Grand mal convulsive seizures are characterized by the sudden loss of consciousness and motor inhibition, followed by tonic flexion and extension, repetitive clonic movements, and motor relaxation and lassitude. Seizures are elicited in all vertebrates that have been tested. The loss of both vigilance and the defenses of fight or flight incur life-threatening risks to the individual. In evolutionary history, we would expect this behavior to be extinguished. Its persistence prompts the query: What are the benefits of seizures?
Despite the ingrained fear that accompanies each seizure, the repeated induction of grand mal seizures has been clinically accepted for use in patients with severe psychiatric disorders for more than eight decades. Melancholia, mania, catatonia, preoccupation with suicide, and florid psychosis are quickly relieved. Its efficacy and speed sustain its use. How do grand mal seizures relieve intractable psychiatric disorders? What brain or systemic functions are altered by these seizures?
Seizures must be induced repeatedly to yield therapeutic benefit.1,2 Nonconvulsive brain stimulation, as in transcranial magnetic stimulation or vagus nerve stimulation, do not offer comparable benefits. The stimulus of induction, whether chemical (as with pentylenetetrazol [Metrazol] or flurothyl [Indoklon]) or electrical (as in electroconvulsive therapy [ECT]), has little effect on outcome as long as full grand mal seizures are induced.1,2
A single induced seizure is rarely clinically effective. Nor are seizures effective when administered at long intervals. To sustain the benefit, seizures are induced weekly or at greater intervals for four to six months, or longer.1-4
Modifiable clinical syndromes
Diverse behaviors are modified. Although introduced for the relief of psychosis, the first studies reported benefits in catatonia, melancholia, and mania. The breadth of effects is disturbing to clinicians and neuroscientists, because it questions the present classification systems that see these syndromes as unique biological entities.
Melancholia is the disorder of mood, motor, and homeostatic functions. Disturbances in all three dimensions are necessary. These are identified by clinical signs using a depression rating scale, by tests of neuroendocrine functions, and validated by the rapid treatment response to tricyclic antidepressants or ECT.3 Mania and depression occur frequently in patients with melancholia, and both are equally responsive to treatment, which encourages the view that depression and mania are features of a single disorder.5
Catatonia is the motor disorder diagnosed by clinical examination using a catatonia rating scale to identify typical signs, verified by the immediate relief afforded by intravenous benzodazepine, and validated by the rapid treatment response to ECT. Catatonia is found in about 10% of patients admitted to academic psychiatric treatment facilities.4
Labels such as psychotic depression, delirious mania, mixed mania, postpartum psychosis, malignant catatonia, and neuroleptic malignant syndrome identify melancholia and catatonia. Patients are commonly relieved of symptoms within four weeks of treatment.3-5 Trials of ECT in patients with schizophrenia, dysthymia, depression secondary to character pathology, and other disorders defined by DSM criteria have varied results with low predictability of outcome and poor specificity.1
Explanations of how seizures modify behavior are focused on brain structure, brain chemistry, electrophysiology, and neuroendocrinology. An analogy to cardioversion has also been offered.
Brain structure. In the late 19th century, studies of cellular neuropathology found low brain glia amounts in patients with dementia praecox and high amounts in patients with epilepsy. Reports that the psychosis of dementia praecox could be relieved with seizures following accidental head injury or systemic infections excited interest in a possible antagonism between seizures and psychosis. Could seizure induction increase glia? Would such proliferation relieve psychosis?6
The first experiments, in a patient with catatonic schizophrenia in 1934, found chemically induced seizures to be well tolerated. The treatments did relieve his illness, and within a year the safety and efficacy of the treatment were widely heralded.6 The ease and safety of the treatments led to trials in other psychiatric disorders, finding efficacy in manic-depressive illness and relief of suicidal risk.2,3
While glial proliferation was not confirmed at that time, recent experimental studies report hippocampal neurogenesis with increased mossy fibers following induced seizures.7 Both hippocampal cell loss and hypometabolism normalize,3 and levels of brain-derived neurotrophic factors increase with successful treatment.8
Catecholamine enhancement. Studies of psychoactive drugs have focused on the drugs effects on catecholamines and their receptors, especially serotonin and epinephrine in depression and dopamine in psychosis.
The antidepressant effects of seizures led to comparisons with the effects of antidepressant medications.9 Each seizure releases a flood of catecholamines, but systematic studies fail to find associations between these releases and clinical outcome.10
The translation from psychopharmacology to convulsive therapy is even more difficult for the antipsychotic effects that are ascribed to the blockade of dopamine receptors with lowered levels of brain dopamine.1,11 An argument against this formulation is the relief patients with the "on-off phenomenon" of parkinsonism experience, a relief that is accompanied by increased cerebrospinal fluid (CSF) and brain levels of dopamine.12 In patients with clinical psychosis, especially those with positive symptom psychosis (the variety best treated with typical and atypical antipsychotic agents), the benefits following induced seizures are not predicted by the present biochemical theories of antipsychotic drug action.
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