title: Hyperadrenergic state following acute withdrawal from clonidine used at supratherapeutic doses.
abstract: Abrupt cessation of clonidine treatment precipitates a physiological withdrawal syndrome, thought to be due to a hyperactive state of central autonomic and cognitive adrenergic neuronal systems dependent on presynaptic alpha 2-adrenoceptors and/or imidazoline receptors. We hereby describe a 36-year-old male with history of end-stage renal disease, hypertension and medication non-compliance, who presented with severe hypertension and remarkable agitation. His daily clonidine intake was estimated to be 10 mg. The patient had abruptly discontinued his clonidine five days prior to admission. The following indices of adrenergic activity were measured in plasma (normal control values in parentheses): noradrenaline (NA) 8.59 nmol/l (1.32-4.56 nmol/l), adrenaline (Adr) 1.86 nmol/l (0.83-4.20) nmol/l), total 3-methoxy-4-hydroxyphenylglycol (MHPG) 152.8 nmol/l (45.1-111.5 nmol/l), and free MHPG 33.0 nmol/l (12.2-31.4 nmol/l). Plasma clonidine level was 3.53 ng/ml (15.9 nmol/l) with the usual therapeutic level being < 2.0 ng/ml (8.9 nmol/l). Initially, the patient received sedatives and was started on clonidine for the first 24 hours only, after which time period prazosin was started, with good response of his blood pressure and reversal of his mental status changes. At that point, the plasma values of indices of adrenergic activity had decreased compared with their corresponding initial values by the following percentages: NA 60.6%, Adr 22.6%, total MHPG 42.2% and free MHPG 11.5%. Plasma clonidine level had decreased now by 43.6% to an absolute value of 1.99 ng/ml (8.85 nmol/l). We emphasize that physicians should be aware of clonidine's abuse potential and caution should be taken, as well as the appropriate route chosen, when prescribing clonidine in patients who show features of poor compliance to medications and especially in patients with psychoses, suicide potential or personality disorders.
authors.affiliation: Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City 84132, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Sarlis
authors.forename: O
authors.initials: O
authors.lastname: Caticha
authors.forename: J L
authors.initials: JL
authors.lastname: Anderson
authors.forename: C
authors.initials: C
authors.lastname: Kablitz
authors.forename: F S
authors.initials: FS
authors.lastname: Shihab
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000009:adverse effects*; D000328:Adult; D000959:Antihypertensive Agents / Q000009:adverse effects*; D003000:Clonidine / Q000009:adverse effects*; D006801:Humans; D008297:Male; D013375:Substance Withdrawal Syndrome; D019966:Substance-Related Disorders; D013997:Time Factors
chemical_list: D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D003000:Clonidine