COPENHAGEN — Repetitive transcranial magnetic stimulation (rTMS) is comparable in efficacy to antidepressants in patients with depression in schizophrenia — but with the advantage of improving cognitive performance, new research suggests.

In a study of more than 60 patients with schizophrenia and major depression who were already taking antipsychotics, rTMS was associated with a marginal improvement in depression scores over antidepressant therapy, and negative symptoms were more than halved.

More notably, patients in the rTMS group experienced marked improvements in a cognitive test of attention and executive function, with a meaningful response shown in the first week of treatment.

Although the results showed that improvement in cognitive test performance was associated with a positive outcome of rTMS, "further studies are needed," noted Nikita Maslenikov, MD, Moscow Research Institute of Psychiatry, Russia.

He presented the findings here at the 32nd European College of Neuropsychopharmacology (ECNP) Congress.

Common Comorbidities

Maslenikov noted that depression is the most common co-occurring syndrome in schizophrenia and is associated with an aggravated course of illness, lower quality of life, and increased mortality rates.

Because patients with depression in schizophrenia have "poor" responses to pharmacologic treatments, there has been growing interest in rTMS, which is associated with fewer adverse effects than electroconvulsive therapy.

Another plus for rTMS is that it may be associated with beneficial effects on cognition, which is an issue in these patients because depressive, negative, and cognitive symptoms in schizophrenia are associated with prefrontal cortex dysfunction.

The researchers recruited 66 patients with schizophrenia who were stable on antipsychotic medication and did not have exacerbations of psychotic symptoms.

All participants had major depression, defined as a score of 6 or greater on the Calgary Depression Scale for Schizophrenia (CDSS), and prevalent negative symptoms, at a mean composite score of -10.9 on the Positive and Negative Syndrome Scale (PANSS).

The patients, all of whom were already receiving antipsychotic therapy, were randomly assigned to receive rTMS or an antidepressant as an active control.

rTMS was administered at 15 Hz on the left dorsolateral prefrontal cortex at 100% intensity and 60-second intervals for five sessions per week for 3 weeks. Antipsychotic therapy was maintained at the same dose throughout.

Better Attention, Executive Function

After 3 weeks, the rate of response, defined as a 50% reduction in CDSS scores, was 62.5% in the rTMS group vs 52.9% in the active control group.

The mean reduction in CDSS scores at 3 weeks was 50.6% vs 47.4%, respectively, with both groups having significant reductions over baseline (P < .05 for both treatment groups).

The average reduction in scores on the PANSS negative subscale at the end of the study period was 15.5% with rTMS and 5.8% with antidepressant therapy. Again, this represented a significant reduction over baseline in both groups (P < .05).

The researchers also administered a battery of cognitive tests on a weekly basis: the "10 Words" test, Benton's test, Coding, Switching Count, and Verbal Fluency.

Results of the cognitive tests were inversely correlated with PANSS negative subscale scores, with the strongest correlation seen for Coding task scores, at a Spearman's rank correlation coefficient of -0.45 (P < .05).

Improvements in the Coding task, which examines attention and executive function, were almost double in the rTMS group than in the active control group (20.3% vs 11.4%), with both groups showing significant improvements over baseline (P < .05).

In addition, patients who experienced a fast cognitive response, defined at a rise in Coding scores after the first week of at least 10%, were more likely to have a positive outcome with rTMS (odds ratio, 1.4).

On the other hand, verbal and visual memory were largely unchanged during the study.

The investigators note that rTMS was associated with "good tolerability, rapid onset of action, improvement in executive function, and more potent reduction of negative symptoms."

However, experts pointed out the preliminary nature of the findings and noted that, although promising, there remain several unanswered questions over the role of rTMS in this patient population.

"Very Preliminary"

Silvana Galderisi, MD, PhD, professor of psychiatry, University of Campania Luigi Vanvitelli, Naples, Italy and immediate past president of the European Psychiatric Association, chaired the poster session where the findings were presented.

During the post-presentation discussion, Galderisi asked Maslenikov whether the intergroup difference in PANSS scores between rTMS and the active control was significant.

Maslenikov said their analysis indicated that, while it was not significant, there was a "tendency" toward significance.

Adrian Heald, MD, PhD, University of Manchester, United Kingdom, pointed out that "depression in schizophrenia presents in different ways and, as people go through their life course in schizophrenia, their depression presents in a different way."

He then asked whether the treatment was "less or more effective in older people," those who had suffered from schizophrenia for a longer period than for a shorter time.

"The majority of the patients in the study were young people. The mean age was around 30 years old," Maslenikov replied.

However, he noted that the literature indicates that rTMS is less effective in older people "because the distance between the scalp and the cortex increases with age."

Maslenikov also qualified that around half of the patients in their study had psychotic depression and the other half had depression in the context of chronic schizophrenia. "But we didn't find a significant difference" between them, he said.

Interestingly, the researchers also found that "the more severe the negative symptoms, the less effective was rTMS," he said.

Galderisi later told Medscape Medical News that the study is very interesting but "very preliminary" — especially because rTMS has been associated with a number of different findings in recent years, some of which were significant and some that were not.

She also noted that because the between-group differences were not significant, the advantage of rTMS over antidepressants is not clear, and "whatever the eventual difference, it is very difficult to explain."

The investigators and commenters have disclosed no relevant financial relationships.

32nd European College of Neuropsychopharmacology (ECNP) Congress: Abstract P.838. Presented September 8, 2019.

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