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Background: The CSP590 randomized trial was designed to estimate the effect of lithium on suicidality. After a third of the intended number of participants were enrolled, the hazard ratio of suicidality was 1.10 (95% CI: 0.77, 1.55). Based on this, the trial was stopped for futility. However, only 17% of patients adhered to the specified protocol., Aims: The objective was to estimate the per-protocol effect of lithium on suicidality, that is, the effect of adhering to the treatment strategies as specified in the protocol., Methods: We stopped individuals' follow-up if/when they showed evidence of nonadherence. We then conducted the analysis in the restricted sample, adjusting for prognostic factors that predict adherence via inverse probability weighting. The primary outcome was the 12-month risk of suicidality (including death from suicide, suicide attempt, interrupted attempt, hospitalization specifically to prevent suicide)., Results: The estimated 12-month risk of suicidality was 18.8% for lithium, and 24.3% for placebo. The risk ratio was 0.78 (95% CI: 0.43, 1.37) and the risk difference -5.5 percentage points (95% CI: -17.5, 5.5). Results were consistent across sensitivity analyses., Conclusions: With one-third of the targeted sample size, lithium effects (compared with placebo) ranging between a 17.5% reduction and a 5.5% increase in the risk of suicidality were highly compatible with the data. Thus, a protective effect of lithium on suicidality among patients with bipolar disorder or major depressive disorder cannot be ruled out. Trials should incorporate adequate per-protocol analyses into the decision-making processes for stopping trials for futility.

Depression in Parkinson's disease (PD) is common, but little is known about its recognition and treatment. The authors report the antidepressant experience (N = 100) and outcome of depression assessment (n = 77) of a convenience sample of patients at a PD center. Subjects were assessed with a psychiatric and neurological battery, and information was gathered on depression treatment. One third (34%) of subjects met criteria for a depressive disorder, and two thirds (65%) of them were not currently receiving antidepressant treatment. Approximately one quarter (23%) of subjects were taking an antidepressant, but almost half (47%) of them still met criteria for a depressive disorder. Few antidepressant users with persistent depression had received either antidepressant treatment at dosages within the highest recommended range (11%) or more than 1 antidepressant trial (33%). Most depressed patients are untreated, and half of antidepressant users remain depressed, suggesting that even when delivered, treatment is often inadequate or ineffective.

There has been limited research into defining what constitutes an adequate first-line antidepressant trial in elderly patients. The authors report the outcome of extended, high-dosage sertraline treatment in a sample of nursing home residents experiencing residual significant depressive symptoms after 10 weeks of treatment with sertraline at a final dosage of 100 mg/day. Subjects who had a Hamilton Depression Rating Scale score > or = 12 after 10 weeks of treatment with sertraline were eligible for the 8-week open-label extension phase, which involved titrating the sertraline dosage to 200 mg/day. The cumulative response rate was 52% for the extension phase, compared with 37% for the acute phase. Examining acute phase nonresponders, 39% responded during the extension phase. Rates of discontinuation due to adverse events were comparable in the 2 phases. Our findings suggest that an extended trial or high dosages of sertraline may benefit some depressed elderly patients with persistent depression after acute treatment.

Over the past 10 to 15 years, there has been marked progress in clinical research on depression in nursing home residents. There have also been significant changes in federal regulations designed to improve the quality of care. In 1987, only 10% of nursing home residents diagnosed with depression were receiving treatment, but by 1999,25% of all residents were receiving antidepressants. We report on two studies: one demonstrating that treatment for depression has a substantial, ecologically relevant impact in the nursing home and another demonstrating that profound changes have occurred in the clinical epidemiology of depression and its treatment in the nursing home. Although the numbers of nursing home residents receiving antidepressants have increased dramatically, there are now second-generation problems that must be addressed to ensure the delivery of effective treatment. Developing models to ensure quality of care will require focused mental health services research.

Studies have shown that the vast majority of patients with dementia experience some psychopathologic symptoms during the course of their illness. Symptoms of this nature, which can include frightening hallucinations or anxiety of phobic proportions, are subjectively distressing and can lead both to unsafe or violent situations as well as to the preventable use of inappropriate medication, physical restraint, and frequently to institutionalization. These psychopathologic manifestations of dementia often prove to be a burden on family, caregivers, and the health care system as well. This article presents an overview of the assessment and management of agitation as it relates to the severity of dementia symptoms and cognitive deterioration. Specifically, the use of anticonvulsant and other non-neuroleptic therapies is examined.

To explore the extent to which treatment of depression affects survival, we evaluated the association between use of antidepressant medications and death rates among the residents of a large residential-care facility for the elderly using a retrospective record-review study (N = 624). One year survival, among those taking antidepressants (10.9%), was 11.8% compared to 11.1% among the remainder of the population. A second study followed a group of 32 patients in the same institution who had participated in a therapeutic trial of nortriptyline treatment for major depression. Patients who experienced adverse medical events during treatment exhibited significantly increased mortality; among treatment completers, there was no significant relationship between mortality and therapeutic response. These findings suggest that the inability to tolerate treatment with an antidepressant can be considered a manifestation of physiologic frailty and increased vulnerability to mortality from disease. The previously reported decrease in survival among residential-care patients with major depression is not paralleled by a similar effect in those taking antidepressants. This may reflect selection factors with respect to the ability to tolerate antidepressants, rather an effect of treatment.

Findings from an exploratory study of the relationships between routine clinical laboratory tests and the clinical status of elderly patients living in a nursing home or congregate housing facility demonstrate that low albumin and anemia are associated with decreased survival and with self-care deficits, cognitive impairment, depression, and summary measures of the severity of medical illness. The interrelationships observed among these variables support the usefulness of the concept of failure to thrive. Although albumin can serve as a nutritional marker, findings on its relationship with sedimentation rate, triiodothyronine uptake, fasting plasma amino acids, and retinol-binding protein levels suggest that the low albumin related to failure to thrive is not a simple reflection of steady-state deficits in protein-calorie nutrition; it appears to be sensitive to more direct effects of disease and inflammation or to the interactions between nutrition and illness.

Several experiments were conducted to validate the use of a two-channel microprocessor-based electroencephalographic (EEG) device for detecting changes in EEG background rhythm in the clinic or at the bedside. The reliability of background measures in healthy individuals was evaluated by obtaining EEG data on 20 control subjects on two occasions separated by at least 1 day. The sensitivity to an experimental toxic encephalopathy was evaluated using measures of EEG and the Buschke Memory Selective Reminding Test after the administration of scopolamine hydrobromide, 0.86 mg subcutaneously, to three healthy volunteers. Postdrug measures of the EEG showed significant group differences from controls at 1 and 2 hours for relative alpha and relative theta power. The drug-induced change for each individual exceeded the predicted range calculated from data on control subjects. These findings suggest the feasibility and the potential utility of this method. This approach was extended to the elderly with measures on 102 subjects (average age, 85 years) living in an institutional setting. EEG measures in the population were of acceptable reliability and were significantly correlated with Mini-Mental State Examination (MMSE) scores (r = -.375 for theta and .357 for beta). Preliminary findings suggest that this method may detect metabolic encephalopathies in the elderly. The study demonstrates the potential value of this approach and suggests the need for further research.

Investigations on the symptoms associated with the use of anticholinergic medications by elderly patients demonstrated that these medications are frequently associated with persistent adverse effects that may go unrecognized by both patients and physicians. An increase in autonomic symptoms was readily demonstrated in a group of elderly outpatients taking anticholinergics. Cognitive effects, however, were not apparent, possibly due to the heterogeneity of the populations studied. A parallel study did, however, demonstrate an association between anticholinergic medications and slowing of EEG background frequency. Findings on the relationship between EEG background frequency and cognitive measures suggest the possible value of the combined use of psychological and electrophysiological measures for identifying patients who require further evaluation of their medication regimen.

We have compared levels of albumin and serum amino acids in a group of 87 recent admissions to a nursing home, average age 83 years, with a group of healthy moderately old subjects, average age 69 years. We found that the nursing home group was characterized by decreased levels of albumin, by increased total levels of the measured amino acids, and by increased levels of the nonessential amino acids. In contrast, there were no significant group differences in the essential amino acids. Among the nursing home patients, there was a negative correlation between essential amino acids and disability, consistent with nutritional deficits in the more disabled patients, and a positive correlation between essential amino acids and subjective complaints of pain, suggesting that pain is associated with breakdown or mobilization of endogenous protein stores. Though the nursing home patients had decreased serum levels of tryptophan, there was no association between serum tryptophan or other variables that could be related to the availability of tryptophan for transport into brain, with ratings of either depression or pain. Glutamine levels were significantly increased in the nursing home residents, and among these patients they were positively correlated with measures of cognitive impairment.