Antidepressant prescribing in nursing homes: is there a place for tricyclics?

OBJECTIVE: To deduce a model describing physicians' choice of antidepressants for treating elderly nursing home patients. METHODS: Subjects were geriatric residents of 137 skilled nursing facilities who regularly received an antidepressant medication for at least one month (n = 3,440, 28% of all residents). Reasons for prescribing antidepressants and physicians' diagnoses of depression and dementia were identified by medical record audit. Residents were grouped by dementia and antidepressant target symptoms (depression, or one or more non-psychiatric symptoms, i.e. insomnia, pain, incontinence, itching). RESULTS: Selective serotonin reuptake inhibitors (SSRIs) were prescribed preferentially over tricyclic antidepressants (TCAs) for treating depression in both demented and non-demented residents, but TCAs were nine times more likely to be prescribed for treating non-psychiatric target symptoms alone. When non-psychiatric target symptoms were present without depression or dementia, both amitriptyline and nortriptyline prescribing was increased, but amitriptyline appeared to be the antidepressant of choice. In all subgroups examined, its use was two to five times more prevalent when such symptoms were present. In patients with dementia, amitriptyline prescribing declined whether or not non-psychiatric target symptoms were present, but nortriptyline prescribing did not; nortriptyline was three times more likely than amitriptyline to be prescribed in the presence of dementia. CONCLUSIONS: Physicians prescribe anticholinergic TCAs principally to treat common non-depressive symptoms in nursing home residents, preferring SSRIs for uncomplicated depression and depression with dementia. They tend to avoid prescribing anticholinergic TCAs other than nortriptyline when they recognize a patient as demented. The data suggest that physicians employ a decision model for antidepressant prescribing that simultaneously recognizes the utility of TCAs in treating non-psychiatric symptoms and the anticholinergic vulnerability of older, especially demented, patients. Whether or not this model leads to optimal patient management requires further study.     

Retrospective review of selective serotonin reuptake inhibitors and falling in older nursing home residents

We compared the rate of falling in older nursing home residents who had been prescribed selective serotonin reuptake inhibitors (SSRIs), other classes of antidepressants, and no antidepressants. Data were obtained from pharmacy records, medical records, fall logs, and incidence reports for one nursing home (1995 data). Older adults on SSRIs were more likely to fall than older adults not on antidepressants (p = .003) and were more likely to have an injurious fall (p = .03). The association with falling remained significant even when including potential confounders (p = .007). Older nursing home residents should be treated for depression. However, SSRIs may also carry an increased risk for falling.     

Probing the safety of medications in the frail elderly: evidence from a randomized clinical trial of sertraline and venlafaxine in depressed nursing home residents

BACKGROUND: In nursing home residents and other frail elderly patients, old age and potential drug-drug and drug-disease interactions may affect the relative safety and efficacy of medications. The purpose of this study was to examine the efficacy and tolerability of venlafaxine and sertraline for the treatment of depression among nursing home residents. METHOD: The study was a 10-week randomized, double-blind, controlled trial of venlafaxine (doses up to 150 mg/day) versus sertraline (doses up to 100 mg/day) among 52 elderly nursing home residents with a DSM-IV depressive disorder and, at most, moderate dementia. The primary measure of outcome was the Hamilton Rating Scale for Depression (HAM-D). Adverse events were monitored and recorded systematically during the trial. RESULTS: Twelve subjects were discontinued due to serious adverse events (SAE), 5 were discontinued due to other significant side effects, and 2 withdrew consent. Tolerability estimated by the time to termination was lower for venlafaxine than sertraline for serious adverse events (log rank statistic = 5.28, p =.022), for serious adverse events or side effects (log rank statistic = 8.08, p =.005), or for serious adverse events, side effects, or withdrawal of consent (log rank statistic = 10.04, p =.002). Mean (SD) HAM-D scores at baseline were 20.2 (3.4) for sertraline and 20.3 (3.7) for venlafaxine; intent-to-treat endpoint HAM-D scores were 12.2 (5.1) and 15.7 (6.2) (F = 3.45; p =.069). There were no differences in categorical responses for the intent-to-treat sample or completers. CONCLUSION: In this frail elderly population, venlafaxine was less well tolerated and, possibly, less safe than sertraline without evidence for an increase in efficacy. This unexpected finding demonstrates the need for systematic research on the safety of drugs in the frail elderly.     

Pharmacologic treatment of depression in nursing home residents: a mental health services perspective

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.     

Comparative efficacy and safety of sertraline versus nortriptyline in major depression in patients 70 and older

BACKGROUND: Few randomized, double-blind studies that examine antidepressant treatment in patients 70 years and older are available. To provide additional data on the safety and efficacy of antidepressants in this rapidly growing population segment, a subgroup analysis of a larger sertraline vs. nortriptyline elderly depression treatment study was performed. METHODS: Outpatients (N = 76) who met DSM-III-R criteria for major depression with a minimum Hamilton Depression Rating Scale (HAM-D) severity score of 18 were randomized to 12 weeks of flexible dose treatment with sertraline (50-150 mg) or nortriptyline (25-100 mg). RESULTS: Both treatments significantly improved depression as measured by the HAM-D and Clinical Global Impression scales. At Weeks 10, 12, and endpoint, sertraline demonstrated a significantly greater reduction in depression severity compared to nortriptyline as measured by improvement on the 24-item HAM-D (mean adjusted change score of 14.8 vs. 7.6, respectively, at Week 12; p = .001). Sixty-five percent of sertraline-treated patients were responders by Week 12 (50% or greater reduction from baseline in 24-item HAM-D score) compared to 26% of nortriptyline-treated patients (p < .05). Sertraline treatment had a significantly more positive effect, when compared to nortriptyline, across almost all associated measures of cognitive function, energy, anxiety, and quality of life and was better tolerated than nortriptyline, with a lower attrition rate/side effect burden. CONCLUSION: The efficacy advantage of sertraline appeared to be even greater in this subgroup of older patients drawn from a larger treatment study of depression that included elderly individuals over the age of 60.     

Drug treatment of depression in frail elderly nursing home residents.

The authors conducted a randomized, double-blind, 10-week clinical trial of two doses of nortriptyline in eight nursing homes. Sixty-nine patients, average age 79.5 years, were randomized to receive regular doses (60 mg-80 mg/day) vs. low doses (10 mg-13 mg/day) of nortriptyline. Among the more cognitively intact patients, there was a significant quadratic relationship defining a "therapeutic window" for nortriptyline plasma levels and clinical improvement. There were also significant differences in plasma level-response relationships between depressed patients who were cognitively impaired and those who were more cognitively intact. Depression remains a syndrome that responds to specific treatment, even in frail nursing home patients, and those depressions that occur in patients with significant dementia may represent a treatment-relevant condition with a different plasma level-response relationship than in depression alone.     

Nortriptyline for treatment-resistant depression

BACKGROUND: Up to 30% of patients with major depression fail to respond to an antidepressant trial, with most taking a selective serotonin reuptake inhibitor (SSRI) as initial treatment. While the tricyclic antidepressants might be effective for SSRI nonresponders, they have been relegated to third- and fourth-line treatment. This study assesses the efficacy of nortriptyline for patients with treatment-resistant major depression. METHOD: 92 patients with treatment-resistant DSM-III-R major depression, with resistance defined by at least 1, but no more than 5, well-documented adequate trials of antidepressants during the current episode, were treated openly with nortriptyline for 6 weeks. Patients were titrated up to full target doses of nortriptyline within 1 week, with target blood levels of 100 ng/mL. Response was defined as a 50% or greater decrease of baseline 17-item Hamilton Rating Scale for Depression score. We performed an intent-to-treat analysis with the last observation carried forward. RESULTS: Approximately 40% of patients were responders (N = 39) and 12% were remitters (N = 11) after 6 weeks of nortriptyline. Over a third of patients were unable to complete the trial. CONCLUSION: Nortriptyline was effective for over a third of patients with treatment-resistant depression, and nortriptyline should be considered as potential treatment if patients fail to respond to other antidepressants.     

A twelve-week, double-blind, randomized comparison of nortriptyline and paroxetine in older depressed inpatients and outpatients.

Selective serotonin reuptake inhibitors may be less efficacious than tricyclic antidepressants in the treatment of severe depression in older patients. The authors compared the 12-week clinical outcome of older depressed patients treated with nortriptyline or paroxetine in a double-blind randomized comparison in 116 psychiatric inpatients and outpatients (mean age: 72+/-8 years) who presented with a major depressive episode or melancholic depression. Discontinuation and response rates were compared in patients who began or who completed treatment. The discontinuation rate due to side effects was significantly higher with nortriptyline than with paroxetine (33% vs. 16%). There were no significant differences between the rates of response in the Intent-to-Treat analysis (nortriptyline: 57% vs. paroxetine: 55% ), or the Completer analysis (nortriptyline: 78% vs. paroxetine: 84%). Although paroxetine appears to be better tolerated than nortriptyline, the efficacy of these two drugs does not appear to differ in the acute treatment of older depressed patients, including hospitalized patients and those with melancholic features.     

Clinical and treatment response characteristics of late-life depression associated with vascular disease: a pooled analysis of two multicenter trials with sertraline

1. The safety and efficacy of sertraline in the treatment of moderate-to-severe major depression in elderly outpatients, aged 60 years and older, with comorbid vascular disease was evaluated. 2. An analysis of the pooled results for the sertraline treatment group drawn from two prospective, randomized, double-blind studies (sertraline vs. fluoxetine, and sertraline vs. nortriptyline) was done. Patients were retrospectively categorized into one of 3 clinical groups: 1) patients with a current diagnosis of hypertension but no other past or present cardiovascular illness (HTN), 2) patients reporting a current or past history of cardiovascular illness, but excluding hypertension (VASC), and 3) patients with no hypertension, and no other comorbid vascular illness (NoVASC). Patients received 12-3. weeks of double-blind treatment with sertraline in flexible daily doses in the range of 50 - 150 mg (in the nortriptyline comparator trial) or 50 - 100 mg (in the fluoxetine comparator trial). 4. Sertraline treatment yielded comparable levels of response in all 3 groups (response criterion: CGI-much or very much improved) at treatment endpoint on both a completer analysis (HTN, 86%; VASC, 89%; NoVASC, 77%) and significantly higher response rates on a 12-week endpoint analysis (HTN, 74%; VASC, 69%; NoVASC, 58%; p < 0.05). Sertraline treatment was well-tolerated, with no between-group differences in rates of adverse events, or in discontinuation due to adverse events. Patients taking 5 or more concomitant medications showed no difference, when compared with patients taking none-or-one concomitant medication, either in rates of adverse events, or in discontinuation due to adverse events. 5. Sertraline was found to be a safe, well-tolerated, and effective as an antidepressant in elderly patients suffering from hypertension and other forms of vascular comorbidity.     

The utility of mandatory depression screening of dementia patients in nursing homes

OBJECTIVE: Current methods for enhancing the recognition and treatment of depression in nursing home patients have been unsuccessful. This study examines the process, outcome, and impact of instituting a mandatory depression screening program for depressed dementia patients in nursing homes. METHOD: The experimental and comparison groups each consisted of two nursing homes of 519 and 363 patients, respectively. Two of the experimental group and one of the comparison group homes were more traditionally staffed facilities; one of the comparison group homes had an enriched staff of psychologists. The Cornell Scale for Depression in Dementia was administered to the residents with dementia. In the experimental group, the patients who scored > or =5 were referred for psychiatric assessment. RESULTS: In the experimental group, 100% of the referred dementia patients who met screening criteria for depression were seen by a psychiatrist. This resulted in a significant increase in the percentage of individuals given antidepressants. This was greater than the percentage of patients receiving antidepressants in the "typical" comparison group home but not the "staff-enriched" comparison group home. White patients were significantly more likely to receive antidepressants; however, screening significantly increased the proportion of depressed nonwhites receiving antidepressants. At the 12-week follow-up, there was a significant difference in scores between patients receiving antidepressants in each group. CONCLUSIONS: Mandatory depression screening can significantly increase the proportion of depressed dementia patients receiving antidepressants, lead to dose adjustments, diminish potential ethnic biases in treatment, and affect the depressive symptoms of treated individuals.     

A randomized,placebo-controlled trial of paroxetine in nursing home residents with non-major depression

Depression is common across a broad spectrum of severity among nursing home residents. Previous research has demonstrated the effectiveness of antidepressants in nursing home residents with major depression, but it is not known whether antidepressants are helpful in residents with less severe forms of depression. We conducted a randomized double-blind placebo-controlled 8-week trial comparing paroxetine and placebo in very old nursing home residents with non-major depression. The main outcome measure was the primary nurse's Clinical Impression of Change (CGI-C). Additional outcome measures were improvement on the interview-derived Hamilton Depression Rating Scale (HDRS) and Cornell Scale for Depression (CS) scores. Twenty-four subjects with a mean age of 87.9 were enrolled and twenty subjects completed the trial. Placebo response was high, and when all subjects were considered, there were no differences in improvement between the paroxetine and placebo groups. Two subjects that received paroxetine developed delirium, and subjects that received paroxetine were more likely to experience a decrease in Mini Mental State Exam scores (P =.03). There were no differences in serum anticholinergic activity between groups. In a subgroup analysis of 15 subjects with higher baseline HDRS and CS scores, there was a trend toward greater improvement in the paroxetine group in an outcome measure that combined the CGI-C and interview-based measures (P =.06). Paroxetine is not clearly superior to placebo in this small study of very old nursing home residents with non-major depression, and there is a risk of adverse cognitive effects. Because of the high placebo response and the trend towards improvement in the more severely ill patients, it is possible that a larger study would have demonstrated a significant therapeutic effect for paroxetine as compared with placebo. The study also illustrates the discordance between patient and caregiver ratings, and the difficulties in studying very elderly patients with mood disorders.     

Effect of increasing the dose and duration of sertraline trial in the treatment of depressed nursing home residents

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.     

The effect of short-term, low-dose tricyclic and tetracyclic antidepressant treatment on satiation, postnutrient load gastrointestinal symptoms and gastric emptying: a double-blind, randomized, placebo-controlled trial.

Antidepressants are commonly prescribed for patients with functional dyspepsia. However, the effect of tricyclic antidepressants on satiation and gastric emptying remains unclear, and there are no data for tetracyclic compounds. To compare the effects of nortriptyline (maximum dose: 50 mg daily) and mirtazapine (30 mg daily) vs placebo on gastric emptying, gastric satiation and postprandial symptoms after a nutrient load in healthy volunteers. Randomized, double-blind, placebo-controlled study evaluated gastric function before and after 14 days of nortriptyline (n = 13), mirtazapine (n = 13), or placebo (n = 14) in healthy volunteers. Validated methods were used to study gastric emptying ((13)C-octanoate) and satiation postnutrient drink test. The three arms were comparable with regard to age, gender, body mass index and hospital anxiety/depression scale. There were no statistically significant effects of mirtazapine or nortriptyline on gastric emptying compared to placebo (P = 0.34). Maximum tolerated volume was similar on drug and placebo (P = 0.56). Aggregate symptom score 30 min postmaximum tolerated volume after nutrient drink challenge on placebo was 132 (+/-21), vs 165 (+/-21) on mirtazapine, and 126 (+/-21) on nortriptyline 50 mg respectively (P = 0.28). Tricyclic and tetracyclic antidepressant agents do not appear to have significant effects on gastric motor or satiation postnutrient challenge in healthy individuals at the doses tested.     

Treatment of premenstrual depression with nortriptyline: a pilot study

There are no reports on treatment of premenstrual syndrome with antidepressants, although depression is a common symptom of the syndrome. Eleven women who met DSM-III-R criteria for late luteal phase dysphoric disorder were treated with nortriptyline in an open pilot study after they failed to respond to placebo or another medication. Eight of 11 patients had a good therapeutic response. The efficacy of antidepressants in the treatment of premenstrual depression needs confirmation with double-blind studies.     

Depression in Alzheimer's disease

Depression is one of the most frequent comorbid psychiatric disorders in Alzheimer's disease and other dementias, and is associated with poorer quality of life, greater disability in activities of daily living, a faster cognitive decline, a high rate of nursing home placement, relatively higher mortality and a higher frequency of depression and burden in caregivers. Depression in Alzheimer's disease is markedly under-diagnosed and most patients with depression are either not treated or are on subclinical doses of antidepressants. Recent randomized controlled trials have demonstrated the efficacy of sertraline and moclobemide to treat depression in Alzheimer's disease. Other psychoactive compounds may be useful as well, but careful consideration must be given to potentially serious side effects.     

Treatment of depression in low-level residential care facilities for the elderly

BACKGROUND: The rate of recognition and treatment of depressed older people in nursing homes is low. Data from the low-level residential care population have not been reported. This study aimed to collect information about the treatment of depression among older persons living in low-level residential care (hostels). METHOD: The participants comprised 300 elderly residents from ten low-level residential care facilities from various suburbs in metropolitan Melbourne. The participants were interviewed by a trained clinical psychologist to determine the presence or absence of major or minor depressive disorder using the Structured Clinical Interview for DSM-IV Axis I Disorder (SCID-I). Each participant was also administered the Standardized Mini-mental State Examination (SMMSE) to determine level of cognitive function. The clinical psychologist then reviewed all cases in consultation with a geropsychiatrist experienced in the diagnosis of depression among older people, prior to assigning a diagnosis of depression. RESULTS: An important finding in this study was the low treatment for currently depressed residents, with less than half of those in the sample who were depressed receiving treatment. However, 61 of the 96 residents out of the sample of 300 who were on antidepressants were not currently depressed. CONCLUSION: There is an under recognition and under treatment of currently depressed older people in low-level residential care facilities (hostels) just as has been reported in studies in nursing homes. However, there are high numbers receiving antidepressants who are not currently depressed.     

The influence of drug use on fall incidents among nursing home residents: a systematic review

ABSTRACTBackground: Falls are a major health problem among the elderly, particularly in nursing homes. Abnormalities of balance and gait, psychoactive drug use, and dementia have been shown to contribute to fall risk.Methods: We conducted a systematic review of the literature to investigate which psychoactive drugs increase fall risk and what is known about the influence of these drugs on gait in nursing home residents with dementia. We included studies with a prospective cohort design on psychoactive drug use in nursing homes with dementia residents and with falls as an outcome measure.Results: Seventeen studies were included in the review. Pooled risk estimates were not calculated because there was no homogeneity across studies. We assessed the strength of evidence for psychoactive drugs as a prognostic factor for falls by defining four levels of evidence: strong, moderate, limited or inconclusive. Strong evidence was defined as consistent findings (>/=80%) in at least two high quality cohorts. We found strong evidence that the use of multiple drugs (3/3 cohorts, effect sizes 1.30-1xs0.30), antidepressants (10/12 cohorts, effect sizes 1.10-7.60), and anti-anxiety drugs (2/2 cohorts, effect sizes 1.22-1.32) is associated with increased fall risk. The evidence for the association of other psychoactive drug classes with fall risk was limited or inconclusive.Conclusions: Research on the contribution of psychoactive drugs to fall risk in nursing home residents with dementia is limited. The scarce evidence shows, however, that multiple drugs, antidepressants and anti-anxiety drugs increase fall risk in nursing home populations with residents with dementia.