Adverse events
Five patients experienced adverse events during the first phase, four of which were associated with rechargeable battery replacement. One experienced akathisia, another experienced behavioral changes, and a third experienced electrical disturbances.
A fourth patient experienced postsurgical hemorrhage of the right internal capsule on day 4, followed by encephalitis at week 8. He had a clinical improvement but experienced relapsed during follow-up.
The fifth patient accidentally switched off the device and withdrew from the study.
During the first randomization phase, DBS was associated with significant improvements on total, positive, and negative PANSS scores in comparison with the postoperative baseline measure in the seven remaining patients (P < .001).
When the team compared the baseline measure with the last observation, the improvement in PANSS scores remained significant for total scores (P = .007) and positive scores (P = .002), but not for negative scores (P = .18).
Three patients entered the second crossover phase of the study. Two began in the off-treatment arm and experienced relapsed within 1 and 2 weeks, respectively. Total PANSS scores increased from 79 to 98 for the first patient and from 47 to 93 for the second patient.
Neuroimaging showed that, among patients who responded to DBS, brain metabolism increased in some brain areas and decreased in others. Dr. Corripio said this suggests a “rebalancing” of neural circuits.
As of July 2020, one of three patients with an electrode placed in the NAcc had experienced remission of positive symptoms and now has predominant negative symptoms. Another experienced significant improvements in negative symptoms. Two patients currently require psychosocial rehabilitation.
Patients for whom an electrode was placed in the ACC required higher voltages and more time to achieve an effect in comparison with those for whom an electrode was placed in the NAcc. Two patients required bilateral stimulation.
However, for all three patients who remained in the study, their clozapine dose was reduced.
Dr. Corripio reported that the team has observed negative thoughts and obsessive symptoms in patients with electrodes in the ACC, and all have needed either psychosocial rehabilitation or cognitive-behavioral therapy.
The investigators are now planning another DBS study involving patients with TRS, although this one will include a clinical recovery program focusing on family interventions and cognitive-behavioral therapy.
“Last-resort” treatment
In the postpresentation debate, Damiaan Denys, PhD, professor and chair of the department of psychiatry at the Academic Medical Canter, University of Amsterdam, said that DBS remains a treatment of “last resort” in TRS.
This is because it is both costly and invasive, and although the associated risk of bleeding and infection is low, he noted that the consequences are significant.
Dr. Denys added that patients need to have the potential for improvement; electrodes can be easily implanted, and the approach may tempt clinicians who sometimes “struggle with a huge amount of treatment-refractory cases.”
He also pointed to results achieved in studies of obsessive-compulsive disorder and depression, in which around 50% of patients responded to DBS.
“I think that’s the reason why we should be reluctant and not treat anyone at any stage, but first look for the more severe cases,” Dr. Denys said.