Apomorphine therapy for patients with disorders of consciousness: a multimodal open-label study

Introduction:
Apomorphine, a repurposed dopaminergic drug, is a promising therapy to improve the recovery of patients with disorders of consciousness (DOC), with a postulated action on the mesocircuit. This prospective open-label study aimed to confirm preliminary results on clinical efficacy and investigate its action on brain function.

Methods:
6 patients with chronic DOC (4 male, 4 traumatic, 38.8 year-old average, 99 days post-onset average) received daily subcutaneous apomorphine therapy for 30 days. Multimodal monitoring was performed from 30 days before to 30 days after treatment. Outcome measures included repeated behavioural scales, high-density electroencephalography (hdEEG) and positron emission tomography (PET).

Results:
Compared to baseline, 3 patients improved their behavioural diagnosis during treatment, 2 additional patients improved during the 12-month follow-up and the last patient emerged before treatment start but improved on all rehabilitation scales during treatment. Mean Coma Recovery Scale-Revised scores improved during treatment (2.1 points) and 30-day washout (5.2 points) periods, compared to baseline (Table 1).
Healthcare staff and family rated the patient’s clinical condition 20.5% and 30.9% better after treatment, respectively (Table 2).
Alpha-band hdEEG functional connectivity measured by network centrality increased by 13.6% on average after treatment (Figure 1). Wholebrain fluorodeoxyglucose metabolism increased by 12.4% on average between PET before and after treatment.

Conclusion:
Multimodal improvements were observed in chronic DOC patients after a 30-day treatment regimen with apomorphine. These results suggest a beneficial action on consciousness that is associated with increased brain connectivity and metabolism. These results will need to be confirmed in a subsequent multicentre randomized placebo-controlled trial (EudraCT: 2018-003144-23; Clinicaltrials.gov: NCT03623828).