Clonidine discontinuation

It is estimated that about 7% of patients receiving clonidine discontinue the drug because of side effects. Although the symptoms are generally mild and tend to subside if therapy is continued for several weeks, as many as 50% of the patients complain of drowsiness and dryness of mouth. Other untoward effects include constipation, nausea or gastric upset, and impotence. These effects are characteristic of interference with the functioning of the sympathetic nervous system. 

Geriatric Considerations - Summary Discontinuation of clonidine is likely to require a slow taper. If the patient is receiving a concomitant beta-blocker, the beta-blocker must be tapered and discontinued before discontinuing clonidine. Clonidine discontinuation in the presence of a beta-blocker can lead to severe hypertension and cardiovascular events due to unopposed alpha-receptor stimulation. CNS effects often preclude its use in older adults. A higher clonidine dose (0.4 mg/day) is generally needed to control peri- or postmenopausal vasomotor symptoms however, adverse effects often make it difficult to achieve effective doses. 

Fyer AJ, Liebowitz MR, Gorman JM, et al Effects of clonidine on alprazolam discontinuation in panic patients a pilot study. J Clin Psychopharmacol 8 270—274,1988 Garvey MJ, Tollefson GD Prevalence of misuse of prescribed benzodiazepines in patients with primary anxiety disorder or major depression. Am J Psychiatry 143 1601-1603, 1986... 

Clonidine, delivered transdermally or orally, is an effective smoking-cessation treatment. It is given for 3 to 10 weeks and should not be discontinued abruptly. Abrupt discontinuation may cause nervousness, agitation, headache, tremor, and rapid rise in blood pressure. 

Geriatric Considerations - Summary The alphaj-adrenergic agonist effect of tizani-dine lowers blood pressure in a manner similar to clonidine but is less potent. Older adults are at risk of hypotension and when discontinued, this drug should be tapered to avoid hypertensive rebound. 

It is necessary to taper clonidine rather than abruptly discontinuing it to decrease the risk of rebound hypertension (Leckman et ah, 1986). Hunt et al. (1990) recommend that if the medication has been used for only 1 week, it can be discontinued immediately. If it has been prescribed for 1-4 weeks, it can be tapered by 0.05 mg daily and if it has been prescribed for over 4 weeks, it should be tapered by 0.05 mg every third day. The possibility of rebound hypertension should also be evaluated in patients on clonidine who are not consistent in their medication-taking behavior. Eess is known about the likelihood of rebound hypertension following discontinuation of guanfacine. Although the PDR lists this as possible, one study found this not to be the case (Wilson et ah, 1986), possibly because of its longer duration of action. 

Gadow et al. (1995), however, found no increase in tics in a placebo-controlled trial of methylphenidate in children with ADHD and a tic disorder. Other trials of stimulants in such children have found little or no average increase in tic severity scores, but clinically significant increases of tics in a handful of subjects severe enough to prompt discontinuation of the stimulant (Castellanos et al., 1997 Law and Schachar, 1999) or to require addition of a medication to control their tic symptoms (Gadow et al., 1999). A multicenter, doubleblind, placebo-controlled, parallel group study of methylphenidate and clonidine, used alone or in combination in 136 children with ADHD and a comorbid... 

Goodnick PJ, Gershon ES Lithium, in Handbook of Neurochemistry. Edited by Lajtha A. New York, Plenum, 1985, pp 103-149 Goodnick PJ, Meltzer HY Neurochemical changes during discontinuation of lithium prophylaxis, 1 increases in clonidine-induced hypotension. Biol Psychiatry 19 883-889, 1984... 

Other than slow taper, no consistently effective treatment to alleviate withdrawal symptoms has been reported. Although several compounds have been studied (e.g., b-blockers, clonidine, carbamazepine, abercamil, ondansetron), results have been contradictory ( 250). Carbamazepine, however, may be useful in seizure-prone patients (251). Valproate (VPA) has also been reported to benefit patients undergoing BZD discontinuation after long-term dependence ( 252), which may be related to VPA s potential anxiolytic properties, its ability to alleviate withdrawal phenomena, or both. The azaspirone anxiolytic buspirone has been reported ineffective in suppressing withdrawal symptoms, particularly in long-term BZD users (253, 254). Hydroxyzine has also been found beneficial in treating patients for lorazepam withdrawal (255). 

Clonidine has also been useful in one controlled study and in a few case reports. Although this agent has the advantage of avoiding acute and chronic EPS associated with neuroleptics, its effects on blood pressure have appropriately constrained its use in this age population. There is also the concern regarding rebound hypertension if this agent is abruptly discontinued (e.g., noncompliance). 

Clonidine is one of the most widely used sedating medications in pediatric and child psychiatry practice, particularly in children with sleep onset delay and ADHD. It is a central alpha2 agonist. Pharmacokinetics show rapid absorption, with an onset action within 1 h, peak effects at 2-4 h and a half-life 6-24 h. Effects on sleep architecture are fairly minimal but may include decreased REM, so that discontinuation can lead to REM rebound. Clonidine has a narrow therapeutic index, and there has been a recent dramatic increase in reports of overdose with this medication. Potentially significant side effects including hypotension, bradycardia, anticholinergic effects, irritability, and dysphoria rebound hypertension may occur on abrupt discontinuation. Tolerance often develops, necessitating increases in dose. 

An 11-year-old boy developed acute dysuria and increased frequency accompanied by gross hematuria. He was taking fluoxetine, valproic acid, benzatropine, haloperidol, clonidine, trazodone, and nasal desmopressin. One week before presentation, risperidone had been introduced instead of haloperidol to improve behavioral control. The risperidone was discontinued and haloperidol resumed, and his symptoms resolved during the following week. 

For ADHD patients, clonidine should generally be discontinued before anficipafed pregnancies... 

A 39-year-old quadriplegic man with poorly controlled pain had many features consistent with autonomic dysfunction (for example a C4 spinal lesion, orthostatic hypotension, hypertension). He routinely used trans-dermal clonidine and transdermal glyceryl trinitrate as needed for control of acute hypertensive episodes. The clonidine was discontinued, after which his blood pressure fell (maximum systolic and diastolic pressures by about 50 and 25 mmHg respectively). 

A high percentage of patients who take clonidine (up to 38%) (34) develop contact allergic reactions, usually due to the active ingredient, at the patch application site (35). This has been reported with a frequency of 15% in 357 African-American hypertensive patients. It can lead to drug discontinuation in 4.2% of patients. 

Schmidt GR, Schuna AA. Rebound hypertension after discontinuation of transdermal clonidine. Clin Pharm 1988 7(10) 772. ... 

Side effects of clonidine therapy include dry mouth, drowsiness, sedation, and constipation. Abrupt discontinuation of therapy may result in a withdrawal syndrome manifested as restless and headache in addition to significant rebound hypertension. Withdrawal can be avoided by tapering therapy over 2-4 days. The incidence of a local dermatitis or an extended dermal reaction with use of the transdermal patch is 15-20%. 

Central a2-agonists Clonidine (Catapres) 0.1-0.8 2 Abrupt discontinuation may cause rebound... 

Clonidine, a prescription drug, is an efficacious smoking cessation treatment. It may be used under a clinician s supervision as a second-line agent to treat tobacco dependence. A recent meta-analysis of six trials showed that clonidine increased smoking cessation rates by 11% (OR 1.89 Cl 1.30 to 2.14). There was a high incidence of dose-dependent side effects, particularly dry mouth and sedation. It should be noted that abrupt discontinuation of clonidine can result in symptoms such as nervousness, agitation, headache, and tremor, accompanied or followed by a rapid rise in blood pressure and elevated catecholamine levels. 

Clonidine initial increase in BP (some 0 j activity) followed by decrease—abrupt discontinuation causes rebound HTN. 

The intensity of symptoms depends both on the drug and on its mode of administration, the dosage that the individual has been using, and the time from abrupt discontinuance. Full agonist opioids used IV, which include heroin, cause the most severe withdrawal symptoms. Management involves administration of oral methadone , buprenorphine, or clonidine, with gradual dose tapering. 

Tyramine present in certain food and beverages can displace NE from sympathetic nerve endings, causing CV stimulation, but only if its metabolism is inhibited by MAO inhibitors. Patients suffering from HTN commonly discontinue medications (without physician consultation) based on perceived undesirable side effects, such as sexual dysfunction. In the case of clonidine, rebound hypertension and tachycardia, especially with abrupt discontinuance, can be problematic. Discontinuance of thiazide is likely to result in fluid retention with weight gain and unlikely to cause tachycardia and marked increase in BP. Ethanol is an effective vasodilator and tends to decrease BP. Tachyphylaxis refers to the development of a decreased response to drug treatment over a time span of minutes to hours, not years. 

The major adverse effects of clonidine are dry mouth and sedation. These responses occur in at least 50% of patients and may require dmg discontinuation. However, they may diminish in intensity after several weeks of therapy. Sexual dysfunction also may occur. Marked bradycardia is observed in some patients. These and some of the other adverse effects of clonidine frequently are related to dose, and their incidence may be lower with transdermal administration of clonidine because antihypertensive efficacy may be achieved while avoiding the relatively high peak concentrations that occur after oral administration of the drug. About 15 to 20% of patients develop contact dermatitis when using clonidine in the transdermal system. Withdrawal reactions follow abrupt discontinuation of long-term therapy with clonidine in some hypertensive patients. 

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