The Problem of “Intractable” Depression

It’s useful to know that something does work.

Posted Feb 15, 2016

They are a familiar sight in any psychiatrist’s office, patients who are deeply sad without being able to say why. They may move and think more slowly than usual. And they have lost the capacity for joy, the ability to experience pleasure. They may even have started asking, “What’s the point?”

This is a description of serious depression, or melancholic depression; the term draws on the classical – and still perfectly valid – description of serious depression as “melancholia.”

So-called “antidepressants,” meaning Prozac and its cousins, are not highly effective in dealing with serious depression. The SSRI antidepressants are being touted now for just about everything under the sun. But experienced clinicians would probably not expect much of a benefit in melancholia. 

So the patients don’t get better, unless they recover spontaneously. Given that depressions usually improve on their own within eight months, if the patient survives, nature herself is a powerful healer. But until that happens, the depression is considered “treatment non-responsive,” or intractable, meaning that the patients don’t respond to Prozac and its cousins.

Actually, “treatment non-responsive depression” really means “undertreated depression.”  Historically, melancholic depression has known some powerful treatments, and while I am not necessarily arguing that all of these should be revived, it’s useful to know that something does work.

Since Antiquity, opium has been used in the treatment of serious depression. It is surprisingly effective – just as narcotic medications have potential wide applicability in psychiatry – and opium experienced a huge revival in the nineteenth century once its alkaloid morphine became injectable. It has the downside, of course, of potential addictiveness. I am not advocating that it be reintroduced, given the alternatives we currently possess. But it's out there.

Earlier generations of antidepressant medication were arguably more effective than Prozac and its cousins (for details see my book How Everyone Became Depressed).  We’re talking about the inhibitors of the enzyme monoamine oxidase (called MAOI inhibitors), and the tricyclic antidepressants (TCAs), introduced in 1957 as the first real antidepressants, and they do work so we don’t need to put ironical quotation marks around the term.

The antipsychotics may confer a considerable benefit in serious depression. The first antipsychotic, called chlorpromazine (Largactil in Canada and Europe, Thorazine in the US), debuted in 1952, was widely used as an antidepressant. Same story for many of the later antipsychotics.

Is the list over (aside from exercise therapy and psychotherapy)? No, it’s not over.  There’s one more item.

Electroconvulsive therapy, also called ECT, or shock therapy -- using electricity to induce a therapeutic seizure of about 30 seconds in the brain -- is safe and effective and counts as the most powerful treatment that psychiatry has on offer. Over 80 percent of patients with melancholic depression respond to it (no medication has anything like that effectiveness).

But the shibboleth of ECT has always been the claim that it causes “memory loss.” The idea of “losing all one’s memories” terrifies patients, and causes even experienced clinicians to change the subject when the patient says, “You mean like Jack Nicholson in One Flew Over the Cuckoo’s Nest? Sitting there with all his brains burned out?”

The clinician sighs and writes “Prozac” on his prescription pad.

But it turns out that a lot of these concerns about memory loss are misplaced. The cognitive disturbance associated with ECT is usually only minor and transitive. The whole memory loss thing, propagated for years by psychologists in particular, turns out to have the same scientific status as the belief that vaccines cause autism. Both are urban myths.

Now, it has long been known that ECT doesn’t wipe out all one’s memories. Study after study has demonstrated this. But the March 2016 issue of the distinguished British journal, Psychological Medicine reports ECT research by a group of academic psychiatrists in Belgrade; it constitutes a powerful scientific reminder that ECT does not have major memory effects.

Applying bitemporal ECT (electrodes on both temples) to thirty adult patients with “major depressive disorder,” they learned that there was no memory loss after ECT (compared with baseline) and that there was an improvement in memory that coincided with the lifting of the depression itself. They concluded, “Our results on learning and memory in relation to ECT during treatment of depression did not bring forth any prolonged and significant bi-temporal ECT-related memory deficit.”

This has actually been known for decades, ever since ECT was introduced in 1938, but each subsequent generation of clinicians tends to forget it -- in the face of the anti-ECT movement, helmed by the Church of Scientology; in the face of  a pharmaceutical industry that fears the competition of convulsive therapy; and in the face of an entire urban culture overly influenced by Hollywood and underinfluenced by science. 

When we reach the point that we no longer need these ongoing reminders, we will know that Psychiatry has become a discipline truly based on science.