Clonidine: pharmacologic observations
BACKGROUND: An alpha-adrenergic agonist, clonidine functions as an antagonist at
receptors on cells of the locus ceruleus (found in the primitive pons) and is widely used to
treat explosive symptoms in children,1 is effective in the treatment of combat-related
post-traumatic stress disorder 2 and is reported effective in treating panic disorder.3,4
When taken at a therapeutic dose, I found clonidine, an alpha-adrenergic agonist, to fully
treat the symptoms of locus ceruleus activation (LCA) (i.e., autonomic hyper-reactivity.
MECHANISM OF ACTION: An alpha-adrenergic agonist (a-2 agonist), clonidine is
known to function as an antagonist at receptors on cells of the locus ceruleus.
Neuroanatomically located in the brain’s primitive pons, the locus ceruleus cells are
evolutionary descendents of the piscine parasympathetic locus. By mechanically blocking
locus ceruleus receptors, the clonidine molecule blocks the mneomic triggered response
to experience reminiscent of life-threatening terror and, hence, the full autonomic hyperreactivity cascade.
TOXICITY AND DOSING: Clonidine’s only side effect is orthostatic hypotension – a
sign of drug toxicity when used in this context. (N.B.The most sensitive indicator of
orthostatic hypotension is the patient’s subjective awareness of feeling “light headed;”
young children “fall asleep.”)
The subjective orthostatic hypotension experienced by patients taking more
clonidine than needed to treat autonomic hyper-reactivity allows use of a 0.1 mg test-dose
of the medication to neurobiologically confirm the clinical diagnosis of autonomic hyperreactivity. Unlike patients without the disorder, patients who have experienced lifethreatening terror tolerate a test-dose of 0.1mg clonidine without subjective orthostatic
hypotension.
Being aware of the drug’s toxicity allows patients with autonomic hyperreactivity to determine their (idiosyncratic) therapeutic dose -- 0.1 mg lower than the dose
causing subjective orthostatic hypotension. Symptoms return with full force when a
therapeutic dose of clonidine is reduced, and disappear when it is resumed.
The therapeutic dose of clonidine appears to be directly related to the extent of
life-threatening terror a patient has experienced. Taken orally, the therapeutic dose is also
dependent on portal liver metabolism (by the same hepatic pathways that metabolize
ethanol and muscle-breakdown products). While convenient and effective, the adhesive
used on the clonidine patch was noted to cause a significant topical allergic reaction in
many patients -- requiring oral administration of the medicine.
With a half-life of 8 hours, clonidine can be quickly titrated to therapeutic dose –
with the dose safely increased every other day. Moreover, the medication can be dosed
specifically to treat symptoms reliably experienced at specific times of the day.
ALTERNATIVE THERAPIES: With significantly less experience prescribing
guanfacine than clonidine, I am less confident about its neuropharmacology. Like
clonidine, it is an a-2 agonist, and I’ve found it to be an effective treatment and easier to
use. The medication’s metabolic properties are different (it is, apparently, not liver
metabolized) and a single dose is has seemed effective without the titration necessary
with clonidine. I would appreciate hearing other people’s clinical impressions. Adults
having experience a single life-threatening trauma are known to respond well to talking
therapies (including relaxation, guided imagery, and progressive exposure). These
therapies are ineffective, painful, and dangerous in children – whose hyper-reactivity is
triggered years of increasingly subtle mnemonic stimuli.
1
Werry JS, Aman MG, eds (1998): Practitioner’s Guide to Psychoactive Drugs for
Children and Adolescents New York: Plenum Medical Book Company pp 451, 447.
2
Kolb LC, Burris BC, Griffiths S (1984). Propranolol and clonidine in the treatment of
the chronic post-traumatic stress disorders of war. In: van der Kolk BA ed. PostTraumatic Stress Disorder: Psychological and Biological Sequelae. Washington DC:
American Psychiatric Press, 97-107.
3
Liebowitz MR, Fyer AJ, Mcgrath P (1981) Clonidine treatment of panic disorder.
Psychopharmacol Bull;17:122–1233.
4
Uhde TW, et al. (1989) Behavioral and physiologic effects of short-term and long-term
administration of clonidine in panic disorder. Arch Gen Psychiatry;46:170–177.