Background & Rationale: Fibromyalgia is characterized by widespread pain, fatigue, mood and
anxiety as well as cognitive complaints. For an unacceptable proportion of patients,
depressive symptoms remain impairing despite multiple treatments.
For such patients, novel treatments include non-invasive brain stimulation. Transcranial
Magnetic Stimulation (TMS) targeting the dorsolateral prefrontal cortex (DLPFC) or the
primary motor cortex (M1) is the non-invasive neurostimulation method with the largest
evidence base in fibromyalgia. It involves generating magnetic fields outside of the body to
change the firing of neurons in the brain, and has a very favorable tolerability profile.
Recent meta-analyses indicate that both the DLPFC and M1 targets are associated with
improvements in pain, mood and anxiety, however the benefits are more persistent when the
DLPFC is targeted (Su et al, 2021 - J Clin Med). The DLPFC is important in fibromyalgia
through its implication in several symptoms domains in fibromyalgia, as well as pain
catastrophization.
Our neurophysiological data and clinical data in depression suggests that we can enhance the
effects of TMS by using an adjunctive medication called D-Cyloserine (DCS, 100mg) in
conjunction with a protocol called intermittent theta-burst stimulation (iTBS). Specifically,
this data indicated that several converging features of fibromyalgia improve with augmented
iTBS, specifically depressive symptoms, anxiety symptoms, fatigue, and cognitive function. We
therefore hypothesize that the combination of D-cycloserine and TMS will lead to greater
improvements in fibromyalgia symptoms than TMS alone.
Although iTBS has not yet been studied in fibromyalgia, it has a well characterized
neurophysiological effect and been shown to be non-inferior to conventional TMS protocols in
conditions such as depression. More importantly, its physiological basis can be manipulated
with D-Cycloserine whereas this has not been convincingly demonstrated with rTMS (see Brown
et al, 2019, 2021 Brain Stim).
Research Question and Objectives: To conduct a randomized placebo-controlled trial of DCS in
adjunct with rTMS in Fibromyalgia. Participants will be randomized to receive 100mg of DCS or
placebo together with TMS.