Perhaps no single development has had more of an impact on the treatment of mood disorders, than the discovery of antidepressant medications, and for bipolar folks, mood stabilizers. Medications are the best-known treatments for mood disorders, and they are what most doctors will want to try first, when someone is initially diagnosed.

While medications are often a tremendous help for a patient, they cannot usually “cure” anyone. They are a step in the right direction, but only one step of many that need to be taken.

That antidepressants and mood stabilizers work is not in doubt — we know that statistically from clinical studies — but we still don’t know how they work. Researchers have made guesses, but that’s all they are — guesses. Too many things about them are uncertain or unknown.

Psychiatry commonly calls mood disorders “imbalances of brain chemicals.” But not only is this not very helpful, it doesn’t actually mean anything! Precisely what is being “balanced” against what? And how does depression represent an “imbalance?” Which chemicals are in question? Is there any way to test someone’s brain chemistry?

There are no answers to these questions, aside from some educated guesses.

Don’t get me wrong. I’m convinced that there is some sort of electrochemical brain malfunction at the heart of mood disorders-that’s not in doubt — I just dislike the phrase “chemical imbalance,” because ultimately, it’s gibberish. We need our terminology to have meaning, not lack it, if we’re to advance the cause of mood-disorder treatment.

Even when researchers thought they were onto something — it often turned out that they weren’t. For example, the inventors of buspirone thought they had devised an antidepressant of the class known as SSRIs (selective serotonin reuptake inhibitors) along the lines of Prozac. But during clinical trials, they discovered that buspirone isn’t effective against depression — but it is effective against anxiety. Ultimately, it was approved by the FDA as Buspar, an anxiolytic (anti-anxiety agent). It’s sometimes given to depression patients, but usually to alleviate associated anxiety, not the depression. Yet, every early indication had been that buspirone would work similarly to other SSRIs, which are effective for depression.

What went wrong with buspirone? No one knows. Chemically, it should work on depression … but it doesn’t.

In the case of bipolar disorder, it was discovered that anticonvulsants, long used to treat epilepsy, were effective in quelling mood fluctuations. Carbamazapine, gabapentin, lamotrigine, and several more, all help in this way — but no one knows what the connection is between convulsions and mania. Furthermore, another mood stabilizer, lithium, is unrelated to these — or anything kind of medication — and its workings are even more of a mystery.

So while we do have some effective medications for mood disorders, we have few answers as to how or why they work, and are at a loss to devise new ones, since even those that appear chemically-promising, can end up not helping.

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