Losing That Restless Feeling: Drug-Induced Akathisia Treatment Options
Akathisia
Akathisia (from the Greek καθίζειν: inability to sit) is one of the most prevalent and distressful psychotropic-induced extrapyrimidal adverse effects. It is a neuropsychiatric syndrome characterized by both subjective (inner feeling) and objective (physical symptoms) restlessness.
Due to this inner restlessness, patients may experience fidgeting, pacing, rocking while standing or sitting, crossing and uncrossing legs while sitting, and constant movement of the feet. Patients have also described these feelings as “wanting to jump out of my skin”and as a “crawling skin sensation.” (4)
Among the drugs used to treat delirium, haloperidol, might be the antipsychotic with the highest risk for development of akathisia. (5) The risk for akathisia in patients with delirium taking antipsychotics appears to be a dose-related phenomenon. Effective and well tolerated treatment is a major unmet need in akathisia that merits a search for new remedies.
Assessment Scales
"Studies using specific scales for evaluation of akathisia in delirium are lacking. Some populations, such as patients with cancer or terminally ill patients in palliative care settings taking antipsychotics for the treatment of delirium, could be at higher risk for development of akathisia as a side effect." (5)
The Barnes Akathisia Rating Scale (BARS) is one such scale.
Treatment
Early management of akathisia is important because it may be associated with poor treatment response and medication noncompliance, and most importantly is distressing to the patient and caregivers. Unfortunately many patients fail to respond to standard management of akathisia (typically benzodiazepines, beta blockers, anticholinergic agents). As medications used to alleviate akathisia symptoms such as anticholinergics and benzodiazepines could potentially worsen delirium, management of akathisia among delirious patients on antipsychotics should be further studied to explore the efficacy of other agents.
In addition to dopaminergic mechanisms, it has been hypothesized that serotonin may play a prominent role in the pathophysiology of akathisia.
Trazodone is an antidepressant agent demonstrating prominent serotonergic antagonistic properties. An open-label pilot study investigated the efficacy of trazodone in the management of akathisia. Nine female patients with a score of at least “mild akathisia” on the Barnes Akathisia Scale, and receiving a stable dose of antipsychotic medication, were administered trazodone, titrated up to a dosage of 100 mg/day over a period of 5 days. The patients demonstrated marked improvement in symptoms of akathisia. In addition, some improvement was noted in symptomatology of anxiety, depression, and psychosis. (3)
Low-dose mirtazapine was found to be efficacious for neuroleptic-induced akathisia. (2) "The
most compelling evidence indicating that 5-HT2A antagonists may represent a new
class of effective anti-akathisia agent comes from the largest-to-date
randomised controlled trial comparing low-dose mirtazapine with propranolol in
90 patients with FGA-induced (first-generation antipsychotics) acute akathisia. Mirtazapine is characterised by
potent presynaptic alpha-2 adrenergic antagonism, which accounts for its
antidepressant activity, and marked 5-HT2A blockade that seems to preponderate
in a low dose and contribute to its anti-akathisia properties. Mirtazapine,
given once daily (15 mg) was as effective as propranolol (80 mg twice daily) in
producing a greater improvement in akathisia compared with placebo (reduction
in BARS global scale: 1.10 (s.d. = 1.37) points (34%) and 0.80 (s.d. = 1.11)
points (29%) v. 0.37 (s.d. = 0.72) points (11%) respectively; P = 0.036).
Responder analysis (BARS global scale reduction 52) yielded a similar robust
anti-akathisia effect in mirtazapine and propranolol v. placebo (43.3% and 30%
v. 6.7% respectively; P = 0.005). Low numbers needed to treat (3 and 4
respectively) support high clinical efficacy of both compounds. Importantly,
mirtazapine achieved an anti-akathisia effect with more convenient dosing than
propranolol and better tolerability, with mild transient sedation as the only
observed side-effect. The favourable mirtazapine safety profile was also
supported by the absence of significant changes in vital signs." (1)
Suggested Approach
Discontinue [alternatively, dose decrease] the offending agent. If this is not possible or ease of symptoms is required, when the decision is to add an anti-akathisia agent
- propranolol (40–80 mg/day twice daily) or
- low-dose mirtazapine (15 mg once daily) as first-line treatment have the most supportive evidence.
- Mianserin (15 mg once daily) and cyproheptadine (8–16 mg/ day) are alternative options
- however, large-scale trials are not yet available. (1)
References
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Akathisia
Among the drugs used to treat delirium, haloperidol, might be the antipsychotic with the highest risk for development of akathisia. (5) The risk for akathisia in patients with delirium taking antipsychotics appears to be a dose-related phenomenon. Effective and well tolerated treatment is a major unmet need in akathisia that merits a search for new remedies.
Assessment Scales
Suggested Approach
- propranolol (40–80 mg/day twice daily) or
- low-dose mirtazapine (15 mg once daily) as first-line treatment have the most supportive evidence.
- Mianserin (15 mg once daily) and cyproheptadine (8–16 mg/ day) are alternative options
- however, large-scale trials are not yet available. (1)
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