Association between Neuropathic Pain and Depression: Focusing on the Transcranial Magnetic Stimulation As a Promising Treatment Approach.

BACKGROUND: Neuropathic pain (NP) affects approximately 7% of the general population and is often accompanied by depressive symptoms with up to 85% of NP patients are suffering from comorbid depression (CD). The noninvasive neuromodulation technique of transcranial magnetic stimulation (TMS) is an established proven clinically effective nonpharmacological treatment for depression, and considered a highly promising option also for reducing the burden of NP by relieving pain perception and increasing patients' quality of life. In this article, we systematically review the various clinical protocols used in TMS treatments in patients suffering from NP and comorbid depression. SUBJECTS AND METHODS: Using Scopus, Elsevier, and PubMed databases, our keyword search identified 639 articles, of which 22 were selected for detailed analysis based on the inclusion criteria and in consideration of the heterogeneous study design of the majority of small trials. We evaluated the clinical efficacy in NP and comorbid depression, in relation to various TMS protocol parameters including coil type, target brain area, locus of increased evoked motor potential, amplitude of stimulation, duration of session, number of sessions per day/month, as well as inter-session-intervals, number and frequency of trains, and number and frequency of pulses. RESULTS: The most effective TMS protocols for treating comorbid NP and depression, as marked by decreased pain and depression scores proved to entail figure-of-8 coils targeting the primary motor area (M1), and applying at least ten daily rTMS sessions using high frequency stimulation (10-20 Hz) with a sub threshold intensity of 80-90% RMT and a total number of pulses of at least 1500 per session. Performing an additional maintenance phase after the acute treatment phase may strengthen and prolong the therapeutic effects of rTMS. CONCLUSIONS: Our database analysis suggests that a specific combination of TMS parameters is most effective for treating NP and comorbid depression. Although results are promising, the heterogeneity within the literature is such that many underpowered studies contribute rather little to the outcome, as evident by our inclusion / exclusion analysis. Moreover, we see a need for consensus on clinical protocols and inclusion of much larger clinical samples. Furthermore, we conclude that future research should entail advanced TMS procedures with multiple brain region stimulation (sequential or concurrent), and address issues of TMS maintenance and improved coil engineering for targeting deeper structures.

Does TMS Influence Verbal Function and Treat the Language Decline in Schizophrenia? Finding Answers via Systematic Review of Current Research.

BACKGROUND: rTMS is an adequately safe intervention that is approved for treatment of various neuropsychiatric conditions. There is ongoing research on the application of rTMS for the treatment of resistant auditory verbal hallucinations (AVH) in schizophrenia (SZ), and also for alleviating negative and cognitive symptoms in patients with chronic SZ states. Language decline, as a part of thought, language and communication disorders, is one of the key symptoms of SZ, having a significant bearing on decreased social/interpersonal functioning of these patients. In this regard rTMS may be a promising treatment approach, while serving as an important research tool in the field of SZ studies. The aim of our present study was to compile and evaluate the existing data on whether rTMS affects verbal function in SZ patients, and if rTMS has any efficacy for the treatment of language disturbances in SZ spectrum disorders. SUBJECTS AND METHODS: Our systematic search over the PubMed database revealed a total of 200 articles, of which 21 met criteria for inclusion in this analysis. We have reviewed in detail the study designs, inclusion and exclusion criteria, rTMS protocols and cognitive (in particular, speech/language domain) assessments reported in these articles. RESULTS: The 21 studies focused on two key topic clusters: (i) low-frequency rTMS treatment of AVH in SZ, and (ii) high-frequency rTMS treatment of negative and cognitive SZ symptoms. The majority of study participants presented with chronic and treatment-resistant states. Most of the low-frequency rTMS studies did not show any difference in verbal test measures in SZ in response to treatment. Less than a half of high-frequency rTMS studies reported a delayed positive effect on language cognitive domains in SZ. There were sporadic reports on dropouts associated with a decline in scores for auditory verbal learning tests. CONCLUSIONS: Our systematic review found rTMS to be generally safe in relation to verbal/speech function, and suggested that verbal memory tests could serve as a measure of safety of this treatment procedure in SZ patients. Speech effects of rTMS have only been registered over long-term observation periods, such that time-frame which should be considered as an important factor for future studies. In our project "Innovative Neuropsychiatry Research Bank: Priority-2030" we plan to clarify (i) efficient rTMS protocols targeting neurocognitive improvement in SZ, and (ii) the cohort of SZ patients with a particular cognitive endophenotype and language profile amenable to treatment with rTMS, with a focus on language scores.