Initial Seizure Threshold Research Articles

Guideline Watch: Practice Guideline for the Treatment of Patients With Major Depressive Disorder, 2nd Edition

Since the publication in 2000 of APA’s Practice Guideline for the Treatment of Patients With Major Depressive Disorder (2nd Edition) (1), two important safety concerns have emerged (hepatotoxicity with nefazodone, and suicide risk and antidepressants), and two new antidepressants have been approved for use (escitalopram and duloxetine). This watch describes these developments as well as evidence that has accrued since 2000 in other areas related to the treatment of major depressive disorder.

Augmentation of Electroconvulsive Therapy Seizures With Sleep Deprivation

Electroconvulsive therapy (ECT) is the fastest and most effective treatment for severe or treatment-resistant affective and psychotic disorders. Its therapeutic effect is obtained through a generalized tonic-clonic seizure of adequate duration. Several factors (older age, male gender, and the sessions of ECT themselves) increase seizure threshold and reduce seizure time. In our work, sleep deprivation was used as a strategy to enhance the ECT seizure. A matched sample design was conducted on the basis of the following variables: gender, age range, and seizure threshold. After the first ECT, when the initial seizure threshold was measured, subjects were assigned to ECT (electroconvulsive therapy) or SD+ECT (sleep deprivation + electroconvulsive therapy). Changes in the variable of seizure threshold were studied in both groups during the treatment course. A nonparametric analysis was implemented for 2 independent groups. During the treatment course, the SD+ECT group showed a decreased seizure threshold, from 190.4 mC in the first ECT session to 176.4 mC in the last ECT session, whereas the ECT group showed an increased seizure threshold, increasing from 190.4 mC to 321.91 mC. Sleep deprivation is an effective and safe technique used to lower the seizure threshold of ECT and to obtain an adequate seizure time without increasing the energy applied.

Induction agents in electroconvulsive therapy: a comparison of methohexitone and propofol

Aims and MethodTo compare methohexitone and propofol in electroconvulsive therapy (ECT). A retrospective within-subject comparison was made of the use of these drugs in separate courses of bilateral ECT in one clinic over 10 years. Patients taking mood stabilising or anti-epileptic drugs were excluded. The initial seizure threshold and seizure duration were of particular interest.ResultsThe median initial seizure thresholds were identical (75 mC). The median initial seizure duration with threshold stimulation was 25% shorter with propofol (21v.28 s). The median total numbers of treatments in the courses were identical (eight treatments).Clinical ImplicationsThe shorter seizure duration observed with propofol was not associated with a commensurate rise in the initial seizure threshold. The shorter seizure duration may therefore have no effect on the therapeutic efficacy of treatment.

ECT use delayed in the presence of comorbid mental retardation: a review of clinical and ethical issues.

The objective is to develop a clinically and ethically supportive literature for the use of electroconvulsive therapy (ECT) in patients with mental retardation who are concurrently experiencing a significant psychiatric illness. A review of both the clinical and ethical literature using traditional, manual library methods and the Medline and Psychlit databases was undertaken. In addition, a record of all patients who had undergone ECT at our facility between 1995 and 2000 was examined for patients with comorbid mental retardation. We found that the use of ECT for people who have both a psychiatric illness and comorbid mental retardation was significantly delayed. However, a rapid response to index, continuation, and maintenance ECT was also noted. Further, this response occurred with routine ECT administered irrespective of age, gender, diagnosis, stimulus parameters, electrode placement, or number of treatments. In addition, the successful use of right-sided unilateral ECT at six times the initial seizure threshold was reported in a patient who had previously responded to bilateral ECT. A cogent ethical justification was developed with the use of the rule of double effect. We concluded that for patients who have mental retardation and who subsequently develop a psychiatric illness, ECT is delayed and left as a treatment of last choice. Although the literature is sparse and uncontrolled, a cogent clinical and ethical justification may help negotiate these and other delays.

Relationships between seizure duration and seizure threshold and stimulus dosage at electroconvulsive therapy: implications for electroconvulsive therapy practice.

Recent studies cast doubt on the usefulness of seizure duration as an index for stimulus dosage adjustment at electroconvulsive therapy (ECT). A retrospective analysis on the relationships between seizure duration and seizure threshold and stimulus dosage was performed for 54 patients who received a standardized ECT dose titration and treatment protocol. Subjects receiving stimulus dosage at seizure threshold had a highly variable motor seizure duration, ranging from 15 to 89 s, and 7.4% of subjects had seizures longer than 60 s. Regression analysis showed that initial seizure threshold and height were independent predictors of motor seizure duration during dose titration and accounted for 34% of its variance. Stimulus dosage was increased by 40-67% between the first and second ECT session; however, 60% of subjects had no lengthening of seizures and motor seizure duration was significantly shorter at the second treatment (mean +/- SD: 35.7 +/- 12.3 vs 31.0 +/- 10.6 s; paired t = 2.9, d.f. = 34, P = 0.006). At the first and second ECT treatment, motor seizure duration was significantly related to stimulus dosage (r = -0.45 and r = -0.41, respectively). Given the negative correlation between seizure duration and stimulus intensity, a policy that recommends an increase of stimulus dosage and its reduction for patients with short and long seizures, respectively, does not necessarily result in 'optimal' seizure duration. A better dosing policy that places less emphasis on seizure duration is proposed.

Initial seizure threshold of bilateral electroconvulsive therapy in Chinese.

This preliminary study examined the initial seizure threshold for bilateral electroconvulsive therapy (ECT) in Chinese and the correlates of this seizure threshold. Fifty-four patients underwent stimulus dose titration in a standardized protocol. The mean initial seizure threshold was 117 mC (range 48-403 mC). Stepwise regression analysis showed that age, body mass index, and gender were independently related to seizure threshold and accounted for 36, 7, and 6% of its variance, respectively. Determination of a relationship between gender and seizure threshold was limited by the higher starting electrical dosage in men. This preliminary study suggests that the seizure threshold for bilateral ECT in Chinese is comparable with that in the Western population. Our finding that body mass index is related to seizure threshold has not been reported previously. We also propose several differences between bilateral and unilateral ECT in the determinants of seizure threshold.

Seizure threshold rise during electroconvulsive therapy in schizophrenic patients

A rise in seizure threshold during a course of electroconvulsive therapy (ECT) has been demonstrated in patients with depression and mania, but no information has been available as to whether the same result occurs in schizophrenia. Ninety-three patients with schizophrenia underwent estimation of the seizure threshold by the dose-titration method, at the first and second, seventh, fourteenth, and twentieth treatments over an index ECT course. The 3-week stabilization period was used as a response criterion. Eighty-six patients (92%) showed a rise in threshold. The magnitude of increment was 269±244%. The rise in seizure threshold could be predicted by the number of treatments, initial seizure threshold and EEG seizure duration, and these factors explained 42% of the variance.

The effect of repeated bilateral electroconvulsive therapy on seizure threshold.

Seizure threshold was measured by empirical titration in 28 patients referred for bilateral electroconvulsive therapy to treat depressive illness at the outset of treatment and after another six treatments. No patient was given antiepileptic drug treatment, and anesthetic technique and concomitant psychotropic drug treatment were fixed. The average (+/- SD) initial seizure threshold measured by set charge was 79.5 mC (+/- 33.4 mC), and this increased to 95.5 mC (+/- 37.9 mC). The average percentage increase was 22.8% (95% confidence interval, 13.7% to 31.8%). The seizure threshold measured by set charge did not change in 15 patients (54%), and there was no significant relation between change in seizure threshold and patient sex, change in seizure duration measured by cuff technique, or global clinical improvement during the course of treatment.

Initial Seizure Threshold in the Clinical Practice of Bilateral Electroconvulsive Therapy in Edinburgh, Scotland

Initial seizure threshold was measured by empirical titration in 137 patients referred for bilateral electroconvulsive therapy (ECT) for the treatment of depressive illness. Treatment was given by an Ectron Series 5A ECT machine. The median and modal thresholds were 75 mC and the range was 50-200 mC. The only statistically significant relationship among initial threshold and age or gender was the correlation of age with threshold in men (rho = 0.46, p < 0.01). All patients (n = 22) younger than 30 years had an initial threshold < 100 mC, but age and gender did not predict threshold accurately for older men or women.

Effects of electroconvulsive therapy on plasma vasopressin and oxytocin

Background: Animal studies suggest that vasopressin has cognitive-enhancing properties and oxytocin may have amnestic effects. A clinical report suggests that the acute increase in oxytocin-associated neurophysin predicts clinical response to electroconvulsive therapy (ECT) in depressed patients. Methods: Medication-free patients with major depression were randomized to receive right unilateral or bilateral ECT administered with electrical stimulus intensity at either just above seizure threshold or at 150% above seizure threshold. The associations between plasma vasopressin, oxytocin, ECT treatment parameters, clinical outcome, and cognitive effects were assessed. Results: The sample comprised 55 patients. At the second ECT, patients receiving ECT at 150% above initial seizure threshold had significantly greater increases in plasma vasopressin than patients receiving low-dose ECT ( ps < .01–.04), with no effects of electrode placement. At the second and ninth ECT treatments, the vasopressin or oxytocin surges were not associated with clinical improvement, seizure duration, time to orientation, or memory test performance. There were inverse trend-level associations between the acute surge in oxytocin levels at the ninth ECT and clinical response, contradicting a report in the literature. Conclusions: Overall, these findings do not support the hypothesis that diencephalic seizure propagation is central to the mechanism of action of ECT.

Initial seizure threshold in bilateral electroconvulsive therapy

The extent to which electrical dose exceeds the seizure threshold is an important determinant of the efficacy of electroconvulsive therapy (ECT) but seizure thresholds have not before been evaluated using an ECT machine made in the UK. In this study seizure threshold was empirically titrated at the outset of bilateral ECT given to 100 consecutive depressed patients treated with an Ectron Series 5A ECT machine. No patient received anti-epileptic drugs. Men and women under 30 years of age (n=14) had low thresholds and men of 60 years or more (n=3) had high thresholds. Seizure thresholds varied at least threefold among other groups, suggesting that empirical titration may be desirable for most patients treated by bilateral ECT.

Seizure threshold in electroconvulsive therapy (ECT) II. The anticonvulsant effect of ECT

To measure the anticonvulsant effects of a course of electroconvulsive therapy (ECT), we used a flexible stimulus dosage titration procedure to estimate seizure threshold at the first and sixth ECT treatments in 62 patients with depression who were undergoing a course of brief pulse, constant current ECT given at moderately suprathreshold stimulus intensity. Seizure threshold increased by approximately 47% on average, but only 35 (56%) of the 62 patients showed a rise in seizure threshold. The rise in seizure threshold was associated with increasing age, but not with gender, stimulus electrode placement, or initial seizure threshold. Dynamic impedance decreased by approximately 5% from the first to the sixth ECT treatment, but there was no correlation between the change in dynamic impedance and the rise in seizure threshold. No relation was found between the rise in seizure threshold and either therapeutic response status or speed of response to the ECT treatment course. These findings confirm the anticonvulsant effect of ECT but suggest that such effects are not tightly coupled to the therapeutic efficacy of moderately suprathreshold ECT.

Seizure threshold in electroconvulsive therapy: I. Initial seizure threshold

We measured initial seizure threshold by means of a structured stimulus dosage titration procedure in a clinical sample of 111 depressed patients undergoing brief-pulse, constant-current electroconvulsive therapy (ECT). Initial seizure threshold was approximately 60 millicoumbs (mc) (10 Joules) on average, but varied widely (6-fold) across patients. Initial seizure threshold was predicted by four variables: electrode placement (higher with bilateral), gender (higher in men), age (higher with increasing age), and dynamic impedance (inverse relationship). Use of neuroleptic medication was associated with a lower seizure threshold. EEG seizure duration was inversely related to initial seizure threshold, but no other relations with seizure duration were found. These findings may have important clinical implications for stimulus dosing strategies in ECT.

Propylene glycol as a drug solvent in pharmacologic studies

Pharmacologic activity of propylene glycol (PG) was evaluated, using several procedures commonly employed in drug screening. Acute pretreatment of mice with 2.08 g/kg of PG (equivalent to administration of 0.01 ml/g of a 20% solution) produced a significant elevation in initial clonic seizure threshold to iv infusion of pentylenetetrazol, not apparent with this dose when a single CD99 dose of convulsant was used. Parallel results were obtained at higher doses of PG vs. strychnine convulsions. Potentiation of hexobarbital sleeping time was observed at doses of PG below the TD50 of 5.77 g/kg. Higher doses decreased spontaneous motor activity. Subchronic administration of PG did not alter hexobarbital sleeping time subsequently determined, but did diminish diphenylhydantoin anti-MES (maximal electroshock seizure) activity. Thus, at cosolvent concentrations which might be employed in animal experiments, PG exhibits weak but significant CNS depressant activity as well as strychnine, pentylenetetrazol, tremorine, and oxotremorine antagonist action. There-fore, use of PG as an “inert” cosolvent in pharmacologic studies cannot be recommended when the ip route is employed.