US Pharm. 2006;5:HS-2-HS-16.

Clonidine was originally developed in 1962 for use as a nasal decongestant.1 However, rapid recognition of its ability to reduce blood pressure led to the FDA approval of this agent for the treatment of hypertension in 1974.2 During the 1970s, clonidine gained popularity as treatment for hypertension since it was not linked with the postural and exercise-induced hypotension common in other antihypertensive regimens. However, unwanted side effects of drowsiness, dry mouth, and sympathetic overactivity upon abrupt discontinuation led to a decline in its use. In 1996, a transdermal formulation renewed interest in the drug, as reported side effects were less pronounced than with oral treatment.

Today, with the development and marketing of newer products, the use of clonidine in the treatment of hypertension is limited; however this agent's ability to modify both central and peripheral adrenergic transmission is proving to be of increasing interest to health care practitioners. Clonidine's unique mechanism of action has prompted many to investigate its therapeutic potential in several different disease states.


Clonidine is available as an oral tablet form, a transdermal therapeutic system (Catapres-TTS), and as an injection for epidural use (Duraclon) (Table 1). The oral and topical formulations are FDA approved only for the treatment of hypertension, while the injectable form is FDA approved only for  intractable cancer pain, in combination with opioids.3-6

Most of the common adverse effects with oral clonidine are mild and tend to diminish with continued treatment or with a reduction in dosage. The most frequent adverse effects seen with oral and transdermal clonidine therapy are dry mouth and drowsiness; however, dizziness, sedation, constipation, and headache are also common reactions noted. Systemic effects with transdermal clonidine appear to be less severe and may occur with less frequency than with oral therapy. Some localized skin reactions have been reported with the transdermal system, with the most common dermatologic reactions being localized pruritus and erythema.3-7

The injectable form of clonidine has an adverse effect profile similar to both the oral and transdermal forms. The most commonly reported adverse event during clinical trials was a major decrease in blood pressure, particularly during the first few days of therapy. Other common side effects include postural hypotension, dry mouth, somnolence, dizziness, and confusion. Accidental dislodging of the catheter can result in rebound hypertension secondary to abrupt withdrawal.3-7

Clonidine is not without its share of drug interactions (see Table 2). Of particular note is the additive effect that is exhibited when combined with central nervous system depressants and anesthetic agents. Tricyclic antidepressants have been found to block the hypotensive effect of clonidine, whereas diuretics and other hypertension agents may enhance the hypotensive effect. Furthermore, clinicians should be aware that beta-adrenergic antagonists might exacerbate hypotension upon withdrawal of clonidine.3-7

The clinical utility of clonidine has been reported in many clinical trials and case reports (table 3). A representative study or report highlights each therapeutic use (Table 4). Notably, there may be more citations published for a given therapeutic use than referenced in this article. The only FDA-approved indication for clonidine is for the treatment of hypertension, and when given epidurally, for cancer pain relief; all other uses described are off-label.

Hypertension:4,6 The recommended regimen is 100 to 200 mcg/day in two divided doses, with a maximum of 2,400 mcg/day. Dosage for the transdermal therapeutic system is 100 mcg per 24 hours every week, with a maximum of 600 mcg per 24 hours every week. Doses up to 5,000 mcg/day have been attempted with unwanted side effects and no additional efficacy.

Hypertensive Emergency: Karachalios7 studied 38 severely hypertensive patients (systolic 175 to 210 mmHg, diastolic 105 to 130 mmHg). After observing patients at rest for one to two hours, an oral loading dose of clonidine 200 mcg was given, followed by 100 mcg/hour, to a maximum total dose of 800 mcg. Thirty-five patients responded well with a decreased mean blood pressure in six hours of 145 ± 20 mmHg systolic and 98 ± 15 mmHg diastolic. Side effects were minimal.

Atrial Fibrillation: In 1992, Roth et al.8 determined that low-dose clonidine was effective in slowing ventricular rate in patients with rapid atrial fibrillation. In 2001, Simpson et al.9 used clonidine to treat atrial fibrillation in 40 patients with new-onset, stable, rapid atrial fibrillation. Thus, clonidine controls ventricular rate with an efficacy comparable to that of digoxin and verapamil.

Congestive Heart Failure (CHF): Manmontri and MacLeod10 studied clonidine in CHF treatment. Clonidine 200 to 400 mcg/day orally significantly reduced heart rate and increased left ventricular ejection fraction, as well as improved New York Heart Association functional status. However, defects in the design require more study before clonidine can be recommended. Azevedo et al.11 studied the effect of intravenous (IV) clonidine on cardiac sympathetic activity and left ventricular function in CHF patients. Nine patients received a 50- or 100-mcg bolus of IV clonidine. The authors concluded that use of clonidine in CHF warrants further exploration.

Orthostatic Hypotension (OH):
Stumpf and Mitrzyk12 conducted a clinical review of treatment options for OH. Oral clonidine was titrated in patients with refractory OH. Patients given doses of 400 and 800 mcg showed improvement in standing time and blood pressure. Dry mouth and sedation were reported as the major side effects; however, these disappeared with long-term use.

Portal Pressure: Lin et al.13 studied the effect of combining propranolol with clonidine in patients with posthepatitic cirrhosis. Twenty patients received an IV injection of 0.1 mg/kg propranolol, followed 30 minutes later by 150 mcg of clonidine. Researchers concluded that the reduction in mean arterial pressure might limit the clinical utility of this combination in patients with already low arterial pressure.

Allodynia: Allodynia is a condition of sympathetically maintained pain, with ongoing pain and hyperalgesia.14 Davis et al. examined the use of topical clonidine patches to treat the hyperalgesia. Clonidine 200 and 300 mcg patches were applied to affected areas; each patch was left in place for two to 10 days. Topical clonidine significantly reduced hyperalgesia.14 Olson et al.15 reported on a patient with an electrical injury who was treated with topical clonidine. Eisenach et al.16 studied the use of intrathecal and IV clonidine to treat hyperalgesia from intradermal capsaicin injection in volunteers. Volunteers were randomized into four treatment groups: IV 50-mcg or 150-mcg injections and intrathecal 50-mcg or 150-mcg injections. Both doses of IV injections and the lower dose intrathecal administration did not produce any relief, whereas the 150-mcg intrathecal dose lessened pain within 45 minutes, with effects lasting at least four hours.

Intraoperative and Postoperative: De Kock et al.17 compared epidural clonidine to sufentanil in the perioperative period. Patients received epidural clonidine or sufentanil for 12 hours. Clonidine improved intraoperative hemodynamic stability and provided the same amount of postoperative analgesia as did sufentanil. Yet, clonidine had a longer-lasting residual analgesic effect, thus decreasing postoperative analgesic demands.

Pediatric Caudal Anesthesia (ages 1 to 7 years): Jamali et al.18 studied pediatric patients ages 1 to 7 years who received 1 mcg/kg of clonidine, 1/200,000 of epinephrine, or control in addition to 1 mL/kg of 0.25% bupivacaine. The duration of postoperative analgesia was significantly increased in the clonidine group, compared to bupivacaine alone or bupivacaine with epinephrine. Fewer clonidine patients required postoperative analgesia.

Intractable Cancer Pain: Eisenach et al.19 conducted a double-blind study in patients unresponsive to morphine who received 30 mcg/hour of epidural clonidine or placebo for 14 days. Pain was assessed using visual analog score and daily epidural morphine use. Patients with neuropathic pain gained the best relief from clonidine, with an overall success rate over placebo.

Cluster Headache Prophylaxis: Leone et al.20 studied transdermal clonidine in doses of 200 to 300 mcg/day. Five of 15 patients reported improvement during days 7 to 12 of therapy. That the improvement was a result of reaching the final phase of the cluster periods could not be ruled out. More studies are needed to clarify the efficacy of transdermal clonidine to treat cluster headaches.

Chronic Headaches: Dalessio21 began therapy with transdermal clonidine 100 mcg/day for women under 130 lb and 200 mcg/day for women more than 130 lb and for all men. After 18 weeks, patients were switched to oral clonidine 100 to 200 mcg/day; dosage was tapered off over three to five days. This protocol was successful in nine of 12 patients with chronic headaches.

Migraine Headaches: A review by Wood22 suggests oral clonidine 50 mcg twice daily, titrated to 75 mcg twice daily, was effective, with mild side effects.

Labor Analgesia: Gautier et al.23 randomized patients requiring labor analgesia to various intrathecal solutions for analgesia, consisting of clonidine and sufentanil. Clonidine injection 30 mcg combined with intrathecal sufentanil significantly increased the duration of analgesia during the first stage of labor without adverse maternal or fetal effects.

Postoperative Pain in Children: Mikawa et al.24 examined clonidine in children undergoing minor surgery. Ninety children ages 5 to 12 years received placebo or clonidine (2 or 4 mcg/kg) 105 minutes before anesthesia induction. Clonidine 4 mcg/kg provided more postoperative analgesia than did the other treatment groups.

Reflex Sympathetic Dystrophy: Rauck et al.25 randomized 26 patients with chronic pain to 300 or 700 mcg of epidural clonidine or placebo. Responders then received a continuous epidural infusion of 10 to 50 mcg/hour of clonidine. Clonidine was shown to provide pain relief.

Spinal Cord Injury Pain:
Siddall et al.26 reported on a patient who had received multiple agents to treat spinal cord injury pain for one year. Intrathecal clonidine 17 mcg/day combined with morphine 10 mg/day produced a 50% reduction in previous pain levels.

Akathisia: Blaisdell27 referenced a study with six patients who showed major improvement, four of whom obtained complete remission. Adler et al.28 titrated oral clonidine to a maximum of 150 to 400 mcg/day and observed significantly reduced akathisia and anxiety at the maximum dose. Sedation was a problematic side effect.

Peripheral Neuropathy: Tan and Croese29 reported cases where excellent pain relief of disabling leg pain was obtained using oral clonidine 75 to 100 mcg/day. Schwartz and Rosenfeld30 reported a case in which oral clonidine 75 mcg twice daily was used with rapid and complete relief of painful muscle cramps and pruritus. Kingery31 reported that transdermal clonidine at doses of 300 mcg daily had little effect on pain, yet a subset of patients did have analgesia. Oral clonidine at doses of 200 mcg/day provided pain relief.

Neuropathic Orofacial Pain: Epstein et al.32 examined 17 patients who applied clonidine in a cream (200 mcg/g) four times daily to the site of pain. Improvement was noticed in patients diagnosed with both neuropathic pain (50% of patients) and neuralgia (67% of patients).

Diabetic Gastroparesis: Rosa-e-Silva et al.33 evaluated the effects of clonidine in patients with longstanding diabetes and evidence of autonomic neuropathy. Treatment with oral clonidine was given in doses ranging from 200 to 600 mcg/day. Results showed that gastric emptying half-time and symptoms decreased in all patients.

Essential Tremor: Koller et al.34 evaluated clonidine in 10 patients randomized to receive either placebo or incremental doses of clonidine until a dose of 600 mcg was reached or unwanted side effects occurred. Neither placebo nor clonidine significantly reduced hand tremor.

Memory Enhancement in Korsakoff's Psychosis: McEntee and Mair35 studied patients with chronic memory disorder to assess if clonidine, d-amphetamine, or methysergide would improve memory. Clonidine was linked with major memory improvement.

Postepidural Shivering: Yang et al.36 studied 40 patients who were randomly assigned to receive either normal saline or clonidine 150 mcg diluted in 10 mL of normal saline 20 minutes before epidural administration. Other studies suggest that shivering occurs in 30% to 64% of people receiving epidural lidocaine. This study showed that the incidence of shivering in the clonidine group was 5%, and clonidine was effective in preventing shivering associated with epidural anesthesia.

Postanesthesia Shivering: Generali and Cada37 conducted a literature review of 295 patients who received a single clonidine dose of 3 mcg/kg at various times throughout the surgical procedure. Single-dose clonidine 3 mcg/kg was as effective as meperidine and superior to placebo in the prevention of postanesthetic shivering.

Restless Legs Syndrome: Zoe et al.38 reported a case that was resistant to traditional therapy. The patient was then treated with clonidine 100 mcg at bedtime, titrated to 900 mcg/day. After 15 months of successful treatment, the dosage was reduced to 450 mcg/day due to the reported side effect of dry mouth.

Hypertonicity: Donovan et al.39 studied the use of clonidine in 55 patients with spasticity after sustaining a spinal cord injury. Over half (56%) of patients treated with oral clonidine 100 to 400 mcg daily showed some relief.

Tetanus-Induced Autonomic Dysfunction: Sutton et al.40 reported the case of a man sustaining a compound fracture in which tetanus had set in. After inadequate response to magnesium sulfate, clonidine 300 mcg every eight hours was added to control sympathetic overactivity. Clonidine dramatically improved cardiovascular instability and allowed reduction of muscle relaxants and sedation.

Hyperkinetic Movement Disorders: Two reviews41,42 suggest that oral clonidine, titrated to a range of 100 to 800 mcg/day, may relieve symptoms in children. Phonic tics were more responsive to clonidine. Main adverse effects included sedation, dry mouth, and potential rebound hypertension upon withdrawal.

Tourette's Syndrome: Leckman et al.43 randomized 47 patients to receive clonidine 4 to 5 mcg/kg to a maximum of 250 mcg/day or placebo. Clonidine reduced symptoms of impulsivity, hyperactivity, and tics associated with Tourette's syndrome.

Substance Withdrawal: Robinson et al.44 examined the effectiveness of clonidine in the treatment of alcohol withdrawal. The study was double-blind, and patients were randomized to receive either clonidine or chlormethiazole. Clonidine was found less effective and had greater serious adverse effects than chlormethiazole. Keshavan et al.45 used oral clonidine 600 mcg/day to treat a patient undergoing benzodiazepine withdrawal. After previous failure of a medically supervised taper of lorazepam, the addition of clonidine allowed lorazepam to be tapered over two weeks without any withdrawal symptoms. McGee and Murray46 reviewed four cases in which clonidine had been used to treat nicotine withdrawal. Doses of 100 to 300 mcg/day were useful adjuncts to a cessation program. Clonidine helped relieve patients' anxiety related symptoms. Cheskin et al.47 compared clonidine to buprenorphine for the treatment of acute opioid detoxification. Patients were randomly assigned to receive either buprenorphine or clonidine. Buprenorphine provided greater relief of withdrawal symptoms and had fewer side effects than clonidine. Sovner48 reported two cases of patients who were experiencing thioridazine withdrawal–induced behavior. They were given oral clonidine 300 mcg twice daily or transdermal clonidine 300 mcg/day. Clonidine enabled a successful withdrawal from thioridazine, and successful tapering of clonidine dosage was later achieved.

Acute Anorexia Nervosa: Casper et al.49 studied four treatment-resistant patients in a placebo-controlled crossover trial. Clonidine was initiated at 150 mcg/day  and was gradually increased to a maximum of 500 to 700 mcg/day. Clonidine was not superior to placebo for promoting weight gain, nor did clonidine intensify the urge to eat before and after meals.

Attention-Deficit/Hyperactivity Disorder (ADHD) and Conduct Disorder: Schvehla et al.50 conducted a retrospective study of 18 prepubescent boys who received clonidine after failed trials of conventional psychostimulants. Each child received oral clonidine 50 mcg/day, titrating upward until clinical improvement or a maximum dose of 400 mcg was reached. The average clonidine dose used was 8 mcg/kg. Eleven of the 18 children exhibited marked clinical improvement. Sedation was the primary side effect, lasting two to three days in 40% of patients following dosage increase.

Behavioral Symptoms of HIV-1 Encephalopathy: Ceseña et al.51 reported the case of a four-year-old boy with AIDS who exhibited hyperactivity and impulsive behavior. The patient was given oral clonidine 25 mcg/day, which was slowly increased to 25 mcg three times daily. Improvement was seen in hyperactivity, impulsivity, and sleeping patterns, and aggressive behavior decreased.

Bipolar Disorder: Janicak et al.52 studied clonidine in the acute mania phase of bipolar disorder. Twenty-one patients received placebo or clonidine for two weeks. The average maximum daily dose of clonidine was 470 mcg. Clonidine was no more effective than placebo, and side effects contributed to a significantly higher dropout rate. Kontaxakis et al.53 reported a case in which oral clonidine was used in the treatment of refractory mixed bipolar disorder. Oral clonidine 125 mcg twice daily was added to the patient's regimen. Within two days, the patient had rapid improvement in psychopathology, followed by a decline in effect. The dose was eventually titrated slowly to 600 mcg/day with no significant side effects noted. Bakchine et al.54 reported a case of a woman with focal brain damage in a manic-like state who was given alternating trials of clonidine 300 mcg twice daily, placebo tablets, carbamazepine, and then levodopa-benserazide. Clonidine produced a marked decrease in manic symptoms and improved cognitive functions.

Narcolepsy: Salín-Pascual et al.55 studied the effects of clonidine on two patients given 150 mcg/m2 in the morning. One week later, they were given placebo, followed by clonidine on two consecutive nights. Following the blind trial, patients were then given oral clonidine 225 mcg at bedtime, and recordings were taken at predefined intervals. A rapid improvement was seen in both patients receiving clonidine. Sleep attacks, daytime sleepiness, and cataplexy disappeared.

Panic Disorder: Puzantian and Hart56 cited four studies demonstrating that oral clonidine in doses of 100 mcg twice daily to 2 mg/day should be considered as a last-line anxiolytic agent. However, no clinical indicators of success were identified.

Posttraumatic Stress Disorder: Kinzie and Leung57 examined patients who received 50 mg of imipramine at night, which was increased to 150 mg over three weeks. If there was no response after three weeks, clonidine 100 mcg twice daily was added. Results showed that combined with imipramine 150 mg/day, all patients receiving clonidine symptomatically improved.

Schizophrenia: Freedman et al.58 compared clonidine to a neuroleptic and placebo in eight patients with schizophrenia. Oral clonidine was dosed initially at 100 mcg twice daily and increased to 900 mcg/day. Results suggested that clonidine and neuroleptics may be equally efficacious as antipsychotics in treating schizophrenia. Clonidine reduced symptoms of psychosis resulting from withdrawal of drugs that have produced tardive dyskinesia.

Sleep Disorders: Horacek59 used clonidine extemporaneously compounded extended-release capsules for sleep disorders. The combination of immediate-release oral clonidine one hour before bedtime with extended-release clonidine several hours before bedtime helped prevent sleep disorders. The immediate-release capsule aids in onset of sleep, while the extended release prevents rebound hyperarousal during the night. The extended-release capsules were compounded to release clonidine over an eight-hour period. Rubinstein et al.60 reported the case of a child with ADHD who had chronic sleep problems due to the use of dextroamphetamine. Oral clonidine 50 mcg was started 45 minutes prior to sleep. Clonidine had an almost immediate impact in the child's sleep pattern, which greatly improved over a two-month period.

Social Phobia: Goldstein61 reported the case of a patient with increased discomfort and anxiety in social situations. After several trials with other agents, clonidine 100 mcg twice daily was started. After one week, the patient had a remarkable decrease in frequency and intensity of panic attacks. After four months, the patient had only infrequent attacks. No side effects were reported.

Carcinoid-Associated Diarrhea: Schwörer et al.62 reported a case in which a man with carcinoid syndrome treated with octreotide and interferon developed diarrhea (six to eight watery stools a day). The patient was treated with oral clonidine 75 mcg three times a day and 150 mcg at bedtime. This reduced stool frequency to two to three stools per day, with no defecation at night. Mild sedation and dry mouth were noted.

High Intestinal Output Associated with Small Bowel Transplant: Rovera et al.63 conducted a study of 13 patients who underwent small bowel transplant to assess the efficacy of clonidine in reducing intestinal output. Oral clonidine was initiated at doses of 25 mcg twice daily in children and 50 mcg twice daily in adults. Loperamide, tincture of opium, paregoric, diphen­ oxylate/atropine, and somatostatin were used alone or in combination for control of output. Results showed that intestinal output was unchanged in children; however, adult output decreased by a mean of 700 mL.

Ulcerative Colitis and Proctitis: Melander et al.64 reported seven cases in which oral clonidine was used to treat ulcerative colitis or proctitis. At doses of 150 to 450 mcg daily, some patients temporarily experienced diminished and more solid stools. Adverse effects of fatigue and nausea seemed to outweigh the possible benefits of clonidine.

Antiemetic in Children: Mikawa et al.65 conducted a trial to determine if preoperatively administered oral clonidine reduced the incidence of vomiting in children following strabismus surgery. One hundred forty children (ages 3 to 12 years) were randomized to placebo, diazepam 0.4 mcg/kg, clonidine 2 mcg/kg, or clonidine 4 mcg/kg in 2 mL/kg of apple juice. Agents were administered 100 minutes prior to induction of anesthesia. The incidence and frequency of vomiting was found to be lower in the clonidine 4 mcg/kg group.

Maintenance of Stable Hemodynamics: Costello and Cormack66 compared clonidine to temazepam in controlling hemodynamics during pin head-holder application during a craniotomy. Fifty patients took oral clonidine 3 mcg/kg or oral temazepam 10 to 20 mg given 90 minutes before induction of anesthesia. Clonidine was effective in reducing mean arterial blood pressure increases that result from pin head-holder application.

Laryngoscopy: Laurito et al.67 studied the effects of oral clonidine premedication on sedation, and hemodynamic responses during preoperative period, laryngoscopy, and postanesthesia recovery. Patients took clonidine 100 mcg, clonidine 200 mcg, triazolam 0.25 mg, or placebo. Oral clonidine 200 mcg given 90 minutes prior to anesthetic induction effectively sedated and blunted the hemodynamic response, but anxiolytic effects were not seen.

Liver Transplantation: De Kock et al.68 examined the effectiveness of clonidine on fluid requirements and hemodynamic stability during liver transplantation surgery. Twenty patients were randomized to receive either slow IV bolus of clonidine 4 mcg/kg during anesthesia induction or control. IV clonidine significantly reduced the need for IV fluids and blood products and did not compromise circulatory stability.

Intraoperative Propofol Requirements: Guglielminotti et al.69 studied 28 patients randomized in this double-blind study to receive hydroxyzine 1 mg/kg or clonidine 5 mcg/kg two hours before induction of anesthesia. Clonidine significantly reduced intraoperative propofol requirements, compared to hydroxyzine, without adverse effects on recovery or hemodynamic stability.

Pharmacy Cost in Preoperative Administration: Vallès et al.70 examined 80 patients randomly assigned to receive 300 mcg of oral, intramuscular, or epidural clonidine or placebo at a set time prior to surgery. Results indicated that in all groups premedicated with clonidine, independent of route of administration, the expense of isoflurane during anesthesia of about two hours' duration was significantly reduced. Notably, the cost of epidural clonidine offset the savings in isoflurane.

Rhinoplasty: Britto et al.71 studied clonidine in 20 patients  randomized to receive temazepam 10 mg or temazepam 10 mg plus clonidine 3 mcg/kg 45 minutes prior to induction of anesthesia. Clonidine with temazepam 10 mg was superior to temazepam alone in decreasing mean arterial blood pressure, attenuating response to intubation, and providing a better blood-free surgical field.

Sedation in Intensive Care: Böhrer et al.72 reported on a patient who underwent distal esophagectomy and proximal gastrectomy who was not achieving adequate sedation through the combination of midazolam and fentanyl infusions. Clonidine 0.014 mcg/kg/min continuous infusion was then added with excellent analgesia and sedation control. Clonidine abrupt withdrawal led to circulatory problems requiring a 12-day weaning period.

Hyperthyroidism: Herman et al.73 studied the effect of clonidine on inhibiting biological effects of catecholamines released during hyperthyroidism. Patients with hyperthyroidism received either nadolol 40 mg twice daily for one week or clonidine 150 mcg twice daily for one week. Clonidine had similar clinical effects to nadolol.

Treatment of Growth Delay: Moreno Esteban et al.74 studied clonidine in 112 prepubescent children. Oral clonidine 75 mcg/m2 was given daily for at least one year. Clonidine may increase growth velocity in at least 65% of prepubescent patients with constitutional growth delay.

Miscellaneous uses have also been documented, including prevention of cyclosporine-induced nephrotoxicity, excessive sweating, hot flashes, trichorrhexis nodosa, and as a diagnostic tool for pheochromocytoma.18,75-83

The clinical utility of clonidine has been demonstrated through many varied applications. This article compiles case reports and studies to clarify dosage and outcomes associated with each therapeutic use. The available literature on clonidine and its clinical utility was reviewed. However, there may be more reports for a given therapeutic use than cited in this article; original references should be checked for more information before the drug is used for the listed disease states. Many of these studies involved the use of oral clonidine, which resulted in an undesirable outcome or a discontinuation of treatment due to unwanted side effects. Sedation and dry mouth are more pronounced with oral therapy and when doses are initiated at 200 mcg/day or greater. Initiating therapy with doses of 100 mcg each night can minimize these adverse effects. Due to the small number of patients in these studies, the findings cannot be extrapolated to the general population. These factors should be considered before applying these data to clinical practice. Although clonidine may have limited use in the initial treatment of hypertension, this article evidences its clinical utility in various disease states.

1. Oesterheld J, Tervo R. Clonidine: a practical guide for usage in children. South Dakota J Med. 1996;234-237.
2. Mahoney A, Seeley H. Clonidine: old friend–new guises. Br J Hosp Med. 1990;44:358-361.
3. Lowenstein J. Drugs five years later: clonidine. Ann Intern Med. 1980;92:74-77.
4. Catapres (clonidine) product information. Ridgefield, CT; Boehringer Ingelheim: 4/98.
5. Duraclon (epidural clonidine) product information. Columbus, Ohio; Roxane Laboratories: 5/00.
6. Clonidine. In: Facts and Comparisons. St. Louis, MO: Facts and Comparisons: 2004.
7. Karachalios GN. Hypertensive emergencies treated with oral clonidine. Eur J Clin Pharmacol. 1986;31:227-229.
8. Roth A, Kaluski E, Felner S, et al. Clonidine for patients with rapid atrial fibrillation. Ann Intern Med. 1992;116:388-390.
9. Simpson CS, Ghali WA, Sanfilippo AJ, et al. Clinical assessment of clonidine in the treatment of new-onset rapid atrial fibrillation: a prospective, randomized clinical trial. Am Heart J. 2001;142:e3.
10. Manmontri A, MacLeod SM. Centrally acting sympatholytic agents in the treatment of congestive heart failure. Drugs. 1990;40:169-175.
11. Azevedo ER, Newton GE, Parker JD. Cardiac and systematic sympathetic activity in response to clonidine in human heart failure. J Am Coll Cardiol. 1999;33:186-191.
12. Stumpf JL, Mitrzyk B. Management of orthostatic hypotension. Am J Hosp Pharm. 1994;51:648-652.
13. Lin HC, Tsai YT, Yang MC, et al. Haemodynamic effects of a combination of propranolol and clonidine in patients with post-hepatitic cirrhosis. J Gastroenterol Hepatol. 1995;10:281-286.
14. Davis KD, Treede RD, Raja SN, et al. Topical application of clonidine relieves hyperalgesia in patients with sympathetically maintained pain. Pain. 1991;47:309-317.
15. Olson EE, Hogan QH, Abram SE. Comments on topical clonidine for relief from allodynia. Pain. 1993;54:361.
16. Eisenach JC, Hood DD, Curry R. Intrathecal, but not intravenous, clonidine reduces experimental thermal or capsaicin-induced pain and hyperalgesia in normal volunteers. Anesth Analg. 1998;87:591-596.
17. De Kock M, Famenne F, Deckers G, Scholtes JL. Epidural clonidine or sufentanil for intraoperative and postoperative analgesia. Anesth Analg. 1995;81:1154-1162.
18. Jamali S, Monin S, Begon C, Dubousset AM. Clonidine in pediatric caudal anesthesia. Anesth Analg. 1994;78:663-666.
19. Eisenach JC, DuPen S, Dubois M, et al. Epidural clonidine analgesia for intractable cancer pain. The Epidural Clonidine Study Group. Pain. 1995;61:391-399.
20. Leone M, Attanasio A, Grazzi L, et al. Transdermal clonidine in the prophylaxis of episodic cluster headache: an open study. Headache. 1997;37:559-560.
21. Dalessio DJ. Clonidine in chronic headaches. Headache. 1991;31:257.
22. Wood RA. The therapeutic uses of clonidine. Scott Med J. 1979;24:226-232.
23. Gautier PE, De Kock M, Fanard L, et al. Intrathecal clonidine combined with sufentanil for labor analgesia. Anesthesiololgy. 1998;88:651-656.
24. Mikawa K, Nishina K, Maekawa N, Obara H. Oral clonidine premedication reduces postoperative pain in children. Anesth Analg. 1996;82:225-230.
25. Rauck RL, Eisenach JC, Jackson K, et al. Epidural clonidine treatment for refractory reflex sympathetic dystrophy. Anesthesiology. 1993;79:1163-1169.
26. Siddall PJ, Gray M, Rutkowski S, Cousins MJ. Intrathecal morphine and clonidine in the management of spinal cord injury pain: a case report. Pain. 1994;59:147-148.
27. Blaisdell GD. Akathisia: a comprehensive review and treatment summary. Pharmacopsychiat. 1994;27:139-146.
28. Adler LA, Angrist B, Peselow E, et al. Clonidine in neuroleptic-induced akathisia. Am J Psychiatry. 1987;144:235-236.
29. Tan YM, Croese J. Clonidine and diabetic patients with leg pains. Ann Intern Med. 1986;105:633-634.
30. Schwartz J, Rosenfeld V. Clonidine for painful diabetic-uremic leg cramps and pruritus–a case report. Angiology. 1993;44:985.
31. Kingery, WS. A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. Pain. 1997;73:123-139.
32. Epstein JB, Grushka M, Le N. Topical clonidine for orofacial pain: a pilot study. J Orofac Pain. 1997;

33. Rosa-e-Silva L, Troncon LE, Oliveira RB, et al. Treatment of diabetic gastroparesis with oral clonidine. Aliment Pharmacol Ther. 1995;9:179-183.
34. Koller W, Herbster G, Cone S. Clonidine in the treatment of essential tremor. Movement Disorders. 1986;1:235-237.
35. McEntee WJ, Mair RG. Memory enhancement in Korsakoff's psychosis by clonidine: further evidence for a noradrenergic deficit. Ann Neurol. 1980;7:466-470.
36. Yang CH, Yu CC, Seah YS, et al. Effect of intravenous clonidine on prevention of postepidural shivering. Acta Anaesthesiol Sin. 1993;31:121-126.
37. Generali J, Cada DJ. Clonidine: postanesthesia shivering. Hosp Pharm. 2005;40:570-581.
38. Zoe A, Wagner ML, Walters AS. High-dose clonidine in a case of restless legs syndrome. Ann Pharmacother. 1994;28:878-881.
39. Donovan WH, Carter RE, Rossi CD, Wilkerson MA. Clonidine effect on spasticity: a clinical trial. Arch Phys Med Rehabil. 1988;69:193-194.
40. Sutton DN, Tremlett MR, Woodcock TE, Nielsen MS. Management of autonomic dysfunction in severe tetanus: the use of magnesium sulphate and clonidine. Intensive Care Med. 1990;16:75-80.
41. Bressman, SB, Greene PE. Treatment of hyperkinetic movement disorders. Neurol Clin. 1990;8:51-75.
42. Jankovic J. Recent advances in the management of tics. Clin Neuropharmacology. 1986;9:S100-S110.
43. Leckman JF, Hardin MT, Riddle MA, et al. Clonidine treatment of Gilles de la Tourette's syndrome. Arch Gen Psychiatry. 1991;48:324-328.
44. Robinson BJ, Robinson GM, Maling TJB, Johnson RH. Is clonidine useful in the treatment of alcohol withdrawal. Alcohol Clin Exp Res. 1989;13:95-98.
45. Keshavan JS, Crammer JL. Clonidine in benzodiazepine withdrawal. Lancet. 1985;1:1325-1326.
46. McGee KH, Murray KM. Clonidine in nicotine withdrawal. DICP Ann Pharmacotherapy. 1989;23:473-474.
47. Cheskin LJ, Fudala PJ, Johnson RE. A controlled comparison of buprenorphine and clonidine for acute detoxification from opioids. Drug Alcohol Dependence. 1994;36:115-121.
48. Sovner R. Thioridazine withdrawal-induced behavioral deterioration treated with clonidine: two case reports. Mental Retardation. 1995;33:221-225.
49. Casper RC, Schlemmer RS Jr, Javaid JI. A placebo-controlled crossover study of oral clonidine in acute anorexia nervosa. Psychiatry Res. 1987;20:249-260.
50. Schvehla TJ, Mandoki MW, Sumner GS. Clonidine therapy for comorbid attention deficit hyperactivity disorder and conduct disorder: preliminary findings in a children's inpatient unit. South Med J. 1994;87:692-695.
51. Ceseña M, Lee DO, Cebollero AM, Steingard RJ. Case study: behavioral symptoms of pediatric HIV-1 encephalopathy successfully treated with clonidine. J Am Acad Child Adolesc Psychiatry. 1995;34:302-306.
52. Janicak PG, Sharma RP, Easton M, et al. A double-blind, placebo-controlled trial of clonidine in the treatment of acute mania. Psychopharmacol Bulletin. 1989;25:243-245.
53. Kontaxakis V, Markianos M, Markidis M, Stefanis C. Clonidine in the treatment of mixed bipolar disorder. Acta Psychiatr Scand. 1989;79:108-110.
54. Bakchine S, Lacomblez L, Benoit N, et al. Manic-like state after bilateral orbitofrontal and right temporoparietal injury: efficacy of clonidine. Neurology. 1989;39:777-781.
55. Salín-Pascual R, de la Fuente J, Fernández-Guardiola A. Effects of clonidine in narcolepsy. J Clin Psychiatry. 1985;46:528-531.
56. Puzantian T, Hart LL. Clonidine in panic disorder. Ann Pharmacother. 1993;27:1351-1353.
57. Kinzie JD, Leung P. Clonidine in Cambodian patients with posttraumatic stress disorder. J Nerv Ment Dis. 1989;177:546-550.
58. Freedman R, Kirch D, Bell J, et al. Clonidine treatment of schizophrenia: double-blind comparison to placebo and neuroleptic drugs. Acta Psychiatr Scand. 1982;65:35-45.
59. Horacek HJ. Extended-release clonidine for sleep disorders. J Am Acad Child Adolesc Psychiatry. 1994;33:1210.
60. Rubinstein S, Silver LB, Licamele WL. Clonidine for stimulant-related sleep problems. J Am Acad Child Adolesc Psychiatry. 1994;33:281-282.
61. Goldstein S. Treatment of social phobia with clonidine. Biol Psychiatry. 1987;22:369-372.
62. Schwörer H, Münke H, Stöckmann F, Ramadori G. Treatment of diarrhea in carcinoid syndrome with ondansetron, tropisetron, and clonidine. Am J Gastroenterol. 1995;90:645-648.
63. Rovera G, Furukawa H, Reyes J, et al. The use of clonidine for the treatment of high intestinal output following small bowel transplantation. Transplantation Proc. 1997;29:1853-1854.
64. Melander M, Almer S, Ström M. Clonidine in ulcerative colitis and proctitis. J Int Med. 1993;233:93-94.
65. Mikawa K, Nishina K, Maekawa N, et al. Oral clonidine premedication reduces vomiting in children after strabismus surgery. Can J Anaesth. 1995;42:977-981.
66. Costello TG, Cormack JR. Clonidine premedication decreases hemodynamic responses to pin head-holder application during craniotomy. Anesth Analg. 1998;86:1001-1004.
67. Laurito CE, Baughman VL, Becker GL, et al. The effectiveness of oral clonidine as a sedative/anxiolytic and as a drug to blunt the hemodynamic responses to laryngoscopy. J Clin Anesth. 1991;3:186-193.
68. De Kock M, Laterre PF, Van Obbergh L, et al. The effects of intraoperative intravenous clonidine on fluid requirements, hemodynamic variables, and support during liver transplantation: a prospective, randomized study. Anesth Analg. 1998;86:468-476.
69. Guglielminotti J, Descraques C, Petitmaire S, et al. Effects of premedication on dose requirements for propofol: comparison of clonidine and hydroxyzine. Br J Anaesth. 1998;80:6:733-736.
70. Vallès J, Samsó E, Vilar X, et al. Pharmacy savings generated by preoperative administration of clonidine. J Clin Anesth. 1998;10:36-40.
71. Britto JA, McCoy D, Fourie LR. Clonidine as premedication for rhinoplasty. Plast Reconstr Surg. 1997;100:548-549.
72. Böhrer H, Bach A, Layer M, Werning P. Clonidine as a sedative adjunct in intensive care. Intensive Care Med. 1990;16:265-266.
73. Herman VS, Joffe BI, Kalk WJ, et al. Clinical and biochemical responses to nadolol and clonidine in hyperthyroidism. J Clin Pharmacol. 1989;29:1117-1120.
74. Moreno Esteban B, Monereo Mejias S, Rodriguez Poyo-Guerrero P, et al. One year treatment with clonidine in children with constitutional growth delay. J Endocrinol Invest. 1991;14:75-79.
75. Luke J, Luke DR, Williams LA, et al. Prevention of cyclosporine-induced nephrotoxicity with transdermal clonidine. Clin Pharm. 1990;9:49-53.
76. Feder R. Clonidine Treatment of excessive sweating. J Clin Psychiatry. 1995;56:35.
77. Lucero MA, McCloskey WW. Alternatives to estrogen for the treatment of hot flashes. Ann Pharmacother. 1997;31:915-917.
78. Parra RO, Gregory JG. Treatment of post-orchiectomy hot flashes with transdermal administration of clonidine. J Urol. 1990;143:753-754.
79. Loprinzi CL, Goldberg RM, O'Fallon JR, et al. Transdermal clonidine for ameliorating post-orchiectormy hot flashes. J Urol. 1994;151:634-636.
80. Goldberg RM, Loprinzi CL, O'Fallon JR, et al. Transdermal clonidine for ameliorating tamoxifen-induced hot flashes. J Clin Oncol. 1994;12:155-158.
81. Sjoberg RJ, Simcic KJ, Kidd GS. The clonidine suppression test for pheochromocytoma: a review of its utility and pitfalls. Arch Intern Med. 1992;152:1193-1197.
82. Camacho-Martinez F. Localized trichorrhexis nodosa. J Am Acad Dermatol. 1989;20:696-697.
83. Houston MC. Clonidine hydrochloride: Review of pharmacologic and clinical aspects. Prog Cardio Dis. 1981;23:337-350.

To comment on this article, contact