FEATURE ARTICLE
Electroshock Revisited
Electroconvulsive therapy, once vilified, is slowly receiving greater interest and use in the treatment of mental illness
Max Fink
How Does ECT Work?
Why are seizures, which are dangerous and damaging when they occur spontaneously, beneficial when induced experimentally? For the moment scientists have no answer to this question—we simply don't understand how ECT has the restorative capacity that it does. For that matter, no hypothesis for the mode of action of any psychiatric treatment—be it electroshock, psychotropic medicines or the "talk" psychotherapies—is satisfactory.
Explanations for the mechanism of ECT tend to be similar to those used to explain the therapeutic actions of the psychoactive drugs. Most commonly the explanations are focused on the messenger molecules, or neurotransmitters, that pass from one neuron to another. Among the more notable of these molecules are dopamine, serotonin, norepinephrine and gamma-amino-butyric acid (GABA)—neurotransmitters that are typically central to biologically based theories of mental illness. Each of these molecules binds to specific receptors on neuronal-cell surfaces and in turn modifies the activity of these neurons. Psychotropic medicines alter the concentrations of these neurotransmitters and so modify the activity of neurons in certain parts of the brain, most notably those areas believed to play important roles in mental disorders. How the activity of these neurons translates into thoughts and feelings is the big question now facing neuroscientists.
There is a fundamental difficulty with extending the neurotransmitter-based hypotheses to the mechanism of electroshock, however—one that goes beyond the question of how these messenger molecules play a role in the brain. Experiments involving seizures induced in animals and people reveal that so many neurotransmitters are released in what appears to be a random way that it is difficult to construct a cogent theory.
Another theory of electroshock's mechanism involves the observation that the threshold needed to induce a seizure rises during the course of a successful series of treatments. After anesthesia, it is possible to stimulate the brain with different dosages of electric current. By selecting currents that are too low to elicit a seizure and repeating this procedure with incremental energies, a seizure threshold can be defined as that amount of energy that is sufficient to elicit an effective grand mal seizure. If the seizure threshold is defined in subsequent treatments, we observe a gradual rise in seizure threshold. If the energies are kept constant, the duration of the elicited seizure falls. In successful courses of treatment, seizure thresholds are known to rise. The rise in seizure threshold varies with the rise in cerebral blood flow, slowing of EEG frequencies and the antidepressant effects of electroshock.
Some authors conclude that the antidepressant efficacy of electroshock is related to the anticonvulsant activity of repeated seizures, as reflected in the rise in seizure threshold. The anticonvulsant theory is also encouraged by the efficacy of anticonvulsant medicines in relieving mania. However, the theory is weakened by the failure of antidepressant drugs to raise seizure thresholds and the inability of benzodiazepines (anxiolytics such as diazepam) and other anticonvulsant drugs to elicit clinical antidepressant activity.
Despite their weaknesses, theories based on neurotransmitters, their receptor molecules and the anticonvulsant activity of electroshock have the most support today.
There is, however, an alternative hypothesis. We know a great deal about what we must do to achieve ECT's clinical benefits. Seizures induced by chemicals are just as effective as those induced by electricity, indicating that electricity is not essential to our explanation. Neither anesthesia nor the electric current alone nor a single seizure is effective. At one time, memory impairment was an explanation for electroshock's effects, but we now achieve clinical efficacy without memory impairment and conclude that memory loss is not in the therapeutic chain.
We also know that ECT is very broadly effective in relieving mental disorders. It relieves depressed and manic moods, thought disorders and the motor disorders of catatonia and parkinsonism with almost equivalent efficacy. The most effective forms of ECT are those that directly stimulate the structures in the middle of the brain, as evidenced by the path of the electric current. What can we make of these observations? Whatever the mechanism involved, it appears to affect a broad range of systems in the body. And the central parts of the brain seem to play a key role in modulating electroshock's benefits.
This train of thought leads us to the hypothalamus, a region deep in the brain that is known to be involved in the expression of emotions and that has a profound control over the rest of the body through its actions on the pituitary gland. The hypothalamus, the pituitary and the pineal glands in the brain produce peptides that circulate in the bloodstream and the cerebrospinal fluid, affecting other glands in the body (including the thyroid, parathyroid, adrenal, pancreas, ovaries and testes) and other parts of the brain.
The importance of the hypothalamus in mental illness is consistent with the observation that hormonal functions in the mentally ill are wildly disordered. In the severely depressed, the adrenal glands produce too much cortisol, whereas the hypothalamus is inhibited in the release of its hormones and the pituitary functions are chaotic. During a seizure, massive amounts of the brain's hormones are released into the cerebrospinal fluid and into the bloodstream. How could such a release relieve mental disorders?
Consider the following scenario. Each electroshock stimulus is focused on the hypothalamus, eliciting an immediate and large discharge of its hormones. In the ensuing cascade of hormonal effects, the pituitary gland discharges its products, and those, in turn, alter the discharge of cortisol from the adrenal glands. The first effects of the brainstem stimulations are transitory, but by the fourth or fifth stimulus, the normal feedback actions of the hormones of the hypothalamic-pituitary-adrenal axis are again in place. Feeding and sleep become normal, and improvements in motor activity, mood, memory and thought follow quickly.
In treating the mentally ill, the improved endocrine functions persist after a course of treatment, and the patient remains well. At other times, the glands quickly revert to their abnormal activities, and the mental disorder is again evident. In such cases, continuation ECT is needed to sustain normal glandular functions and a normal mental state.
How the rush of hormones resets the endocrine balance is not known. I propose that the brain secretes a hormone-like substance that regulates mental functions. Unfortunately, research into such a relation is not encouraged by government agencies, which are wary of the public's apprehension toward electroshock. The pharmaceutical industry tends to follow a safe course of finding "me-too" substances that can be marketed, and academic leaders often perceive ECT research as academically incorrect. Nevertheless, the broad efficacy of electroshock warrants greater attention to its therapeutic mechanism and to a campaign of education that will encourage its use for the many mentally ill who are poorly served by other therapies.
Bibliography
- Abrams, R. 1997. Electroconvulsive Therapy. New York: Oxford University Press.
- Fink, M. 1979. Convulsive Therapy: Theory and Practice. New York: Raven Press.
- Fink, M. 1990. How does convulsive therapy work? Neuropsychopharmacology 3:73–82.
- Fink, M. 1999. Electroshock: Restoring the Mind. New York: Oxford University Press.
- Freeman, H. 1999. Taking the horror out of shocks. Nature 401:327. [CrossRef]
- Satcher, David. 1999. Mental Health: A Report of the Surgeon General. http://www. surgeongeneral.gov/library/mentalhealth/ home.html
