The Natural History of Depression

I’m still reading Peter Cramer’s book Against Depression, which is his follow-up to Listening to Prozac, his groundbreaking book about depression and Prozac. This is a fascinating book, as good as Listening to Prozac. I continue to be impressed by his scholarship and ability to pull interesting research together. If you have any interest at all in learning more about depression, I would strongly recommend this book, which is a philosophical and scientific exploration of depression.

What is the natural history of depression? That is, what happens later in life if you get depressed now? Do you recover, or do you have more depressions?

We have good data on this issue from some studies funded by the National Institute of Mental Health. These studies followed depressed patients over many years. The findings are astounding, at least to me.

They show that if you are diagnosed as being depressed today, there is a 20 percent chance you will still be depressed 2 years later, and a 7 percent chance you will still be depressed ten years later, and a 6 percent chance you will be depressed 15 years later!

Even if you recovered, your probability of relapse is high. In these studies, most patients had subsequent depressions: 40 percent at two years, 60 percent at five years, 75 percent at ten years, and 87 percent at 15 years.

And with each episode of depression the prognosis worsens. After the second episode of depression, the 2 year recurrence rate soars to 75 percent!

One likely explanation for this effect is called kindling. The kindling model was first developed to explain how epilepsy works. In epilepsy, each seizure you have makes you more likely to have more seizures. This is because the seizure damages the brain.

We now think that each major depression may alter the brain as well. Particularly it may cause a shrinking of cells in several important areas of the brain. One of these is the hippocampus, which governs the formation of short term memory. Another is the prefrontal cortex, which has many functions in reasoning.

And how many patients got treatment? Only 3 percent of the patients who were diagnosed with depression had ever received even a single one month trial of anti-depressant medication! This is shameful in a country that claims to have good health care.

So what do we learn from these studies?

  1. Depression is a chronic disease, and relapse is very high.
  2. Each relapse makes you more susceptible to future depressions. Each depression erodes the resilience of the brain.
  3. A small but substantial percentage of depressed patients remain depressed for years on end.
  4. Prevention of initial depressions, early treatment of major depression, and prevention of future depressions can change the natural history of depression, and prevent a lifetime of depression.

The other important thing to realize about these studies is that they only looked at major depression. That is, at depression with many serious symptoms. Later studies that have looked at milder versions of depression have found that even mild depressions predict future major depressions. A future post will talk about minor depression, or dysthymia.

Copyright 2006 The Psychology Lounge/TPL Productions


Dr. Andrew Gottlieb is a clinical psychologist in Palo Alto, California. His practice serves the greater Silicon Valley area, including the towns of San Jose, Cupertino, Santa Clara, Sunnyvale, Mountain View, Los Altos, Menlo Park, San Carlos, Redwood City, Belmont, and San Mateo. Dr. Gottlieb specializes in treating anxiety, depression, relationship problems, OCD, and other difficulties using evidence-based Cognitive Behavioral Therapy (CBT). CBT is a modern no-drug therapy approach that is targeted, skill-based, and proven effective by many research studies. Visit his website at or watch Dr. Gottlieb on YouTube. He can be reached by phone at (650) 324-2666 and email at: Dr. Gottlieb Email.

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