Repetitive transcranial magnetic stimulation treatment of major depressive disorder and comorbid chronic pain: response rates and neurophysiologic biomarkers

Abstract

Background Major depressive disorder (MDD) and chronic pain are highly comorbid, and pain symptoms are associated with a poorer response to antidepressant medication treatment. It is unclear whether comorbid pain also is associated with a poorer response to treatment with repetitive transcranial magnetic stimulation (rTMS). Methods 162 MDD subjects received 30 sessions of 10 Hz rTMS treatment administered to the left dorsolateral prefrontal cortex (DLPFC) with depression and pain symptoms measured before and after treatment. For a subset of 96 patients, a resting-state electroencephalogram (EEG) was recorded at baseline. Clinical outcome was compared between subjects with and without comorbid pain, and the relationships among outcome, pain severity, individual peak alpha frequency (PAF), and PAF phase-coherence in the EEG were examined. Results 64.8% of all subjects reported pain, and both depressive and pain symptoms were significantly reduced after rTMS treatment, irrespective of age or gender. Patients with severe pain were 27% less likely to respond to MDD treatment than pain-free individuals. PAF was positively associated with pain severity. PAF phase-coherence in the somatosensory and default mode networks was significantly lower for MDD subjects with pain who failed to respond to MDD treatment. Conclusions Pain symptoms improved after rTMS to left DLPFC in MDD irrespective of age or gender, although the presence of chronic pain symptoms reduced the likelihood of treatment response. Individual PAF and baseline phase-coherence in the sensorimotor and midline regions may represent predictors of rTMS treatment outcome in comorbid pain and MDD.

Absence of early mood improvement as a robust predictor of rTMS nonresponse in major depressive disorder

“…Additionally, these subjects were treated in the setting of an academic medical center with the majority of subjects reporting pain or other medical comorbidities that have been shown to increase treatment resistance (Corlier et al, 2021;Leuchter et al, 2010). Academic medical center populations that might be more treatment refractory have largely been excluded from some large registry studies (Sackeim et al, 2020).…”

The cAMP Response Element- Binding Protein/Brain-Derived Neurotrophic Factor Pathway in Anterior Cingulate Cortex Regulates Neuropathic Pain and Anxiodepression Like Behaviors in Rats

“…At the same time, the transmission of long-term nociceptive signals induces plasticity changes in the structure and function of some brain regions such as the medial prefrontal cortex (mPFC) ( Mecca et al, 2021 ), ACC ( Smith et al, 2021 ), amygdala ( Murugappan et al, 2021 ), and hippocampus ( Toledo et al, 2021 ), which are also involved in the regulation of emotion and cognitive functions, so that nociceptive signals not only include pain components but also cover emotion-related components in the brain ( De Ridder et al, 2021 ). Clinical studies also point out that patients with neuropathic pain are often comorbid with disorders of emotional function ( Fonseca-Rodrigues et al, 2021 ), and patients with anxiety and depression often have allodynia and hyperalgesia ( Corlier et al, 2021 ), which exacerbates the vicious circle between pain and psychiatric disorders. Therefore, developing a novel and effective therapy for mental illnesses associated with neuropathic pain remains a significant issue.…”

Systematic Review and Meta-Analysis of High-Frequency rTMS over the Dorsolateral Prefrontal Cortex .on Chronic Pain and Chronic-Pain-Accompanied Depression

“…Therefore, it is necessary to update the data and analyze the effect of HF rTMS on the DLPFC on chronic pain. Moreover, chronic pain is usually accompanied by other physical symptoms, such as depressive symptoms . The DLPFC area is widely related to emotional problems .…”

“…Moreover, chronic pain is usually accompanied by other physical symptoms, such as depressive symptoms. 9 The DLPFC area is widely related to emotional problems. 14 Thus, we also evaluated the effect of HF rTMS on the DLPFC on depressive symptoms with chronic pain.…”

“…Much research has shown that safe, noninvasive repetitive transcranial magnetic stimulation (rTMS) can reduce chronic pain . This may be effective for patients with unobvious responses to conventional pharmacology. , It is reported that high-frequency (HF) rTMS on the dorsolateral prefrontal cortex (DLPFC) can effectively treat pain syndromes, such as neuropathic pain (NP), migraine, and fibromyalgia. , However, in recent years, some high-quality articles have shown that, compared with sham stimulation, HF rTMS on the DLPFC does not effectively reduce NP, fibromyalgia, and headache. − In conclusion, some papers recently published are not in line with the view of analgesia of HF rTMS on the DLPFC.…”