Electroconvulsive therapy plays an irreplaceable role in treatment of major depressive disorder

Major depressive disorder is a serious and common neuropsychiatric disorder that affects more than 350 million people worldwide. Electroconvulsive therapy is the oldest and most effective treatment available for the treatment of severe major depressive disorder. Electroconvulsive therapy modifies structural network changes in patients with major depressive disorder and schizophrenia. And it can also affect neuroinflammatory responses and may have neuroprotective effects. Electroconvulsive therapy plays an irreplaceable role in the treatment of major depressive disorder.     

An alternative mechanism of actions for neuroleptic and antidepressant drugs

It has earlier been proposed by the author that the aetiology of schizophrenic symptomatology may be due to the presence of abnormally connected interhemispheric fibres which link specialised functions in the brains of schizophrenics that are not connected in normal subjects, and that the neuroleptic drugs may produce their action through a local anaesthetic-like effect in suppression of conduction in these fibres. This line of thought has been extended here to consider the possible mechanism of action of the neuroleptic drugs in more detail, as well as that of the tricyclic antidepressant drugs which are derivatives of the phenothiazine group. Pharmacological similarities with the local anaesthetics both structurally and functionally have been considered, as well as the effects that these drug groups may have in common with the lithium salts. It has been suggested that these drugs all produce their primary effect on cell membranes, though not necessarily at the synapse, that the time course of their clinical effect may correlate with their incorporation into various cell membranes within the CNS, and that they may thus bring about a fundamental alteration in cell membrane microstructure. The possible role of electroconvulsive therapy has also been considered. The corollary of this argument is that the affective disorders may be genetically determined diseases of cell membrane microstructure.     

Effectiveness of electroconvulsive therapy in community settings.

BACKGROUND: Clinical trials indicate that electroconvulsive therapy (ECT) is the most effective treatment for major depression, but its effectiveness in community settings has not been examined. METHODS: In a prospective, naturalistic study involving 347 patients at seven hospitals, clinical outcomes immediately after ECT and over a 24-week follow-up period were examined in relation to patient characteristics and treatment variables. RESULTS: The sites differed markedly in patient features and ECT administration but did not differ in clinical outcomes. In contrast to the 70%-90% remission rates expected with ECT, remission rates, depending on criteria, were 30.3%-46.7%. Longer episode duration, comorbid personality disorder, and schizoaffective disorder were associated with poorer outcome. Among remitters, the relapse rate during follow-up was 64.3%. Relapse was more frequent in patients with psychotic depression or comorbid Axis I or Axis II disorders. Only 23.4% of ECT nonremitters had sustained remission during follow-up. CONCLUSIONS: The remission rate with ECT in community settings is substantially less than that in clinical trials. Providers frequently end the ECT course with the view that patients have benefited fully, yet formal assessment shows significant residual symptoms. Patients who do not remit with ECT have a poor prognosis; this underscores the need to achieve maximal improvement with this modality.     

Evidence that the enhancement of dopamine function by repeated electroconvulsive shock requires concomitant activation of D1-like and D2-like dopamine receptors

In this study, the behavioural response to dopamine D₁-like receptor agonists (SKF 38393, SKF 81297 and SKF 77434) and D₂-like receptor agonists (quinpirole and RU 24213), administered alone and in combination to rats treated repeatedly with electroconvulsive shock (five ECS over 10 days) or sham, was tested. Agonist-induced behaviour was monitored by automated activity meters and direct observation using a checklist scoring method. Repeated ECS (compared to sham controls) had no significant effect on the behavioural response to SKF 38393 (7.5 mg/kg SC), SKF 81297 (0.2 mg/kg SC), SKF 77434 (0.1 mg/kg SC), quinpirole (0.1 and 0.25 mg/kg SC) or RU 24213 (0.3 mg/kg SC), when administered alone. In contrast, repeated ECS markedly increased locomotion (activity counts and scores) induced by the non-selective dopamine agonist apomorphine (0.5 mg/kg SC) and by co-administration of a D₁-like agonist plus a D₂-like agonist [SKF 38393 (7.5 mg/kg SC) plus quinpirole (0.25 mg/kg SC), SKF 81297 (0.2 mg/kg SC) plus quinpirole (0.1 mg/kg SC), and SKF 77434 (0.1 mg/ kg SC) plus RU 24213 (0.3 mg/kg SC)]. This ECS-induced enhancement of dopamine-mediated behaviour was observed for up to 3 weeks after cessation of ECS treatment. In addition, ECS also enhanced the locomotor response to intra-accumbens SKF 38393 plus quinpirole (0.4 and 1.0 μg/side, respectively). These results provide evidence that the enhancement of dopamine function by repeated ECS requires concomitant stimulation of both D₁-like and D₂-like receptors, and that this effect is long-lasting. Received: 24 January 1997 /Final version: 5 March 1997     

Reduction of ECS produced retrograde amnesia by post-trial introduction of strychnine

Strychnine sulfate was used to reduce the amount of retrograde amnesia induced by electroconvulsive shock (ECS). Male Swiss-Webster mice were trained on the step-down passive avoidance task, given ECS and then injected intraperitoneally with either 0.1 mg/kg strychnine or saline. The animals were tested in the apparatus one to twenty-four hours later. Mice given ECS alone displayed partial memory for the training (by responding with longer latencies) if tested within two hours after training, but did not display retention twenty-four hours later. Animals given strychnine following ECS had significantly longer step-down latencies at twenty-four hours than did the saline or no injection controls. Further experiments replicated the basic results, and also showed that strychnine injections delayed two hours after the training trial attenuated ECS-induced retrograde amnesia, but that a three hour injection delay was ineffective. The results were interpreted in terms of changes in short-term and long-term memory.     

Autonomic Correlates of Depression and Clinical Improvement Following Electroconvulsive Shock Therapy

Electrodermal responses (EDRs) and heart rate (HR) were recorded during a variety of tasks from 20 hospitalized depressed patients before and after a series of electroconvulsive shock treatments (ECTs). The depressed patients, compared to nondepressed controls during the pre-ECT test, exhibited lower skin conductance levels, smaller phasic skin conductance responses with longer latencies, higher tonic HR, and smaller HR changes to stimuli. This response pattern suggests a complex state of “environmental rejection” coupled with “low arousal” in the depressed patients. Certain EDR measures were related to the severity of depressive symptomatology while tonic HR was related to the agitation/retardation symptoms. Patients who subsequently responded well following ECT were more like the controls on certain pre-treatment measures than those who failed to respond favorably. There were little EDR or HR changes following ECT and what changes did occur were unrelated to differences in clinical improvement. It was suggested that, despite temporary clinical improvement following ECT, depressed patients have a chronic affective disorder which is reflected in the EDR and HR measures.     

ECS produced disruption or facilitation of discriminated active avoidance performance in rats

Two experiments investigated the effect of electroconvulsive shock on the performance of a one-way active avoidance response. In the first experiment it was found that if the response was learned under scopolamine, ECS given prior to relearning failed to produce a deficit. The second experiment demonstrated that ECS facilitated relearning of a response trained to a low criterion level while it disrupted performance of a response trained to a strict criterion. These results support other indications that Deutsch's memory model has predictive value for proactive effects of ECS on relearning (retrieval).     

Chlorimipramine,electroconvulsive shock and combination thereof: Differential effects of chronic treatment on apomorphine-induced behaviours and on striatal and mesocortical dopamine turnover

Summary We studied the influence of different pretreatment regimens (Chlorimipramine-Cmi, electroconvulsive shock-ECS, and Cmi+ECS all regimens being applied for either 2 or 15 days) on the open field behaviour, on the striatal and on the prefrontal dopamine-PFC DA turnover in rats injected with either apomorphine-AP 25 g/kg (stimulating presynaptic DA receptors), AP 200 g/kg (stimulating postsynaptic DA receptors), or vehicle (control).In the controls, AP 25 g/kg reduced the locomotor activity and the striatal, but not the PFC DA turnover. AP 200 g/kg increased the locomotor activity and reduced the striatal but not the PFC DA turnover.Short-term pretreatment: ECS and Cmi+ECS prevented the decrease of striatal DA turnover after AP 25 g/kg. No other influence of any pretreatment on behaviour or DA-turnover became significant.Long-term pretreatment: Chronic Cmi: marginally increased the open field behaviour and marginally decreased the PFC DA turnover; significantly increased the effect of AP (200 g/kg) on striatal DA turnover and the effect of AP (25 and 200 g/kg) on PFC DA turnover. Repeated ECS: decreased locomotion and rearing and increased PFC DA turnover; increased the effect of AP (200 g/kg) on locomotion and on striatal DA turnover; decreased the effect of AP (25 and 200 g/kg) on PFC DA turnover.Chronic Cmi+ECS: decreased locomotion and rearing and marginally decreased PFC DA turnover; increased the effect of AP on hyperlocomotion and on striatal DA turnover. No other influence of any chronic pretreatment on behaviour or on DA turnover became significant.The data support the view that chronic AD therapies increase DAergic functions related to postsynaptic rather than to presynaptic structures. It is suggested that the different effects of chronic Cmi and repeated ECS on AP-evoked PFC DA turnover help to understand the different influences exerted by both treatments on rats' behaviour.