Depression is a common mental disorder and one of the leading causes of disability around the world. Monoaminergic antidepressants often take weeks to months to work and are not effective for all patients. This has led to a search for a better understanding of the pathogenesis of depression as well as to the development of novel antidepressants. One such novel antidepressant is ketamine, which has demonstrated both clinically promising results and contributed to new explanatory models of depression, including the potential role of neuroplasticity in depression. Early clinical trials are now showing promising results of serotonergic psychedelics for depression; however, their mechanism of action remains poorly understood. This paper seeks to review the effect of depression, classic antidepressants, ketamine, and serotonergic psychedelics on markers of neuroplasticity at a cellular, molecular, electrophysiological, functional, structural, and psychological level to explore the potential role that neuroplasticity plays in the treatment response of serotonergic psychedelics.

Background: Fibromyalgia (FM) is a chronic medical condition characterized by widespread pain, sleep disturbance, and cognitive dysfunction. Sleep disorders are thought to play a prominent role in the etiology and symptomatic management of FM, specifically obstructive sleep apnea (OSA). In order to provide collaborative care, we need a better understanding of any overlapping presentation of FM and OSA. We conducted a site-wide review of patients from 2012–2016 to identify FM patients diagnosed with OSA. Methods: Charts were reviewed in patients aged 18 and above from 2012–2016 using ICD codes from a clinical data repository. Intersection of patients with a diagnosis of FM and OSA in clinics of psychiatry, sleep, rheumatology, and other outpatient clinics was compared. Polysomnography order patterns for FM patients were investigated. Results: Co-morbidity was highest in the sleep clinic (85.8%) compared to psychiatry (42.0%), rheumatology (18.7%), and other outpatient clinics (3.6%) ( p <0.001). In the rheumatology and other outpatient clinics, 93.5% and 96% of patients respectively, had no polysomnography ordered. Pairwise comparison of co-morbidity in clinics: sleep vs psychiatry, sleep vs rheumatology, sleep vs other clinics, psychiatry vs rheumatology, psychiatry vs other clinics, and rheumatology vs other clinics were statistically significant after applying a Sidak adjustment to the p -values (all p <0.001). Conclusion: Our analysis suggests that there could be a correlation between FM and OSA, and referral to sleep studies is recommended in the management of patients with FM. The varying prevalence of FM patients with co-morbid OSA in sleep clinics when compared to other outpatient clinics suggests a discrepancy in the identification of FM patients with OSA. When properly screened, OSA co-morbidity has the potential to be higher in other outpatient clinics.

Background: Racemic (R,S)-ketamine is a glutamatergic drug with potent and rapid acting antidepressant effects. An intranasal formulation of (S)-ketamine was recently approved by the US Food and Drug Administration (FDA) to be used in individuals with treatment-resistant depression (TRD). There are no data directly comparing outcomes on depression or other comorbidities between these two formulations of ketamine. However, recent meta-analyses have suggested that IV racemic ketamine may be more potent than IN-(S)-ketamine. Methods: We retrospectively analyzed clinical outcomes in 15 Veterans with comorbid TRD and post-traumatic stress disorder (PTSD) who underwent ketamine treatment at the VA San Diego Neuromodulation Clinic. All Veterans included in this analysis were given at least 6 intranasal (IN)-(S)-ketamine treatments prior to switching to treatment with IV racemic ketamine. Results: Veterans receiving ketamine treatment ( across both IN-(S)-ketamine and IV-(R,S)-ketamine) showed significant reductions in both the Patient HealthQuestionnaire-9 (PHQ-9), a self-report scale measuring depression symptoms (rm ANOVA F(14,42) = 12.6, p < 0.0001), and in the PTSD checklist for DSM-5 (PCL-5), a self-report scale measuring PSTD symptoms (rm ANOVA F(13,39) = 5.9, p = 0.006).Post hoc testing revealed that PHQ-9 scores were reduced by an average of 2.4 ± 1.2 compared to baseline after (S)-ketamine treatments (p = 0.1) and by an average of 5.6 ± 1 after IV-ketamine treatments (p = 0.0003) compared to pretreatment baseline scores. PCL-5 scores were reduced by an average of 4.3 ± 3.3 after IN (S)-ketamine treatments (p = 0.6) and 11.8 ± 3.5 after IV-ketamine treatments (p = 0.03) compared to pretreatment baseline scores.Conclusions: This work suggests that off-label IV-(R,S)-ketamine could be considered a reasonable next step in patients who do not respond adequately to the FDA-approved

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