Wednesday, October 12, 2022

Effectiveness of iTBS for Major Depression May Be Improved by Addition of D-Cycloserine

Individuals with major depressive disorder (MDD) who received intermittent theta burst stimulation (iTBS) augmented by the antibiotic D-cycloserine experienced greater improvement in depressive symptoms than those who received iTBS and a placebo, according to a report in JAMA Psychiatry.

iTBS is a new form of transcranial magnetic stimulation that can deliver therapeutic doses of magnetic energy in as little as three minutes. D-cycloserine is used to treat tuberculosis, but it has also been studied as an add-on treatment for trauma, anxiety-related disorders, and obsessive-compulsive disorder. This antibiotic targets the NDMA receptor in the brain, which is important in synaptic plasticity—the ability of neurons to adjust the connections with their neighbors. “[T]here are several lines of evidence to suggest that synaptic plasticity is not intact in MDD,” wrote lead author Alexander McGirr, M.D., Ph.D., of the University of Calgary and colleagues.

Fifty patients who had a primary diagnosis of moderate to severe MDD received 20 sessions of iTBS over four weeks supplemented with 100 mg of D-cycloserine or placebo for the first two weeks. All participants had a score of 18 or more on the Hamilton Depression Rating Scale.

The primary outcome was change in depressive symptoms as measured by the Montgomery-├ůsberg Depression Rating Scale (MADRS) at the end of treatment. Secondary outcomes included clinical response (50% or more reduction in MADRS score), clinical remission (MADRS score ≤10), and Clinical Global Impression (CGI) scores.

Those receiving iTBS plus D-cycloserine had an average decrease in MADRS score of 16.16 compared with 10.20 for those receiving iTBS and placebo. Rates of clinical response were higher in the iTBS plus D-cycloserine group than in the iTBS plus placebo group (73.9% vs 29.3%), as were rates of clinical remission (39.1% vs 4.2%).

The authors concluded: “Replication [of these results] in a larger multisite study is required, as is additional investigation into intersectional approaches with other dosing regimens and precision medicine targeting approaches.”

For more information see the Psychiatric News article “New TMS Protocol Turns Six Weeks of Treatment Into One.”

(Image: iStock/solar22)

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