Biomedical subjects

M S Nobler

Publications and source records attributed to M S Nobler.

33 records · Page 2Linked to original sources

PubMed1998

The relative efficiency of altering pulse frequency or train duration when determining seizure threshold.

In 12 depressed inpatients referred for bilateral electroconvulsive therapy (ECT), each patient was titrated at the first treatment session by using an ascending method-of-limits procedure with a step-wise increase in pulse frequency (frequency titration) or train duration (duration titration). At the second treatment session, seizure threshold was redetermined by using the method (frequency or duration titration) not used at the first treatment. Frequency or duration was maintained at the lowest level when the other parameter was titrated. Seizure threshold was significantly lower with duration titration (mean, 90 mC; SD, 27.3) than frequency titration (mean, 114 mC; SD, 35.6; p = 0.03). On average, patients in the duration-titration group required 1.2 (SD, 0.6) subconvulsive stimulations before a seizure was elicited, and patients in the frequency-titration group required 1.7 (SD, 0.9) subconvulsive stimulations before a seizure was elicited, a nonsignificant difference. These findings suggest that to elicit a seizure during ECT, increasing train duration may be slightly more efficient than increasing frequency. Basic and other clinical research findings indicate that increasing pulse width may be an inefficient way to elicit a seizure. Therefore the following sequence in the determination of seizure threshold is worth considering when using dose-titration or related techniques: the train duration should be increased first before increasing pulse frequency, and the decision to increase pulse width should be reserved for patients who do not seize at the maximal duration and frequency settings. Further empiric research is needed to establish the utility of this approach.

Adult↗

PubMed1997

Fluoxetine discontinuation in elderly dysthymic patients.

A group of 23 elderly outpatients with dysthymic disorder participated in a 13-week fluoxetine trial. Twelve responders received open continuation treatment and subsequently discontinued fluoxetine (mean: 32 weeks on medication). During the 24 weeks after discontinuation, 6 of the 12 patients relapsed. Clinical features, dose, and duration of fluoxetine treatment were not predictive of relapse. The 50% relapse rate in this small sample is lower than that reported in young adult dysthymic patients but is high enough to warrant clinical caution.

Adult↗

PubMed1997

Quantifying the speed of symptomatic improvement with electroconvulsive therapy: comparison of alternative statistical methods.

Although electroconvulsive therapy (ECT) is believed to have a rapid onset of antidepressant activity, there has been limited investigation in this area. This study contrasted alternative statistical methods for testing treatment group differences in the rapidity of clinical response to ECT. Patients with major depression were randomly assigned to receive right unilateral or bilateral ECT and low or high electrical dosage relative to seizure threshold. The 24-item Hamilton Rating Scale for Depression (HRSD) was administered by blinded clinical raters twice weekly (non-treatment days). We evaluated four alternative statistical strategies. Two methods considered time to improvement as a dependent variable: (a) time (treatment number) to reach various cutoffs for percentage decrease in HRSD from baseline; and (b) survival analysis using the same cutoffs for percentage decreases as endpoints. Two methods considered time to improvement as an independent variable: (c) the slope of linear regression of HRSD scores against treatment number; and (d) a random regression model using the HRSD scores as repeated measures. The statistical methods differed in whether or not omnibus group differences were observed, the criterion level of improvement associated with group differences, and the results of pairwise comparisons establishing specific therapeutic advantages. Survival analysis generally displayed the greatest sensitivity in detecting treatment group differences.

Analysis of Variance↗

PubMed1996

The effects of electroconvulsive therapy on quantitative electroencephalograms. Relationship to clinical outcome.

BACKGROUND: The efficacy of electroconvulsive therapy (ECT) is determined by stimulus electrical intensity and electrode placement. Three theories offer different accounts for why increasing the stimulus dosage of right unilateral ECT enhances antidepressant effects. This study examined the effects of ECT on interictal quantitative electroencephalograms (EEGs), contrasting these theories in their predictions regarding global, lateralized, and topographic changes in ECT-induced slow-wave activity. The time course of EEG changes and associations with efficacy were also determined. METHODS: Sixty-two inpatients with major depressive disorder were randomized to ECT conditions that differed in stimulus intensity (low vs high dosage) and electrode placement (right unilateral vs bilateral). Resting, eyes closed, 19-lead EEG recordings were obtained at pretreatment, following a single treatment, following an average of 7 treatments, during the week following the ECT course, and after a 2-month follow-up period. RESULTS: Electroconvulsive therapy produced a marked short-term increase in delta and theta power. At a 2-month follow-up, there were no significant alterations in any frequency band. The ECT treatment conditions differed markedly in efficacy. Global and lateralized EEG effects did not distinguish effective and ineffective forms of treatment. Effective forms of ECT resulted in increased delta power in prefrontal regions, and this change was associated with the magnitude of symptomatic improvement. CONCLUSION: The induction of slow-wave activity in prefrontal cortex is linked to the efficacy of ECT.

Delta Rhythm↗

PubMed1996

Who responds to electroconvulsive therapy? A comparison of effective and ineffective forms of treatment.

BACKGROUND: It has been reported that real ECT is more effective than simulated treatment among depressed patients with delusions and/or retardation, and that ECT is not effective among depressed patients who lack these features. METHOD: In two randomised, double-blind studies, 143 patients with major depression were subtyped regarding psychosis, retardation and agitation. In both studies, low dosage, right unilateral ECT was ineffective compared with other forms of ECT. This report examined whether the depressive subtypes differed in clinical response to the ineffective and effective forms of ECT. RESULTS: The therapeutic advantage of effective forms of ECT was similar across the depression subtypes. Patients who lacked both psychosis and retardation showed this pattern. CONCLUSIONS: The findings cast doubt on the utility of these depression subtypes in predicting ECT response. ECT is a viable treatment option for patients with major depression regardless of the presence or absence of psychosis, retardation and/or agitation.

Adult↗

PubMed1996

Fluoxetine treatment of dysthymia in the elderly.

BACKGROUND: Despite their prevalence, little is known about the treatment of mild depressive syndromes in older patients. The purpose of this study was to evaluate the efficacy of fluoxetine in dysthymic disorder in the elderly. METHOD: Twenty-three elderly outpatients with dysthymic disorder (DSM-III-R criteria) entered a 13-week study of fluoxetine (2-week placebo run-in period and 11 weeks of fluoxetine treatment with a dose range of 20-60 mg/day). Ratings to assess clinical response included the Hamilton Rating Scale for Depression (HAM-D), the Clinic Global Impression (CGI), and the Cornell Dysthymia Rating Scale (CDRS). RESULTS: Nine patients (39%) had never received psychiatric treatment during the index episode, despite a long duration of illness (mean +/- SD = 18.5 +/- 17.1 years). Twenty of the 23 patients completed the entire study. The mean +/- SD HAM-D (24-item) score decreased from 14.6 +/- 3.7 to 7.9 +/- 5.0 during the trial, and the CDRS score decreased from 28.1 +/- 9.1 to 15.7 +/- 10.0. When response criteria of a 50% reduction from baseline in the HAM-D score, final HAM-D score < or = 8, and a CGI score of 1 or 2 (very much or much improved) were used, 12 (60%) of the completers were responders. Side effects were uncommon, and the fluoxetine was generally well tolerated. CONCLUSION: These preliminary findings suggest that fluoxetine is an effective treatment in elderly patients with dysthymic disorder. Double-blind, placebo-controlled studies are warranted.

Adult↗

PubMed1996

Dangerous hyperglycemia associated with electroconvulsive therapy.

The literature on the effect of electroconvulsive therapy (ECT) on diabetes mellitus remains controversial, with evidence of both amelioration and worsening of hyperglycemia. Both clinical reports and animal models suggest that a critical factor in glucose homeostasis may be whether or not the diabetes is insulin dependent. We present a case in which ECT was associated with extreme hyperglycemia in a patient without known preexisting diabetes. The patient subsequently required treatment with an oral hypoglycemic agent, and eventually needed insulin. The possibility of an unmasking or exacerbation of diabetic pathology during a course of ECT must be considered. Various mechanisms by which ECT may influence hyperglycemia are discussed.

Adult↗

PubMed1996

Exceptionally high seizure threshold: ECT device limitations.

Three patients had exceptionally high seizure threshold, as determined by an empirical titration procedure. Initial seizure threshold was 896 mC in two of the patients. The third patient had an initial threshold of 336 mC that increased to 840 mC at the end of the course of electroconvulsive therapy (ECT), and remained elevated during a second course of ECT. All three patients were elderly men with complicated medical histories and ongoing low-dose benzodiazepine use. Each patient had an excellent response to ECT delivered with a custom modified device, capable of delivering more than twice the charge of ECT devices presently commercially available in the United States. Implications for the administration of ECT in patients with exceptionally high seizure threshold and the limitations of current device output are discussed.

Aged↗

PubMed1994

Regional cerebral blood flow in mood disorders, III. Treatment and clinical response.

BACKGROUND: Global and regional deficits in cerebral blood flow and glucose metabolism have been reported in major depression, but there is limited information on the effects of somatic treatment and clinical recovery on these abnormalities. METHODS: We assessed cortical blood flow with the xenon 133 technique in depressed patients prior to a course of electroconvulsive therapy (ECT), 30 minutes before and 50 minutes after a single treatment, and during the week following ECT. Acute (preictal and postictal) effects of a single treatment also were studied in manic patients. RESULTS: In the depressed and manic groups, larger blood flow reductions in the acute period, both globally and in particular patterns of brain regions, were associated with a superior clinical outcome following the treatment course. In depressed patients, similar patterns were observed for the blood flow changes over a full treatment course. Blood flow reductions in anterior cortical regions were strongly associated with a positive clinical response in both depression and mania. CONCLUSIONS: The findings indicated that cerebral blood flow abnormalities in major depression were not reversed by successful treatment with ECT. Rather, particularly in responders, ECT resulted in additional perfusion reductions. The therapeutic properties of ECT are related to reduced functional brain activity in specific neural regions.

Adult↗

PubMed1994

Is dysthymia a different disorder in the elderly?

OBJECTIVE: This study evaluated elderly dysthymic patients in a late life depression clinic and compared their clinical features to previous findings in young adult dysthymic patients. METHOD: Of 224 consecutive elderly outpatients, 40 (17.9%) met criteria for dysthymic disorder. A semistructured interview was used to obtain history, the Structured Clinical Interview for DSM-III-R--Patient Version and the Structured Clinical Interview for DSM-III-R Personality Disorders were used to make DSM-III-R diagnoses, and standard rating instruments for depression were administered. RESULTS: The gender distribution was equal and major stressors were common. The mean age at onset of dysthymia was 55.2 years (SD = 15.4), with an average illness duration of 12.5 years (SD = 14.2). Early onset (before 21 years of age) and secondary dysthymia were rare. A history of major depression earlier during the course of dysthymic illness, comorbid anxiety disorders, and personality disorders were relatively uncommon. Cross-sectionally, cognitive and functional symptoms were more prominent than vegetative symptoms. CONCLUSIONS: Dysthymia is not uncommon among depressed elderly outpatients who present for treatment. Elderly dysthymic patients differ from young adult dysthymic patients, who are mostly female with an early onset and who frequently have comorbid axis I and axis II disorders. Most elderly dysthymic patients do not appear to be young dysthymic patients who simply grew older, and the DSM-III-R subtyping of dysthymia into early/late onset and primary/secondary may not apply to the elderly. Further clinical studies of "pure" dysthymic disorder appear feasible in the elderly, and these are clearly needed.

Adult↗

PubMed1994

Physical properties and quantification of the ECT stimulus: I. Basic principles.

The physical properties of the electroconvulsive therapy (ECT) stimulus markedly affect both efficacy and side effects. We review basic principles in characterizing these physical properties and in quantifying the ECT stimulus. The topics discussed include the application of Ohm's law, alternative composite units of ECT dosage (energy and charge), the use of constant-current, constant-voltage, and constant-energy principles in ECT devices, the nature of current shunting in ECT and the determinants of impedance, the relations between impedance and seizure threshold, the seizure-eliciting efficiency of alternative stimulus waveforms and of stimulus parameter configurations, and the role of reactive components (capacitance and inductance) in the ECT circuit. New findings are also presented regarding several of these issues.

Electric Impedance↗

PubMed1993

EEG manifestations during ECT: effects of electrode placement and stimulus intensity.

This study examined the ictal electroencephalographic (EEG) characteristics of four forms of electroconvulsive therapy (ECT) known to differ in efficacy. Previously, we demonstrated that titrated, low-dose right unilateral ECT reliably produces generalized seizures of adequate duration, but is remarkably weak in antidepressant effects. Using a new rating scale, we found that specific features of the ictal and immediate postictal EEG varied significantly with ECT stimulus intensity and electrode placement. The low-dose right unilateral condition differed from more effective forms of ECT in having the longest polyspike phase duration, averaging twice that of the other conditions; it was also the condition least likely to manifest bioelectric suppression immediately following seizure termination. In contrast, high-dose bilateral ECT--a treatment with particularly rapid antidepressant effects--resulted in the greatest peak slow-wave amplitude in both hemispheres. Total seizure duration did not differ among the four treatment conditions. These findings indicate that seizure duration is not a useful marker of therapeutic efficacy, and instead provide preliminary evidence that other features of the EEG may be more useful markers of treatment adequacy.

Adult↗

PubMed1989

Tourette-like symptoms associated with neuroleptic therapy in an autistic child.

A 5 1/2-year-old autistic boy developed a Tourette-like syndrome after neuroleptic withdrawal. The child was studied prospectively and any abnormal movements were compared with predrug baseline assessment and information. Differential diagnosis and some of the difficulties in evaluating neuroleptic related abnormal movements are discussed. The need for a baseline assessment of patients before the administration of neuroleptics is stressed.

Autistic Disorder↗

PubMed1985

The acute effects of antidepressant drugs on the performance of conditioned avoidance behavior in rats.

The effects of acute administration of 10 different antidepressant drugs were examined on the performance of a two-way conditioned avoidance response in rats. The antidepressant drugs impaired avoidance behavior by decreasing avoidance responding and increasing the number of escape failures. The order of effectiveness for increasing overall response latency at a common dose of 10 mg/kg was: desipramine, maprotiline, protriptyline, (+) oxaprotiline, nortriptyline, imipramine, amitriptyline, (-) oxaprotiline, fluoxetine, and chlorimipramine. Avoidance behavior was impaired most by those antidepressant drugs that are also potent inhibitors of norepinephrine uptake.

Animals↗

PubMed1984

Differential actions of serotonin antagonists on two behavioral models of serotonin receptor activation in the rat.

Ligand binding studies have identified certain serotonin (5-HT) antagonists with selective affinity for 5-HT2 receptors and other serotonin antagonists with affinity for both 5-HT1 and 5-HT2 receptors. This study compared the actions of ketanserin and pipamperone, selective 5-HT2 receptor antagonists, with metergoline and methysergide, nonselective 5-HT antagonists, on two behavioral responses in rats that are produced by the activation of 5-HT receptors: 1) the head shake response and 2) the 5-HT syndrome. Both the selective and the nonselective 5-HT antagonists blocked the head shake response produced by 5-hydroxy-L-tryptophan. The order of relative potency was: metergoline greater than ketanserin greater than pipamperone greater than methysergide. All four antagonists also blocked the head shake response produced by the 5-HT agonist quipazine. In contrast, the symptoms of the 5-HT syndrome produced by 5-methoxy-N,N-dimethyltryptamine were blocked by pretreatment with the nonselective 5-HT receptor antagonists but not by the 5-HT2 receptor antagonists. The differential actions of 5-HT antagonists on these behavioral responses suggest that different 5-HT receptors are involved in the head shake response and the 5-HT syndrome. That the order of relative potency for these drugs to block the head shake response was the same as their reported affinity for the 5-HT2 receptor suggests that the 5-HT2 receptor is involved in the head shake response. In contrast, the ability of 5-HT antagonists with affinity for the 5-HT1 receptor to block the 5-HT syndrome and the inability of 5-HT2 receptor antagonists to block the syndrome suggests that this behavioral response probably involves the activation of 5-HT1 receptors.

Animals↗