The COVID-19 pandemic may profoundly harm the mental health and emotional well- being of many older adults. Public health interventions to minimize the spread of the virus have had the unintended consequences of worsening social isolation, financial stress, and unemployment. Results of early research efforts assessing the impact of these interventions on the mental health of older adults have been mixed. Available findings suggest that a subset of community-dwelling older adults have been less negatively impacted than younger adults, while people of color, the poor, residents of nursing homes and other communal living environments, and those living with dementia and their caregivers are more likely to suffer from COVID-related health problems. This manuscript describes two older adults for whom COVID-19 associated stresses caused significant worsening in their psychiatric illnesses, including the emergence of suicidal ideation, summarizes the literature on the impact of interactions between psychosocial stresses and biological factors on the mental health and well-being of older adults, and discusses interventions to help older adults whose mental health has worsened due to COVID-19. Timely and accurate diagnosis, prompt provision of individualized care using both pharmacologic and psychotherapeutic interventions, adoption of new technologies that permit care to be provided safely at a distance and which allow for virtual social interactions, coupled with ongoing advocacy for policy changes that address significant health care disparities and provide older adults continued access to health care and relief from financial hardship, will help older adults remaining as healthy as possible during the pandemic.

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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