Rehabilitation of Neuropsychiatric Symptoms in Patients With Long COVID: Position Statement.

Long COVID, a term used to describe ongoing symptoms after COVID-19 infection, parallels the course of other postviral syndromes. Neuropsychiatric symptoms of long COVID can be persistent and interfere with quality of life and functioning. Within the biopsychosocial framework of chronic illness, rehabilitation professionals can address the neuropsychiatric sequelae of long COVID. However, current practice models are not designed to address concurrent psychiatric and cognitive symptoms in adults living with long COVID. Thus, we present a biopsychosocial framework for long COVID and provide treatment strategies based on evidence from current literature of postviral chronic illness. These recommendations will guide rehabilitation professionals in identifying common neuropsychiatric symptoms in long COVID that can be targeted for intervention and addressing these symptoms via integrative interventions taking into account the biopsychosocial presentation of long COVID symptoms.

Modifiable predictors of nonresponse to psychotherapies for late-life depression with executive dysfunction: a machine learning approach.

The study aimed to: (1) Identify distinct trajectories of change in depressive symptoms by mid-treatment during psychotherapy for late-life depression with executive dysfunction; (2) examine if nonresponse by mid-treatment predicted poor response at treatment end; and (3) identify baseline characteristics predicting an early nonresponse trajectory by mid-treatment. A sample of 221 adults 60 years and older with major depression and executive dysfunction were randomized to 12 weeks of either problem-solving therapy or supportive therapy. We used Latent Growth Mixture Models (LGMM) to detect subgroups with distinct trajectories of change in depression by mid-treatment (6th week). We conducted regression analyses with LGMM subgroups as predictors of response at treatment end. We used random forest machine learning algorithms to identify baseline predictors of LGMM trajectories. We found that ~77.5% of participants had a declining trajectory of depression in weeks 0-6, while the remaining 22.5% had a persisting depression trajectory, with no treatment differences. The LGMM trajectories predicted remission and response at treatment end. A random forests model with high prediction accuracy (80%) showed that the strongest modifiable predictors of the persisting depression trajectory were low perceived social support, followed by high neuroticism, low treatment expectancy, and low perception of the therapist as accepting. Our results suggest that modifiable risk factors of early nonresponse to psychotherapy can be identified at the outset of treatment and addressed with targeted personalized interventions. Therapists may focus on increasing meaningful social interactions, addressing concerns related to treatment benefits, and creating a positive working relationship.

The Structural and Functional Neuroanatomy of Post-Stroke Depression and Executive Dysfunction: A Review of Neuroimaging Findings and Implications for Treatment.

Post-stroke depression and executive dysfunction co-occur and are highly debilitating. Few treatments alleviate both depression and executive dysfunction after stroke. Understanding the brain network changes underlying post-stroke depression with executive dysfunction can inform the development of targeted and efficacious treatment. In this review, we synthesize neuroimaging findings in post-stroke depression and post-stroke executive dysfunction and highlight the network commonalities that may underlie this comorbidity. Structural and functional alterations in the cognitive control network, salience network, and default mode network are associated with depression and executive dysfunction after stroke. Specifically, post-stroke depression and executive dysfunction are both linked to changes in intrinsic functional connectivity within resting state networks, functional over-connectivity between the default mode and salience/cognitive control networks, and reduced cross-hemispheric frontoparietal functional connectivity. Cognitive training and noninvasive brain stimulation targeted at these brain network abnormalities and specific clinical phenotypes may help advance treatment for post-stroke depression with executive dysfunction.

Dimensions of Poststroke Depression and Neuropsychological Deficits in Older Adults.

OBJECTIVE: Poststroke depression (PSD) has a heterogeneous presentation and is often accompanied by cognitive impairment. This study aimed to identify distinct dimensions of depressive symptoms in older adults with PSD and to evaluate their relationship to cognitive functioning. DESIGN: Cross-sectional factor and correlational analyses of patients with poststroke depression. SETTING: Patients were recruited from the community and from acute inpatient stroke rehabilitation hospitals. PARTICIPANTS: Participants had suffered a stroke and met DSM-IV criteria for major depression (≥18 Montgomery Åsberg Depression Scale; MADRS). INTERVENTION: None. MEASUREMENTS: MADRS was used to quantify depression severity at study entry. Neuropsychological assessment at the time of study entry consisted of measures of Global Cognition, Attention, Executive Function, Processing Speed, Immediate Memory, Delayed Memory, and Language. RESULTS: There were 135 (age ≥50) older adult participants with PSD and varying degrees of cognitive impairment (MMSE Total ≥20). Factor analysis of the MADRS identified three factors, that is sadness, distress, and apathy. Items comprising each factor were totaled and correlated with neuropsychological domain z-score averages. Symptoms of the apathy factor (lassitude, inability to feel) were significantly associated with greater impairment in executive function, memory, and global cognition. Symptoms of the sadness and distress factors had no relationship to cognitive impairment. CONCLUSION: PSD consists of three correlated dimensions of depressive symptoms. Apathy symptoms are associated with cognitive impairment across several neuropsychological domains. PSD patients with prominent apathy may benefit from careful attention to cognitive functions and by interventions that address both psychopathology and behavioral deficits resulting from cognitive impairment.

Neuroanatomical Abnormalities in Older Depressed Adults With Apathy: A Systematic Review.

OBJECTIVE: Apathy is a common phenomenon in late-life depression and is associated with poor outcomes. Apathy is often unrecognized in older depressed adults, and efficacious treatment options are lacking. This review provides a systematic review of the neuroanatomical abnormalities associated with apathy in late-life depression. In addition, the review summarizes the neuroimaging findings from studies of neurodegenerative and focal brain injury conditions that frequently present with apathy. The goal is to elucidate cerebral network abnormalities that give rise to apathy in older adults with mood disturbances and to inform future treatment targets. METHOD: Systematic literature review. RESULTS: The few studies that have directly examined the neuroanatomical abnormalities of apathy in late-life depression suggest disturbances in the anterior cingulate cortex, insula, orbital and dorsal prefrontal cortex, striatum, and limbic structures (ie, amygdala, thalamus, and hippocampus). Studies examining the neuroanatomical correlates of apathy in other aging populations are consistent with the pattern observed in late-life depression. CONCLUSIONS: Apathy in late-life depression appears to be accompanied by neuroanatomical abnormalities in the salience and reward networks. These network findings are consistent with that observed in individuals presenting with apathy in other aging-related conditions. These findings may inform future treatments that target apathy.

Anxiety and Type 1 Diabetes Management: Guardian and Child Report in a Pediatric Endocrinology Clinic.

BACKGROUND: Childhood anxiety prevents optimal diabetes management yet may be underrecognized by guardians. OBJECTIVE: We aimed to investigate associations among anxiety, diabetes treatment adherence, and diabetes symptom control through child and guardian report. METHODS: Cross-sectional pilot study surveying a convenience sample of children (ages 2-21) in a pediatric endocrinology clinic. Behavior Assessment System for Children, Second Edition 2, Self-Care Inventory Report, and Pediatric Quality of Life measured anxiety, diabetes treatment adherence, and diabetes symptom control. Analyses were performed with Spearman correlations. RESULTS: Prevalence of anxiety and related behaviors was higher when reported by children (13% and 24%) vs. guardians (5% and 13%). Child-reported anxiety was associated with worse symptom control in all ages (Pediatric Quality of Life [rs = -0.55, P < 0.01]) and worse treatment adherence in children aged ≤12 (Self-Care Inventory Report [rho = -0.601, P = 0.023]). Guardian-reported anxiety was associated with worse symptom control (Peds QL [rs = -0.38, P = 0.02]). Child- and guardian-reported anxiety were positively correlated (rho = 0.426, P = 0.017)-particularly for children aged >12 (rho = 0.686, P = 0.003)-although not significantly for children ≤ 12 (rho = 0.201, P = 0.473). CONCLUSION: Anxiety in children with type 1 diabetes varies with the domain of diabetes management (treatment adherence vs. symptom control) and reporting source (child vs. guardian). Children aged ≤12 exhibited a stronger relationship between higher anxiety and worse diabetes management with worse treatment adherence and symptom control in the presence of higher anxiety. Guardians of younger children were less effective at recognizing symptoms. Challenges identifying anxiety and its detrimental effects on diabetes management suggest routine screening of anxiety in pediatric endocrinology clinics is especially salient.

Minocycline augmentation in older adults with persistent depression: an open label proof of concept study.

Less than 40% of depressed older adults treated with an antidepressant achieve remission. Incomplete response to treatment is common. Current augmentation strategies have limited efficacy, and many have side effects that restrict their utilization in older adults. We conducted the first open pilot trial of minocycline augmentation in older adults who had failed to achieve remission after adequate psychopharmacologic treatment. Subjects older than 55 years of age with major depression and failure to achieve substantial improvement of depressive symptoms after at least 6 weeks of antidepressant treatment were given augmentation with minocycline 100 mg twice daily over an 8-week period. At the end of 8 weeks of augmentation with minocycline, 31% (4/13) patients achieved remission. Remitters had higher baseline ratings of hopelessness and apathy. Minocycline was well tolerated with no reported adverse events or discontinuation due to intolerance. Larger placebo-controlled studies are needed to evaluate the effects of minocycline augmentation in older adults who had failed to achieve remission after adequate treatment with antidepressants.

Depression, cognitive, and functional outcomes of Problem Adaptation Therapy (PATH) in older adults with major depression and mild cognitive deficits.

OBJECTIVES: Antidepressants have limited efficacy in older adults with depression and cognitive impairment, and psychosocial interventions for this population have been inadequately investigated. Problem Adaptation Therapy (PATH) is a psychosocial intervention for older adults with major depression, cognitive impairment, and disability. DESIGN: This study tests the efficacy of PATH versus Supportive Therapy for Cognitively Impaired Older Adults (ST-CI) in reducing depression (Montgamery Asberg Depression Rating Scale [MADRS]) and disability (World Health Organization Disability Assessments Schedule-II [WHODAS-II]) and improving cognitive outcomes (Mini Mental State Examination [MMSE]) over 24 weeks (12 weeks of treatment and 12-week post-treatment follow-up). SETTING: Participants were recruited through collaborating community agencies of Weill Cornell Institute of Geriatric Psychiatry. Both interventions and all research assessments were conducted at home. PARTICIPANTS: Thirty-five older adults (age ≥ 65 years) with major depression and cognitive impairment no dementia (CIND). INTERVENTIONS: PATH aims to increase emotion regulation by incorporating a problem-solving approach, teaching compensatory strategies, and inviting caregiver participation. Supportive Therapy aims to facilitate the expression of affect, as well as promote empathy. MEASUREMENTS: Depression was measured using the MADRS, disability using the WHODAS-II, and cognition using the MMSE. RESULTS: PATH participants showed significantly greater reduction in MADRS total score (7.04 points at 24 weeks, treatment group by time interaction: F[1,24.4] = 7.61, p = 0.0108), greater improvement in MMSE total score (2.30 points at 24 weeks, treatment group by time interaction: F[1,39.8] = 13.31, p = 0.0008), and greater improvement in WHODAS-II total score (2.95 points at 24 weeks, treatment group by time interaction: F[1,89] = 4.93, p = 0.0290) than ST-CI participants over the 24-week period. CONCLUSIONS: PATH participants had better depression, cognitive, and disability outcomes than ST-CI participants over 6 months. PATH may provide relief to depressed older adults with CIND who currently have limited treatment options.

"Engage" Therapy: Behavioral Activation and Improvement of Late-Life Major Depression.

OBJECTIVE: Engage is a treatment for late-life depression developed to match the skills of community clinicians based on the theory that dysfunction in the Research Domain Criteria Project positive valence systems is a critical mechanism of late-life depression. Accordingly, it uses "reward exposure" (engagement in meaningful, rewarding activities) as its principal intervention. This study tests the hypothesis that change in behavioral activation, an index of positive valence systems function, during successive treatment periods with Engage and during follow-up predicts depression at the end of each period. METHODS: Forty-eight nondemented, older adults with unipolar major depression were treated openly with 9 weekly sessions of Engage and assessed 36 weeks after entry. Depression severity was assessed with the 24-item Hamilton Depression Rating Scale (HAM-D) and behavioral activation with the Behavioral Activation for Depression Scale (BADS) at baseline, 6 weeks (mid-treatment), 9 weeks (end of treatment), and 36 weeks. RESULTS: A mixed-effects model examined whether change in BADS in successive periods occurring during Engage treatment and during follow-up predicts depression at the end of each period. Both BADS change (F1,52 = 18.63, p < 0.0001) and time (F2,52 = 7.68, p = 0.0012) predicted HAM-D scores at the end of each observation period. Every point of increase in BADS change reduced the HAM-D by 0.105 points. HAM-D at each point did not predict subsequent change in BADS (F1,52 = 2.17, p = 0.146). CONCLUSION: During Engage treatment and follow-up, change in behavioral activation is followed by improvement of depressive symptoms and signs.

Clinical Case Management versus Case Management with Problem-Solving Therapy in Low-Income, Disabled Elders with Major Depression: A Randomized Clinical Trial.

OBJECTIVE: To test the hypotheses that (1) clinical case management integrated with problem-solving therapy (CM-PST) is more effective than clinical case management alone (CM) in reducing depressive symptoms of depressed, disabled, impoverished patients and that (2) development of problem-solving skills mediates improvement of depression. METHODS: This randomized clinical trial with a parallel design allocated participants to CM or CM-PST at 1:1 ratio. Raters were blind to patients' assignments. Two hundred seventy-one individuals were screened and 171 were randomized to 12 weekly sessions of either CM or CM-PST. Participants were at least 60 years old with major depression measured with the 24-item Hamilton Depression Rating Scale (HAM-D), had at least one disability, were eligible for home-based meals services, and had income no more than 30% of their counties' median. RESULTS: CM and CM-PST led to similar declines in HAM-D over 12 weeks (t = 0.37, df = 547, p = 0.71); CM was noninferior to CM-PST. The entire study group (CM plus CM-PST) had a 9.6-point decline in HAM-D (t = 18.7, df = 547, p <0.0001). The response (42.5% versus 33.3%) and remission (37.9% versus 31.0%) rates were similar (χ(2) = 1.5, df = 1, p = 0.22 and χ(2) = 0.9, df = 1, p = 0.34, respectively). Development of problem-solving skills did not mediate treatment outcomes. There was no significant increase in depression between the end of interventions and 12 weeks later (0.7 HAM-D point increase) (t = 1.36, df = 719, p = 0.17). CONCLUSION: Organizations offering CM are available across the nation. With training in CM, their social workers can serve the many depressed, disabled, low-income patients, most of whom have poor response to antidepressants even when combined with psychotherapy.

Effects of Problem-Solving Therapy and Clinical Case Management on Disability in Low-Income Older Adults.

OBJECTIVE: To test the following hypotheses: (1) Clinical case management integrated with problem-solving therapy (CM-PST) is more effective than clinical case management alone (CM) in improving functional outcomes in disabled, impoverished patients and (2) improvement in depression, self-efficacy, and problem-solving skills mediates improvement of disability. METHODS: Using a randomized controlled trial with a parallel design, 271 individuals were screened and 171 were randomized to 12 weekly sessions of either CM or CM-PST at 1:1 ratio. Raters were blind to patients' assignments. Participants were at least age 60 years with major depression, had at least one disability, were eligible for home-based meals services, and had income no more than 30% of their counties' median. The WHO Disability Assessment Scale was used. RESULTS: Both interventions resulted in improved functioning by 12 weeks (t = 4.28, df = 554, p = 0.001), which was maintained until 24 weeks. Contrary to hypothesis, CM was noninferior to CM-PST (one-sided p = 0.0003, t = -3.5, df = 558). Change in disability was not affected by baseline depression severity, cognitive function, or number of unmet social service needs. Improvements in self efficacy (t = -2.45, df = 672, p = 0.021), problem-solving skill (t = -2.44, df = 546, p = 0.015), and depression symptoms (t = 2.25, df = 672, p = .025) by week 9 predicted improvement in function across groups by week 12. CONCLUSION: CM is noninferior to CM-PST for late-life depression in low-income populations. The effect of these interventions occur early, with benefits in functional status maintained as long as 24 weeks after treatment initiation (clinicaltrials.gov; NCT00540865).

Untangling therapeutic ingredients of a personalized intervention for patients with depression and severe COPD.

OBJECTIVE: We developed a personalized intervention for depressed patients with COPD (PID-C) aimed to mobilize patients to participate in the care of both conditions. We showed that PID-C reduced depressive symptoms and dyspnea-related disability more than usual care over 28 weeks. This study focused on untangling key therapeutic ingredients of PID-C. DESIGN: Randomized controlled trial. SETTING: Community. PARTICIPANTS: 138 patients who received the diagnoses of COPD and major depression after screening 898 consecutive admissions for acute inpatient pulmonary rehabilitation. INTERVENTION: Nine sessions of PID-C compared with usual care over 28 weeks. MEASUREMENTS: Primary outcome measures were the 17-item Hamilton Depression Rating Scale and the Pulmonary Functional Status and Dyspnea Questionnaire-Modified. Other measures were adherence to rehabilitation exercise (≥2 hours per week) and adherence to adequate antidepressant prescriptions. RESULTS: Low severity of dyspnea-related disability and adherence to antidepressants predicted subsequent improvement of depression. Exercise and low depression severity predicted improvement of dyspnea-related disability. CONCLUSIONS: PID-C led to an interacting spiral of improvement in both depression and disability in a gravely medically ill population with a 17% mortality rate over 28 weeks and an expected deterioration in disability. The interrelationship of the course of depression and dyspnea-related disability underscores the need to target adherence to both antidepressants and chronic obstructive pulmonary disease rehabilitation. PID-C may serve as a care management model for depressed persons suffering from medical illnesses with a deteriorating course.

Ketamine for major depressive disorder during an inpatient psychiatric admission: Effectiveness, adverse events, and lessons learned.

OBJECTIVE: Most studies examining the efficacy of ketamine for Major Depressive Disorder (MDD) have been conducted in outpatient or mixed inpatient/outpatient settings. Less is known about effectiveness and tolerability of ketamine for psychiatrically hospitalized patients. Efficacy and tolerability data from a naturalistic sample of acute inpatients may help inform institutions considering ketamine therapy for inpatient services. METHODS: We performed a retrospective chart review of inpatients with non-psychotic MDD treated during the initial 3 years of a ketamine infusion program. Treatment effectiveness was defined using change in Montgomery Asberg Depression Rating Scale (MADRS) scores over five infusions. MDD treatment response was defined by a 50 % reduction of MADRS score, and remission was defined as MADRS score ≤ 10 at any point during the treatment. We also report the frequency of adverse events. RESULTS: 41 patients with MDD were treated and had outcome data. 19 patients (46.5 %) met criteria for response and 15 patients (26.5 %) met criteria for remission during treatment. Four patients (10 %) had adverse psychological or behavioral outcomes. LIMITATIONS: MADRS scales were administered by psychiatrists, psychologists, and trainees in each discipline who did not undergo standardized training in scale administration. Consistent data regarding the race/ethnicity of the patients was not available. CONCLUSION: Twice weekly racemic ketamine infusion is an effective treatment option for patients hospitalized with MDD. Unmonitored or at home ketamine therapy may pose substantial risks.

Personalised intervention for people with depression and severe COPD.

Chronic obstructive pulmonary disease (COPD) is often complicated by depression and exemplifies the challenge in managing chronic illnesses that require active patient participation in care. In a clinical trial (NCT00151372), we compared a novel personalised intervention for depression and COPD (PID-C) targeting treatment adherence with treatment as usual (TAU). In 138 patients with major depression and severe COPD, PID-C led to a higher remission rate and a greater reduction in depressive symptoms and in dyspnoea-related disability than TAU over 28 weeks and 6 months after the last session. If replicated, PID-C may serve as a care model for patients with both depression and medical illnesses with a deteriorating course.

The incidence of tardive dyskinesia in the study of pharmacotherapy for psychotic depression.

Tardive dyskinesia (TD) is a debilitating adverse effect associated with antipsychotic treatment. Older age and the presence of mood disorder have been identified as risk factors for the development of TD. Thus, we assessed the incidence of TD in younger and older patients with major depressive disorder with psychotic features who participated in a 12-week clinical trial comparing olanzapine plus sertraline versus olanzapine plus placebo. All subjects (n = 259) were assessed with the Abnormal Involuntary Movement Scale at baseline and after 4, 8, and 12 weeks of treatment (or at termination). We used 7 different published criteria to estimate the prevalence of TD at baseline and the incidence over the duration of the trial. We compared the incidence of TD in subjects 60 years or older and those younger than 60 years. The overall prevalence and incidence of TD varied almost 10-fold, depending on the criteria (prevalence range, 1.2%-8.9%; incidence range, 0.0%-5.9%). Tardive dyskinesia was observed as a clinical adverse event in only 1 subject (0.4%). Whereas older subjects had a higher prevalence of TD at baseline, the incidence in younger and older subjects did not differ significantly. The incidence of TD was relatively low in both younger and older patients with major depressive disorder with psychotic features treated acutely with olanzapine. However, the estimate of the risk of TD varies widely, depending on the criteria used to define TD.

Low COVID-19 Vaccination Rates Among Psychiatric Inpatients: Implications for Institutional Settings and Outreach Efforts.

OBJECTIVE: This study sought to determine COVID-19 vaccination rates for individuals with serious mental illness admitted to a large health system in New York State. METHODS: Vaccination rates among 12,714 patients admitted to psychiatric units and to medical and surgical units were compared between April 6, 2021, and September 30, 2021. RESULTS: Only 40% (N=416 of 1,029) of patients admitted to psychiatric services had at least one COVID-19 vaccination, whereas 64.4% (7,523 of 11,685) of patients admitted to medical and surgical services had at least one vaccination. After adjustment for differences in key demographic and clinical characteristics, patients admitted to psychiatric services had a significantly lower likelihood of vaccination during the study period (risk ratio=0.78, 95% confidence interval=0.73-0.85, p<0.001). Black psychiatric patients had the lowest vaccination rate (28%). CONCLUSIONS: Psychiatric patients with acute illness had low COVID-19 vaccination rates. Targeted outreach for COVID-19 vaccination is necessary to reach this population.

Semantic organizational strategy predicts verbal memory and remission rate of geriatric depression.

OBJECTIVE: This study tests the hypothesis that the use of semantic organizational strategy during the free-recall phase of a verbal memory task predicts remission of geriatric depression. METHODS: Sixty-five older patients with major depression participated in a 12-week escitalopram treatment trial. Neuropsychological performance was assessed at baseline after a 2-week drug washout period. The Hopkins Verbal Learning Test-Revised was used to assess verbal learning and memory. Remission was defined as a Hamilton Depression Rating Scale score of ≤ 7 for 2 consecutive weeks and no longer meeting the DSM-IV-TR criteria for major depression. The association between the number of clusters used at the final learning trial (trial 3) and remission was examined using Cox's proportional hazards survival analysis. The relationship between the number of clusters utilized in the final learning trial and the number of words recalled after a 25-min delay was examined in a regression with age and education as covariates. RESULTS: Higher number of clusters utilized predicted remission rates (hazard ratio, 1.26 (95% confidence interval, 1.04-1.54); χ(2) = 4.23, df = 3, p = 0.04). There was a positive relationship between the total number of clusters used by the end of the third learning trial and the total number of words recalled at the delayed recall trial (F(3,58) = 7.93; p < 0.001). CONCLUSIONS: Effective semantic strategy use at baseline on a verbal list learning task by older depressed patients was associated with higher rates of remission with antidepressant treatment. This result provides support for previous findings indicating that measures of executive functioning at baseline are useful in predicting antidepressant response.

Ecosystem focused therapy in poststroke depression: a preliminary study.

OBJECTIVE: Poststroke depression (PSD) occurs in the context of abrupt, often catastrophic disability that finds the patient and his or her family unprepared. We developed the ecosystem focused therapy (EFT), a systematic intervention aimed to increase the PSD patient's and his or her ecosystem's abilities to address the "psychosocial storm" of PSD and utilize available treatments effectively and efficiently. This is a preliminary study of its efficacy. DESIGN: A total of 24 PSD patients were randomly assigned to receive weekly sessions of EFT or a comparison condition consisting of systematic Education on Stroke and Depression and their treatment for 12 weeks. RESULTS: Ecosystem Focused Therapy may be more efficacious than Education on Stroke and Depression in reducing depressive symptoms and signs, in leading to a higher remission rate, and in ameliorating disability in PSD. Reduction of disability in the early part of the trial mediated later improvement in depressive symptomatology. Similarly, reduction in depressive symptoms and signs early on mediated later improvement in disability. CONCLUSION: These encouraging findings require replication. Beyond its potential direct benefits in PSD, EFT may provide an appropriate context for efficient and timely administration of pharmacotherapy and of physical, speech, and occupational therapy thus maximizing their efficacy.