Deep Brain Stimulation May Offer Hope for Severe Schizophrenia

Liam Davenport

September 05, 2017

PARIS ― Deep brain stimulation (DBS) may be an effective therapy for treatment-resistant schizophrenia, results of a new pilot study suggest.

Investigators found use of DBS in two areas of the brain achieved a symptomatic response in patients with treatment-resistant schizophrenia, which accounts for approximately 30% of all schizophrenia patients.

However, study investigator Alexandra Roldán, MD, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain, and colleagues caution that the data are preliminary and that the surgical risks of electrode implantation need to be taken into account.

The findings were presented here at the 30th European College of Neuropsychopharmacology (ECNP) Congress.

Potential Treatment Targets

Although previous studies have shown that DBS can be effective in patients with treatment-resistant depression and obsessive-compulsive disorder, no investigations of have been conducted on the use of DBS for patients with schizophrenia, in part owing to a lack of consensus as to where to place the electrodes.

The subgenual anterior cingulate cortex (sgACC) has been shown to have altered activity in schizophrenia, and the nucleus accumbens (Nacc) has been suggested as a potential interventional target in the disease.

The study included eight patients with a DSM-IV diagnosis of schizophrenia who were resistant to ≥2 atypical antipsychotics, clozapine (multiple brands) as monotherapy or combination therapy, and to electroconvulsive therapy.

Participants were initially randomly assigned to having the electrodes placed either in the sgACC or the Nacc, followed by DBS treatment. Follow-up was conducted every 2 weeks until a stable clinical response was achieved.

The team then randomly assigned the patients to "on" and "off" arms for the electrodes. The patients in the off arm who experienced relapse were crossed over to the on arm, and those in the on arm who experienced relapse were withdrawn from the study.

The mean age of the patients was 42.4 years, and 50% of study participants were female. The mean age at onset of schizophrenia was 24.9 years.

Mean baseline scores on the Positive and Negative Symptom Scale (PANSS) were 88.7 for total scores, 23.0 on the positive subscale, 25.1 on the negative subscale, and 40.6 on the general subscale.

The team report that in the first randomization phase, during which all patients were treated with DBS, six of the eight patients achieved a symptomatic response, defined as an improvement in PANSS total scores of ≥25%.

At the end of the precrossover phase, mean PANSS total scores were 58.7%, with scores of 15.0 on the positive subscale, 14.7 on the negative subscale, and 29.0 on the general subscale.

So far, three patients have been assigned to the on/off phase of the study, and three patients have been excluded. One exclusion was due to a serious adverse event related the surgery, in which the patient experienced a subcortical hematoma and infection of the prosthesis.

Another patient was excluded while on the off arm because of a serious relapse that involved suicidal ideation and that required changes in pharmacologic treatment. The third patient was excluded after failing to experience improvement following 6 months of treatment.

The investigators note that although the study showed that DBS was effective in treatment-resistant schizophrenia, the surgical risks need to be taken into account.

Dr Roldán said that, owing to the small number of patients and the early stage of the study, the current data were "only descriptive." He noted that further data will be presented at a later date.

She told Medscape Medical News that it is not possible to say at this time whether there is a difference in outcomes between stimulation at the sgACC and at the Nacc. DBS at both sites appears to be effective.

However, coinvestigator Iluminada Corripio, MD, PhD, also from Universitat Autònoma de Barcelona, said the researchers "have the clinical impression that, maybe with the accumbens, the response is earlier, but we didn't do a comparison.

"This study is not definitive, and we need to finish the complete analysis of the patients."

Dr Roldán pointed out that because the surgery is "very expensive," if it were to be used, it would only be for the severest, most resistant cases.

"But we'll see, because, for example, in obsessive-compulsive disorder, they are doing the surgery in Barcelona. So we think that if it's successful, we can do it in the future," she said.

A Step in the Right Direction

Commenting on the findings, Michael Bloomfield, PhD, Division of Psychiatry, University College London, United Kingdom, who was not involved in the study, told Medscape Medical News that DBS in treatment-resistant schizophrenia "is potentially very exciting, but I think a lot more work's needed.

"I think one of the key issues is that, at the moment...there isn't a control arm, which means that it's impossible to say whether or not there's a placebo effect going on there. The researchers need to perform more statistical analyses on what they've done to see if there's a significant difference in the findings. I think the early results are promising, they're going in the right direction, but they need to go through robust statistical analysis," he said

Dr Bloomfield also sounded a note of caution concerning implantation of the device. He highlighted the serious adverse surgical event reported by the researchers.

"But I think that needs to be balanced against the fact that someone who has a very treatment-resistant illness has a very, very poor quality of life, and if this treatment is effective, then it has the potential to really help quite a lot of people."

With respect to the regions of the brain that are targeted by DBS, Dr Bloomfield said that future research should investigate which area achieves the greatest effect, "and maybe they just focus on one area, or maybe they try a different area."

Should the final results indicate that neither area achieves an appreciable effect, "then looking in a different brain area still may be worth pursuing." He also noted there are different ways of administering the electrical current and different patterns of current delivery that could be explored.

The study was supported by the Catalonian government and Plan Estatal de Investigaci ó n Cientifica, T é cnica y de Innovación and was cofunded by the Instituto de Salud Carlos III–Subdirección General de Evaluación y Fomento de la Investigació n and the European Regional Development Fund, Miguel Servet Research Contract and Projects programs. The investigators have disclosed no relevant financial relationships.

30th European College of Neuropsychopharmacology (ECNP) Congress. Poster P.3.d.032, presented September 4, 2017.

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