From the Guidelines
Clonidine, an alpha-2 adrenergic agonist, helps alleviate anxiety by suppressing sympathetic nervous system outflow throughout the brain, leading to a reduction in peripheral vascular resistance and consequently lower blood pressure, and by enhancing noradrenergic neurotransmission in the prefrontal cortex, which strengthens the regulatory role of the prefrontal cortex responsible for top-down guidance of attention, thought, and working memory 1.
Mechanism of Action
The mechanism of action of clonidine involves agonistic effects at alpha-2 adrenergic receptors throughout the brain, which leads to:
- Reduction in peripheral vascular resistance and lower blood pressure
- Enhanced noradrenergic neurotransmission in the prefrontal cortex
Dosage
The typical dose range for clonidine in anxiety management is 0.1-0.3 mg per day, divided into two to three doses, with a maximum daily dose of 0.6 mg 1.
Key Points
- Clonidine is generally reserved as a last-line treatment due to significant CNS adverse effects, especially in older adults
- Abrupt discontinuation of clonidine may induce hypertensive crisis, and it must be tapered to avoid rebound hypertension
- Treatment duration is usually long-term, with some patients requiring ongoing therapy for several months or even years to maintain therapeutic efficacy
From the FDA Drug Label
CLINICAL PHARMACOLOGY Clonidine stimulates alpha-adrenoreceptors in the brain stem. The exact relationship of these pharmacologic actions to the antihypertensive effect of clonidine has not been fully elucidated DOSAGE AND ADMINISTRATION Adults The dose of clonidine hydrochloride tablets, USP must be adjusted according to the patient’s individual blood pressure response. The therapeutic doses most commonly employed have ranged from 0.2 mg to 0.6 mg per day given in divided doses.
The mechanism by which clonidine helps alleviate anxiety is not directly stated in the provided drug labels. However, it is known that clonidine stimulates alpha-adrenoreceptors in the brain stem, which may have an indirect effect on anxiety. The dosage of clonidine for anxiety is not specified, but the therapeutic doses for blood pressure response have ranged from 0.2 mg to 0.6 mg per day 2 2.
From the Research
Mechanism of Clonidine in Alleviating Anxiety
- Clonidine is an alpha-2 agonist that has been used to treat various psychiatric disorders, including attention-deficit hyperactive disorder (ADHD), tic disorders, and post-traumatic stress disorder (PTSD) 3, 4, 5.
- The mechanism of clonidine in alleviating anxiety is thought to be related to its ability to reduce impulsivity, inattention, and hyperactivity associated with attention deficit disorder with hyperactivity 6.
- Clonidine may also have a sedating effect, which can help reduce anxiety and symptoms of posttraumatic stress disorder 5.
Dosage of Clonidine for Anxiety
- The median clonidine dose used in studies for post-traumatic stress disorder (PTSD) was 0.15 mg/day, with a range of 0.1-0.5 mg/day 4.
- In a study on autistic individuals, clonidine was administered at a dose of approximately 0.005 mg/kg/day via a transdermal patch 6.
- The dosage of clonidine for anxiety may vary depending on the specific condition being treated and the individual patient's response to the medication 4, 5, 6.