Relationship of seizure duration to antidepressant efficacy in electroconvulsive therapy

BACKGROUND: Aprotinin and epsilon-aminocaproic acid are routinely used to reduce bleeding during cardiac surgery. The marked difference in average wholesale cost between these two drug therapies (aprotinin, $1,080 vs. epsilon-aminocaproic acid, $11) has generated significant controversy regarding their relative efficacies and costs. METHODS: In a multicenter, randomized, prospective, blinded trial, patients having repeated cardiac surgery received either a high-dose regimen of aprotinin (total dose, 6 x 10(6) kallikrein inactivator units) or epsilon-aminocaproic acid (total dose, 270 mg/kg). RESULTS: Two hundred four patients were studied. Overall (data are median [25th-75th percentiles]), aprotinin-treated patients had less postoperative thoracic drainage (511 ml [383-805 ml] vs. 655 ml [464-1,045 ml]; P = 0.016) and received fewer platelet transfusions (0 [range, 0-1] vs. 1 [range, 0-2]; P = 0.036). The surgical field was more likely to be considered free of bleeding in aprotinin-treated patients (44% vs. 26%; P = 0.012). No differences, however, were seen in allogeneic erythrocyte transfusions or in the time required for chest closure. Overall, direct and indirect bleeding-related costs were greater in aprotinin- than in epsilon-aminocaproic acid-treated patients ($1,813 [$1,476-2,605] vs. $1,088 [range, $511-2,057]; P = 0.0001). This difference in cost per case varied in magnitude among sites but not in direction. CONCLUSIONS: Aprotinin was more effective than epsilon-aminocaproic acid at decreasing bleeding and platelet transfusions. Epsilon-aminocaproic acid, however, was the more cost-effective therapy over a broad range of estimates for bleeding-related costs in patients undergoing repeated cardiac surgery. A cost-benefit analysis using the lower cost of half-dose aprotinin ($540) still resulted in a significant cost advantage using epsilon-aminocaproic therapy (P = 0.022).     

Neurobiological mechanisms involved in antidepressant therapies

Selective serotonin reuptake inhibitors (SSRIs) are effective in alleviating the symptoms of depression. However, clinical improvement is only obtained after several weeks of treatment. SSRIs, when administered acutely to animals, have little effect on synaptic levels of serotonin. This suggests the existence of one or more regulatory mechanisms controlling serotonergic neurotransmission. The firing rate of dorsal raphe serotonergic neurons is under the control of somatodendritic 5-hydroxytryptamine 1A (5-HT1A) autoreceptors, the release of serotonin from nerve terminals is under the control of 5-HT autoreceptors (5-HT1B subtype in rodents, 5-HT1D in other species), whereas the control of the activity of tryptophan hydroxylase, the rate-limiting enzyme of serotonin synthesis, is complex, involving 5-HT1A but possibly other 5-HT receptors including the 5-HT1B/D subtype. During prolonged administration with a SSRI, these three feedback systems become desensitized and their regulatory effects on serotonergic neurotransmission are weakened or lost. This has the effect of allowing the synaptic levels of serotonin to rise with a consequently increased stimulation of one or more types of postsynaptic 5-HT receptor. Thus, it is only after prolonged administration that the pharmacological activity of SSRI is fully expressed in terms of synaptic serotonin levels. This may explain the latency of antidepressant action seen with these drugs in humans. Various other classes of antidepressant therapies (tricyclic antidepressants and monoamine oxidase inhibitor drugs, electroconvulsive therapy) have long-term effects on one or more of the feedback mechanisms such that an increase in synaptic concentrations of serotonin may be a common mechanism of many antidepressant therapies.     

Buspirone augmentation of antidepressant therapy

Thirty outpatients meeting DSM-III-R or DSM-IV criteria for major depression, single or recurrent episode, and failing to respond to an adequate trial of an antidepressant (>6 weeks at recommended dosage) received buspirone (20-30 mg/day) for 4 or 5 weeks in addition to their existing antidepressant. Of the 22 patients who had buspirone added to their selective serotonin reuptake inhibitor antidepressant regimen (fluoxetine, paroxetine, or citalopram), 59% (13/22) showed complete or partial remission of their depressive symptomatology. Similarly, 63% (5/8) of patients treated with buspirone in addition to clomipramine showed complete or partial remission. The mean score on the Clinical Global Impressions Scale fell by 64% (from 4.7 to 1.7; p < 0.0001) in treatment responders (complete and partial). No serious side effects were observed during combination therapy. Seventy-nine percent (11/14) of initial responders (both complete and partial) who remained on augmentation therapy for at least 4 months were symptom-free at follow-up. Buspirone augmentation may produce marked clinical improvement in depressed patients who are initially unresponsive to standard antidepressant therapy.     

Use of EEG in electroconvulsive therapy

BACKGROUND: From the point of view of time we can divide the use of EEG in the electroconvulsive therapy into 1) screening before starting the treatment, 2) the EEG correlates of the ECT: recording of the paroxysm, immediate postparoxysmal recording, interparoxysmal recording during a series of ECT, and persistent changes after finishing the series of ECT. METHODS AND RESULTS: EEG screening has shown that the patients with abnormal EEG do not respond well to ECT. In the recording of the paroxysm EEG correlates with therapeutic effect of ECT are looked for--particularly the length of the paroxysm on the EEG, intensity and pattern of the paroxysmal activity, and the suppression of the EEG curve in the terminal part of the paroxysm. The suppression models are in the focus of interest also in the immediate postparoxysmal recording. In the interparoxysmal recordings during a series of ECT the associations of the generalised slowing in the range of the theta and delta activity with the therapeutic effect were looked for, particularly in the past. Persistent changes after finishing the ECT are usually examined especially to look if ECT does not cause persistent abnormalities of the EEG recording which would be an evidence for brain damage or for epileptic kindling. The results in this direction have been negative so far.     

History of electroconvulsive therapy in the United States in the last decades

Despite its acknowledged efficacy and safety in the treatment of patients with severe affective and psychotic illnesses, as well as extensive efforts at professional and public education, electroconvulsive therapy is a neglected treatment, its use in the U.S. being mainly restricted to academic and private hospitals. Widespread use between 1935 and 1960, a rapid decline following the introduction of psychoactive drugs, and a slow resurgence in clinical interest since 1975 characterizes its history. The use of ECT has been encouraged by repeated favorable evaluations and by new procedures which improve both its efficacy and its safety. The experience in the United States provides a lesson for other nations where its use is inhibited.     

Successful electroconvulsive therapy of Cotard syndrome with bitemporal hypoperfusion

A case study is presented to illustrate a rare condition described by Cotard as "délire de négation". The central symptom is a nihilistic delusion with denial of one's own existence of oneself and that of the external world. In the present case, the syndrome became manifest as an escalation of a recurrent depressive disorder late in life. After initial resistance to therapy, the syndrome was successfully treated with electroconvulsive therapy. For the first time, we report the regional cerebral blood flow measured by 99mTc-HMPAO-SPECT before and after therapy. Before treatment, significant bitemporal hypoperfusion relative to the cerebellum was found, which was no longer demonstrable on remission.     

Psychophysical correlates of intratympanic reflex action.

A review is presented of research on the intratympanic muscle reflexes. Among topics covered are a discussion of the methods employed for observation of reflex action, discussion of the natural protection against traumatic noise afforded by the reflexes and its limitation, and discussion of various types of stimulation (especially acoustic and cutaneous) which may be used to elicit the reflexes. Also described are possible practical uses of artificial reflex elicitation to provide enhanced protection against noise and for certain kinds of clinical diagnosis. Implications for damage risk criteria and for certain areas of psychological and physiological research are discussed. (25 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

A successful treatment of drug-resistant depression with electroconvulsive therapy

A woman aged 56 had been treated at the age of 23 for a psychotic depression with vital characteristics in the context of a bipolar disorder. The treatment included electroconvulsive therapy (ECT). From the age of 47, she suffered relapses; drug treatment proved inadequate. For the last 3 years, ECT was administered, which resulted in a good condition. ECT is an effective treatment in patients with depression resistant to medication. However, in spite of continuation pharmacotherapy, the proportion of patients relapsing within 6 months after successful ECT is large. For these patients, continuation ECT may be an efficacious method.     

Incidence of asystole in electroconvulsive therapy in elderly patients

We hypothesize that selective brain cooling (SBC) can occur in hyperthermic humans despite the fact that humans have no carotid rete, a vascular structure that facilitates countercurrent heat exchange and that is located at the base of the skull in some mammals. We postulate that an increase in emissary and angular ocular venous flows contributes to SBC. The efficiency of SBC is increased by evaporation of sweat on the head and by ventilation through the nose. A body position that increases the intravenous pressure gradient across the skull increases emissary flows and hence enhances the efficiency of SBC. The validity of using tympanic temperature as an index of brain temperature is also postulated.     

Dexmedetomidine failed to block the acute hyperdynamic response to electroconvulsive therapy

BACKGROUND: Orally administered clonidine (0.2-0.3 mg) has been reported to decrease the acute hypertensive response to electroconvulsive therapy (ECT) without prolonging early recovery. This preliminary study was designed to evaluate the acute hemodynamic effects of the investigational alpha2-adrenergic agonist, dexmedetomidine, in patients undergoing a series of ECT treatments. METHODS: Six patients undergoing a series of three to six consecutive ECT treatments were studied according to a randomized, double-blind, placebo-controlled protocol All patients received either saline or dexmedetomidine, 0.5 or 1.0 microg/kg intravenously, 10-30 min before induction of anesthesia for ECT using a standardized anesthesia protocol. In addition to assessing the cardiovascular variables, the duration of seizure activity, degree of sedation, and time to discharge from the Phase I recovery unit were assessed. RESULTS: Although dexmedetomidine produced dose-related increases in the level of sedation before the ECT procedure, it failed to decrease the peak blood pressure and heart rate responses after the ECT treatment. The 0.5 and 1.0 microg/kg doses of dexmedetomidine prolonged the times to orientation and to discharge from the Phase I unit. CONCLUSIONS: The results of this pilot study suggest that dexmedetomidine (0.5-1.0 microg/kg given intravenously) is not beneficial in controlling the acute hyperdynamic response after ECT.     

The ictal electroencephalogram as a marker for the efficacy of electroconvulsive therapy

The question of how to define a therapeutically adequate electroconvulsive therapy (ECT) has been under discussion since the early days of ECT. Although convention has asserted a demand for minimum seizure times, the complex electrophysiological conditions involved in developing a generalized seizure make it problematic for therapeutic efficacy of ECT to be linked only with seizure duration. Within the framework of an open clinical study of 40 patients, selected parameters of the ictal electroencephalogram (EEG) have now been examined with respect to differentiation between therapeutically effective and ineffective treatments. For this purpose a rating scale covering both quantitative and qualitative features of the ictal EEG was used. Although this study recorded no correlations between seizure duration and clinical improvement, correlations were established between clinical improvement, on the one hand, and the frequency of epileptic discharges and their slowing during the spike-wave phase as well as the stereotypy of the discharge or a "stable" pattern of rhythmic spike-wave or sharp wave complexes, on the other. The results suggest that several of these EEG parameters might be combined to form a marker for therapeutically adequate ECT, and that treatment might be controlled accordingly.     

Is electroconvulsive therapy unsuitable for children and adolescents?

Electroconvulsive therapy (ECT) as a treatment option for adults with affective disorders has a long history. ECT with children and adolescents, however, has not been widely used, and no empirical studies or controlled evaluations have been conducted. A review of the literature on ECT with minors reveals that it has an unknown mechanism of action, with a domain of applicability diminished yearly by legislation, litigation, and a wide range of intervention alternatives.     

Autobiographical memory and mood: Effects of electroconvulsive therapy.

An Autobiographical Memory Interview (AMI) was administered to 75 depressed inpatients and 16 nondepressed controls. Patients were randomized to 1 of 4 forms of electroconvulsive therapy (ECT) that varied in electrode placement and stimulus intensity. Short-term retrograde amnesia was assessed during the week following the randomized phase. Bilateral ECT produced more marked deficits than right unilateral ECT. At a 2-mo follow-up, persistent amnesic deficits were related to having received a second ECT course and, to a lesser extent, bilateral ECT during the randomized phase. The magnitude of clinical improvement was not associated with amnesia scores at either time point. There were no differential amnesic effects as a function of the affective valence of memories. It appears that retrograde amnesia for autobiographical information after ECT and mood congruence effects on recall are independent phenomena. The magnitude and persistence of retrograde amnesia is related to how ECT is performed and not to changes in clinical state or the affective valence of memories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)