Combined clozapine and valproic acid treatment-induced agranulocytosis.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to S Hirschmann.
Explore the source record for details and available documents.
BACKGROUND: In practice psychiatrists rely on their own experience and intuition to evaluate the suicide potential of individual patients, but the algorithms for the decision-making process remain unclear. OBJECTIVES: (1) to establish models for the decision making process for evaluating suicide risk; (2) to simulate the impact of information concerning the number of previous suicide attempts on the clinician's ability to detect patients who performed medically serious suicide attempts (MSSAs). METHODS: Four decision models (linear, dichotomized, hyperbolic, and undifferentiated) depicting the influence of the number of previous suicide attempts on the clinician's recognition of MSSAs in 250 psychiatric inpatients were elicited and tested by a series of discriminant analyses. RESULTS: The dichotomized model ("all or none") was found to be the most efficient in detecting medically serious suicide attempts. CONCLUSION: The "all or none" paradigm seems to be the most appropriate way to evaluate the weight of previous suicide attempts in the decision-making process identifying medically serious suicide attempt patients.
Explore the source record for details and available documents.
Treatment of aggression in schizophrenic patients is a major challenge. We sought to examine the efficacy of augmentation of antipsychotic treatment with pindolol in the amelioration of aggression. Thirty male inpatients meeting DSM-IV criteria for schizophrenia, aged 20-65 years involved in four or more aggressive incidents in the two previous months, were enrolled in a double-blind crossover study. Aggression was evaluated per incident, with the Overt Aggression Scale (OAS). Positive and Negative Syndrome Scale (PANSS) was administered at baseline, crossover and at endpoint. Patients received either pindolol or placebo augmentation 5 mg x three times a day until crossover, then switched. No significant differences were found in the PANSS scores between the placebo and pindolol treatments. OAS scores were significantly reduced for number of aggressive incidents towards objects and other persons during pindolol treatment (0.59 versus 1.46, F = 6.09, P < 0.02; 1.96 versus 3.23, F = 4.17, P < 0.05, respectively). Similar results were obtained for severity of incidents (0.89 versus 3.58, F = 19.42, P < 0.0001; 2.89 versus 6.85, F = 10.11, P < 0.004, respectively). Pindolol, with its dual beta and 5-HT1A blocking effect ameliorated both number and severity of aggressive acts. Influence on severity may be associated with a 5-HT1A antagonistic effect.
BACKGROUND: The rubber hand illusion is a tactile sensation referred to as an alien limb. The illusion has been explained by a spurious reconciliation of visual and tactile inputs reflecting functional connectivity in the brain and was used to explore alterations of functional connectivity in schizophrenia. METHODS: The rubber hand illusion was achieved when two paintbrushes simultaneously stroke the hand of the subject hidden from vision by a screen, as well as an artificial hand placed in view of the subject. The rubber hand illusion was assessed with a questionnaire affirming or denying the occurrence of the illusion. RESULTS: Schizophrenic subjects felt the illusion stronger and faster then did normal control subjects. Some rubber hand illusion effects correlated with positive symptoms of schizophrenia but not with negative symptoms. CONCLUSIONS: Altered functional integration of environmental inputs could constitute the basis for erroneous interpretations of reality, such as delusions and hallucinations.
OBJECTIVE: To evaluate the efficacy of pindolol augmentation in treatment-resistant obsessive compulsive disorder (OCD) patients who were unsuccessfully treated with serotonin reuptake inhibitors. METHOD: Fourteen treatment-resistant OCD patients were treated with paroxetine for 17.4+/-2.1 weeks up to 60 mg/d after they failed at least two other serotonin reuptake inhibitor trials. The patients, who did not respond to open-label paroxetine treatment, were assigned to a double-blind, placebo-controlled pindolol (2.5 mgx3/d) augmentation. All the subjects were evaluated biweekly for a six-week period with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAM-Anx), and Montgomery Asberg Depression Rating Scale (MADRS). Data was analyzed by paired t-test, and ANOVA with repeated measures. RESULTS: Pindolol augmentation to paroxetine (n=8) as compared to placebo augmentation (n=6), was associated with a significant (P<0.01) improvement in Y-BOCS as measured by paired t-test after the fourth week of the treatment and by ANOVA with repeated measures (df: 4.9, f: 3,3, P<0.006). Although no significant differences were found between placebo and pindolol groups on HAM-Anx and MADRS, a trend for improvement in the pindolol group was noted. CONCLUSIONS: The results of our study demonstrated that pindolol may augment the therapeutic effect of paroxetine in treatment-resistant OCD patients.
The risk of sudden death during clozapine treatment is controversial. The authors present a review of sudden deaths that occurred at Sha'ar Menashe Mental Health Center between January 1991 and August 1997. The number of cases of deceased inpatients was retrieved from the hospital's computerized database and divided into three groups: sudden death, suicide, and disease-related death. Copies of mandatory reports of sudden death filed with the Ministry of Health were obtained, and the corresponding patient records were reviewed. The rates of sudden death, suicide, and disease-related deaths were calculated for clozapine-treated patients (CTPs) during and after treatment and for patients treated with other psychiatric agents (non-CTPs). Among 561 CTPs, there were 4 sudden deaths during treatment, 2 sudden deaths after treatment, 2 suicides during treatment, and 2 disease-related deaths during treatment. Among 4918 non-CTPs, there were 14 sudden deaths, 5 suicides, and 86 disease-related deaths, all of which occurred during treatment with other psychiatric agents. CTPs who experienced sudden death were 10.37 years younger and healthier than non-CTPs who experienced sudden death. The sudden death rate was 3.8 times higher for CTPs than for non-CTPs, whereas the rate of disease-related death was 5 times higher for non-CTPs than for CTPs. Contrary to expectations, the rate of suicide among patients currently receiving clozapine in this sample was 3.6 times higher than among non-CTPs. Because CTPs who experienced sudden death were also younger and healthier, it seems that treatment with clozapine may present a greater risk for sudden death than treatment with other psychiatric medications. The limited number of sudden death cases and deaths from other causes should be noted so that these findings are considered with caution.
The objective of this study was to determine the efficacy of pindolol as an augmentor of fluoxetine in treatment-resistant panic disorder (PD). Twenty-five outpatients having PD with or without agoraphobia were included. These patients had not responded to two different trials with antidepressants and an 8-week trial of fluoxetine 20 mg/day. Treatment-resistant PD was defined as a less than 20% reduction in score on the Panic Self-Questionnaire (number of attacks per week) (PSQ) and the Clinical Anxiety Scale With Panic Attacks (CAS+PA). These patients continued to receive fluoxetine 20 mg/day and were randomly assigned to additionally receive either pindolol (2.5 mg three times daily) or placebo for the following 4 weeks. Evaluations were performed weekly using the Hamilton Rating Scale for Anxiety, the Hamilton Rating Scale for Depression (HAM-D), the CAS+PA, the NIMH Anxiety Scale, the PSQ, and the Clinical Global Impression Scale. The data were analyzed using a repeated-measures analysis of variance (ANOVA) and a t-test for independent samples. Patients treated with the combination of pindolol and fluoxetine (N = 13) demonstrated a significant improvement over the patients treated with fluoxetine and placebo on all rating scales, with the exception of HAM-D. The statistical differences were shown using the repeated-measures ANOVA (baseline, week 2, week 4) and also with t-tests from the second week of the trial. These preliminary results demonstrate that pindolol has an augmenting effect on fluoxetine in patients with treatment-resistant PD.
BACKGROUND: Studies in laboratory animals suggest that repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive shock (ECS) increase seizure inhibition acutely. This study was designed to explore whether chronic rTMS would also have seizure inhibition properties. METHODS: To this purpose we administered rTMS (Magstim Rapid) and sham rTMS twice daily (2.5 T, 4-sec train duration, 20 Hz) to two groups of 10 rats for 16 days. The rTMS coil was a 50-mm figure-8 coil held directly over the rat's head. Raters were blind to experimental groups. On days 11, 17, and 21 (5 days after the last rTMS) ECS was administered with a Siemens convulsator using three electrical charge levels. Variables examined were the presence or absence of seizures and seizure length (measured from the initiation of the tonic contraction until the end of the limb movement). RESULTS: At day 11 rTMS had no effect on seizures, and both rTMS and sham rTMS animals convulsed equally. At day 17, however, rTMS-treated animals convulsed significantly less (both at presence/absence of seizures, and at seizure length) than sham rTMS animals. At day 21 the effects of rTMS had disappeared. CONCLUSIONS: These findings suggest that rTMS administered chronically leads to changes in seizure threshold similar to those reported for ECS and ECT; however, these effects were short-lived.
Electroconvulsive therapy (ECT) is considered to be one of the most effective treatments for patients with major depression and persistent psychosis. Seizure characteristics probably determine the therapeutic effect of ECT; as a consequence, short seizures are accepted as one of the factors of poor outcome. During most ECT courses seizure threshold increases and seizure duration decreases. Methylxanthine preparations, caffeine, and theophylline have been used to prolong seizure duration. The use of aminophylline, more readily available than caffeine, has not been well documented. The objective of this study was to test the effects of aminophylline on seizure length. Fourteen drug-free patients with diagnoses of affective disorder or psychotic episode receiving ECT participated in this study. Seizure length was assessed clinically and per EEG. Statistical comparisons were done using paired t tests. A significant increase (p < 0.04) in seizure length was achieved and maintained on three subsequent treatments with aminophylline. No adverse events were noted from the addition of aminophylline.
Explore the source record for details and available documents.
OBJECTIVE: The authors' goal was to examine the hypnotic effects of slow-release melatonin during the initial 4 weeks of treatment with fluoxetine in 19 patients with major depressive disorder. METHOD: Twenty-four outpatients with major depressive disorder were included in the study; 19 completed the study. Ten patients were treated with fluoxetine plus slow-release melatonin and nine were given fluoxetine plus placebo in a double-blind protocol for 4 weeks. Response was assessed by using rating scales for depression and sleep. RESULTS: The 10 patients given slow-release melatonin reported significantly better scores on the Pittsburgh Sleep Quality Index than the nine patients given placebo. No significant differences in the rate of improvement in depressive symptoms were noted between the two groups. No particular side effects were noted from the combination of fluoxetine and slow-release melatonin. CONCLUSIONS: Slow-release melatonin was effective in improving the sleep of patients with major depressive disorder. Slow-release melatonin had no effect on the rate of improvement in symptoms of major depressive disorder. The authors conclude that the role of slow-release melatonin for sleep disturbances in major depressive disorder should be investigated further.
Labetalol, a combined alpha- and beta-adrenergic blocker is often used to attenuate the transient increases in heart rate and blood pressure that accompany electroconvulsive therapy (ECT). It has been suggested that labetalol should not be administered during ECT without the protection provided by anticholinergic medications, because of its potential severe bradycardic effects. We present our experience with 32 patients from all age groups who received labetalol without anticholinergic treatment during ECT. None of the patients demonstrated adverse bradycardic effects. We conclude that administration of labetalol during ECT does not routinely require premedication with anticholinergic drugs and does not lengthen asystole.
The response to electroconvulsive therapy (ECT) was monitored with sleep polysomnography studies (SPS) performed pre- and post-ECT, in 25 patients with major depressive disorder (MDD). Patients included in this study met research diagnostic criteria for MDD and had been free of psychotropic medication for at least 10 days before SPS were performed. We compared ECT responders and nonresponders on SPS, demographic, and clinical parameters. Many SPS parameters, regardless of the clinical response, changed significantly with ECT. The presence of delusions was significantly associated with SOREM post-ECT. The presence of sleep-onset REM periods post-ECT was associated with poor response to ECT. SPS performed during a course of ECT may help identify patients at risk of responding less well to this modality of treatment.
OBJECTIVE: To define the pathologic changes underlying the mechanism of shrinkage of uterine leiomyomata in patients treated with luprolide acetate. DESIGN: Retrospective study of pathologic changes seen in leiomyomata removed by hysterectomy or myomectomy in treated and untreated patients, matched by age and size of uteri and leiomyomata. PATIENT(S): Gross description and histologic slides of 30 treated and 30 untreated patients. INTERVENTION(S): Histologic examination performed blindly (without knowledge of treatment). Statistical work-up using chi 2 analysis with 1 df. MAIN OUTCOME MEASURE(S): Degree of hyaline and hydropic degeneration, cellularity, nuclear atypia, necrosis, and obliteration of interface. RESULT(S): Confluent nodular hyaline degeneration representing a scarlike retraction, geographic hydropic degeneration necrosis and obliteration of the interface between myoma and myometrium were found in higher proportions in the treated patients; differences in cellularity, nuclear atypia, and edema were not statistically significant. CONCLUSION(S): The decrease in size of the treated leiomyomata occurs as an accelerated postmenopausal shrinkage because of the antiestrogenic effect of the therapy. Obliterated cleavage planes may explain the difficult enucleation of myomatous nodules in some of the treated patients.
Premature ejaculation is a common sexual disturbance among men. Both open-label and double-blind studies have demonstrated the effectiveness of serotonergic medications for this disorder. These studies support the hypothesis that the serotonergic system has an important role in the modulation of sexual response, especially attainment of orgasm. Serotonergic dysfunction also has been linked to the pathogenesis of panic disorder. Several studies have demonstrated the efficacy of serotonergic drugs in this disorder. The purpose of the present study was to examine the efficacy of fluoxetine, a serotonin selective reuptake inhibitor for the treatment of comorbid premature ejaculation and panic disorder, in 10 men in an open-label design. The patients were given 20 mg of fluoxetine for 8 weeks of the study. Parameters pertaining to sexual function and measures of anxiety were examined. Improvement of premature ejaculation was noted as of week 2 of the study, whereas measures of panic and sexual satisfaction became statistically significant only as of week 4. Further studies with larger samples and longer periods of follow-up are needed in order to determine the usefulness of fluoxetine for the treatment of comorbid premature ejaculation and panic disorder.
Electroconvulsive therapy (ECT) in patients with impaired cardiac output may be associated with significant cardiovascular morbidity and mortality because of its hemodynamic effects. Many clinicians are reluctant to treat these patients with ECT because of the high risk associated with the treatment. In this report, we present a clinically appropriate protocol for ECT treatment of patients with impaired cardiac output and major depressive disorder. Three patients, ages 59-78 years, with resistant major depression and impaired cardiac output (ejection fraction 20-25%), were successfully treated with ECT according to this protocol.
Anorexia nervosa (AN) in older patients is not often described. We present a 70-year-old woman with AN which started at the age of 50 after her menopause. We suggest that AN starting after the menopause is a unique disturbance with characteristics different from those in younger age groups. The causes of anorexia in the older patient and its special dynamics should be recognized. It may be necessary to create a different diagnostic system and devise special treatment for AN in post-menopausal women.