Reviews
Selective serotonin reuptake inhibitor-induced akathisia

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Objective

To review available information in the literature about akathisia (inner restlessness) caused by the selective serotonin reuptake inhibitors (SSRIs).

Data sources

Databases searched included Medline, PsychInfo, the International Pharmaceutical Abstracts, and Google Scholar. Search terms included drug-induced akathisia, psychomotor agitation, drug-induced side effect, movement disorders, and extrapyramidal symptoms. These search terms were cross-referenced with selective serotonin reuptake inhibitors and each of the currently marketed SSRIs: fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram, and escitalopram.

Study selection

Relevant articles were chosen if they specifically mentioned the word akathisia. Case reports were chosen based on a clear view that an SSRI was a contributing or causative agent of akathisia.

Data synthesis

Recognizing akathisia is important because it can be very bothersome and may cause suicidal ideations. Akathisia can be recognized by examining symptoms, looking at predisposing factors, and using the Barnes Akathisia Rating Scale (BARS). Predisposing factors include use of multiple akathisia-inducing drugs, recent increases in SSRI dose, previous development of akathisia, baseline psychiatric disorders, and brain trauma. Treatment options include the addition of a centrally acting beta-blocker, a benzodiazepine, or an anticholinergic agent.

Conclusion

Pharmacists can play an active role in recognizing akathisia by being aware of its characteristics, conducting a thorough medication history to identify causative agents, and using BARS to evaluate patients. These efforts may preclude unnecessary discomfort for the patient and reduce the potential for nonadherence induced by akathisia.

Section snippets

Presentation

Akathisia is most often referred to as a feeling of inner restlessness, but many patients may be unable to describe this feeling unless asked directly.5 Instead, patients sometimes confuse it with feelings of anxiety or agitation. An author of the current report (Dr. Makela) had a patient describe this feeling as “an itch inside that I can't scratch.” In a case presented by Walker,6 the patient described feelings of “wanting to jump out of my skin.” Altshuler et al.7 described a patient who

Importance of recognition

Akathisia is not always easy to recognize. Many patients taking SSRIs have preexisting psychiatric disorders, and misinterpreting akathisia symptoms can occur easily. These symptoms may be mistaken for agitated depression, anxiety, withdrawal, bipolar disorder, worry, or even restless leg syndrome.1,3,8,11., 12., 13. Misdiagnosing akathisia as an underlying psychiatric disorder could lead to an increase in dosage of the offending agent or the addition of a new, unnecessary medication such as an

Etiology

Although speculation exists, akathisia may result from a deficiency of dopamine in the brain. Reports in the literature suggest that this deficiency is caused by serotonergic-induced inhibition of dopamine in the mesocorticolimbic pathway projecting from the ventral tegmental area (VTA) of the brain to the prefrontal cortex.3,5 Like serotonin, noradrenalin acts similarly to inhibit dopamine in the VTA.3 Therefore, drugs increasing the stimulation of serotonergic or noradrenergic receptors in

Diagnosis

The Barnes Akathisia Rating Scale (BARS)22 can be used to assess a patient with suspected akathisia. This scale, developed in 1989 by Thomas Barnes, measures the subjective and objective aspects of akathisia. For the objective portion, the evaluator rates the amount of movement the patient displays on a scale from 0 (normal) to 3 (inability to remain still). The subjective portion is divided into two parts, awareness of restlessness and distress related to restlessness, both of which are

Predisposing factors

Reports from the literature have suggested several risk factors for developing akathisia (Table 2). The use of multiple akathisia-inducing drugs, a sudden increase in SSRI dose, and a previous history of akathisia may predispose patients to developing akathisia with SSRIs. The half-life and anticholinergic properties of individual SSRIs also may affect the risk of developing akathisia. Patients with baseline anxiety or panic conditions or patients with previous brain trauma appear to have

Management

Several treatment options for akathisia exist (Table 4). As discussed below, adding a centrally acting beta-blocker such as propranolol appears to be the most frequently used therapy. Benzodiazepines and anticholinergic drugs serve as other treatment options. Another choice for treatment is to switch to an alternative antidepressant or to change to another SSRI. In some cases, akathisia may subside over time without treatment.

The addition of a beta-blocker to a patient's regimen is an excellent

Conclusion

Akathisia is not a benign adverse effect. The effect can be extremely egregious, and some reports have linked akathisia with suicidality. With the increasing use of medications from this drug class for a variety of indications, identification of predisposing factors, early recognition of akathisia, and proper management are imperative. Beta-blockers and benzodiazepines are well-established treatment options for akathisia.

Pharmacists can play an active role in recognizing akathisia by being

Assessment Questions

Instructions: The assessment test for this activity must be taken online; please see “CPE Processing” below for further instructions. There is only one correct answer to each question. This CPE will be available online at www.pharmacist.com no later than March 31, 2009.

  • 1.

    A.B. is a 54-year-old woman who comes to your pharmacy regularly. You sit down to talk with her and observe her crossing and uncrossing her legs excessively. It appears that she can't sit still. She claims that she doesn't feel

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    Continuing pharmacy education (CPE) credits: See learning objectives below and assessment questions at the end of this article, which is ACPE universal activity number 202-000-09-116-H01-P in APhA's educational program. To take the CPE test for this article, go to www.pharmacist.com/education, and follow the links to the APhA CE center.

    Disclosure: The authors and APhA's editorial staff declare no conflicts of interest or financial interests in any products or services mentioned in this article, including grants, employment, gifts, stock holdings, or honoraria.

    Published concurrently in Pharmacy Today and the Journal of the American Pharmacists Association.

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