for clonidine and guanfacine.
Compared with placebo [4][5][6][7]; amphetamines, methylphenidate, atomoxetine and modafinil, in network comparisons [4]; placebo added to stimulants [5]
The numbers and sources
- Effect
- In a network meta-analysis at about 12 weeks, clinician-rated ADHD symptoms improved more than placebo with clonidine (SMD -0.71, 95% CI -1.17 to -0.24) and guanfacine (SMD -0.67, 95% CI -0.85 to -0.50). Teacher ratings for guanfacine did not clearly differ from placebo (SMD -0.63, 95% CI -1.62 to 0.35). Guanfacine was less well tolerated than placebo (OR 2.64, 95% CI 1.20 to 5.81) [4]. Another meta-analysis found alpha-2 agonists alone reduced overall symptoms (SMD -0.59) and, added to stimulants, by a smaller amount (SMD -0.36). Alone, they had fewer all-cause discontinuations than placebo (RR 0.70, NNT 10) [5].
- Population
- 10,068 children and adolescents in the efficacy analysis of 133 trials, with no adult trials of clonidine or guanfacine found [4]; 2,276 young people in 12 trials [5].
- Sources
- [4], [5]
- Caveats
- Evidence quality was moderate for both drugs against placebo [4]. Amphetamines (SMD -1.02) and methylphenidate (SMD -0.78) had larger point estimates against placebo in the same analysis [4].
Quitting smoking
Shown to raise quit rates against placebo, with about 1.9 times the odds, in a Cochrane review of six small trials, with frequent dry mouth and sedation.
Compared with placebo [8]
The numbers and sources
- Effect
- The pooled odds ratio for quitting with clonidine against placebo was 1.89 (95% CI 1.30 to 2.74). Only one of the six trials was significant on its own. Dose-dependent side effects, particularly dry mouth and sedation, were frequent [8].
- Population
- Smokers in six trials, three of oral and three of patch clonidine, most with counseling [8].
- Sources
- [8]
- Caveats
- Few trials, with potential sources of bias [8]. Clonidine is not approved for quitting smoking.
Opioid withdrawal
Shown to make severe opioid withdrawal less likely and completing withdrawal more likely than placebo, with results similar to a methadone taper but more low blood pressure.
Compared with placebo and reducing doses of methadone [9]
The numbers and sources
- Effect
- Against placebo, alpha-2 agonists lowered the chance of severe withdrawal (RR 0.32, 95% CI 0.18 to 0.57) and raised treatment completion (RR 1.95, 95% CI 1.34 to 2.84). Against a methadone taper, withdrawal severity and completion did not differ significantly, symptoms resolved sooner, and hypotensive or other adverse effects were more likely (RR 1.92, 95% CI 1.19 to 3.10) [9].
- Population
- 1,728 people withdrawing from heroin or methadone in 26 trials, 148 in the placebo comparisons [9].
- Sources
- [9]
- Caveats
- The review pooled clonidine with lofexidine, and the placebo comparisons were small [9].
Hot flashes
Shown to reduce hot flashes in menopausal women by about one a day against placebo, an effect smaller than estrogen.
Compared with placebo [10]
The numbers and sources
- Effect
- Across four trials, clonidine reduced daily hot flashes by 0.95 more than placebo (95% CI -1.44 to -0.47) [10].
- Population
- Menopausal women in 10 clonidine trials, 4 of them pooled for frequency [10].
- Sources
- [10]
- Caveats
- Most trials had methodological deficiencies, and the authors state effects are smaller than for estrogen [10].
Not shown to help1
Anxiety and PTSD
Small trials of guanfacine found no difference from placebo on anxiety scales in children or on PTSD symptoms in veterans.
Compared with placebo [11][12]
The numbers and sources
- Effect
- In children with anxiety disorders, anxiety rating scale scores did not differ between guanfacine and placebo, while clinicians rated more children as much improved (54.2% against 31.6%), in a study not designed for statistical testing [11]. In veterans with PTSD, guanfacine did not differ from placebo on clinician-rated or self-reported outcomes [12].
- Population
- 83 children aged 6 to 17 with anxiety disorders over 12 weeks [11]; a small sample of mostly male combat veterans over 8 weeks [12].
- Sources
- [11], [12]
- Caveats
- Both were pilot trials. No trial of clonidine for anxiety disorders was located.
Doses studied
The clonidine tablet label starts at 0.1 mg twice a day, lists 0.2 to 0.6 mg a day as the most common range, and states that studies found 2.4 mg a day to be the highest dose with added effect, rarely used [13]. The six-drug trial used 0.2 to 0.6 mg a day [1], and the resistant hypertension trial 0.1 to 0.3 mg twice a day [3]. For ADHD, extended-release clonidine trials used 0.2 or 0.4 mg a day alone, and up to 0.4 mg a day added to stimulants [6]. The guanfacine label lists 1 to 7 mg once a day (0.05 to 0.12 mg/kg), and its fixed-dose trials used 1 to 4 mg [7].
Risks
Reported risks9
Drowsiness and fatigue
Shown to raise drowsiness, in 38% on guanfacine against 11% on placebo and 31% to 38% on extended-release clonidine against 4%, with about 4 treated for one extra case.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In ADHD trials, somnolence occurred in 38% on 0.2 mg and 31% on 0.4 mg extended-release clonidine against 4% on placebo, and fatigue in 16% and 13% against 1% [6]. On guanfacine, somnolence occurred in 38% across doses against 11%, rising from 28% at 1 mg to 51% at 4 mg, and fatigue in 14% against 3% [7]. A meta-analysis found numbers needed to harm of 4 for somnolence, 10 for fatigue and 17 for sedation [5]. The clonidine tablet label reports drowsiness in about 33 of 100 people [13].
- Population
- 230 children and adolescents in a fixed-dose clonidine trial [6]; 513 on guanfacine and 149 on placebo [7]; 2,276 young people in 12 trials [5].
- Sources
- [6], [7], [5], [13]
- Caveats
- Somnolence led to stopping in 11% at the highest guanfacine dose [7].
Dry mouth, dizziness and constipation
The clonidine tablet label reports dry mouth in about 40 of 100 people, dizziness in 16 and constipation in 10, mostly dose-related and easing over time.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- The most frequent effects on clonidine tablets were dry mouth (about 40 in 100), drowsiness (about 33), dizziness (about 16), and constipation and sedation (about 10 each), mostly dose-related [13]. In children with ADHD, dry mouth occurred in 5% on 0.4 mg against 1% and constipation in 6% against 0% [6].
- Population
- Adults on clonidine tablets [13]; children and adolescents on extended-release clonidine [6].
- Sources
- [13], [6]
- Caveats
- The tablet label gives no placebo rates.
Low blood pressure, slow heart rate and fainting
Shown to lower blood pressure and heart rate in ADHD trials, with low blood pressure in 7% on guanfacine against 3%, and reports of severe slow heart rhythms.
The numbers and sources
- How common
- Common: between 1 in 100 and 1 in 10 people.
- Effect
- Hypotension occurred in 7% on guanfacine and 3% on placebo [7], and bradycardia in 4% on 0.4 mg extended-release clonidine against 0% [6]. A meta-analysis found greater falls in blood pressure and heart rate with clonidine and QTc prolongation with guanfacine than with placebo [5]. The labels report fainting and severe bradycardia needing atropine, isoproterenol or temporary pacing in people with conduction problems or taking other drugs that slow the heart [13][6].
- Population
- Children and adolescents in ADHD trials [7][6][5]; postmarketing reports [13].
- Sources
- [7], [6], [5], [13]
- Caveats
- Rates are from children's trials. The guanfacine label states the falls lessened over time [7].
Nightmares, irritability and insomnia in children
Shown in children's ADHD trials to raise nightmares, 9% at 0.4 mg against 0% on placebo, along with irritability and insomnia.
The numbers and sources
- How common
- Common: between 1 in 100 and 1 in 10 people.
- Effect
- In children on extended-release clonidine, nightmares occurred in 4% at 0.2 mg and 9% at 0.4 mg against 0% on placebo, irritability in 9% and 5% against 4%, and insomnia in 5% and 6% against 1% [6].
- Population
- 154 children and adolescents on clonidine and 76 on placebo [6].
- Sources
- [6]
- Caveats
- Rates from one 8-week trial.
Rebound high blood pressure on stopping
The labels warn that stopping clonidine or guanfacine suddenly can cause a rapid rise in blood pressure, with rare reports of brain swelling from hypertension, stroke and death.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Sudden cessation of clonidine has caused nervousness, agitation, headache and tremor with a rapid rise in blood pressure and raised catecholamines, more likely after high doses or with continued beta-blocker treatment. Rare hypertensive encephalopathy, stroke and death have been reported [13]. The guanfacine label reports clinically significant, persistent rebound hypertension after abrupt stopping, including hypertensive encephalopathy [7]. In a small patch trial, no rebound was seen after stopping [2].
- Population
- Adults with hypertension and children with ADHD, in label reports [13][7]; 15 adults on a clonidine patch [2].
- Sources
- [13], [7], [2]
- Caveats
- The labels give no rate. No studies of abrupt stopping in children with ADHD were done [6].
Heart rate drugs: beta-blockers, calcium channel blockers and digoxin
The label reports severe slow heart rate needing a pacemaker with diltiazem or verapamil, and a greater rebound risk when beta-blockers continue after clonidine is stopped.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- The label calls for heart rate monitoring with drugs that affect the sinus node or AV conduction, such as digitalis, calcium channel blockers and beta-blockers, and reports sinus bradycardia leading to hospitalization and pacemaker insertion with diltiazem or verapamil. Rebound on stopping is more likely with continued beta-blocker treatment [13].
- Population
- Postmarketing reports and labeling statements [13].
- Sources
- [13]
- Caveats
- No rates are given.
Alcohol and sedating drugs
The labels warn that clonidine and guanfacine may add to the sedation of alcohol, barbiturates, benzodiazepines and other sedating drugs.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Clonidine may potentiate the central nervous system depressant effects of alcohol, barbiturates and other sedating drugs [13]. The ADHD labels advise considering additive sedation with phenothiazines, barbiturates, benzodiazepines and other central depressants [6][7].
- Population
- Labeling statements [13][6][7].
- Sources
- [13], [6], [7]
- Caveats
- No rates are given.
Other interactions
The labels state tricyclic antidepressants can blunt clonidine's blood pressure effect, and drugs that block or speed the liver enzyme CYP3A4 change guanfacine levels.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- With tricyclic antidepressants, clonidine's blood pressure lowering may be reduced. With neuroleptics, low blood pressure on standing, dizziness and fatigue may occur or worsen [13]. Strong and moderate CYP3A4 inhibitors such as ketoconazole and fluconazole raise guanfacine exposure, and inducers such as rifampin and efavirenz lower it [7].
- Population
- Labeling statements drawn from interaction studies [13][7].
- Sources
- [13], [7]
- Caveats
- No rates of harm are given.
Allergic skin reactions
The labels report that people sensitized to the clonidine patch may develop a widespread rash, hives or swelling when switched to clonidine tablets. They give no rate.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- In people with localized contact sensitization to the clonidine patch, continuing the patch or switching to oral clonidine may produce a generalized rash, urticaria or angioedema [6].
- Population
- Labeling statement [6].
- Sources
- [6]
- Caveats
- No rate is given.
Checked, no increase found1
Pregnancy
The labels state decades of use in pregnancy have not identified a raised risk of birth defects or miscarriage with clonidine or guanfacine, though guanfacine use has been infrequent.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Published experience with clonidine in pregnancy, including controlled trials, a retrospective cohort and case reports, has not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Rats and mice had more resorptions at high doses [6]. Data on guanfacine have not identified a risk, but its use in pregnancy has been infrequent [7].
- Population
- Published literature summarized in the labels [6][7].
- Sources
- [6], [7]
- Caveats
- The labels give no counts of exposed pregnancies.
Claims tested and not found
Related
Sources
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- Popli S. Transdermal Clonidine in Mild Hypertension: A Randomized, Double-blind, Placebo-Controlled Trial. Archives of Internal Medicine. 1986. https://doi.org/10.1001/archinte.1986.00360230056009
- Krieger EM, Drager LF, Giorgi DM, et al. Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension: The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment). Hypertension. 2018. https://doi.org/10.1161/HYPERTENSIONAHA.117.10662
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- U.S. Food and Drug Administration. INTUNIV (guanfacine) extended-release tablets, prescribing information. 2025. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b972af81-3a37-40be-9fe1-3ddf59852528
- Gourlay SG, Stead LF, Benowitz N. Clonidine for smoking cessation. Cochrane Database of Systematic Reviews. 2004. https://doi.org/10.1002/14651858.CD000058.pub2
- Gowing L, Farrell M, Ali R, et al. Alpha2-adrenergic agonists for the management of opioid withdrawal. Cochrane Database of Systematic Reviews. 2016. https://doi.org/10.1002/14651858.CD002024.pub5
- Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA. 2006. https://doi.org/10.1001/jama.295.17.2057
- Strawn JR, Compton SN, Robertson B, et al. Extended Release Guanfacine in Pediatric Anxiety Disorders: A Pilot, Randomized, Placebo-Controlled Trial. Journal of Child and Adolescent Psychopharmacology. 2017. https://doi.org/10.1089/cap.2016.0132
- Davis LL, Ward C, Rasmusson A, et al. A placebo-controlled trial of guanfacine for the treatment of posttraumatic stress disorder in veterans. Psychopharmacology Bulletin. 2008. https://pubmed.ncbi.nlm.nih.gov/18362867/
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