Lorazepam in the Treatment of Lithium-Induced Akathisia

(From: Journal of Clinical Psychopharmacology, Vol. 9, No. 1, February 1989, p. 70.)

Ramzy Yassa, M.D.
Bernard Groulx, M.D.
Ste. Anne's Hospital
Veterans Administration Medical Hospital
Sainte-Anne, Quebec, Canada

Extrapyramidal side effects, including cogwheel rigidity1 aggravation and/or precipitation of tardive dyskinesia^2-3 and the appearance of dystonic symptoms,⁴ have been reported in the course of lithium therapy, with or without lithium intoxication. More recently, two cases of akathisia were described.^5-6 In one patient,⁵ akathisia developed 2 years after the initiation of lithium therapy while in the other patient,⁶ it developed only 10 days after lithium treatment. In both patients no concomitant neuroleptic therapy was given and no evidence of intoxication was noted. Both patients showed concomitant extrapyramidal side effects manifested as cogwheel rigidity, hand tremors, and dysarthric speech. Anti-parkinsonian drugs cleared the akathisia within 36 hours.

We present another patient who developed akathisia after 4 years of the same lithium dose.

A 64-year-old man with bipolar disorder was receiving lithium carbonate 1200 mg/day for 4 years, as well as thyroid tablets 0.2 mg/day due to a lithium-induced hypothyroidism. He had not received neuroleptics for 8 years prior to this examination.

The patient presented himself to the outpatient department of the Veterans Administration hospital in Montreal in April 1987 complaining of "feeling jumpy, anxious, restless, and unable to sit still." He stated that for the previous 7 days he could not relax in his chair as usual and needed to take long walks to "stretch his legs," a feeling he had never had before. On examination, he was noted to be restless, crossing and uncrossing his legs while sitting in his chair, and to have to stand up and walk while being interviewed. There was no evidence of cogwheel rigidity, hand tremors, or tardive dyskinesia on clinical examination. There was no evidence of intoxication clinically and by testing for his plasma lithium level, which was found to be 0.75 mEq/liter 12 hours after the last dose. Lorazepam 1 mg twice a day was prescribed and the patient's symptoms cleared within 48 hours. Follow-up for more than 1 year indicates no further recurrences, even after lorazepam discontinuation, although the patient continues to receive lithium (his dose was reduced to 900 mg/day 4 months later).

Reports to date suggest that extrapyramidal side effects in the course of lithium therapy are a dose-independent idiosyncratic reaction. Both patients who were reported to have developed akathisia while receiving lithium were noted to exhibit it while prophylactic lithium was prescribed. As in our patient, none was receiving concomitant neuroleptic medication and none developed clinical evidence of intoxication.

The mechanism of lithium-induced akathisia is not known. It may decrease the amount of dopamine in rat striatum and limbic forebrain.⁷ It may also affect other neurotransmitters, for example,⁸ cholinergic and serotonergic.⁹ Thus, the action of lithium on neurotransmitters is complex.

While anticholinergic drugs were the treatment of choice in two previously reported cases,5-6 our patient's symptoms responded to lorazepam. Lorazepam has been reported to be an effective medication in reducing akathisia, extrapyramidal symptoms, and agitated states.10-12 It seems to exert this effect through its GABA-ergic facilitation, thus counterbalancing noradrenergic overactivity,11 which may be the underlying mechanism in akathisia.

While awaiting a definite answer to the mechanism of lithium-induced akathisia, we wish to alert the treating physicians to akathisia as a possible side effect of lithium and to its possible treatment with lorazepam.

References

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