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Biomedical subjects

S Zisook

Publications and source records attributed to S Zisook.

At least 19 recordsLinked to original sources

Citalopram augmentation of antipsychotic treatment in older schizophrenia patients.

BACKGROUND: Depressive symptoms are common in older patients with schizophrenia; yet, few studies have examined the usefulness of antidepressants in this population. OBJECTIVE: We conducted a 10-week single-blind trial of citalopram (20-40 mg/day) vs no citalopram augmentation in 19 middle-aged and elderly patients with schizophrenia hospitalized for more than six of the last 12 months. At study-entry, the patients had been on stable doses of antipsychotics for at least two weeks, and had a 17-item Hamilton Depression Rating (HAM-D) scale score of 12 or greater. Nine patients were randomly assigned to citalopram augmentation, and 10 to no augmentation of antipsychotics. RESULTS: Patients in both groups improved on positive and negative symptoms, but the citalopram group had significantly greater improvement in HAM-D and Clinical Global Impression Scale scores than the control group. There were no major side effects. CONCLUSION: Larger double-blind studies are needed to follow up on these preliminary findings.

Aged↗

A comparison of community-dwelling older schizophrenia patients by residential status.

OBJECTIVE: Differences in residential status may contribute to the diversity of findings observed in community-based samples of patients with schizophrenia. We compared older out-patients living independently with those in assisted-care facilities. METHOD: Two hundred and fifty-one out-patients with schizophrenia or schizoaffective disorder, aged 40-97 years, who had been referred to our Intervention Research Center were examined. RESULTS: Assisted living status was associated with an earlier age at onset of illness, longer illness duration, lower probability of having ever been married, more severe negative symptoms, worse cognitive impairment, and a poorer health-related quality of wellbeing. Independent living and assisted-care patients had similar levels of positive and depressive symptoms, and were on comparable doses of neuroleptic medication. Significant 'predictors' of residential status were marital status, cognitive impairment and quality of wellbeing. CONCLUSION: Among schizophrenia out-patients, one needs to consider residential status in evaluating heterogeneity in cognitive performance or quality of wellbeing.

Adult↗

Bupropion sustained release for bereavement: results of an open trial.

OBJECTIVE: The present study was conducted to assess whether DSM-IV-defined bereavement responds to bupropion sustained release (SR). METHOD: Twenty-two subjects who had lost their spouses within the previous 6 to 8 weeks and who met DSM-IV symptomatic/functional criteria for a major depressive episode were evaluated. Subjects completed the Hamilton Rating Scale for Depression (HAM-D), the Clinical Global Impressions scale, the Texas Revised Inventory of Grief, and the Inventory of Complicated Grief at baseline and follow-up. Subjects were treated with bupropion SR, 150 to 300 mg/day, for 8 weeks. RESULTS: Improvement was noted in both depression and grief intensity. For the intent-to-treat group. 59% experienced a reduction of > or = 50% on HAM-D scores. The correlations between changes in the HAM-D scores and the grief scale scores were high, ranging from 0.61 (p = .006) to 0.44 (p = .054). CONCLUSION: Major depressive symptoms occurring shortly after the loss of a loved one (i.e., bereavement) appear to respond to bupropion SR. Treatment of these symptoms does not intensify grief; rather, improvement in depression is associated with decreases in grief intensity. The results of this study challenge prevailing clinical wisdom that DSM-IV-defined bereavement should not be treated. Larger, placebo-controlled studies are indicated.

Aged↗

An open-label, 12-week clinical and sleep EEG study of nefazodone in chronic combat-related posttraumatic stress disorder.

BACKGROUND: We examined the effects of nefazodone on polysomnographic sleep measures and subjective reports of sleep quality and nightmares. as well as other symptoms, in patients with chronic combat-related posttraumatic stress disorder (PTSD) during a 12-week, open-label clinical trial. To our knowledge, this is the first polysomnographic study of treatment in patients with PTSD. METHOD: The subjects were 12 male veterans (mean age = 54 years) who met DSM-IV diagnostic criteria for PTSD (mean duration = 30 years). All but I patient also met DSM-IV criteria for major depressive disorder. Patients were evaluated weekly with clinical ratings in an open-label clinical trial. Polysomnographic recordings for 2 consecutive nights were obtained before treatment and at 2, 4, 8, and 12 weeks. The dose of nefazodone was adjusted according to individual clinical needs. Final mean daily dose was 441 mg. RESULTS: The patients reported significantly fewer nightmares and sleep problems during treatment. Nevertheless, contrary to studies in depressed patients, nefazodone did not significantly affect polysomnographic sleep measures compared with baseline. In addition, the patients showed significant improvement in the Clinical Global Impressions of PTSD symptoms (global score, hyperarousals and intrusions subscales), the Clinician-Administered PTSD Scale (global, hyperarousal, and intrusions subscales), the Hamilton Rating Scale for Depression (HAM-D). and the Beck Depression Inventory (BDI). CONCLUSION: These patients with chronic, treatment-resistant, combat-related PTSD showed significant improvement of subjective symptoms of nightmares and sleep disturbance, as well as depression and PTSD symptoms. in this 12-week open-label clinical trial. Nevertheless, objective polysomnographic sleep measures did not change. Further studies, including double-blind. placebo-controlled trials, are needed to extend these findings and to understand the relationships between the physiology of sleep and symptoms of poor sleep and nightmares.

Arousal↗

Association of depressive symptoms with worse functioning in schizophrenia: a study in older outpatients.

BACKGROUND: Subsyndromal depressive symptoms are highly prevalent and associated with substantial impairments of daily function in the general population. Depressive symptoms are common in schizophrenia. However, few studies have examined the relationship of functioning and well-being to the presence of depressive symptoms in schizophrenia. METHOD: 202 middle-aged or elderly outpatients with schizophrenia (DSM-III-R or DSM-IV criteria) were categorized by severity of depressive symptoms on the Hamilton Rating Scale for Depression (HAM-D) using previously validated cutoff points, i.e., HAM-D total score < or = 6 (low), from 7 to 16 (medium), and > or = 17 (high). We also assessed severity of positive and negative symptoms, movement disorders, neurocognitive performance, daily functioning, and health-related quality of well-being with standardized measures. RESULTS: A total of 11.4% of patients had HAM-D scores > or = 17, and 56.4% had HAM-D scores from 7 to 16. Even after adjusting for severity of other psychopathology, patients with more severe depressive symptoms had significantly worse everyday functioning (p < .02), except for physical functioning, and health-related quality of well-being (r = -.365, p < .001) than did those with lower HAM-D scores. These differences were unrelated to those in demographics, extrapyramidal symptoms, tardive dyskinesia, neurocognitive performance, or number of physical illnesses. CONCLUSION: The results suggest the importance of evaluating schizophrenia patients for the presence of depressive symptoms. Effectiveness of adjunct treatment of depressive symptoms with antidepressants and psychosocial management in improving functioning of schizophrenia patients deserves further study.

Age Factors↗

The psychological and physical health of hospice caregivers.

This study explores the psychological distress of caring for a dying family member and examines the differences in depression, anxiety, health, social and occupational functioning, and social support among hospice caregivers and community controls. It compares psychological functioning of spousal and adult child hospice caregivers. Caregivers of terminally ill hospice patients were assessed prior to death as a part of a longitudinal bereavement study. Caregivers reported experiencing higher levels of depression, anxiety, anger, and health problems than controls. Hospice caregiving was associated with deterioration in physical health and in social and occupational functioning. The comparisons between adult children and spouse caregivers revealed that levels of psychological and physical morbidity were very similar for the two generations of caregivers. An awareness of distress symptoms among hospice caregivers could lead to timely proactive clinical intervention that may prevent bereavement complications.

Adult↗

Cross-sectional study of older outpatients with schizophrenia and healthy comparison subjects: no differences in age-related cognitive decline.

OBJECTIVE: Little is known about the progression of cognitive deficits in older, community-dwelling patients with schizophrenia, especially in comparison to healthy subjects. METHOD: The authors examined the relationship of age to performance on the Mattis Dementia Rating Scale in 116 outpatients with schizophrenia and 122 normal comparison subjects. Subjects ranged in age from 40 to 85 years. RESULTS: Dementia Rating Scale scores were lower in the schizophrenia group but correlated negatively with age in both groups, with no significant differences seen between the schizophrenia and normal comparison groups in slopes that depicted age-related variation. CONCLUSIONS: This cross-sectional study suggests a relatively stable long-term course of cognitive impairment in individuals with schizophrenia, with no evidence of faster cognitive decline in outpatients with schizophrenia than in normal comparison subjects.

Adult↗

Nefazodone in patients with treatment-refractory posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a highly prevalent and often chronic disorder among combat veterans, persisting in as many as 15% of Vietnam veterans for at least 20 years. Treatment response in veterans with combat-related PTSD has been disappointing. Although anxiolytics, anticonvulsants, antipsychotics, and antidepressants have been tried, none has been consistently associated with improvement in all primary symptom domains (i.e., intrusive recollections, avoidance/numbing, and hyperarousal). This open-label study evaluated the use of nefazodone in a group of Vietnam veterans with chronic, treatment-refractory symptoms of PTSD. METHOD: Male outpatients with DSM-IV PTSD who had failed a minimum of 3 previous medication trials were eligible for the study. Nineteen Vietnam combat veterans entered the study and were treated with nefazodone, 100-600 mg/day, for 12 weeks. PTSD symptoms, anxiety, depression, sleep, sexual functioning, and adverse events were assessed weekly. RESULTS: Severity of depression lessened, as did PTSD symptoms of intrusive recollections, avoidance, and hyperarousal. Depressive symptom severity as measured by the Beck Depression Inventory decreased by a mean of 30%. Similarly, there was an overall drop in the intensity of PTSD symptoms as measured by the Clinician Administered PTSD Scale of 32% with a 26% improvement for symptoms of intrusion, 33% for avoidance, and 28% for arousal. In addition, improvements in sleep and sexual functioning were reported. The mean daily dose of nefazodone after 12 weeks was 430 mg (range, 200-600 mg/day). The most frequently reported side effects were headaches (53%), dry mouth (42%), and diarrhea (42%), but side effects tended to be mild and transient. CONCLUSION: In this group of Vietnam veterans with chronic treatment-refractory PTSD and multiple comorbid Axis I psychiatric disorders, nefazodone was well tolerated and effective. Larger, controlled studies are warranted.

Ambulatory Care↗

Effects of noradrenergic and serotonergic antidepressants on chronic low back pain intensity.

To understand the relative efficacy of noradrenergic and serotonergic antidepressants as analgesics in chronic back pain without depression, we conducted a randomized, double-blind, placebo-control head-to-head comparison of maprotiline (a norepinephrine reuptake blocker) and paroxetine (a serotonin reuptake blocker) in 103 patients with chronic low back pain. Of these 74 completed the trial; of the 29 who did not complete, 19 were withdrawn because of adverse effects. The intervention consisted of an 8-week course of maprotiline (up to 150 mg daily) or paroxetine (up to 30 mg daily) or an active placebo, diphenhydramine hydrochloride (up to 37.5 mg daily). Patients were excluded for current major depression. Reduction in pain intensity (Descriptor Differential Scale scores) was significantly greater for study completers randomized to maprotiline compared to placebo (P=0.023), and to paroxetine (P=0.013), with a reduction of pain by 45% compared to 27% on placebo and 26% on paroxetine. These results suggest that at standard dosages noradrenergic agents may provide more effective analgesia in back pain than do selective serotonergic reuptake inhibitors.

Adrenergic Uptake Inhibitors↗

Nefazodone in post-traumatic stress disorder: results from six open-label trials.

Nefazodone, an antidepressant which blocks serotonin (5-HT)2 receptors and 5-HT reuptake, was evaluated in the treatment of post-traumatic stress disorder (PTSD) in six open-label studies involving both civilians and combat veterans. Our objective was to report this available pooled data to characterize the response of this drug in PTSD. Specifically, we looked at response rates using three different criteria, the effect of nefazodone on each PTSD cluster and individual symptoms and, lastly, variables that might predict response. One hundred and five outpatients with chronic PTSD were treated with nefazodone titrated up to 600 mg/day, 92 of whom were entered in an intent to treat analysis. We used the percentage drop in score between baseline and endpoint on main scale as a common measure to evaluate outcome. The response criterion of a drop in score of at least 30%, 40% and 50% revealed response rates of 46, 36 and 26%, respectively. Nefazodone showed a broad spectrum of action on PTSD symptoms. This profile might make nefazodone a useful drug to treat PTSD. Predictors of response include age, sex and trauma type. Double-blind, placebo-controlled clinical trials in PTSD are in progress to assess the utility of nefazodone as a treatment in this disorder.

Adult↗

Does an increase in sulcal or ventricular fluid predict where brain tissue is lost?

Quantitative volumes of cerebrospinal fluid (CSF) and brain tissue were measured on magnetic resonance images (MRIs) of 287 individuals from 5 diagnostic groups: Alzheimer's disease (AD), chronic alcoholics (ALC), individuals positive for human immunodeficiency virus (HIV), schizophrenia subjects (SZ), and normal comparison subjects (NC) older than 50 years of age. Within each group, mean volumes were calculated for ventricular CSF, cortical (sulcal) CSF, cortical gray matter, total white matter, basal ganglia gray matter, and thalamic gray matter. Correlations of CSF measures with brain tissue measures were determined, and multiple regression analyses were performed to try and predict volume of gray matter or white matter region from volume of CSF compartment. Results indicated the following: 1. Enlarged cortical fluid volume significantly predicts cortical gray matter deficits for subjects with AD and those who are ALC and SZ but not for subjects with HIV or NC. 2. Enlarged cortical fluid volume also significantly predicts white matter deficits in all five groups. 3. Enlarged ventricular fluid volume significantly predicts basal ganglia deficits in AD, HIV, and NC but not in SZ or ALC. 4. Enlarged ventricular volume has no predictive value for thalamic volume for any of the groups. This study supports the clinical practice of predicting brain tissue volume loss from CSF enlargement but not for all brain regions in all diagnoses.

Adult↗

Depressive symptoms in schizophrenia.

OBJECTIVE: The authors assessed the presence and severity of depressive symptoms, as well as their associations with other clinical measures, in a group of mid- to late-life patients with schizophrenia who were not in a major depressive episode or diagnosed with schizoaffective disorder. METHOD: Sixty outpatients with schizophrenia between the ages of 45 and 79 years and 60 normal comparison subjects without major neuropsychiatric disorders, proportionally matched for age and gender, were studied. Depressive symptoms were rated primarily with the Hamilton Depression Rating Scale. Standardized instruments were also used to measure global psychopathology, positive and negative symptoms, abnormalities of movement, and global cognitive status. RESULTS: Depressive symptoms were more frequent and more severe in schizophrenic patients than in normal comparison subjects; 20% of the women with schizophrenia had a Hamilton depression scale score of 17 or more. Severity of depressive symptoms correlated with that of positive symptoms but not with age, gender, negative symptoms, extrapyramidal symptoms, or neuroleptic dose. CONCLUSIONS: Depressive symptoms are common in older patients with schizophrenia. They may be an independent, core component of the disorder or, alternatively, may be a by-product of severe psychotic symptoms.

Age Factors↗

Consensus criteria for traumatic grief. A preliminary empirical test.

BACKGROUND: Studies suggest that symptoms of traumatic grief constitute a distinct syndrome worthy of diagnosis. AIMS: A consensus conference aimed to develop and test a criteria set for traumatic grief. METHOD: The expert panel proposed consensus criteria for traumatic grief. Receiver operator characteristic (ROC) analyses tested the performance of the proposed criteria on 306 widowed respondents at seven months post loss. RESULTS: ROC analyses indicated that three of four separation distress symptoms (e.g. yearning, searching, loneliness) had to be endorsed as at least 'sometimes true' and four of the final eight traumatic distress symptoms (e.g. numbness, disbelief, distrust, anger, sense of futility about the future) had to be endorsed as at least 'mostly true' to yield a sensitivity of 0.93 and a specificity of 0.93 for a diagnosis of traumatic grief. CONCLUSIONS: Preliminary analyses suggest the consensus criteria for traumatic grief have satisfactory operating characteristics, and point to directions for further refinement of the criteria set.

Grief↗

PTSD following bereavement.

Until quite recently, the only stressor considered consistent with the diagnosis of PTSD was a catastrophic, out of the ordinary, trauma that almost anyone could be expected to have a severe reaction to. Thus, PTSD was considered relatively rare among non-military populations. More recently, epidemiologic surveys have suggested that PTSD may be much more prevalent than heretofore recognized, and the DSM-IV has opened the door to a much larger variety of stressors (the "A" criterion). Yet, bereavement is not considered the type of stressor capable of producing PTSD. In this study, 350 newly bereaved widows and widowers were assessed for the prevalence of PTSD, its chronicity, comorbidity, and consequences. The diagnosis of PTSD was made on the basis of questionnaire items approximating the DSM-IV criteria for PTSD. At 2 months after the spouse's death, 10% of those whose spouses died after a chronic illness met criteria for PTSD, 9% of those whose spouses died unexpectedly met criteria, and 36% of those whose spouses died from "unnatural" causes (suicide or accident) had PTSD. Symptoms tended to be chronic in at least 40% of the subjects, almost always were associated with comorbid depression, and created substantial morbidity. The results suggested that PTSD may occur after bereavement, and, by extension, other stressors not recognized by official diagnostic systems. The "A" criterion needs further examination.

Accidents↗

Treatment of major depression in HIV-seropositive men. HIV Neurobehavioral Research Center Group.

BACKGROUND: The purpose of this randomized double-blind, placebo-controlled study was to compare the efficacy and safety of fluoxetine plus group psychotherapy versus group psychotherapy alone in HIV-seropositive men (based on 1986 CDC classes II, III, and IV.C.2) who had been diagnosed with major depressive disorder (DSM-III-R). METHOD: During a 7-week trial, patients were treated with fluoxetine 20-60 mg or placebo 1-3 capsules per day and were seen in weekly supportive group psychotherapy. In addition, subjects were rated on the 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinical Global Impressions scales for Improvement (CGI-I) and Severity of Illness (CGI-S), and the short version of the Beck Depression Inventory (BDI-13). Of the 47 patients enrolled in the study, 25 were administered fluoxetine and 22 were given placebo. RESULTS: Subjects who received fluoxetine began to show significantly more improvement than patients who received placebo on both self- and observer-rated scales by the end of the first week of treatment. By endpoint, patients treated with fluoxetine experienced greater mean changes from baseline compared with placebo-treated patients on the HAM-D-17 (12.1 vs. 6.6; F = 6.53, df = 1,45; p < .05) and BDI-13 (5.9 vs. 1.2; F = 5.73, df = 1,45; p < .05), and a greater percentage of fluoxetine-treated patients experienced a > or = 50% in HAM-D-17 scores (64% vs. 23%; chi2= 8.60, df = 1, p < .01). Differences were particularly apparent in subjects whose initial depressive episodes were rated as severe (i.e., HAM-D-17 score > or = 24). Severely depressed patients treated with fluoxetine had an endpoint CGI-I of 1.4 compared with an endpoint CGI-I of 2.7 for patients treated with placebo (F = 6.02, df = 1,11; p < .05). Further, side effects were generally mild and transient. The most frequently noted effects reported by subjects treated with fluoxetine were nausea, dry mouth, headache, and diarrhea, in decreasing order of frequency. CONCLUSION: This study supports the efficacy and safety of fluoxetine over and above group psychotherapy for the treatment of HIV-associated major depression.

Adult↗

A prospective safety surveillance study for bupropion sustained-release in the treatment of depression.

BACKGROUND: This prospective 105-site study was conducted to determine the rate of seizures and other serious adverse experiences associated with the therapeutic use of the sustained-release formulation of bupropion (bupropion SR). METHOD: 3100 patients with a DSM-III-R diagnosis of depression without a current or past diagnosis of an eating disorder and with no personal or family history of seizure disorders were treated for up to 8 weeks with bupropion SR in an open-label study. Dosing was initiated at 50 mg b.i.d. and increased to a maximum of 150 mg b.i.d. unless not tolerated. Patients had the option to continue treatment with bupropion SR (50 mg b.i.d. to 150 mg b.i.d.) in a continuation phase lasting up to 1 year. During the acute and continuation phases, patients were evaluated for the occurrence of seizures and other serious adverse experiences. Clinical response to and tolerability of bupropion SR were also evaluated. RESULTS: Three patients each experienced a seizure associated with the therapeutic use of bupropion SR during the acute and continuation phases combined. The observed seizure rate during the 8-week acute phase was 2 seizures in 3094 evaluable patients, or 0.06%. The observed seizure rate for the acute and continuation phases combined was 3 seizures in 3094 patients, or 0.10%. Survival analysis yielded a cumulative seizure rate of 0.08% for the acute phase and 0.15% for both phases combined. Two patients who intentionally overdosed with bupropion SR also experienced seizures; however, these events were not included in calculations of the overall seizure rate. Therapeutic doses of bupropion SR were well tolerated and clinically efficacious. CONCLUSION: The therapeutic use of bupropion SR at total daily doses up to 300 mg/day in depressed patients without predisposition to seizures is associated with a seizure rate that is well within the range observed with other marketed antidepressants.

Adolescent↗

Diagnosis and treatment of depression in late life.

Major depression and dysthymia are common and often disabling disorders in late life. Several features of late-life depression, such as its frequent association with general medical conditions, polypharmacy, cognitive disturbances, and adverse life events, make accurate diagnosis a substantial clinical challenge. Yet, prompt diagnosis is an important component of implementing appropriate treatment strategies. An ideal treatment program integrates patient and family education, focused psychotherapy, and pharmacotherapy. Because of pharmacokinetic and pharmacodynamic changes associated with aging, lower doses of medication and more gradual dose increases than are required in younger adults are needed in the treatment of elderly depressed patients. In addition, medications should be selected that have minimal antihistaminic, anticholinergic, and antiadrenergic effects, minimal cardiovascular risk, and minimal drug-drug interactions. Since depression in late life tends to be at least as chronic and/or recurrent as depression earlier in life, treatment for acute depressive episodes should last at least 6-8 months, and long-term maintenance treatment should be considered in selected individuals.

Adult↗

The many faces of depression following spousal bereavement.

While it is becoming increasingly clear that mood disorders tend to be chronic, intermittent and/or recurrent conditions with different manifestations over time, little is known of the variability or course of mood disorders that are associated with severe psychosocial stress. This paper reports on the prevalence and course of major, minor, and subsyndromal depressions in 328 widows and widowers followed prospectively from 2 to 25 months following one of the most disruptive of all naturally occurring stressors, spousal bereavement. The results are consistent with the following conclusions: (1) past major depression (prior to the death) predicts an increased risk for major depression following bereavement; (2) membership in any of the unipolar subgroups, in turn, predicts future depression throughout the unipolar depressive spectrum; (3) subsyndromal and minor depression stand between major depression, on the one hand, and no depression, on the other, in terms of their effects on overall adjustment to widowhood. Thus, the results support the validity of subsyndromal depression, and that the three subgroups (major, minor and subsyndromal depression) are pleiomorphic manifestations of the same unipolar depression disorder.

Adaptation, Psychological↗