Depression is not caused by a chemical imbalance

ast week an article examined selective serotonin reuptake inhibitors, called SSRIs. It concluded that depression was not caused by a deficiency of serotonin, or 5-HT, in the brain as previously thought. In other words, depression is not really a chemical imbalance as everybody believed.

These drugs, including fluoxetine (Prozac), citalopram (Cipramil), and sertraline (Lustral), are widely prescribed. The study^[1], which the authors call an ‘umbrella review,’ looks at meta-reviews and original papers and concludes

The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.

I have to admit it never occurred to me that anyone besides patients and social workers actually took it literally that depression was a chemical imbalance.

Even as a child it was clear to me that the concept of a chemical imbalance in the brain was a fiction invented to destigmatize the disorder. It was clear even then that the concept was so vague as to be nonsensical and that patients were merely taking comfort in the belief that depression was not a personal failing but a simple biochemical phenomenon that could be cured by drugs.

Yes, I was an obnoxious little brat. But I'm not little anymore and it's still true. Saying that there's an imbalance of two chemicals in the brain is easy for patients to understand, but it has no explanatory value: why would there be an imbalance, why doesn't the brain automatically correct it, and how does that translate into the subjective feelings patients experience?

Pharmacology textbooks all say that antidepressants are contraindicated for bipolar depression because they increase the patient's energy. Instead of being too depressed to move they now have enough energy to commit suicide. Psychiatrist Ronald W. Maris described in his book on the topic a patient who may have overused antidepressants, causing psychosis that ended tragically.

In past decades doctors used to prescribe monoamine oxidase inhibitors like imipramine. Many of these drugs are irreversible MAO inhibitors, so patients were given low doses over a long period of time. Their use was discontinued when it was realized they caused dangerously high blood pressure.

Yet they undeniably had effects on the brain. Several years ago we gave our rats a monoamine oxidase inhibitor called tranylcypromine. The effects were amazing: they were the biggest, cleanest rats I ever saw. They practically lined their food pellets up in neat rows. Instead of just lying there, they stood up expectantly whenever we opened the cage.

The latest hypothesis for the cause of depression is immunological: depression could be, it is thought, a type of sickness behavior: a choreographed response to infection that encourages a person to avoid contact with others to prevent spread of disease. Or it could be a response to stress, whereby repeated failure forces the brain to rewire itself by eliminating synaptic connections between neurons as it waits for the patient to find a new, more productive way of dealing with the world. Or it could be something as simple as aggression directed against the self instead of others. Research is needed.

The Molecular Psychiatry article made waves because it was clearly and forthrightly written, avoided jargon, and stated its conclusion without hedging. The authors clearly wanted to dispel the myth, and they succeeded.

jul 22 2022, 6:09 am