and disinhibition-induced aggression in all patients.
Anticholinergics such as trihexyphenidyl are more commonly used for EPS associated with parkinsonian symptoms or side effects but can be partially effective for akathisia.3 Anticholinergics block the CNS cholinergic activity that causes parkinsonian symptoms.
Cyproheptadine, clonidine, and mianserin have shown some positive results against akathisia in clinical trials.6-8 Iron, nicotine patches, and amantadine have shown limited effectiveness against akathisia in research studies and case reports.3,9
Restarting risperidone at a lower dosage—rather than adding a medication— might have resolved Ms. K’s akathisia, but because she was morbidly despondent over her akathisia, we felt we had no time to experiment. We also believed Ms. K’s would respond well to a neuroleptic with a lower EPS risk—such as quetiapine.1,10
DSM-IV-TR criteria for acute akathisia
A. Subjective complaints of restlessness after exposure to neuroleptics
B. At least 1 of the following is observed:
- Fidgety movements or swinging of the legs
- Rocking from foot to foot while standing
- Pacing to relieve restlessness
- Inability to sit or stand still for at least several minutes
C. Symptoms develop within 4 weeks of starting or raising the dosage of a neuroleptic or after reducing a medication used to treat extrapyramidal symptoms
D. Criterion A symptoms are not better accounted for by a mental disorder
E. Criterion A symptoms are not caused by a nonneuroleptic or a general medical condition
Source: Adapted from reference 2 with permission
TREATMENT: Trying trials
We perform a complete medical workup to rule out an underlying medical problem. We then start valproic acid, 500 mg bid, for Ms. K’s mania; quetiapine, 50 mg bid, for psychosis and mania; and propranolol, 30 mg bid, for akathisia.
We titrate quetiapine by 100 mg/d every 2 days to 400 mg/d, but after 10 days her akathisia, irritable mood, decreased sleep, and suicidal thoughts persist. We cannot increase propranolol because her blood pressure is 90/60 mm Hg, and adding lorazepam, 0.5 mg tid, does not control her movements. Three days later, we add trihexyphenidyl, 5 mg bid.
Fifteen days after admission, Ms. K remains akathisic, dysphoric, and suicidal despite a 5-drug regimen. Her “nervousness” prevents her from attending groups or other unit activities, and her uncontrollable foot swaying still keeps her awake at night.
The authors’ observations
Neither propranolol, clonazepam, nor trihexyphenidyl alleviated Ms. K’s akathisia. Switching to another neuroleptic with a relatively low EPS risk—such as olanzapine—might help. Olanzapine reduced akathisia in 3 case reports,11 and we hope its strong anticholinergic and antiserotonergic action will help resolve Ms. K’s akathisia.
with patients receiving therapeutic dosages of risperidone.12 In another study, olanzapine showed anticholinergic activity at therapeutic doses but risperidone did not.13 Researchers believe these features reduce olanzapine’s EPS risk compared with other antipsychotics.
TREATMENT: Drug works, but …
Three weeks after Ms. K’s presentation, we stop all psychotropics, start olanzapine, 10 mg nightly, for psychosis and mania, and continue propranolol, 30 mg bid, for akathisia. Within 2 days, Ms. K’s akathisia improves significantly.
We also start lithium, 150 mg bid, for mania, and increase it 4 days later to 300 mg bid to maintain serum lithium at approximately 1 mEq/L. We check serum lithium every 3 days after dosage adjustment. Although lithium can induce akathisia, we thought it would most effectively control her mania.
Six days after we started the new medications, Ms. K’s mania and psychosis begin to improve and she becomes euthymic. She is able to sit calmly during group therapy and community meetings.
Ten days after we start olanzapine and lithium, Ms. K appears bloated. Weight check shows an approximate 5-lb weight gain since starting the medications, both of which can cause weight gain and other metabolic side effects.
At Ms. K’s request, we stop olanzapine and start aripiprazole, 5 mg/d, to try to control her weight gain. We continue lithium and propranolol, which have been controlling her mood and akathisia. The next day—after 1 dose of aripiprazole—her akathisia returns.
The authors’ observations
Because aripiprazole was started as soon as olanzapine was discontinued, it is unclear which action aggravated Ms. K’s akathisia or if both were to blame.
Akathisia’s underlying cause is uncertain. Researchers believe dopamine receptor blockade in the mesocortical dopamine system might be responsible.3 Positron-emission tomography studies suggest that D2 receptor occupancy in the striatum contributes to akathisia, and noradrenergic and serotonergic systems also play a role.3,14