Optimally combining transcranial magnetic stimulation with antidepressants in major depressive disorder: A systematic review and Meta-analysis.

There is a critical knowledge gap in optimally combining transcranial magnetic stimulation (TMS) and antidepressants to treat patients with major depressive disorder (MDD). TMS is effective in treating MDD in patients who have failed at least one antidepressant trial, with accelerated protocols showing faster remission in treatment-resistant depression (TRD). Although clinicians routinely augment antidepressants with TMS, there is a knowledge gap in stopping versus continuing antidepressants or the dosing strategies when starting or tapering TMS. These considerations are important when considering maintenance TMS (delivered alone or in combination with suitable antidepressants) to maintain remission in MDD after the index course of TMS. As the first step towards filling this knowledge gap, we reviewed randomized controlled trials (RCTs) and open-label trials from 2 databases (PubMed/Medline and EMBASE) that compared active TMS combined with a pre-specified antidepressant dosed in the same manner for adults with MDD versus sham TMS combined with the same antidepressant as in the active arm. All studies were published between January 1, 2000, and December 31, 2023. We excluded case reports, case series, and clinical studies that augmented TMS with antidepressants and vice versa. We found 10 RCTs (n = 654 participants) and performed a meta-analysis. This showed active TMS combined with pre-specified antidepressants had greater efficacy for MDD treatment than sham TMS combined with the same antidepressants as in the active arm (Hedge's g = 1; 95 % CI [0.27, 1.73]). The review and meta-analysis indicate greater short-term efficacy in combining antidepressants with TMS from the get-go in MDD. Given the increasing role of accelerated TMS protocols in expediting remission in MDD and the results of our meta-analysis, we advocate for RCTs examining the short-term and long-term effects of various antidepressant classes on these TMS protocols in MDD. This can also optimize and individualize maintenance TMS protocols to prevent relapse in MDD.

Discriminating Fake From True Brain Injury Using Latency of Left Frontal Neural Responses During Old/New Memory Recognition.

Traumatic brain injury (TBI) is a major public health concern that affects 69 million individuals each year worldwide. Neuropsychologists report that up to 40% of individuals undergoing evaluations for TBI may be malingering neurocognitive deficits for a compensatory reward. The memory recognition test of malingering detection is effective but can be coached behaviorally. There is great need to develop a novel neural based method for discriminating fake from true brain injury. Here we test the hypothesis that decision making of faking memory deficits prolongs frontal neural responses. We applied an advanced method measuring decision latency in milliseconds for discriminating true TBI from malingerers who fake brain injury. To test this hypothesis, latencies of memory-related brain potentials were compared among true patients with moderate or severe TBI, and healthy age-matched individuals who were assigned either to be honest or faking memory deficit. Scalp signals of electroencephalography (EEG) were recorded with a 32-channel cap during an Old/New memory recognition task in three age- and education-matched groups: honest (n = 12), malingering (n = 15), and brain injured (n = 14) individuals. Bilateral fractional latencies of late positive ERP at frontal sites were compared among the three groups under both studied (Old) and non-studied (New) memory recognition conditions. Results show a significant difference between the fractional latencies of the late positive component during recognition of studied items in malingerers (averaged latencies = 396 ms) and the true brain injured subjects (mean = 312 ms) in the frontal sites. Only malingers showed asymmetrical frontal activity compared to the two other groups. These new findings support the hypothesis that that additional frontal processing of malingering individuals is measurably different from those of actual patients with brain injury. In contrast to our previous reported method using difference waves of amplitudes at frontal to posterior midline sites during new items recognition (Vagnini et al., 2008), there was no significant latency difference among groups during recognition of New items. The current method using delayed left frontal neural responses during studied items reached sensitivity of 80% and specificity of 79% in detecting malingers from true brain injury.