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Pain and depression frequently co-occur. Due to its antidepressant and analgesic properties, ketamine has been used for the management of treatment-resistant depression and pain. This systematic review examined the literature on the efficacy of sub-anesthetic doses of ketamine in individuals experiencing comorbid depression and chronic pain (CDCP), as well as comorbid depression and acute pain (CDAP). A secondary objective was to provide an assessment of dosage, route, and adverse effects of ketamine treatment for CDCP and CDAP. A literature search was conducted on MEDLINE, PsycINFO, and Embase databases, coupled with a manual screening of the bibliography sections of included articles. In addition, registered ongoing and planned trials were searched on Clinicaltrials.gov. The end date of the search was April 9th, 2022. Included studies assessed changes in depression and pain in patients receiving at least one sub-anesthetic dose of ketamine. Assessment of quality was conducted using the GRADE checklist. Of the 7 CDCP clinical trials, 3 reported a reduction in depression and pain, 3 reported a reduction in depression or pain only, and 1 reported no improvement in either comorbidity. Among the 7 CDAP clinical trials, 4 studies found improvements in depression and pain while the remaining 3 reported improvements in only one parameter. Ten of the 12 case studies and 2 of the 3 observational studies assessing CDCP and CDAP found improvements in pain and depression scores post-treatment with effects of variable duration. The planned methodologies of the registered clinical trials are in line with those of the published research. Preliminary evidence supports the efficacy of ketamine in treating CDCP and CDAP. However, the current review identified a small number of heterogeneous studies with mixed results, preventing comprehensive conclusions. More longitudinal placebo-controlled studies are needed to identify the effects of ketamine for patients with CDCP and CDAP.

BACKGROUND Deep transcranial magnetic stimulation (dTMS) is a novel non-invasive treatment option for psychiatric and cognitive disorders, including obsessive-compulsive disorder, substance use disorder, major depressive disorder (MDD), and Alzheimer’s Disease. With the use of Hesed-coil (H-coil) devices, dTMS can stimulate deeper regions of the brain compared to traditional repetitive transcranial magnetic stimulation (rTMS), resulting in more widespread effects. OBJECTIVE This review’s primary objective is to conduct a systematic review of the empirical literature on dTMS for psychiatric and cognitive disorders and, if feasible, a meta-analysis to compare the efficacy of active dTMS vs. sham/control for psychiatric disorders. Dementia, and related cognitive disorders, will also be examined. A secondary objective will be to examine subgroup differences (by age, sex, H-coil variety, and dTMS parameters [i.e., pulses per session, % motor threshold (%MT), session duration, number of sessions, etc.]) to evaluate whether dTMS differentially influences clinical outcomes based on these factors. METHODS A comprehensive search of the APA PsycINFO, Embase, Medline, and PubMed databases will be conducted using an appropriate search strategy. Two authors (A.D and M.D) will be responsible for screening relevant articles, assessing article eligibility (according to predetermined inclusion and exclusion criteria), and data extraction. Article eligibility discrepancies, if present, will be resolved by an independent third arbitrator (J.M.). All included articles will undergo a quality and risk of bias assessment. Data from included articles will be summarized qualitatively in a systematic review. If a sufficient number of equivalent studies are available, a meta-analysis will be performed to first (1) determine the effect of active vs. sham dTMS (or controls without a sham coil) stimulation across psychiatric and cognitive disorders, and second (2) examine subgroup effects of clinical outcomes. RESULTS N/A CONCLUSIONS We will outline the evidence relating to the clinical efficacy of dTMS in various psychiatric and cognitive disorders. The results of this review will provide clinicians with valuable insight into the clinical (i.e., participant, age, sex, psychiatric or cognitive disorder, etc.) and methodological factors (i.e., H-coil design, dTMS parameters, etc.) which may contribute to dTMS efficacy, and thereby may assist clinicians in their decision to prescribe dTMS for specific psychiatric and cognitive disorders. CLINICALTRIAL PROSPERO Registration Number: CRD42022360066

Preliminary evidence supports the use of psychedelics for major depressive disorder (MDD). However, less attention has been given to the neural mechanisms behind their effects. We conducted a systematic review examining the neuroimaging correlates of antidepressant response following psychedelic interventions for MDD. Through MEDLINE, Embase, and APA PsycINFO, 187 records were identified and 42 articles were screened. Six published studies and one conference abstract were included. Five ongoing trials were included from subjective outcomesTrials.gov. Our search covered several psychedelics, though included studies were specific to psilocybin, ayahuasca, and lysergic acid diethylamide. Three psilocybin studies noted amygdala activity and functional connectivity (FC) alterations that correlated with treatment response. Two psilocybin studies reported that FC changes in the medial and ventromedial prefrontal cortices correlated with treatment response. Two trials from a single study reported global decreases in brain network modularity which correlated with antidepressant response. One ayahuasca study reported increased activity in the limbic regions following treatment. Preliminary evidence suggests that the default mode and limbic networks may be a target for future research on the neural mechanisms of psychedelics. More data is required to corroborate these initial findings as the evidence summarized in this review is based on four datasets.

Background Transcranial magnetic stimulation (TMS) is a widely used noninvasive brain stimulation technique for psychiatric and cognitive disorders. In recent years, deep TMS (dTMS) has shown promise as an enhanced form of TMS able to stimulate deeper brain structures and target broader networks. Various magnetic Hesed-coil (H-coil) designs—a novel feature of dTMS—have been used to stimulate brain regions implicated in the pathophysiology of specific psychiatric and cognitive disorders, thereby producing therapeutic effects. Given the novelty of dTMS in psychiatry, little is known about the clinical efficacy of dTMS across psychiatric and cognitive disorders—that is, whether dTMS performs superiorly to sham or control. Objective In this paper, we outline a protocol for a systematic review investigating the clinical efficacy of dTMS. The primary objective is to conduct a systematic review of the literature on dTMS for psychiatric and cognitive disorders and, if feasible, a meta-analysis to compare the efficacy of active dTMS versus sham/control for psychiatric disorders. Dementia and related cognitive disorders will also be examined. A secondary objective will be to examine subgroup differences (by age, sex, H-coil design, and dTMS parameters [ie, pulses per session, percentage of motor threshold, etc]) to evaluate whether dTMS differentially influences clinical outcomes based on these factors. Methods A comprehensive search of the APA PsycINFO, Embase, MEDLINE, and PubMed databases will be conducted using keywords such as “H-coil” and “dTMS.” Two authors (AD and MD) will be responsible for screening relevant articles, assessing article eligibility (according to predetermined inclusion and exclusion criteria), and data extraction. All included articles will undergo a quality and risk of bias assessment. Data from included articles will be summarized qualitatively in a systematic review. If a sufficient number of equivalent studies are available, a meta-analysis will be performed to (1) determine the effect of active versus sham dTMS (or another control arm) across psychiatric and cognitive disorders, and (2) examine subgroup effects of clinical outcomes. Results The preliminary search rendered a total of 1134 articles from the APA PsycINFO, Embase, and MEDLINE databases. After full-text screening, 21 eligible articles remained. One additional article was identified from the references section of an existing systematic review. In total, 22 eligible articles were included. Data extraction and quality of assessment procedures are ongoing. Conclusions We will outline the evidence relating to the clinical efficacy of dTMS in various psychiatric and cognitive disorders. The results of the prospective systematic review will provide clinicians with valuable insight into the clinical (ie, participant age, sex, psychiatric or cognitive disorder, etc) and methodological factors (ie, H-coil design, dTMS parameters, etc) which may contribute to dTMS efficacy, and thereby may assist clinicians in their decision to prescribe dTMS for specific psychiatric and cognitive disorders. Trial Registration PROSPERO CRD42022360066; https://tinyurl.com/5ev6byrn International Registered Report Identifier (IRRID) DERR1-10.2196/45213