Objective-To determine the prevalence of depressive disorders and symptoms in patients with late-stage ALS, to identify possible risk and protective factors associated with depression, and to determine whether depression increases as death approaches.Methods-Semistructured interviews were conducted monthly with hospice-eligible patients with ALS and caregivers until the study endpoints of death or tracheostomy. Standardized measures were administered to assess depressive disorders and symptoms, hopelessness, spiritual beliefs, attitudes toward hastened death, quality of life, and related constructs.Results-Sixty-three percent of eligible patients were enrolled. Of the 80 participants, 17 were seen only once; the number of monthly assessments for the others ranged from 2 to 18. For the 53 patients who died, median interval between last assessment and death was 30 days. At study baseline, 81% had no depressive disorder, 10% had minor depression, and 9% had symptoms consistent with major depression. Diagnoses of depression were made on 16% of 369 monthly assessments. Fifty-seven percent of patients never had a depression diagnosis at any visit, and 8% were depressed at all visits. There was no trend toward increasing depression as death approached. Presumed protective factors including spiritual beliefs, spouse as care partner, financial situation, depression in caregiver, and hospice participation did not distinguish between those who were depressed and those who were not.Conclusions-Results of multiple measures of depression and distress converged to indicate that major depression in people with late-stage ALS is rare, although transient depressive symptoms may occur, and depression does not generally increase as death approaches.To many people, professional and lay, it seems self-evident that depression is a "normal" response to the diagnosis of progressive and lethal disease, as AIDS was in the 1980s and ALS is today. The corollary assumption is that depressive symptoms increase as physical disability worsens and death approaches. However, there is little evidence for seriously medically ill patients in general and ALS patients in particular. Published findings are inconsistent. 1,2 It is not known whether depressive symptoms worsen or diminish as death approaches. Accurate identification of depressive disorders can lead to effective therapeutic interventions to improve the quality of life of both the patient and the caregiver, while at the same time reducing prescription of antidepressant medication based solely on the assumption that it is only natural for ALS patients to be depressed as their physical symptoms worsen.Five years ago, we reported prevalence rates of depression in ambulatory ALS patients and noted the paucity and inconsistency of evidence. 3 This is still true. To our knowledge, only two studies have used standardized methods to generate psychiatric diagnoses. In one investigation, 4 clinical depression was assessed using the Diagnostic Interview Schedule; 11%

These findings suggest caution in concluding that the desire to hasten dying in end-stage disease is simply a feature of depression.

MRS is highly sensitive, somewhat more than TMS, and shows good correlation with clinical UMN signs. Combining MRS and TMS results in the same patient with further refinement may help in the early diagnosis of ALS.

The type and quality of end-of-life care varies greatly in ALS; the time to initiate end-of-life care is not defined, and decision making is hampered by logistical and financial barriers. There has been no systematic review of these issues in ALS. The goals of this initiative are to: 1) improve end-of-life care for patients with ALS and families based on what limited evidence is available; 2) increase awareness, interest, and debate on the end-of-life care in ALS; and 3) identify areas needed for new prospective clinical research. The ALS Peer Workgroup reviewed the literature and 1) identified the current state of knowledge, 2) analysed the gaps in care, and 3) provided recommendations for standard of care and future research. It was shown that areas of investigation are needed on the incorporation of an interdisciplinary approach to care in ALS that includes: psychosocial evaluation and spiritual care; the use of validated instruments to assess patient and caregiver quality of life; and the establishment of proactive caregiver programs. Several public policy changes that will improve coverage for medical care, hospice, and caregiver costs are also reviewed. More clinical evidence is needed on how to provide optimal end-of-life care specifically in ALS.

Patients with ALS were able to express their preferences for life-extending or ameliorative technologies and made choices consistent with these preferences. However, patient preferences may change over time, and clinical education efforts are required throughout the course of disease.