Tuesday, July 21, 2015

Losing That Restless Feeling: Drug-Induced Akathisia Treatment Options


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.


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)



Friday, July 10, 2015

Opioids Available in Canada

The following table highlights currently available prescription opioids in Canada, including formulations and strengths. Any of the coverage notes are specific to the province of Alberta.

Click on the download icon (upper right hand corner) or the title below to view table in full screen mode.

Opioids Available in Canada:

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About Onco-PRN

Welcome and thanks for visiting Onco-P.R.N. - The oncology website with a focus on all things oncology pharmacy/pain/palliative care-related. It is intended to be an information resource for those pharmacist and relevant health care professionals involved in whatever fashion with cancer and palliative care. Stay tuned for the latest and greatest links and information with respect to: oncology medications, continuing education, pharmaceutical care initiatives, pain and symptom control, supportive care topics, and whatever else that might fit into the theme.

*Note: This website is not affiliated with Alberta Health Services (AHS) or CAPhO and the opinions expressed herewithin are that of the author(s).

Pharmacy History

"The earliest known compilation of medicinal substances was ARIANA the Sushruta Samhita, an Indian Ayurvedic treatise attributed to Sushruta in the 6th century BC. However, the earliest text as preserved dates to the 3rd or 4th century AD.
Many Sumerian (late 6th millennium BC - early 2nd millennium BC) cuneiform clay tablets record prescriptions for medicine.[3]

Ancient Egyptian pharmacological knowledge was recorded in various papyri such as the Ebers Papyrus of 1550 BC, and the Edwin Smith Papyrus of the 16th century BC.

The earliest known Chinese manual on materia medica is the Shennong Bencao Jing (The Divine Farmer's Herb-Root Classic), dating back to the 1st century AD. It was compiled during the Han dynasty and was attributed to the mythical Shennong. Earlier literature included lists of prescriptions for specific ailments, exemplified by a manuscript "Recipes for 52 Ailments", found in the Mawangdui tomb, sealed in 168 BC. Further details on Chinese pharmacy can be found in the Pharmacy in China article."

From Wikipedia:

Journal of Palliative Medicine - Table of Contents

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