Editing Clonidine (section)

==Medical uses==
[[Image:Clonidine pills and patch.jpg|thumb|left|200px|Clonidine tablets and transdermal patch]]

Clonidine is used to treat [[hypertension|high blood pressure]], [[attention deficit hyperactivity disorder]] (ADHD); [[drug withdrawal]], including from ([[Alcohol withdrawal syndrome|alcohol]], [[Opioid withdrawal|opioids]], and/or [[Nicotine withdrawal|nicotine]]); [[menopause|menopausal flushing]], [[diarrhea]], and certain pain conditions. In addition, it also sees some use off-label for episodic [[insomnia]], and [[tics]] (e.g. from [[Tourette Syndrome]], [[restless legs syndrome]], and [[anxiety]], among others).<ref name=AHFS2019/>

===Resistant hypertension===
Clonidine may be effective for lowering blood pressure in people with [[Hypertension#Resistant hypertension|resistant hypertension]].<ref>{{cite journal |vauthors=Viera AJ |title=Hypertension Update: Resistant Hypertension |journal=FP Essent |volume=469 |pages=20–25 |date=June 2018 |pmid=29863319 }}</ref>

Clonidine works by slowing the [[pulse rate]] and exerts a reduction of serum concentrations of [[renin]], [[aldosterone]], and [[catecholamines]].<ref name="DailyMed">{{cite web | title=Catapres- clonidine hydrochloride tablet | website=DailyMed | date=6 September 2016 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d | access-date=21 December 2019 | quote=Slowing of the pulse rate has been observed in most patients given clonidine, but the drug does not alter normal hemodynamic response to exercise. Other studies in patients have provided evidence of a reduction in plasma renin activity and in the excretion of aldosterone and catecholamines. | archive-date=4 August 2020 | archive-url=https://web.archive.org/web/20200804180055/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d | url-status=live }}</ref>

===Attention deficit hyperactivity disorder===
Clonidine may improve symptoms of attention deficit hyperactivity disorder in some people but causes many adverse effects and the beneficial effect is modest.<ref>{{cite journal | vauthors = Connor DF, Fletcher KE, Swanson JM | title = A meta-analysis of clonidine for symptoms of attention-deficit hyperactivity disorder | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 38 | issue = 12 | pages = 1551–1559 | date = December 1999 | pmid = 10596256 | doi = 10.1097/00004583-199912000-00017 }}</ref> In [[Australia]], clonidine is an accepted but not approved use for ADHD by the [[Therapeutic Goods Administration|TGA]].<ref name="AMH">{{cite book | editor = Rossi, S | isbn = 978-0-9805790-9-3 | title = Australian Medicines Handbook | place = Adelaide | publisher = The Australian Medicines Handbook Unit Trust | year = 2013 | edition = 2013 }}</ref> Clonidine, along with [[methylphenidate]], has been studied for treatment of ADHD.<ref name="Clonidine for attention-deficit">{{cite journal | vauthors = Palumbo DR, Sallee FR, Pelham WE, Bukstein OG, Daviss WB, McDERMOTT MP | title = Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 47 | issue = 2 | pages = 180–188 | date = February 2008 | pmid = 18182963 | doi = 10.1097/chi.0b013e31815d9af7 }}</ref><ref>{{cite journal | vauthors = Daviss WB, Patel NC, Robb AS, McDERMOTT MP, Bukstein OG, Pelham WE, Palumbo D, Harris P, Sallee FR | title = Clonidine for attention-deficit/hyperactivity disorder: II. ECG changes and adverse events analysis | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 47 | issue = 2 | pages = 189–198 | date = February 2008 | pmid = 18182964 | doi = 10.1097/chi.0b013e31815d9ae4 }}</ref><ref name="Effects">{{cite journal | vauthors = Kornfield R, Watson S, Higashi AS, Conti RM, Dusetzina SB, Garfield CF, Dorsey ER, Huskamp HA, Alexander GC | title = Effects of FDA advisories on the pharmacologic treatment of ADHD, 2004-2008 | journal = Psychiatric Services | volume = 64 | issue = 4 | pages = 339–346 | date = April 2013 | pmid = 23318985 | pmc = 4023684 | doi = 10.1176/appi.ps.201200147 }}</ref> While not as effective as methylphenidate in treating ADHD, clonidine does offer some benefit;<ref name="Clonidine for attention-deficit"/> it can also be useful in combination with [[stimulant]] medications.<ref>{{cite journal | vauthors = Kollins SH, Jain R, Brams M, Segal S, Findling RL, Wigal SB, Khayrallah M | title = Clonidine extended-release tablets as add-on therapy to psychostimulants in children and adolescents with ADHD | journal = Pediatrics | volume = 127 | issue = 6 | pages = e1406–e1413 | date = June 2011 | pmid = 21555501 | pmc = 3387872 | doi = 10.1542/peds.2010-1260 }}</ref> Some studies show clonidine to be more [[Sedation|sedating]] than [[guanfacine]], which may be better at bedtime along with an arousing [[stimulant]] in the morning.<ref>{{cite journal | vauthors = Jäkälä P, Riekkinen M, Sirviö J, Koivisto E, Kejonen K, Vanhanen M, Riekkinen P | title = Guanfacine, but not clonidine, improves planning and working memory performance in humans | journal = Neuropsychopharmacology | volume = 20 | issue = 5 | pages = 460–470 | date = May 1999 | pmid = 10192826 | doi = 10.1016/S0893-133X(98)00127-4 | doi-access = free }}</ref><ref>{{Cite journal |url = http://cpnp.org/resource/mhc/2014/01/clonidine-and-guanfacine-ir-vs-er-old-drugs-new-formulations |title = Clonidine and Guanfacine IR vs ER: Old Drugs With "New" Formulations |access-date = 1 August 2014 |journal = Mental Health Clinician |year = 2014 |doi = 10.9740/mhc.n186955 |vauthors = Freeland K, Turner A, Gormley L |volume = 4 |pages = 22–26 |doi-access = free |archive-date = 9 August 2014 |archive-url = https://web.archive.org/web/20140809181310/http://cpnp.org/resource/mhc/2014/01/clonidine-and-guanfacine-ir-vs-er-old-drugs-new-formulations |url-status = live }}</ref> Clonidine has been used to reduce sleep disturbances in ADHD, including to help offset stimulant-associated [[insomnia]].<ref name="pmid24027233">{{cite journal | vauthors = Nguyen M, Tharani S, Rahmani M, Shapiro M | title = A review of the use of clonidine as a sleep aid in the child and adolescent population | journal = Clinical Pediatrics | volume = 53 | issue = 3 | pages = 211–216 | date = March 2014 | pmid = 24027233 | doi = 10.1177/0009922813502123 | s2cid = 742140 }}</ref><ref name="pmid15853572">{{cite journal | vauthors = Hoban TF | title = Assessment and treatment of disturbed sleep in attention deficit hyperactivity disorder | journal = Expert Review of Neurotherapeutics | volume = 4 | issue = 2 | pages = 307–316 | date = March 2004 | pmid = 15853572 | doi = 10.1586/14737175.4.2.307 | s2cid = 35000868 }}</ref><ref name="SchacharIckowicz1999">{{cite book | editor-first = | title = Handbook of Disruptive Behavior Disorders |  vauthors = Schachar R, Ickowicz A | chapter = Pharmacological Treatment of Attention-Deficit/HyperactivityDisorder | date = 1999 | pages = 221–254 | publisher = Springer US | doi = 10.1007/978-1-4615-4881-2_10 | isbn = 978-1-4613-7214-1| url = }}</ref><ref name="pmid8169189">{{cite journal | vauthors = Wilens TE, Biederman J, Spencer T | title = Clonidine for sleep disturbances associated with attention-deficit hyperactivity disorder | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 33 | issue = 3 | pages = 424–426 | date = 1994 | pmid = 8169189 | doi = 10.1097/00004583-199403000-00018 }}</ref> Unlike stimulant medications, clonidine is regarded as having no abuse potential, and may even be used to reduce abuse of drugs including nicotine and cocaine.<ref name="Walker2014">{{cite journal | vauthors = Clemow DB, Walker DJ | title = The potential for misuse and abuse of medications in ADHD: a review | journal = Postgraduate Medicine | volume = 126 | issue = 5 | pages = 64–81 | date = September 2014 | pmid = 25295651 | doi = 10.3810/pgm.2014.09.2801 | s2cid = 207580823 }}</ref>

In the US, only the extended-release form of clonidine is approved for ADHD treatment.<ref name="FDA_PI">{{cite web |title=Highlights of Prescribing Information: Kapvay |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022331s014lbl.pdf |archive-url=https://web.archive.org/web/20160327193722/http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022331s014lbl.pdf |url-status=dead |archive-date=27 March 2016 |publisher=US FDA |access-date=31 March 2024}}</ref>

===Drug withdrawal===
Clonidine may be used to ease drug withdrawal symptoms associated with abruptly stopping the long-term use of [[opioids]], [[alcohol (drug)|alcohol]], [[benzodiazepines]], and [[nicotine]].<ref>{{cite journal | vauthors = Fitzgerald PJ | title = Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine | journal = Substance Abuse | volume = 7 | pages = 171–183 | date = October 2013 | pmid = 24151426 | pmc = 3798293 | doi = 10.4137/SART.S13019 }}</ref> It can alleviate [[opioid withdrawal]] symptoms by reducing the [[sympathetic nervous system]] response such as [[tachycardia]] and [[hypertension]], [[hyperhidrosis]] (excessive sweating), hot and cold flashes, and [[akathisia]].<ref>{{ cite book | vauthors = Giannini AJ | title = Drugs of Abuse | edition = 2nd | location = Los Angeles | publisher = Practice Management Information | year = 1997 }}</ref> It may also be helpful in aiding smokers to quit.<ref>{{cite journal | vauthors = Gourlay SG, Stead LF, Benowitz NL | title = Clonidine for smoking cessation | journal = The Cochrane Database of Systematic Reviews | volume = 2008 | issue = 3 | pages = CD000058 | date = 2004 | pmid = 15266422 | pmc = 7038651 | doi = 10.1002/14651858.CD000058.pub2 }}</ref> The sedation effect can also be useful. Clonidine may also reduce severity of [[neonatal withdrawal|neonatal abstinence syndrome]] in infants born to mothers that are using certain drugs, particularly opioids.<ref>{{cite journal | vauthors = Streetz VN, Gildon BL, Thompson DF | title = Role of Clonidine in Neonatal Abstinence Syndrome: A Systematic Review | journal = The Annals of Pharmacotherapy | volume = 50 | issue = 4 | pages = 301–310 | date = April 2016 | pmid = 26783353 | doi = 10.1177/1060028015626438 | s2cid = 40652097 }}</ref> In infants with neonatal withdrawal syndrome, clonidine may improve the [[neonatal intensive care unit]] Network Neurobehavioral Score.<ref>{{cite journal | vauthors = Disher T, Gullickson C, Singh B, Cameron C, Boulos L, Beaubien L, Campbell-Yeo M | title = Pharmacological Treatments for Neonatal Abstinence Syndrome: A Systematic Review and Network Meta-analysis | journal = JAMA Pediatrics | volume = 173 | issue = 3 | pages = 234–243 | date = March 2019 | pmid = 30667476 | pmc = 6439896 | doi = 10.1001/jamapediatrics.2018.5044 }}</ref>

Clonidine has also been suggested as a treatment for rare instances of [[dexmedetomidine]] withdrawal.<ref>{{cite journal | vauthors=Kukoyi A, Coker S, Lewis L, Nierenberg D | title = Two cases of acute dexmedetomidine withdrawal syndrome following prolonged infusion in the intensive care unit: Report of cases and review of the literature | journal = Human & Experimental Toxicology |date=January 2013 | volume = 32 |issue = 1 | pages = 107–110 | doi = 10.1177/0960327112454896 | pmid = 23111887 | s2cid = 31570614 }}</ref>

=== Spasticity ===
Clonidine has some role in the treatment of spasticity caused by spinal cord injury, acting principally by inhibiting excessive sensory transmission{{clarify span|below the level of injury.|date=March 2024}} Its use, however, is mainly as a second or third line agent, due to side effects such as [[hypotension]], [[bradycardia]], and [[drowsiness]].<ref>{{cite journal | vauthors = Chang E, Ghosh N, Yanni D, Lee S, Alexandru D, Mozaffar T | title = A Review of Spasticity Treatments: Pharmacological and Interventional Approaches | journal = Critical Reviews in Physical and Rehabilitation Medicine | volume = 25 | issue = 1–2 | pages = 11–22 | date = 2013 | pmid = 25750484 | pmc = 4349402 | doi = 10.1615/CritRevPhysRehabilMed.2013007945 }}</ref> Clonidine can be administered [[intrathecal]]ly,<ref name="PMID18443642">{{cite journal | vauthors = Smith HS, Deer TR, Staats PS, Singh V, Sehgal N, Cordner H | title = Intrathecal drug delivery | journal = Pain Physician | volume = 11 | issue = 2 Suppl | pages = S89–S104 | date = March 2008 | doi = 10.36076/ppj.2008/11/S89 | pmid = 18443642 }}</ref> which confers various benefits, including a reduction or prevention of the blood pressure lowering effects and increased effectiveness against spasticity.<ref name="PMID11723871">{{cite journal | vauthors = Rémy-Néris O, Denys P, Bussel B | title = Intrathecal clonidine for controlling spastic hypertonia | journal = Physical Medicine and Rehabilitation Clinics of North America | volume = 12 | issue = 4 | pages = 939–51, ix | date = November 2001 | doi = 10.1016/S1047-9651(18)30040-8 | pmid = 11723871 }}</ref> The effectiveness of intrathecal clonidine is comparable to that of intrathecal baclofen for spasticity.<ref name=PMID11723871/>

===Clonidine suppression test===
The reduction in circulating norepinephrine by clonidine was used in the past as an investigatory test for [[phaeochromocytoma]], which is a [[Neuroendocrine tumor|catecholamine-synthesizing tumor]], usually found in the [[adrenal medulla]].<ref name="pmid12788870">{{cite journal | vauthors = Eisenhofer G, Goldstein DS, Walther MM, Friberg P, Lenders JW, Keiser HR, Pacak K | title = Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 6 | pages = 2656–2666 | date = June 2003 | pmid = 12788870 | doi = 10.1210/jc.2002-030005 | doi-access = free }}</ref> In a clonidine suppression test, plasma catecholamine levels are measured before and 3 hours after a 0.3&nbsp;mg oral test dose has been given to the patient. A positive test occurs if there is no decrease in plasma levels.<ref name="pmid12788870"/>

===Other uses===
Clonidine also has several [[off-label use]]s, and has been prescribed to treat [[psychiatric disorder]]s including [[Stress (biology)|stress]], [[Fight-or-flight response|hyperarousal]] caused by [[post-traumatic stress disorder]], [[borderline personality disorder]], and other [[anxiety disorder]]s.<ref>{{cite journal | vauthors = van der Kolk BA | title = The drug treatment of post-traumatic stress disorder | journal = Journal of Affective Disorders | volume = 13 | issue = 2 | pages = 203–213 | date = September–October 1987 | pmid = 2960712 | doi = 10.1016/0165-0327(87)90024-3 }}</ref><ref>{{cite journal | vauthors = Sutherland SM, Davidson JR | title = Pharmacotherapy for post-traumatic stress disorder | journal = The Psychiatric Clinics of North America | volume = 17 | issue = 2 | pages = 409–423 | date = June 1994 | pmid = 7937367 | doi = 10.1016/S0193-953X(18)30122-9 }}</ref><ref>{{cite journal | vauthors = Southwick SM, Bremner JD, Rasmusson A, Morgan CA, Arnsten A, Charney DS | title = Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder | journal = Biological Psychiatry | volume = 46 | issue = 9 | pages = 1192–1204 | date = November 1999 | pmid = 10560025 | doi = 10.1016/S0006-3223(99)00219-X | s2cid = 32148292 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Strawn JR, Geracioti TD | title = Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder | journal = Depression and Anxiety | volume = 25 | issue = 3 | pages = 260–271 | date = 2008 | pmid = 17354267 | doi = 10.1002/da.20292 | s2cid = 33940152 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Boehnlein JK, Kinzie JD | title = Pharmacologic reduction of CNS noradrenergic activity in PTSD: the case for clonidine and prazosin | journal = Journal of Psychiatric Practice | volume = 13 | issue = 2 | pages = 72–78 | date = March 2007 | pmid = 17414682 | doi = 10.1097/01.pra.0000265763.79753.c1 | s2cid = 1607064 }}</ref><ref>{{cite journal | vauthors = Huffman JC, Stern TA | title = Neuropsychiatric consequences of cardiovascular medications | journal = Dialogues in Clinical Neuroscience | volume = 9 | issue = 1 | pages = 29–45 | date = 2007 | pmid = 17506224 | pmc = 3181843 | doi = 10.31887/DCNS.2007.9.1/jchuffman }}</ref><ref>{{cite journal | vauthors = Najjar F, Weller RA, Weisbrot J, Weller EB | title = Post-traumatic stress disorder and its treatment in children and adolescents | journal = Current Psychiatry Reports | volume = 10 | issue = 2 | pages = 104–108 | date = April 2008 | pmid = 18474199 | doi = 10.1007/s11920-008-0019-0 | s2cid = 23494905 }}</ref><ref>{{cite journal | vauthors = Ziegenhorn AA, Roepke S, Schommer NC, Merkl A, Danker-Hopfe H, Perschel FH, Heuser I, Anghelescu IG, Lammers CH | title = Clonidine improves hyperarousal in borderline personality disorder with or without comorbid posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial | journal = Journal of Clinical Psychopharmacology | volume = 29 | issue = 2 | pages = 170–173 | date = April 2009 | pmid = 19512980 | doi = 10.1097/JCP.0b013e31819a4bae | s2cid = 31292297 }}</ref> Clonidine is also a mild [[sedative]], and can be used as [[premedication]] before surgery or procedures.<ref name=premed>{{cite journal | vauthors = Fazi L, Jantzen EC, Rose JB, Kurth CD, Watcha MF | title = A comparison of oral clonidine and oral midazolam as preanesthetic medications in the pediatric tonsillectomy patient | journal = Anesthesia and Analgesia | volume = 92 | issue = 1 | pages = 56–61 | date = January 2001 | pmid = 11133600 | doi = 10.1097/00000539-200101000-00011 | s2cid = 18885497 | doi-access = free }}</ref> It has also been studied as a way to calm acute [[mania|manic]] episodes.<ref>{{ cite journal | vauthors = Giannini AJ, Extein I, Gold MS, Pottash AL, Castellani S | title = Clonidine in mania | journal = Drug Development Research | volume = 3 | issue = 1 | pages = 101–105 | year = 1983 | doi = 10.1002/ddr.430030112 |s2cid=85093127 }}</ref> Its epidural use for pain during heart attack, and postoperative and intractable pain has also been studied extensively.<ref>{{cite journal | vauthors = Patel SS, Dunn CJ, Bryson HM | title = Epidural clonidine: a review of its pharmacology and efficacy in the management of pain during labour and postoperative and intractable pain | journal = CNS Drugs | year = 1996 | volume = 6 | issue = 6 | pages = 474–497 | doi = 10.2165/00023210-199606060-00007 |s2cid=72544106 }}</ref> Clonidine can be used in [[restless legs syndrome]].<ref name="RLS medscape">{{cite web |title=Treatment and Management of RLS |url=https://www.medscape.org/viewarticle/522010_6 |website=www.medscape.org |publisher=WebMD LLC |access-date=3 October 2018 |archive-date=29 September 2017 |archive-url=https://web.archive.org/web/20170929042337/http://www.medscape.org/viewarticle/522010_6 |url-status=live }}</ref> It can also be used to treat facial flushing and redness associated with [[rosacea]].<ref>{{cite journal | vauthors = Blount BW, Pelletier AL | title = Rosacea: a common, yet commonly overlooked, condition | journal = American Family Physician | volume = 66 | issue = 3 | pages = 435–440 | date = August 2002 | pmid = 12182520 | url = http://www.aafp.org/afp/2002/0801/p435.html | access-date = 12 February 2012 | archive-date = 26 July 2011 | archive-url = https://web.archive.org/web/20110726103851/http://www.aafp.org/afp/2002/0801/p435.html | url-status = live }}</ref> It has also been successfully used topically in a clinical trial as a treatment for [[diabetic neuropathy]].<ref>{{cite journal | vauthors = Campbell CM, Kipnes MS, Stouch BC, Brady KL, Kelly M, Schmidt WK, Petersen KL, Rowbotham MC, Campbell JN | title = Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy | journal = Pain | volume = 153 | issue = 9 | pages = 1815–1823 | date = September 2012 | pmid = 22683276 | pmc = 3413770 | doi = 10.1016/j.pain.2012.04.014 }}</ref> Clonidine can also be used for [[migraine]] headaches and [[hot flash]]es associated with [[menopause]].<ref name="Web MD">{{cite web | title = Clonidine Oral Uses | url = http://www.webmd.com/drugs/drug-11754-Clonidine.aspx?drugid=11754&drugname=Clonidine | publisher = [[WebMD]] | access-date = 30 May 2007 | archive-date = 25 October 2007 | archive-url = https://web.archive.org/web/20071025030547/http://www.webmd.com/drugs/drug-11754-Clonidine.aspx?drugid=11754&drugname=Clonidine | url-status = live }}</ref><ref>{{cite web | title = Clonidine | url = https://www.drugs.com/clonidine.html | publisher = Drugs.com | access-date = 25 May 2017 | archive-date = 14 April 2017 | archive-url = https://web.archive.org/web/20170414001745/https://www.drugs.com/clonidine.html | url-status = live }}</ref> Clonidine has also been used to treat refractory [[diarrhea]] associated with [[irritable bowel syndrome]], [[fecal incontinence]], diabetes, diarrhea associated with opioid withdrawal, [[Short bowel syndrome|intestinal failure]], [[neuroendocrine tumor]]s, and [[cholera]].<ref>{{cite journal | vauthors = Fragkos KC, Zárate-Lopez N, Frangos CC | title = What about clonidine for diarrhoea? A systematic review and meta-analysis of its effect in humans | journal = Therapeutic Advances in Gastroenterology | volume = 9 | issue = 3 | pages = 282–301 | date = May 2016 | pmid = 27134659 | pmc = 4830099 | doi = 10.1177/1756283X15625586 }}</ref> Clonidine can be used in the treatment of [[Tourette syndrome]] (specifically for [[tics]]).<ref>{{cite journal | vauthors = Egolf A, Coffey BJ | title = Current pharmacotherapeutic approaches for the treatment of Tourette syndrome | journal = Drugs of Today | volume = 50 | issue = 2 | pages = 159–179 | date = February 2014 | pmid = 24619591 | doi = 10.1358/dot.2014.50.2.2097801 }}</ref> Clonidine has also had some success in clinical trials for helping to remove or ameliorate the symptoms of [[hallucinogen persisting perception disorder]] (HPPD).<ref>{{cite journal | vauthors = Martinotti G, Santacroce R, Pettorruso M, Montemitro C, Spano MC, Lorusso M, di Giannantonio M, Lerner AG | title = Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives | journal = Brain Sciences | volume = 8 | issue = 3 | page = 47 | date = March 2018 | pmid = 29547576 | pmc = 5870365 | doi = 10.3390/brainsci8030047 | doi-access = free }}</ref>

Injection of [[Alpha-2 adrenergic receptor|α<sub>2</sub>-adrenergic receptor agonists]] into the knee joint space, including clonidine, may reduce the severity of knee pain after [[Arthroscopy|arthroscopic]] knee surgery.<ref>{{cite journal |vauthors=Ryan TJ, Holyoak R, Vlok R, Melhuish T, Hodge A, Binks M, Hurtado G, White L |title=Intra-articular Alpha-2 Agonists as an Adjunct to Local Anesthetic in Knee Arthroscopy: A Systematic Review and Meta-Analysis |journal=J Knee Surg |volume=32 |issue=2 |pages=138–145 |date=February 2019 |pmid=29534270 |doi=10.1055/s-0038-1636909 |s2cid=3861878 }}</ref>

Light-activated derivatives of clonidine (adrenoswitches) have been developed for research purposes and shown to control pupillary reflex with light in blind mice by topical application.<ref>{{cite journal | vauthors = Prischich D, Gomila AM, Milla-Navarro S, Sangüesa G, Diez-Alarcia R, Preda B, Matera C, Batlle M, Ramírez L, Giralt E, Hernando J, Guasch E, Meana JJ, de la Villa P, Gorostiza P | title = Adrenergic Modulation With Photochromic Ligands | journal = Angewandte Chemie | volume = 60 | issue = 7 | pages = 3625–3631 | date = February 2021 | pmid = 33103317 | doi = 10.1002/anie.202010553 | publisher = Wiley | hdl-access = free | hdl = 2434/778579 }}</ref>

===Pregnancy and breastfeeding===
It is classified by the TGA of Australia as pregnancy category B3, which means that it has shown some detrimental effects on fetal development in animal studies, although the relevance of this to human beings is unknown.<ref name = TGA/> Clonidine appears in high concentration in breast milk; a nursing infant's serum clonidine concentration is approximately 2/3 of the mother's.<ref>{{cite book |title=Drugs and Lactation Database (LactMed) |date=2006 |publisher=National Library of Medicine (US) |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK501628/ |access-date=5 January 2019 |chapter=Clonidine |pmid=30000689 |archive-date=5 December 2020 |archive-url=https://web.archive.org/web/20201205111454/https://www.ncbi.nlm.nih.gov/books/NBK501628/ |url-status=live }}</ref> Caution is warranted in women who are pregnant, planning to become pregnant, or are breastfeeding.<ref>{{cite web | url = http://drugsdb.eu/drug.php?d=Clonidine&m=Physicians%20Total%20Care,%20Inc.&id=b65742b7-5db5-41cf-bf69-41700cdd2c59.xml | title = Clonidine | work = Prescription Marketed Drugs | publisher = www.drugsdb.eu | access-date = 2 August 2011 | archive-date = 28 March 2012 | archive-url = https://web.archive.org/web/20120328060203/http://drugsdb.eu/drug.php?d=Clonidine&m=Physicians%20Total%20Care,%20Inc.&id=b65742b7-5db5-41cf-bf69-41700cdd2c59.xml | url-status = dead }}</ref>