Drug-Induced Akathisia in Children and Adolescents

Introduction

Akathisia is a neuropsychiatric syndrome characterized by a feeling of unease, an inner feeling of restlessness with a compulsion to move that involves mainly the legs but can also affect the arms or trunk. Objectively, akathisia presents with fidgetiness of the legs and sometimes the limbs, and complex repetitive motor movements such as swinging or crossing and uncrossing of legs and feet (Espi Forcen 2015).

In clinical settings, akathisia is generally seen as a side effect from medications, especially, antipsychotics are the most common causing this side effect followed by antiemetics and serotonergic reuptake inhibitors. Of all antipsychotics, first generation and some new antipsychotics such as aripiprazole and asenapine have been thought to have a higher risk for akathisia (Espi Forcen et al. 2015). In fact, akathisia has been reported as the most common side effect of aripiprazole long acting. (Kane et al. 2010).

The prevalence of drug-induced akathisia in children and adolescents has not been vigorously studied. Our objective is, therefore, to determine such prevalence in a pediatric population taking different psychotropics.

Methods

The Barnes Akathisia Rating Scale (BARS) was described by Thomas Barnes in 1985 and is the most frequently used scale for the measurement of akathisia (Barnes and Braude 1985). The BARS was implemented in the electronic medical record system (Epic) of our hospital. Clinicians were encouraged to use this scale as part of their regular care provided for the assessment of patients who were taking akathisia-inducing medications. An Institutional Review Board (IRB) exemption was obtained at The University of Chicago to collect data retrospectively and to determine akathisia prevalence in our child and adolescent psychiatry clinic.

Results

During a 3-month period, 40 patients between 8 and 18 years old were assessed for drug-induced akathisia at our pediatric outpatient clinic. The most common diagnoses were attention-deficit/hyperactivity disorder (ADHD), mood, anxiety, and eating disorders.

A total of four subjects developed akathisia (10%). Three out of these four were taking an antipsychotic in combination with another drug and developed a mild form of akathisia. One of them was taking risperidone 0.75 mg daily and amphetamine/dextroamphetamine extended-release 20 mg daily. The second was on risperidone 1 mg daily and the third was on a combination of sertraline 50 mg and quetiapine 25 mg daily. Lastly, one patient developed marked akathisia despite not taking antipsychotic medication. This patient was taking a combination of methylphenidate extended-release 36 mg and fluoxetine 20 mg daily. Of the total sample, two patients (5%) had questionable akathisia according to BARS. Finally, two more patients (5%) reported subjective inner feeling of restlessness but had no objective symptoms of akathisia. Of the total sample, at least 8/40 (20%) of patients have subjective restlessness and 3/9 (33%) of the patients taking an antipsychotic among other medications developed akathisia as reflected in the BARS (Table 1).

Discussion

Akathisia is a relatively frequent problem in outpatient pediatric clinics, especially for patients under neuroleptic medication. Children and adolescents could be more prone to development of antipsychotic-induced akathisia than adults.

Our data do not support the existence of pediatric akathisia in patients taking stimulants or antidepressants. In our sample, akathisia may overlap with hyperactivity–impulsivity in patients with ADHD and hypergymnasia syndrome in eating disorders. Stimulants have an action in the ventral striatum. As a result, the so-called rebound syndrome in patients with ADHD after wearing off from stimulants could be explained by akathisia symptomatology.

The mechanism of antipsychotic-induced akathisia is thought to be related to dopaminergic D2/D3 receptor blockage in the ventral striatum. A study carried out by Kim et al. (2011) showed a positive association between higher scores on the Liverpool University Neuroleptic Side Effects Rating Scale and D2/D3 receptor occupancy in the ventral striatum.

Our article shows prevalence of akathisia in 10% (4/40) of patients in a regular outpatient pediatric population taking a combination of different medications. Thirty-three percent (3/9) of patients on antipsychotic medication in combination had akathisia. Two patients were on risperidone and one on quetiapine. In our literature search, we were not able to find similar pediatric akathisia studies on the general population. Nonetheless, data from controlled clinical trials on antipsychotics show a variable incidence of akathisia. For instance, one study with 10 patients taking risperidone for conduct disorder showed a 10% prevalence of restlessness (Findling et al. 2000). A clinical trial with quetiapine in youth with schizophrenia and bipolar disorder showed a 3.7% incidence of the side effect (Findling et al. 2013b). A ziprasidone study in adolescents with schizophrenia showed a 6.7% rate of akathisia (Findling et al. 2013a). This study explores the prevalence of akathisia in a general pediatric population on combined psychotropic medication for the treatment of several psychiatric conditions. Clinicians may benefit from learning about these findings as it may reflect more accurately the reality of regular psychiatric practice in the pediatric population. Nonetheless, these results must be taken with caution. Sample size and interviewer biases are potential limitations. Further research is needed on the incidence of akathisia in youth on combined psychopharmacological treatments.