IL-1ß and BDNF are associated with improvement in hypersomnia but not insomnia following exercise in major depressive disorder.

Given the role of sleep in the development and treatment of major depressive disorder (MDD), it is becoming increasingly clear that elucidation of the biological mechanisms underlying sleep disturbances in MDD is crucial to improve treatment outcomes. Sleep disturbances are varied and can present as insomnia and/or hypersomnia. Though research has examined the biological underpinnings of insomnia in MDD, little is known about the role of biomarkers in hypersomnia associated with MDD. This paper examines biomarkers associated with changes in hypersomnia and insomnia and as predictors of improvements in sleep quality following exercise augmentation in persons with MDD. Subjects with non-remitted MDD were randomized to augmentation with one of two doses of aerobic exercise: 16 kilocalories per kilogram of body weight per week (KKW) or 4 KKW for 12 weeks. The four sleep-related items on the clinician-rated Inventory of Depressive Symptomatology (sleep onset insomnia, mid-nocturnal insomnia, early morning insomnia and hypersomnia) assessed self-reported sleep quality. Inflammatory cytokines (tumor necrosis factor-alpha, interleukin (IL)-1ß, IL-6) and brain-derived neurotrophic factor (BDNF) were assessed in blood samples collected before and following the 12-week intervention. Reduction in hypersomnia was correlated with reductions in BDNF (ρ = 0.26, P = 0.029) and IL-1ß (ρ = 0.37, P = 0.002). Changes in these biomarkers were not associated with changes in insomnia; however, lower baseline levels of IL-1ß were predictive of greater improvements in insomnia (F = 3.87, P = 0.050). In conclusion, improvement in hypersomnia is related to reductions in inflammatory markers and BDNF in persons with non-remitted MDD. Distinct biological mechanisms may explain reductions in insomnia.

Pro-inflammatory cytokines as predictors of antidepressant effects of exercise in major depressive disorder.

Exercise is an efficacious treatment for major depressive disorder (MDD) and has independently been shown to have anti-inflammatory effects in non-depressed subjects. Patients with MDD have elevated inflammatory cytokines but it is not known if exercise affects inflammation in MDD patients and whether these changes are clinically relevant. In the TReatment with Exercise Augmentation for Depression (TREAD) study, participants who were partial responders to a selective serotonin reuptake inhibitor were randomized to receive one of two doses of exercise: 16 kilocalories per kilogram of body weight per week (KKW), or 4 KKW for 12 weeks. Blood samples were collected before initiation and again at the end of the 12-week exercise intervention. Serum was analyzed using a multiplexed ELISA for interferon-γ (IFN-γ), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Higher baseline levels of TNF-α were associated with greater decrease in depression symptoms over the 12-week exercise period (P<0.0001). In addition, a significant positive correlation between change in IL-1ß and change in depression symptom scores was observed (P=0.04). There were no significant changes in mean level of any cytokine following the 12-week intervention, and no significant relationship between exercise dose and change in mean cytokine level. Results suggest that high TNF-α may differentially predict better outcomes with exercise treatment as opposed to antidepressant medications for which high TNF-α is linked to poor response. Our results also confirm findings from studies of antidepressant medications that tie decreasing IL-1ß to positive depression treatment outcomes.

Does exercise improve self-reported sleep quality in non-remitted major depressive disorder?

BACKGROUND: Sleep disturbances are persistent residual symptoms following remission of major depressive disorder (MDD) and are associated with an increased risk of MDD recurrence. The purpose of the current study was to examine the effect of exercise augmentation on self-reported sleep quality in participants with non-remitted MDD. Method Participants were randomized to receive selective serotonin reuptake inhibitor (SSRI) augmentation with one of two doses of exercise: 16 kilocalories per kilogram of body weight per week (KKW) or 4 KKW for 12 weeks. Depressive symptoms were assessed using the clinician-rated Inventory of Depressive Symptomatology (IDS-C). The four sleep-related items on the IDS-C (Sleep Onset Insomnia, Mid-Nocturnal Insomnia, Early Morning Insomnia, and Hypersomnia) were used to assess self-reported sleep quality. RESULTS: Significant decreases in total insomnia (p < 0.0001) were observed, along with decreases in sleep onset, mid-nocturnal and early-morning insomnia (p's <0.002). Hypersomnia did not change significantly (p = 0.38). Changes in total, mid-nocturnal and early-morning insomnia were independent of changes in depressive symptoms. Higher baseline hypersomnia predicted a greater decrease in depression severity following exercise treatment (p = 0.0057). No significant moderating effect of any baseline sleep on change in depression severity was observed. There were no significant differences between exercise treatment groups on total insomnia or any individual sleep item. CONCLUSIONS: Exercise augmentation resulted in improvements in self-reported sleep quality in patients with non-remitted MDD. Given the prevalence of insomnia as a residual symptom following MDD treatment and the associated risk of MDD recurrence, exercise augmentation may have an important role in the treatment of MDD.

Diagnostic utility of the Quick Inventory of Depressive Symptomatology (QIDS-C16 and QIDS-SR16) in the elderly.

OBJECTIVE: To evaluate psychometric properties and comparability ability of the Montgomery-Asberg Depression Rating Scale (MADRS) vs. the Quick Inventory of Depressive Symptomatology-Clinician-rated (QIDS-C(16)) and Self-report (QIDS-SR(16)) scales to detect a current major depressive episode in the elderly. METHOD: Community and clinic subjects (age >or=60 years) were administered the Mini-International Neuropsychiatric Interview (MINI) for DSM-IV and three depression scales randomly. Statistics included classical test and Samejima item response theories, factor analyzes, and receiver operating characteristic methods. RESULTS: In 229 elderly patients (mean age = 73 years, 39% male, 54% current depression), all three scales were unidimensional and with nearly equal Cronbach alpha reliability (0.85-0.89). Each scale discriminated persons with major depression from the non-depressed, but the QIDS-C(16) was slightly more accurate. CONCLUSION: All three tests are valid for detecting geriatric major depression with the QIDS-C(16) being slightly better. Self-rated QIDS-SR(16) is recommended as a screening tool as it is least expensive and least time consuming.

Dyadic discord at baseline is associated with lack of remission in the acute treatment of chronic depression.

BACKGROUND: Dyadic discord, while common in depression, has not been specifically evaluated as an outcome predictor in chronic major depressive disorder. This study investigated pretreatment dyadic discord as a predictor of non-remission and its relationship to depressive symptom change during acute treatment for chronic depression. METHOD: Out-patients with chronic depression were randomized to 12 weeks of treatment with nefazodone, the Cognitive Behavioral Analysis System of Psychotherapy or their combination. Measures included the Marital Adjustment Scale (MAS) and the Inventory of Depressive Symptomatology - Self Report (IDS-SR30). Of 681 original patients, 316 were partnered and 171 of these completed a baseline and exit MAS, and at least one post-baseline IDS-SR30. MAS scores were analysed as continuous and categorical variables ('dyadic discord' v. 'no dyadic discord' defined as an MAS score >2.36. Remission was defined as an IDS-SR30 of 14 at exit (equivalent to a 17-item Hamilton Rating Scale for Depression of 7). RESULTS: Patients with dyadic discord at baseline had lower remission rates (34.1%) than those without dyadic discord (61.2%) (all three treatment groups) (chi2=12.6, df=1, p=0.0004). MAS scores improved significantly with each of the treatments, although the change was reduced by controlling for improvement in depression. Depression remission at exit was associated with less dyadic discord at exit than non-remission for all three groups [for total sample, 1.8 v. 2.4, t(169)=7.3, p<0.0001]. CONCLUSIONS: Dyadic discord in chronically depressed patients is predictive of a lower likelihood of remission of depression. Couple therapy for those with dyadic discord may increase remission rates.

Anticipated Benefits of Care (ABC): psychometrics and predictive value in psychiatric disorders.

BACKGROUND: Attitudes and expectations about treatment have been associated with symptomatic outcomes, adherence and utilization in patients with psychiatric disorders. No measure of patients' anticipated benefits of treatment on domains of everyday functioning has previously been available. METHOD: The Anticipated Benefits of Care (ABC) is a new, 10-item questionnaire used to measure patient expectations about the impact of treatment on domains of everyday functioning. The ABC was collected at baseline in adult out-patients with major depressive disorder (MDD) (n=528), bipolar disorder (n=395) and schizophrenia (n=447) in the Texas Medication Algorithm Project (TMAP). Psychometric properties of the ABC were assessed, and the association of ABC scores with treatment response at 3 months was evaluated. RESULTS: Evaluation of the ABC's internal consistency yielded Cronbach's alpha of 0.90-0.92 for patients across disorders. Factor analysis showed that the ABC was unidimensional for all patients and for patients with each disorder. For patients with MDD, lower anticipated benefits of treatment was associated with less symptom improvement and lower odds of treatment response [odds ratio (OR) 0.72, 95% confidence interval (CI) 0.57-0.87, p=0.0011]. There was no association between ABC and symptom improvement or treatment response for patients with bipolar disorder or schizophrenia, possibly because these patients had modest benefits with treatment. CONCLUSIONS: The ABC is the first self-report that measures patient expectations about the benefits of treatment on everyday functioning, filling an important gap in available assessments of attitudes and expectations about treatment. The ABC is simple, easy to use, and has acceptable psychometric properties for use in research or clinical settings.

The Inventory of Depressive Symptomatology, Clinician Rating (IDS-C) and Self-Report (IDS-SR), and the Quick Inventory of Depressive Symptomatology, Clinician Rating (QIDS-C) and Self-Report (QIDS-SR) in public sector patients with mood disorders: a psychometric evaluation.

BACKGROUND: The present study provides additional data on the psychometric properties of the 30-item Inventory of Depressive Symptomatology (IDS) and of the recently developed Quick Inventory of Depressive Symptomatology (QIDS), a brief 16-item symptom severity rating scale that was derived from the longer form. Both the IDS and QIDS are available in matched clinician-rated (IDS-C30; QIDS-C16) and self-report (IDS-SR30; QIDS-SR16) formats. METHOD: The patient samples included 544 out-patients with major depressive disorder (MDD) and 402 out-patients with bipolar disorder (BD) drawn from 19 regionally and ethnicically diverse clinics as part of the Texas Medication Algorithm Project (TMAP). Psychometric analyses including sensitivity to change with treatment were conducted. RESULTS: Internal consistencies (Cronbach's alpha) ranged from 0.81 to 0.94 for all four scales (QIDS-C16, QIDS-SR16, IDS-C30 and IDS-SR30) in both MDD and BD patients. Sad mood, involvement, energy, concentration and self-outlook had the highest item-total correlations among patients with MDD and BD across all four scales. QIDS-SR16 and IDS-SR30 total scores were highly correlated among patients with MDD at exit (c = 0.83). QIDS-C16 and IDS-C30 total scores were also highly correlated among patients with MDD (c = 0.82) and patients with BD (c = 0.81). The IDS-SR30, IDS-C30, QIDS-SR16, and QIDS-C16 were equivalently sensitive to symptom change, indicating high concurrent validity for all four scales. High concurrent validity was also documented based on the SF-12 Mental Health Summary score for the population divided in quintiles based on their IDS or QIDS score. CONCLUSION: The QIDS-SR16 and QIDS-C16, as well as the longer 30-item versions, have highly acceptable psychometric properties and are treatment sensitive measures of symptom severity in depression.

An analysis of reported deaths following electroconvulsive therapy in Texas, 1993-1998.

Since 1993, Texas law has required that all deaths that occur within 14 days of electroconvulsive therapy (ECT) be reported to the Texas Department of Mental Health and Mental Retardation. This study attempted to differentiate deaths that may have been due to ECT or the associated anesthesia from those due to other causes. Among more than 8,000 patients who received 49,048 ECT treatments between 1993 and 1998, a total of 30 deaths were reported to the mental health department between 1993 and 1998. Only one death, which occurred on the same day as the ECT, could be specifically linked to the associated anesthesia. An additional four deaths could plausibly have been associated with the anesthesia, for which the calculated mortality rate is between two and ten per 100,000, but probably not with the stimulus of the ECT or seizure. The mortality rate associated with ECT (less than two per 100,000 treatments) in Texas is extremely low.

Response in relation to baseline anxiety levels in major depressive disorder treated with bupropion sustained release or sertraline.

Our objective was to determine if pretreatment anxiety levels were associated with preferential response to bupropion sustained release (n = 122) or sertraline (n = 126) during a 16-week randomized acute phase treatment study. Both agents had comparable antidepressant activity, and comparable anxiolytic effects using the intent-to-treat sample. Baseline anxiety levels were not related to antidepressant efficacy, and they did not differentiate responders to each agent. Time to clinically significant anxiolysis did not differentiate between treatment groups or between responders to each agent. These results contradict the commonly held, but unsubstantiated, belief that in clinically depressed anxious patients, serotonergic antidepressants are especially anxiolytic and that such patients preferentially benefit from the antidepressant or anxiolytic effects of selective serotonin reuptake inhibitors. Thus, the clinical decision to select between these two agents when treating depressed outpatients cannot rest on either levels of pretreatment anxiety or on anticipation of more rapid or more complete anxiolysis.

Does pretreatment anxiety predict response to either bupropion SR or sertraline?

BACKGROUND: A common clinical belief is that more sedating and/or serotonin-selective antidepressants are preferred for depressed patients with symptoms of anxiety compared with more activating and/or catecholamine-selective antidepressants. The purpose of this study was to determine whether higher baseline anxiety is associated with different antidepressant responses to bupropion sustained release (SR) or sertraline. METHODS: A retrospective data analysis was conducted using pooled data from two identical 8-week, randomized, double-blind, placebo-controlled multicenter studies of bupropion SR (n=234), sertraline (n=225), and placebo (n=233) in adult outpatients with recurrent, major depressive disorder. Anxiety symptoms were measured using the 14-item Hamilton Anxiety Rating Scale scores. RESULTS: Baseline anxiety levels were not related to antidepressant response to treatment with either bupropion SR or sertraline, nor did they differentiate between responders to bupropion SR and responders to sertraline. CONCLUSIONS: Baseline anxiety levels do not appear to be a basis for selecting between bupropion SR and sertraline in the treatment of outpatients with major depressive disorder.

Severe delayed thrombocytopenia associated with abciximab (ReoPro) therapy.

Acute thrombocytopenia associated with abciximab therapy has been well described, although the exact mechanism remains obscure. We report a case of delayed severe thrombocytopenia associated with abciximab therapy for percutaneous coronary intervention that occurred following hospital discharge. The detection of this phenomenon is important as it may portend heightened risk for severe or profound thrombocytopenia on subsequent reexposure to abciximab therapy.

Which depressed patients respond to nefazodone and when?

BACKGROUND: Retrospective data analyses were conducted of a single-blind trial of 993 outpatients with nonpsychotic major depression (DSM-III-R) treated for 12 weeks with nefazodone to provide a more specific picture of the nature and timing of response or remission to acute-phase treatment. METHOD: All patients participated in a single-blind, 16-week lead-in to obtain responders eligible for a subsequent double-blind, randomized continuation phase trial. Outcomes were defined by the 17-item Hamilton Rating Scale for Depression (HAM-D). A > or = 50% reduction from baseline defined response, and a total HAM-D exit score of < or =8 defined remission. RESULTS: Of all patients who entered the trial, 41.8% (last observation carried forward) responded at or before week 4 (early responders), and an additional 25.2% responded thereafter; 18.3% achieved remission at or before week 4; 33.6% achieved remission after week 4. Thus, 77.3% of those responding ultimately remitted. On average, remission followed response by 2 weeks. The average end-of-treatment dose was 376 mg/day at exit (last observation carried forward). Responders or remitters (as opposed to nonresponders or nonremitters) had lower baseline depressive symptomatology and were more likely to be married or cohabiting. CONCLUSION: The full symptomatic benefit of antidepressant medication may not be apparent until completion of an 8- to 10-week trial. A high number of responders ultimately attained remission. Baseline demographic and clinical features were not highly predictive of who would or would not benefit from nefazodone. For routine care, a minimal acute-phase trial, using a 50% reduction in baseline symptom severity to define response, should be 8 weeks. Whether ultimate nonresponders can be identified earlier than 8 weeks deserves further study.

Do bupropion SR and sertraline differ in their effects on anxiety in depressed patients?

OBJECTIVE: To examine the effects of bupropion sustained release (SR) and sertraline on anxiety in outpatients with recurrent DSM-IV-defined major depressive disorder. METHOD: This retrospective analysis was conducted using pooled data from 2 identical, 8-week, acute-phase, double-blind, placebo-controlled, parallel-group studies of bupropion SR (N = 234), sertraline (N = 225), and placebo (N = 233). Symptoms of anxiety and depression were measured using the 14-item Hamilton Rating Scale for Anxiety (HAM-A) and the 21-item Hamilton Rating Scale for Depression (HAM-D-21), respectively. Percentage reduction in baseline HAM-A total score for each treatment week was calculated to determine whether the time to onset of anxiolytic activity differed among antidepressant responders to each agent. Central nervous system (CNS) adverse events were tabulated. RESULTS: Bupropion SR and sertraline were comparably effective, both were superior to placebo in reducing depressive symptoms. and they did not differ in their effect on anxiety symptoms. Antidepressant responders (> 50% reduction in baseline HAM-D-21 score) in both groups showed marked and comparable reductions in HAM-A scores (baseline to exit). There were no differences between bupropion SR and sertraline in the median time (4 weeks) to reach a clinically significant anxiolytic effect (> or = 50% reduction in baseline HAM-A score). CNS adverse events were comparable for bupropion SR and sertraline, except for somnolence, which was more common in sertraline-treated patients. CONCLUSION: Bupropion SR and sertraline had comparable antidepressant and anxiolytic effects and an equally rapid onset of clinically significant anxiolytic activity. There was no difference in the activating effects between the 2 antidepressants. Selection between these 2 agents cannot be based on either anticipation of differential anxiolytic activity or differential CNS side effect profiles.

A comparison of alternative assessments of depressive symptom severity: a pilot study.

This study compared the performance of an itemized symptom self-report (Inventory of Depressive Symptomatology - Self-Report; IDS-SR), patient global ratings, and clinician global ratings with an itemized clinician-rated symptom severity measure (Inventory of Depressive Symptomatology - Clinician-Rated; IDS-C) in detecting treatment effects in patients with major depressive disorder (MDD). A total of 28 inpatients (30.8% psychotic) and 34 outpatients (17.9% psychotic) with MDD began treatment that followed the Texas medication algorithm. The clinicians completed the IDS-C and a Physician Global Rating Scale (PhGRS) at each assessment visit, while the patients completed the IDS-SR and a Patient Global Rating Scale (PtGRS). Change scores from the baseline to subsequent weeks were computed for all subjects, utilizing all four measures. The IDS-SR was a significant independent predictor of the response to treatment as compared to the two global ratings. The IDS-SR was as sensitive to change as the IDS-C. While the clinician-rated itemized symptom severity rating scale remains the standard to assess the symptomatic outcome of the treatment of MDD, a self-report of identical symptomatology may be a reasonable alternative for many patients.

A comparison of alternative assessments of depressive symptom severity: a pilot study.

This study compared the performance of an itemized symptom self-report (Inventory of Depressive Symptomatology - Self-Report; IDS-SR), patient global ratings, and clinician global ratings with an itemized clinician-rated symptom severity measure (Inventory of Depressive Symptomatology - Clinician-Rated; IDS-C) in detecting treatment effects in patients with major depressive disorder (MDD). A total of 28 inpatients (30.8% psychotic) and 34 outpatients (17.9% psychotic) with MDD began treatment that followed the Texas medication algorithm. The clinicians completed the IDS-C and a Physician Global Rating Scale (PhGRS) at each assessment visit, while the patients completed the IDS-SR and a Patient Global Rating Scale (PtGRS). Change scores from the baseline to subsequent weeks were computed for all subjects, utilizing all four measures. The IDS-SR was a significant independent predictor of the response to treatment as compared to the two global ratings. The IDS-SR was as sensitive to change as the IDS-C. While the clinician-rated itemized symptom severity rating scale remains the standard to assess the symptomatic outcome of the treatment of MDD, a self-report of identical symptomatology may be a reasonable alternative for many patients.

Effect size of lithium, divalproex sodium, and carbamazepine in children and adolescents with bipolar disorder.

OBJECTIVE: To develop effect sizes for 3 mood stabilizers--lithium, divalproex sodium, and carbamazepine--for the acute-phase treatment of bipolar I or II disorder, mixed or manic episode, in children and adolescents aged 8 to 18 years. METHOD: Forty-two outpatients with a mean age of 11.4 years (20 with bipolar I disorder and 22 with bipolar II disorder) were randomly assigned to 6 weeks of open treatment with either lithium, divalproex sodium, or carbamazepine. The primary efficacy measures were the weekly Clinical Global Impression Improvement scores and the Young Mania Rating Scale (Y-MRS). RESULTS: Using a > or = 50% change from baseline to exit in the Y-MRS scores to define response, the effect size was 1.63 for divalproex sodium, 1.06 for lithium, and 1.00 for carbamazepine. Using this same response measure with the intent-to-treat sample, the response rates were as follows: sodium divalproex, 53%; lithium, 38%; and carbamazepine, 38% (chi 2(2) = 0.85, p = .60). All 3 mood stabilizers were well tolerated, and no serious adverse effects were seen. CONCLUSIONS: Divalproex sodium, lithium, and carbamazepine all showed a large effect size in the open treatment of children and adolescents with bipolar I or II disorder in a mixed or manic episode.

Local delivery of nadroparin via hydrogel-coated angioplasty balloon: effect on platelet deposition and smooth muscle cell proliferation--an experimental study.

PURPOSE: To assess the feasibility of intravascular delivery of nadroparin, a low-molecular-weight heparin, via hydrogel-coated angioplasty balloons, and the effects of nadroparin delivered in this manner on platelet deposition and smooth muscle cell (SMC) proliferation. MATERIALS AND METHODS: Tritiated nadroparin was used to determine the nadroparin-carrying capacity of the hydrogel-coating, kinetics of release from the balloons, and, in four pigs, delivery of the nadroparin to the iliac arterial wall. Platelet deposition in nadroparin-treated iliac arteries versus contralateral iliac arteries dilated with saline-loaded, hydrogel-coated balloons was quantified in seven pigs using 111Indium-labeled platelets. Smooth muscle cell proliferation in nadroparin and saline-treated iliac arteries in 10 pigs was evaluated 7 days after angioplasty with use of proliferating cell nuclear antigen. RESULTS: Approximately 98 international units of nadroparin were delivered by the hydrogel-coated balloon, the majority to the angioplasty site and distal vessel. There was a trend toward decreased platelet deposition in nadroparin-treated arteries, but statistical significance was not achieved (P = .1563). Medial SMC proliferation was decreased in the nadroparin-treated arteries in nine of 10 pigs (P = .0137). CONCLUSIONS: Hydrogel-coated balloons may be used to deliver nadroparin to the arterial wall, with measurable levels of the drug delivered to the site of angioplasty, and with resultant decrease in SMC proliferation.

Acute and continuation pharmacological treatment of children and adolescents with bipolar disorders; a summary of two previous studies.

We report the results of an acute-phase and continuation-phase study of the pharmacological treatment of children and adolescents with bipolar disorders. The acute phase study, with a duration of 6-8 weeks, aimed at developing effect sizes (ES) for lithium, divalproex sodium, and carbamazepine, in the acute phase treatment of Bipolar I or II children and adolescents during a mixed or manic episode. During the acute-phase of treatment, 42 outpatients with a mean age of 11.4 yr. (20 with Bipolar I Disorder and 22 with Bipolar II Disorder) were randomly assigned to 6-8 weeks of open treatment with either lithium, divalproex sodium, or carbamazepine. The primary efficacy measures were the weekly CGI Improvement scores and the Young Mania Rating Scale. Using a ≥ 50% change from baseline to exit in the Y-MRS scores to define response, the effect size for divalproex sodium was 1.63,1.06 for lithium, and 1.00 for carbamazepine. Using this same response measure with the intent-to-treat sample, the response rates were: sodium divalproex 53%; lithium 38%; and carbamazepine 38% (x 2=0.85, 2 d.f., p=0.60). Thirty-five subjects continued in open, treatment for another 16-18 weeks, for a total of 24 weeks of prospective treatment. Overall, of the thirty-five continuation phase subjects, thirty (85%) were categorized as responders at the end of the continuation phase of treatment. Of these thirty-five subjects, 13 (37%) were only on a single mood stabilizer and no other psychotropic agents at the end of the continuation phase. Thirty-one percent of subjects in continuation were also treated with a stimulant medication in addition to mood stabilizers.

Structured diagnostic assessment and depot fluphenazine treatment of multiple suicide attempters in the emergency department.

The aim of this study was to compare the efficacy of two doses of monthly intramuscular (i.m.) injections of fluphenazine decanoate in reducing self-harm behaviours in outpatients with histories of multiple suicide attempts. Fifty-eight patients who presented to a psychiatric emergency service after an attempted suicide and who had histories of multiple suicide attempts, were randomized to receive monthly i.m. injections of fluphenazine decanoate. Thirty patients received monthly 12.5 mg ('low' dose), and 28 patients received monthly 1.5 mg ('ultra low' dose) under double-blind conditions. DSM-III-R diagnoses were obtained on all patients using the Structured Clinical Interview for DSM-III-R-Patient Version (SCID-P) and SCID for DSM-III-R Personality Disorders (SCID-II). Outcomes were assessed by the Parasuicide History Inventory and the Abnormal Involuntary Movement Scale, collected monthly for 6 months. Patients had an average of six current Axis I and 2.6 Axis II diagnoses, with borderline personality (85%) and alcohol dependence (58%) occurring most frequently in the sample. Both the low dose and ultra-low dose groups showed a marked reduction in self-harm behaviours. For 'serious' self-harm behaviours, there was a trend for a greater effect of the low dose over the ultra-low dose group, however, the differences did not reach statistical significance. A survival analysis indicated that the presence of 'acute' stressors at baseline and female sex were risk factors for continuing (post-randomization) 'serious' self-harm behaviours, while younger age and the absence of concurrent general medical conditions were risk factors for all self-harm behaviours.

Brachytherapy for the prevention of stenosis in a canine hemodialysis graft model: preliminary observations.

PURPOSE: To determine whether gamma brachytherapy can prevent in-stent stenosis in hemodialysis grafts. MATERIALS AND METHODS: Six-millimeter polytetrafluoroethylene arteriovenous grafts were created bilaterally in six dogs. After 1 month, Wallstents spanning the venous anastomosis were placed to accelerate restenosis. Gamma irradiation (12 Gy) was delivered endoluminally to one of the two grafts by using an iridium 192 source; thus, each animal served as its own control. Fistulography was performed monthly for 10 months or until graft thrombosis, with measurement of stenosis at each time point. At the conclusion of the study period, the treated area was examined histologically, and a computer model was used to calculate the volume of intimal hyperplasia. RESULTS: Delayed stent migration resulted in exclusion of one dog. In the remaining five dogs; maximum stenosis across all time intervals was less for the treated side (P < .04), and the volume of intimal hyperplasia was less for the treated side (P < .045). In one animal studied at 1 year, this trend reversed in terms of percentage stenosis but not total neointimal volume. CONCLUSION: Brachytherapy with 192Ir (gamma) delivered at the time of stent placement reduces restenosis in this hemodialysis graft model, but, depending on the parameter evaluated (stenosis vs total volume of neointima), the benefit may wane or even reverse with time.