Extended antidepressant maintenance and discontinuation syndromes

Unipolar and bipolar depression are episodic, recurrent illnesses for the majority of patients. Because each episode engenders considerable costs for patients, families, and society, prevention of recurrences has high priority. Numerous studies demonstrate that maintenance antidepressants or mood stabilizing medications are efficacious in preventing recurrences. A review of maintenance studies supports the view that all antidepressants perform significantly better than placebo in preventing recurrences of depression—with the stipulation that full antidepressant doses be employed. Earliest studies, conducted two decades ago, evaluated tricyclics (TCAs), heterocyclics, and lithium, while recent studies have focused on selective serotonin reuptake inhibitors (SSRIs). Compliance is essential. Strategies for enhancing compliance include selection of medications with reported safety and few side effects, education of patients and families, referral to patient advocacy groups, and use of new technological compliance aids. Preliminary data suggest that SSRIs are better tolerated than TCAs; fewer patients discontinue these agents due to side effects. Selection criteria for maintenance treatment have not been well determined, but three or more prior episodes is recognized as a relatively strong indicator. Other clinical or genetic criteria have also been suggested. For various reasons, patients may discontinue medications, and when this happens withdrawal phenomena may occur. Withdrawal effects are well documented for all antidepressants and can be profound with TCAs. After stopping some SSRIs, a few withdrawal symptoms may have similarities with those following discontinuation of TCAs, but unique “CNS-like” effects are frequently described, including brief recurrent episodes of dizziness, lightheadedness, vertigo, electric shock-like sensations, and gait instability. These appear to be half-life dependent, with agents with shorter half-lives having more discontinuation symptoms. If antidepressant medications must be discontinued, a gradual taper is preferable, perhaps extending three to six months or longer to prevent discontinuation effects, enable adaptation at the receptor level and allow earlier recognition and treatment of recurrent depressive symptoms. Depression and Anxiety, Volume 8, Supplement 1:43–53, 1998. © 1998 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35217/1/7_ftp.pd

Adrenergic Dysregulation and Pain With and Without Acute Beta-Blockade in Women With Fibromyalgia and Temporomandibular Disorder

In patients with fibromyalgia syndrome (FMS) and temporomandibular disorder (TMD), stress and pain may chronically enhance sympathetic activity, altering cardiovascular responses and worsening pain. This study examined cardiovascular, epinephrine (EPI), norepinephrine (NE), cortisol and clinical pain responses in 54 female patients with these disorders and 34 controls. In a subsample of 10 FMS, 10 TMD patients and 16 controls, using a counterbalanced, double-blind, cross-over design, the same responses were assessed after intravenous administration of low dose propranolol vs. placebo. Testing included baseline, postural, speech and ischemic pain stressors. FMS patients showed lesser heart rate (HR) increases to posture challenge but greater blood pressure (BP) increases to postural and speech tasks than Controls, as well as higher overall BP and greater total vascular resistance (TVR) than TMDs or Controls. TMDs showed higher overall cardiac output and lower TVR than Controls. Both FMS and TMD groups showed lower baseline NE than Controls, and TMDs showed lower overall EPI and NE levels. Group differences in HR, EPI and NE were abolished after propranolol although BP, CO and TVR differences persisted. In both FMS and TMD, number of painful body sites and ratings of total clinical pain obtained 4 times during each session were significantly lower after beta-blockade vs. placebo

Protocol for an observational cohort study identifying factors predicting accurately end of life in dementia with Lewy bodies and promoting quality end-of-life experiences: the PACE-DLB study

Introduction Dementia with Lewy bodies (DLB) is one of the most common degenerative dementias. Despite the fact that most individuals with DLB die from complications of the disease, little is known regarding what factors predict impending end of life or are associated with a quality end of life.Methods and analysis This is a multisite longitudinal cohort study. Participants are being recruited from five academic centres providing subspecialty DLB care and volunteers through the Lewy Body Dementia Association (not receiving specialty care). Dyads must be US residents, include individuals with a clinical diagnosis of DLB and at least moderate-to-severe dementia and include the primary caregiver, who must pass a brief cognitive screen. The first dyad was enrolled 25 February 2021; recruitment is ongoing. Dyads will attend study visits every 6 months through the end of life or 3 years. Study visits will occur in-person or virtually. Measures include demographics, DLB characteristics, caregiver considerations, quality of life and satisfaction with end-of-life experiences. For dyads where the individual with DLB dies, the caregiver will complete a final study visit 3 months after the death to assess grief, recovery and quality of the end-of-life experience. Terminal trend models will be employed to identify significant predictors of approaching end of life (death in the next 6 months). Similar models will assess caregiver factors (eg, grief, satisfaction with end-of-life experience) after the death of the individual with DLB. A qualitative descriptive analysis approach will evaluate interview transcripts regarding end-of-life experiences.Ethics and dissemination This study was approved by the University of Florida institutional review board (IRB202001438) and is listed on clinicaltrials.gov (NCT04829656). Data sharing follows National Institutes of Health policies. Study results will be disseminated via traditional scientific strategies (conferences, publications) and through collaborating with the Lewy Body Dementia Association, National Institute on Aging and other partnerships

Patient- and proxy-reported quality of life in advanced dementia with Lewy bodies

Little is known regarding quality of life (QoL) in dementia with Lewy bodies (DLB), particularly in advanced stages.Dyads of individuals with moderate-advanced DLB and their primary caregivers were recruited from specialty clinics, advocacy organizations, and research registries. The study collected demographics, disease-related measures, and measures of patient/caregiver experiences.The Quality of Life in Alzheimer's Disease (QoL-AD) was completed by the person with DLB and the caregiver (proxy) in 61 dyads; 85 dyads had only a proxy-completed QoL-AD. Patient- and proxy-reported scores were moderately correlated (r = 0.57, P < 0.0001). Worse patient-reported QoL correlated with daytime sleepiness, autonomic symptom burden, and behavioral symptoms. Proxy ratings correlated with dementia severity, daytime sleepiness, behavioral symptoms, dependence in activities of daily living, and caregiver experience measures.Patient- and proxy-reported quality of life (QoL) should be assessed separately in advanced DLB. Some symptoms associated with QoL have available therapeutic options. Research is needed regarding strategies to optimally improve QoL in DLB.Patient and proxy quality of life (QoL) ratings had moderate correlation in advanced dementia with Lewy bodies. Daytime sleepiness affected patient- and proxy-reported QoL. Behavioral symptoms affected patient- and proxy-reported QoL. Autonomic symptom burden affected patient-reported QoL. Dementia severity, dependence, and caregiver experiences affected proxy ratings

Caregiver Experiences and Burden in Moderate-Advanced Dementia With Lewy Bodies

Dementia with Lewy bodies (DLB) is a common degenerative dementia, but research on caregiver experiences in late stages is lacking. This study aimed to investigate the caregiving experience in moderate-advanced DLB to identify opportunities for improving care and support. Dyads of individuals with moderate-advanced DLB and their primary informal caregivers were recruited from specialty clinics, advocacy organizations, and research registries. The study collected demographics, disease-related measures, and measures of the caregiver experience relating to caregiver support, burden, grief, self-efficacy, depression, quality of life, and coping. Spearman correlation coefficients and Wilcoxon rank-sum tests evaluated the relationships of caregiver measures with patient and caregiver variables with adjustments for multiple testing. Caregivers (n = 143) were mostly women (83.5%) and spouses (84.7%) (mean age 68 years; range 37-85). Almost 40% reported high burden and/or depression. Caregiver measures correlated with fluctuation and behavioral symptom severity, sleepiness, and autonomic symptoms of the person with DLB. Higher burden correlated with worse caregiver quality of life, higher depression, and grief. Greater self-efficacy, social support, and resilience correlated with lower caregiver burden. The most frequently reported caregiver concerns were being unable to plan for the future, having to put the needs of the person with DLB ahead of the caregiver's own needs, and worry that the person with DLB would become too dependent on the caregiver, but many additional concerns were endorsed. Caregivers were generally satisfied with medical team support. The lowest reported satisfaction related to information regarding disease progression and how well medical teams shared information with each other. Various patient-related and caregiver-related factors influence caregiver experiences in moderate-advanced DLB. Clinicians can target caregiver needs by providing support resources and DLB education and treating bothersome patient symptoms. Future research should investigate what interventions can modify and improve caregiver experiences in advanced DLB and identify therapeutics for patient symptoms currently without adequate treatments (e.g., fluctuations, daytime sleepiness). NCT04829656