The Effects of Transcranial Magnetic Stimulation on Cognitive Functioning in Bipolar Depression: A Systematic Review

The features of bipolar affective disorder (BAD) include mood swings, recurring episodes of mania, depression, and mixed states. Numerous studies of people living with BAD have found the presence of cognitive impairments that affect patients' daily social functioning and quality of life. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique recommended for the treatment of bipolar depression (BD). The effect of TMS on cognitive function in BD patients remains mostly unclear.

We carried out a systematic search in the databases of PubMed and Scopus for the whole publication period until March 30^th, 2022. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) was used to identify all data published in English language and related to the use of TMS in the treatment of depression in BAD and its impact on cognitive function. Articles related to TMS, cognition, and BD were identified using predefined term search algorithms. Articles on clinical trials and case reports were included, but reviews were excluded. The PICOS (Population Intervention Comparison Outputs Study) formula in our review included: P - patients with bipolar depression, I - TMS treatment, C - patients without TMS treatment / placebo TMS, O - changes in cognitive functions, S - all types of original studies.

Within the primary screening for assessment of full texts, 25 documents met our selection criteria to test the effect of TMS on cognitive functioning in BD. Based on a secondary screening of the full-text analysis, 10 articles (N=259 patients) were included into the current review. Among these, the majority of articles were based on the randomized controlled trials (RCTs, N=6), whereas the remaining four presented a case report, an open unblinded study, an open-label study, and a pilot study, respectively. Most of the studies produced mixed result. However, the limited data strongly suggested that TMS is without detriment to cognition in BD patients and is indeed beneficial in specific domains of cognitive function, namely (i) verbal fluency, (ii) verbal memory, and (iii) executive functioning. Small sample sizes, heterogeneity across the study designs, lack of the control groups data in some of the trials, different TMS protocols parameters and outcome measures represent significant limitations for comparing and analyzing the available results.

Thus, present data on the effects of TMS in improving cognition in BD patients remains limited. To our mind, in order to evaluate properly the effectiveness of TMS in cognitive functioning improvement in BD, there is need for further randomized controlled trials and the corresponding development of the clinical standards for research recommendations. Such studies could define the appropriate methods for valid assessments of cognitive functions, and guide the selection of optimal TMS protocols when planning RCTs. We suggest that efforts should be expended to organize centralized large-scale clinical trials to determine the optimal parameters of TMS procedures and the range of effects of this treatment on various indicators of cognitive functioning in BD. This applies equally to other socially significant mental disorders marked by perturbations in cognitive functioning.