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BACKGROUND: A case series suggested efficacy for lithium to treat agitation in dementia, but no placebo-controlled trials have been conducted. OBJECTIVES: To evaluate low-dose lithium treatment of agitation in Alzheimer’s disease (AD). METHOD: In a four-site trial, patients with AD and agitation/aggression score ≥ 4 on the Neuropsychiatric Inventory (NPI) were randomized, double-blind, to lithium carbonate 150–600 mg daily or placebo for 12 weeks. Primary efficacy outcome was change in NPI agitation/aggression; secondary efficacy outcome was treatment response (30% reduction in NPI score for agitation/aggression plus psychosis and a Clinical Global Impression (CGI) score of much or very much improved). Safety profile of lithium was assessed. RESULTS: Fifty-eight of 77 patients (75.3%) completed the trial. In linear mixed effects model analyses, lithium was not significantly superior to placebo for agitation/aggression. Proportion of responders was 31.6% on lithium and 17.9% on placebo (χ(2)=1.26, p=0.26). Moderate or marked improvement (CGI) was greater on lithium (10/38=36.8%) than placebo (0/39=0%, Fisher’s exact test p

Treatment strategies for patients with depression and cognitive impairment (DEP-CI), who are at high risk to develop a clinical diagnosis of dementia, are not established. This issue is addressed in the donepezil treatment of cognitive impairment and depression (DOTCODE) pilot clinical trial. The DOTCODE study is the first long-term treatment trial that assesses differences in conversion to dementia and cognitive change in DEP-CI patients using a study design of open antidepressant medication plus add-on randomized, double-blind, placebo-controlled treatment with the acetylcholinesterase inhibitor donepezil. In Phase 1, DEP-CI patients receive optimized antidepressant treatment for 16 weeks. In Phase 2, antidepressant treatment is continued with the addition of randomized, double-blind treatment with donepezil or placebo. The total study duration for each patient is 78 weeks (18 months). Eighty DEP-CI outpatients (age 55 to 95 years) are recruited: 40 at New York State Psychiatric Institute/Columbia University and 40 at Duke University Medical Center. The primary outcome is conversion to a clinical diagnosis of dementia. The secondary outcomes are cognitive change scores in Selective Reminding Test (SRT) total recall and the modified Alzheimer's Disease Assessment Scale (ADAS-cog). Other key assessments include the 24-item Hamilton Depression Rating Scale and antidepressant response; Clinical Global Impression (CGI) for depression, cognition, and global status; neuropsychological test battery for diagnosis; informant report of functional abilities (Pfeffer FAQ); and Treatment Emergent Symptom Scale (TESS) for somatic side effects. Apolipoprotein E ε4 status, odor identification deficits, and MRI entorhinal/hippocampal cortex atrophy at baseline are evaluated as neurobiological moderators of donepezil treatment effects.

Objective The authors compared the efficacy and side effects of fluoxetine and placebo in elderly outpatients with dysthymic disorder. Methods Patients were randomly assigned to fluoxetine (20 mg–60 mg/day) or placebo for 12 weeks in a double-blind trial. Results Of 90 randomized patients, 71 completed the trial. In the intent-to-treat sample, random regression analyses of the Hamilton Rating Scale for Depression (Ham-D; 24-item) and Cornell Dysthymia Rating Scale (CDRS) scores at each visit produced significant time × treatment group interactions favoring the fluoxetine group. Analysis of percentage change in Ham-D scores yielded no effect for treatment group, but a similar analysis of percentage change in CDRS scores yielded a main effect for treatment group, favoring fluoxetine over placebo. In the intent-to-treat sample, response rates were 27.3% for fluoxetine and 19.6% for placebo. In the completer sample, response rates were 37.5% for fluoxetine and 23.1% for placebo. Conclusion Fluoxetine had limited efficacy in elderly dysthymic patients. The clinical features of elderly dysthymic patients are typically distinct from those of dysthymic disorder in young adults, and the findings suggest that treatments effective for young adult dysthymic patients may not be as useful in elderly dysthymic patients. Further research is needed to identify efficacious treatments for elderly patients with dysthymic disorder, and investigative tools such as electronic/computerized brain scans and neuropsychological testing may help identify the factors that moderate antidepressant treatment response and resistance.

Age of onset may affect clinical features and prognosis in elderly patients with major depression (MDD), but there is a lack of such data in elderly patients with dysthymic disorder (DD) and systematic comparisons of late onset MDD and DD have not been conducted.In a Late Life Depression Clinic, patientsor = 60 years old who met DSM-III-R or DSM-IV criteria for MDD or DD were studied. The 24-item Hamilton Rating Scale for Depression (HRSD) and SCID-P were completed, family history was obtained, and medical illnesses were assessed.In the total sample (n=370; 211 MDD and 159 DD), compared to early onset patients, late onset (onsetor =60 years) patients had a higher rate of cardiovascular disease (chi(2)=4.12, df=1, P0.05), lower rate of anxiety disorder (chi(2)=4.19, df=1, P0.05), and a lower rate of family history of affective disorder (chi(2)=9.37, df=1, P0.002). Late onset DD patients were more likely to have cardiovascular disease than early onset DD patients (chi(2)=5.63, df=1, P0.02), but the rate of cardiovascular disease did not differ between late and early onset MDD patients (chi(2)=0.35, df=1, P0.6). Late onset MDD patients were less likely to have a family history of affective disorder than early onset MDD patients (chi(2)=10.71, df=1, P0.001). Prevalence of anxiety disorders did not differ between the early and late onset MDD patients (chi(2)=0.07, df=1, P0.79), but was more common in the early onset DD compared to the late onset DD patients (17.98% versus 4.29%, chi(2)=6.98, df=1, P0.01). Late onset DD did not differ from late onset MDD in the rates of cardiovascular disease, anxiety disorders, and family history of affective disorder. Excluding patients with double depression (n=32) did not alter the cardiovascular or family history findings, but the difference in anxiety disorders between early and late onset DD patients was no longer significant.Academic clinic sample results may not generalize to community populations.In the elderly, late-onset DD is typically different from early onset DD. Cerebrovascular disease appears to play a role in the etiology of late onset DD. The similarities between late onset DD and late onset MDD suggest a single condition along a continuum.

OBJECTIVE This study investigated whether measurement of plasma levels may be useful in monitoring clinical efficacy and side effects during oral haloperidol (HL) treatment of psychosis and behavioral dyscontrol in patients with Alzheimer disease (AD). METHODS After a single-blind placebo period of 1 week, 71 outpatients with AD were randomized to a 6-week, double-blind, placebo-controlled trial of HL 2 mg–3 mg/day (standard dose), HL 0.5 mg–0.75 mg/day (low dose), or placebo, with plasma levels for HL drawn at the end of 6 weeks. RESULTS Of the 40 patients who received active HL for 6 weeks, 35 had plasma levels drawn. Plasma levels were all below the lower limit of the postulated therapeutic range in schizophrenia. Nonetheless, HL plasma level significantly correlated with clinical efficacy as measured by reduction in Brief Psychiatric Rating Scale Total score, Psychosis factor, and Hostile-Suspiciousness factor, the Behavioral Syndromes Scale for Dementia Psychomotor Agitation scale, and with the severity of extrapyramidal side effects (EPS). Oral dose did not significantly correlate with any of these efficacy or side-effect measures. Plasma levels significantly correlated with HL dose. When both HL dose and HL plasma level were included as independent variables in linear-regression analyses, only HL plasma level was a significant predictor of efficacy and EPS. CONCLUSION Measurement of HL plasma levels may have potential usefulness as an adjunct in monitoring treatment response to oral HL in AD patients with psychosis or disruptive behavior.

Background: Previous work has suggested that acute depletion of the serotonin (5-HT) precursor tryptophan (TRP) causes transient compensatory changes in the 5-HT system that might be exploited for their antidepressant effects. In this study, neuroendocrine and mood responses to intravenous (i.v.) infusion of TRP were examined in order to evaluate central 5-HT function in depressed patients undergoing acute TRP depletion. Methods: Thirty-eight drug-free patients with DSM-III-R major depression participated. Each patient underwent two randomized, double-blind TRP depletion tests, one sham and one active. At the estimated time of maximum TRP depletion, each patient received an i.v. infusion of TRP 100 mg/kg. Blood was obtained for serum cortisol, prolactin, and growth hormone. Mood was assessed using standardized rating scales. Results: The cortisol response to i.v. TRP was significantly greater during TRP depletion than during sham depletion. Depressive symptoms showed a tendency to decrease after i.v. TRP following active, but not sham, TRP depletion. Conclusions: These findings are consistent with the present hypothesis and previous evidence that acute TRP depletion in drug-free depressed patients induces compensatory upregulation of postsynaptic 5-HT receptors. These changes are insufficient to serve as a means of effecting clinical improvement, but suggest that the antidepressant properties of rapid, marked manipulations of 5-HT function warrant further study.

One-hundred thirty mobile intensive care unit paramedics were trained in the technique of direct laryngoscopic endotracheal intubation of cardiac arrest or deeply comatose patients. Three attempts at intubation were permitted. Of the 779 patients studied, 701 (90.0 percent) were successfully intubated: 57.9 percent on the first attempt, 26.1 percent and 5.5 percent on the second and third respectively. Reported and observed complications of the procedure numbered 74 (9.5 percent) of the 779 patients included in the study. There were three unrecognized esophageal intubations. The success rate rose to more than 94 percent toward the end of the study. It is concluded that endotracheal intubation of deeply comatose patients is a field procedure safely and skillfully performed by well-trained and monitored paramedical personnel, with success and complication rates at least comparable to other invasive airway techniques.