Brainstem reflexes are hyperactive in patients with drug-induced akathisia

Abstract

Akathisia is a sensori-motor phenomenon which is generally encountered as an adverse effect of antidopaminergic medications suggesting involvement of dopaminergic pathways. We recently showed nociceptive flexor reflex was altered in akathisia as compared to restless legs syndrome and therefore, these findings may indicate co-involvement of pathways other than dopaminergic ones. To examine functional status of different pathways, we investigated auditory startle reflex (ASR), startle response to somatosensory input (SSS), and trigemino-cervical reflex (TCR) in a group of patients with akathisia. Consecutive seven patients with drug-induced akathisia and age- and gender-matched healthy subjects were prospectively included in the study. The diagnosis was made by appropriate clinical criteria. Brainstem reflexes, ASR, SSS, and TCR were examined in all participants. The probability, onset latency, amplitude, and duration were measured and compared between groups. The probability and amplitudes of ASRs were significantly increased and durations of ASRs and TCRs were prolonged in the patient group. Latencies of all responses as well as patterns of startle responses were similar between groups. The results reveal hyperactivity of the ASR and TCR in drug-induced akathisia. Hyperactive ASRs and TCRs also confirm suprasegmental hypodopaminergic state in akathisia. Although we keep in mind the confounding effects due to concurrent antidopaminergic treatments and the small sample group, we speculate that hyperactive ASRs and TCRs might be related to deficient control by forebrain and limbic-mainly amygdala-network in patients with drug-induced akathisia.

Dopamine-receptor blocking agent-associated akathisia: a summary of current understanding and proposal for a rational approach to treatment

“…63 For example, DRBA-A may result from an intrinsic homeostatic response to the depletion of dopaminergic activity in the ventral striatum portion of the brain. 64 The nucleus accumbens is an area specifically implicated in the pathophysiology of akathisia due to its importance for reward and movement. It is theorized that compensatory overstimulation of this region may result in "senseless" behaviors and feelings of dysphoria observed with akathisia.…”

Neurological Soft Signs, Spontaneous and Treatment Emergent Extrapyramidal Syndromes in Black Africans With First Episode Schizophrenia

“…Whereas we found that spontaneous EPS is associated with treatment-emergent Akathisia, prior studies implementing a longer term follow-up of up to 24 months have demonstrated this relationship for treatment-emergent dyskinesia ( 13 ). Compared with dyskinesia, akathisia is an earlier onset antipsychotic induced EPS ( 30 ). We have implemented a short-term (3-months) follow-up in the present study.…”

Technical Aspects of Eliciting Trigeminocervical and Trigeminospinal Reflexes in Humans: A Scoping Review

“…Thirty-two studies evaluated TCR or TSR long-latency responses. Trigeminocervical reflex and TSR were assessed by stimulation of the supraorbital nerve in 17 studies, 1,3,5,11,12,18,21,26,31,34,[36][37][38][39][41][42][43] infraorbital nerve in 14 studies, 1,2,4,5,9,10,[15][16][17]19,20,22,25,36 mental nerve in four studies, 5,32,33,36 and masseteric nerve in one study. 40 Stimulation parameters, feasibility in healthy participants, and topographic distribution of long-latency TCR and TSR recordings with electrical single-pulse stimulation of the supraorbital, infraorbital, and mental nerves are summarized in Table 2.…”