Biomedical subjects

B H Mulsant

Publications and source records attributed to B H Mulsant.

At least 37 records · Page 2Linked to original sources

PubMed2001

Selective serotonin reuptake inhibitors for late-life depression: a comparative review.

Late-life depression is a serious health problem that is challenging to manage but generally responds well to pharmacotherapy. Selective serotonin (5-hydroxytryptamine: 5-HT) reuptake inhibitors (SSRIs), the most commonly prescribed antidepressants, are usually used as first-line agents for elderly patients with depression. Like most drugs, SSRIs have not been widely tested in clinical trials that approximate 'real-life' geriatric situations. However, studies completed to date provide valuable information about the efficacy, safety and tolerability of this class of antidepressants among older patients with depression, including those with depression secondary to stroke or dementia and those with other comorbid physical disorders. Although one SSRI may be more efficacious or better tolerated by elderly patients than another, existing data do not support such claims. However, other distinguishing features may influence the choice of agent. For example, fluoxetine, fluvoxamine and paroxetine are more likely to be involved in significant drug-drug interactions than are citalopram or sertraline. In contrast to the other SSRIs, fluoxetine has a half-life well in excess of 1 day, which can be an advantage when weaning the patient off therapy in that it may reduce the incidence of discontinuation symptoms, but a significant disadvantage if the patient cannot tolerate the drug or experiences an adverse drug-drug interaction.

Aged↗

PubMed2001

Narrowing the gap in treatment of depression.

OBJECTIVE: Although effective treatments for depression exist, under or non-treatment of depression is common. Efforts were made in the early 1990s to improve recognition and treatment of depression, with many of those efforts targeted at groups most vulnerable to under-treatment. The purpose of this study is to assess treatment rates in 1993-1994 and 1996-1997. METHOD: Using nationally representative surveys of office-based practice covering the years 1993, 1994, 1996, and 1997, we obtained estimates of visits by adults in which depression was diagnosed and a prescription for antidepressant medication and/or psychotherapy was provided or ordered. RESULTS: The proportion of physician office visits in which a depression diagnosis was recorded did not change from 1993-1994 (3.48 percent) to 1996-1997 (3.40 percent). However, the rate of antidepressant prescription or psychotherapy rose from 74.2 percent of visits with a depression diagnosis in 1993-1994 to 82.3 percent of these visits in 1996-1997. Significantly lower rates of treatment for depression during office visits made by African American patients, elderly patients, and patients on Medicaid occurred in 1993-1994, but were not evident in 1996-1997, reflecting improved rates of depression treatment in these populations. CONCLUSIONS: Although rates of diagnosis of depression during office visits have not increased, treatment rates for depression are improving among those who are diagnosed, including groups of people who historically were less likely to be offered treatment. Additional efforts to improve recognition and diagnosis of depression in ambulatory medical practice and to improve dissemination of treatment are needed.

Adolescent↗

PubMed2001

A double-blind randomized comparison of nortriptyline plus perphenazine versus nortriptyline plus placebo in the treatment of psychotic depression in late life.

OBJECTIVE: To conduct the first randomized study comparing the efficacy of an antidepressant alone versus an antidepressant plus a neuroleptic in the treatment of late-life psychotic depression. METHOD: The efficacy of nortriptyline plus placebo versus nortriptyline plus perphenazine was compared in 36 patients aged 50 years or older presenting with a major depressive episode with psychotic features (DSM-III-R criteria). Patients were started openly on nortriptyline treatment titrated to therapeutic levels. They were then randomly assigned under double-blind conditions to addition of perphenazine or placebo. Outcomes were compared in the 2 treatment groups using measures including the Hamilton Rating Scale for Depression (HAM-D) and the Brief Psychiatric Rating Scale (BPRS); side effects were assessed with the Geriatric Movement Disorder Assessment. RESULTS: Both treatments were well tolerated. Of the 36 randomly assigned patients, 2 (1 in each group) dropped out due to treatment-related adverse effects. Four additional patients dropped out for administrative reasons. Thirty patients received nortriptyline for at least 4 weeks combined with either perphenazine (N = 14) or placebo (N = 16) for at least 2 weeks (median = 9 weeks). There was no significant difference between the completers in the 2 treatment groups when comparing their scores on the HAM-D, the BPRS, its psychoticism subscale, or any side effects measure. Rates of response (defined as resolution of both depression and psychosis) did not differ significantly in the 2 groups (nortriptyline-plus-perphenazine group, 50% vs. nortriptyline-plus-placebo group, 44%). CONCLUSION: When treating older patients with psychotic depression, the addition of a moderate dose of a traditional neuroleptic to a tricyclic antidepressant was well tolerated but did not improve efficacy. This finding supports existing data suggesting that the pathophysiology (and thus the required treatment) of psychotic depression may be different early and late in life.

Affective Disorders, Psychotic↗

PubMed2001

The association of late-life depression and anxiety with physical disability: a review of the literature and prospectus for future research.

Depression and anxiety disorders are associated with excess disability. The authors searched the recent geriatric literature for studies associating late-life depression or anxiety with physical disability. Studies showed depression in old age to be an independent risk factor for disability; similarly, disability was found to be a risk factor for depression. Anxiety in late life was also found to be a risk factor for disability, although not necessarily independently of depression. Increased disability due to depression is only partly explained by differences in socioeconomic measures, medical conditions, and cognition. Physical disability improves with treatment for depression; comparable studies have not been done for anxiety. The authors discuss how these findings inform current concepts of physical disability and discuss the implications for future intervention studies of late-life depression and anxiety disorders.

Activities of Daily Living↗

PubMed2001

Treatment outcome in suicidal vs. non-suicidal elderly patients.

The authors investigated treatment outcome in elderly suicidal and non-suicidal patients with recurrent major depression. Patients without suicidal ideation in the current episode (Non-Ideators; n=150) were compared with 30 patients who expressed suicidal ideation (Ideators). Patients received combined pharmacotherapy and psychotherapy during acute and continuation treatment. Ideators had higher numbers of lifetime suicide attempts and reported significantly higher levels of depression, anxiety, and hopelessness before starting treatment. Ideators and Non-Ideators had almost identical remission rates (77% vs. 78%), but Ideators had higher relapse rates during continuation treatment (26% vs. 13%) and were more likely to receive augmentation pharmacotherapy. Anxiety and use of adjunctive medication, but not suicidal ideation, were negatively related to both remission and relapse. Our data suggest that elderly suicidal patients have an overall favorable treatment outcome. However, treatment response may be more brittle and may require the continuing use of adjunctive medications to prevent early relapse.

Aged↗

PubMed2001

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.

Aged↗

PubMed2001

The effect of patient and visit characteristics on diagnosis of depression in primary care.

OBJECTIVES: The purpose of our study was to determine if factors other than the patient' clinical presentation were associated with the likelihood of depression being recognized during a physician office visit. STUDY DESIGN: We used a cross-sectional design. POPULATION: Data from the 1997 and 1998 National Ambulatory Medical Care Surveys were examined. OUTCOMES MEASURED: We assessed the association of factors such as age, sex, race, physician specialty, type of insurance, and visit duration with a recorded depression diagnosis during office visits to primary care physicians. RESULTS: After controlling for symptom presentation, primary care physicians were 56% less likely to record a diagnosis of depression during visits made by elderly patients, 37% less likely to do so during visits by African Americans, and 35% less likely to do so during visits by Medicaid patients. Visits with a depression diagnosis were, on average, 2.9 minutes longer in duration (16.4 vs 19.3) than visits without a depression diagnosis. Family practice and general practice physicians were 65% more likely to record a diagnosis of depression than internists. CONCLUSIONS: Many factors were associated with making and recording a depression diagnosis beyond the patient' reported symptoms. If rates of diagnosis are to improve, interventions that go beyond getting physicians to recognize the symptoms of depression are needed.

Adult↗

PubMed2000

Sertraline in the treatment of minor depression in nursing home residents: a pilot study.

'Minor' depression affects up to 50% of residents in long-term care facilities and is associated with considerable discomfort, disability and risk of morbidity. Despite the prevalence of this problem, few studies addressing the treatment of these patients have been conducted. In an open clinical trial, 12 nursing home residents who met the DSM-IV description for minor depressive disorder were treated with sertraline for 6 weeks. Adverse effects and clinical response were monitored. All residents tolerated their medication without any significant side-effects. At the completion of the study, the Hamilton Depression Rating Scale and Global Assessment Scale change scores both indicated significant improvement and 75% of the residents met criteria for 'remission'. This preliminary study provides evidence that nursing home residents with minor depression tolerated treatment with sertraline and improved clinically.

Aged↗

PubMed2000

Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression.

The relationship of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) to antidepressant response was examined in 95 elderly patients receiving a protocolized treatment for depression with paroxetine or nortriptyline. Patients were treated for up to 12 weeks and assessed weekly with clinical ratings and measurements of plasma drug concentrations. Twenty-one of the paroxetine-treated subjects were found to have the ll genotype and 30 had at least one s allele. There were no baseline differences between these groups in pretreatment Hamilton Rating Scale for Depression (HRSD) scores or anxiety symptoms. During acute treatment with paroxetine, mean reductions from baseline in HRSD were significantly more rapid for patients with the ll genotype than for those possessing an s allele, despite equivalent paroxetine concentrations. Onset of response to nortriptyline was not affected. Allelic variation of 5-HTTLPR may contribute to the variable initial response of patients treated with a selective serotonin reuptake inhibitor.

Adrenergic alpha-Agonists↗

PubMed2000

Decreased working memory and processing speed mediate cognitive impairment in geriatric depression.

BACKGROUND: While neuropsychological dysfunction is common in geriatric depression, not all aspects of cognition are equally affected. It has been suggested that depressed patients are impaired only in tasks that make heavy demands on processing resources and that a resource decrement therefore underlies the neuropsychological decrements seen in geriatric depression. The present study examined whether processing resources in the form of working memory and information processing speed are decreased in depression and whether a decrease in these resources actually mediates neuropsychological impairment. METHODS: Measures of processing resources were administered to elderly depressed patients prior to treatment and to age-matched controls. Patients whose depression remitted were retested as were the controls. Subjects also received neuropsychological tests of episodic memory and visuospatial performance. RESULTS: Depressed patients performed significantly worse on measures of both processing speed and working memory. While performance on these measures improved in patients whose depression remitted, the amount of improvement was no greater than that seen in the controls with repeat testing. Hierarchical regression analyses showed that depression explained a significant amount of variance on the neuropsychological tasks. However, if the variance associated with processing resources was removed first, depression no longer accounted for a significant amount of neuropsychological variance. CONCLUSIONS: Processing resources are decreased in elderly depressed patients and this decrease in resources appears to mediate impairments in several areas of neuropsychological functioning including episodic memory and visuospatial performance. The resource decrement persists after remission of the depression and thus may be a trait marker of geriatric depression.

Aged↗

PubMed2000

Pharmacologic profile of perphenazine's metabolites.

The authors have previously reported that in elderly patients treated with low doses of perphenazine, few extrapyramidal symptoms (EPS) developed in those who were not poor CYP2D6 metabolizers. The authors hypothesized that this atypical side effect profile is due to perphenazine's principal metabolite, n-dealkylperphenazine (DAPZ), which is usually present in vivo at concentrations 1.5 to 2 times that of the parent drug. Perphenazine, DAPZ, and 7-hydroxyperphenazine affinities were examined in vitro by competition-binding analysis to isolated human receptors expressed in transfected cell lines. Perphenazine and metabolite effects were examined in vivo in 54 older patients who were treated with perphenazine, at a target dose of 0.1 mg/kg, for 10 to 17 days. Drug concentrations were determined by high-performance liquid chromatography with electrochemical detection. In in vitro binding studies, DAPZ demonstrated a higher affinity for serotonin-2A receptors than for dopamine-2 receptors to an extent comparable to that of some atypical neuroleptic agents. In contrast, perphenazine and 7-hydroxyperphenazine demonstrated a higher affinity for dopamine-2 receptors than for serotonin-2A receptors. The mean +/- SD concentrations in the 54 subjects were the following: perphenazine, 1.5 +/- 1.4 ng/mL; DAPZ, 2.0 +/-1.6 ng/mL; and 7-hydroxyperphenazine, 0.8 +/- 1.9 ng/mL. The mean +/- SD quotient for the DAPZ/perphenazine concentration was 1.7 +/- 1.1 and for the 7-hydroxyperphenazine/perphenazine was 0.54 +/-1.6. EPS onset was not correlated with the perphenazine concentration, the metabolite concentrations, the DAPZ/perphenazine quotient, or the 7-hydroxyperphenazine/perphenazine quotient. Despite a moderately atypical receptor-binding profile, DAPZ does not seem to moderate perphenazine effects in vivo in older patients. This outcome likely reflects the low potency of DAPZ for dopamine-2 and serotonin-2A receptors relative to the potency of perphenazine for these receptors. Further exploration of atypical properties of DAPZ should include de novo administration of this metabolite in animal models.

Aged↗

PubMed2000

Determinants of seizure threshold in ECT: benzodiazepine use, anesthetic dosage, and other factors.

The electrical dosage of the ECT stimulus impacts on efficacy and cognitive side effects, yet seizure threshold (ST) may vary as much as 50-fold across patients. It would be desirable to predict ST on the basis of patient and treatment characteristics. In particular, concerns have been raised that benzodiazepine use and higher dosage of barbiturate anesthetics elevate ST. In a three-site study, ST was quantified at the first ECT session using an identical empirical titration procedure in 294 patients who met RDC and DSM-IIIR criteria for a major depressive episode. ST varied over a 35-fold range across patients treated with right unilateral (RUL) (n = 267) and bilateral (BL) (n = 27) ECT. Higher ST was associated with BL electrode placement (p = 0.001). Among patients treated with RUL ECT, univariate analyses indicated that higher ST was associated with advanced age (p < 0.001), male gender (p < 0.001), greater burden of medical illness (p < 0.001), weight (p < 0.01), duration of mood disorder (p < 0.01), and history of previous ECT (p < 0.05). Average lorazepam dose in the 48 hours prior to ECT was not associated with ST, but was associated with decreased seizure duration (p < 0.01). Absolute, but not weight-adjusted, methohexital dose was associated with ST (p < 0.01). Multivariate analyses in patients treated with unilateral ECT showed that only 27.6% of the variance in ST (p < 0.0001) could be predicted. In the multivariate analyses, only age (p = 0.0001), gender (p = 0.01), and methohexital dose (p = 0.0001) were independently related to ST. Low dosage of lorazepam and methohexital dosage below 1 mg/kg are unlikely to impact on ST. Given the limited capacity to predict ST, empirical titration remains the only accurate method to determine electrical dosage in RUL ECT.

Adolescent↗

PubMed2000

Changes in cognitive functioning following treatment of late-life depression.

OBJECTIVE: Knowledge of the relationship between various clinical characteristics and cognitive functioning is advancing, but little is known about the cognitive response to treatment for geriatric depression. The purpose of this study was to examine the cognitive response to treatment for patients with late-life depression. METHOD: Subjects included 45 nondemented, elderly depressed patients who achieved remission after 12 weeks of antidepressant treatment and 20 elderly comparison subjects. All subjects were administered a battery of clinical measures, including cognitive screening instruments, before and after treatment. RESULTS: As a group, the elderly depressed patients showed a small improvement in overall cognitive functioning after treatment. Among depressed patients with concomitant cognitive impairment at baseline, performance on the Mattis Dementia Rating Scale domains of conceptualization and initiation/perseveration improved significantly relative to those of depressed patients with normal cognition. Despite the improvement following treatment, the overall level of cognitive functioning in the elderly depressed patients with cognitive impairment at baseline remained mildly impaired, especially in the memory and initiation/perseveration domains. CONCLUSIONS: Elderly depressed patients with cognitive impairment may experience improvement in specific domains following antidepressant treatment but may not necessarily reach normal levels of performance, particularly in memory and executive functions. This subgroup of late-life depression patients is likely at high risk of developing progressive dementia.

Aged↗

PubMed2000

Comorbid anxiety disorders in depressed elderly patients.

OBJECTIVE: Anxiety disorders are common in adults with depressive disorders, but several studies have suggested a relatively low prevalence of anxiety disorders in older individuals with depression. This cross-sectional study measured current and lifetime rates and associated clinical features of anxiety disorders in depressed elderly patients. METHOD: History of anxiety disorders was assessed by using a structured diagnostic instrument in 182 depressed subjects aged 60 and older seen in primary care and psychiatric settings. Associations between comorbid anxiety disorders and baseline characteristics were measured. The modified structured instrument allowed detection of symptoms that met inclusion criteria for generalized anxiety disorder in a depressive episode. RESULTS: Thirty-five percent of older subjects with depressive disorders had at least one lifetime anxiety disorder diagnosis, and 23% had a current diagnosis. The most common current comorbid anxiety disorders were panic disorder (9.3%), specific phobias (8.8%), and social phobia (6.6%). Symptoms that met inclusion criteria for generalized anxiety disorder, measured separately, were present in 27.5% of depressed subjects. Presence of a comorbid anxiety disorder was associated with poorer social function and a higher level of somatic symptoms. Symptoms of generalized anxiety disorder were associated with a higher level of suicidality. CONCLUSIONS: Contrary to previous reports, the present study found a relatively high rate of current and lifetime anxiety disorders in elderly depressed individuals. Comorbid anxiety disorders and symptoms of generalized anxiety disorder were associated with a more severe presentation of depressive illness in elderly subjects.

Age Factors↗

PubMed2000

Fluvoxamine pharmacotherapy of anxiety disorders in later life: preliminary open-trial data.

The authors present data from an open trial of fluvoxamine (median daily dosage: 200 mg) in the treatment of generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder in 19 older outpatients (mean age = 66.8). Of the 12 subjects completing the 21-week trial, 8 achieved a good response (50% reduction in symptom measures) and 7 were rated as much or very much improved. Fluvoxamine pharmacotherapy also had a significant effect in reducing comorbid depressive symptoms and in increasing levels of functioning. These data support the effectiveness of fluvoxamine in older subjects with anxiety disorders (particularly generalized anxiety disorder) and warrant further double-blind, placebo-controlled evaluation.

Aged↗

PubMed2000

Effect of paroxetine on plasma vasopressin and water load testing in elderly individuals.

Hyponatremia sometimes occurs in elderly depressed patients treated wtih a serotonin reuptake inhibitor (SRI). The cause of the hyponatremia is not yet understood. The objective of this study was to determine the effects of paroxetine, an SRI, on osmoregulated release of vasopressin (also termed antidiuretic hormone) in elderly depressed patients with normal serum sodium. Four women and one man ages 61 to 74 years with a major depressive disorder were administered a water load after they had been treated with a therapeutic dose of paroxetine for 3 to 11 months. Three healthy elderly subjects not receiving paroxetine served as controls. Both the patients and the control subjects excreted > 90% of the ingested water and lowered urine osmolality to < 100 mosmol/kg. We conclude that long-term treatment with paroxetine alone does not appear to affect the ability to excrete a water load or appropriately dilute the urine during a water load (both indices of vasopressin function) in a small group of elderly patients without other risk factors for the development of hyponatremia.

Aged↗

PubMed2000

Use of electroconvulsive therapy in a state hospital: a 10-year review.

BACKGROUND: The use of electroconvulsive therapy (ECT) in the state hospital setting currently represents a very small percentage of the total overall use of this modality in the treatment of the mentally ill. METHOD: Using records kept by a state hospital, we retrospectively identified all patients who had received ECT between the years 1986 and 1995. A review of the records at the state hospital from where patients were referred and the university hospital where ECT was administered was undertaken. Demographic and clinical characteristics, reasons for referral, symptom profile, ECT parameters, clinical outcomes, and restraint/ seclusion data were assessed. RESULTS: Over 10 years, 21 patients were treated with ECT, representing 0.4% of all admissions to the state hospital. Of these subjects, 17 records could be retrieved. The majority were women (N = 12; 71%) and were diagnosed with a mood disorder. Ten subjects (59%) were over the age of 60 years, 4 of whom were 70 years or older. Most patients had a state hospital length of stay of 1 year or less. The mean number of ECT treatments was 12.2. There were no medical complications that led to premature termination of ECT. Eleven patients (65%) were discharged either directly from the university hospital or within 10 days of readmission to the state hospital. Six of 7 patients who had restraint and seclusion episodes prior to ECT were found to have no further episodes afterwards. The seventh experienced a dramatic decrease in number and total hours of episodes. CONCLUSION: For a substantial minority of patients in this state hospital setting, ECT appears to have been an effective and safe form of treatment, and its use should be considered early rather than late in the course of hospitalization.

Adult↗

PubMed2000

Effect of nortriptyline and paroxetine on extrapyramidal signs and symptoms: A prospective double-blind study in depressed elderly patients.

Selective serotonin-reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) have been reported to induce extrapyramidal signs and symptoms (EPS). The authors examined the change from baseline EPS, measured by an objective rating scale, in a group of elderly depressed patients participating in an ongoing randomized, double-blind comparison of nortriptyline and paroxetine. Mild baseline EPS were present in both groups. After 6 weeks of antidepressant treatment, patients in the nortriptyline group showed a significant decrease in total EPS scores. Patients in the paroxetine group showed a similar decrease in EPS from baseline, which did not reach statistical significance. There was no significant difference between nortriptyline and paroxetine in the change in EPS.

Aged↗