Siddhartha Mukherjee’s captivating essay on depression

Not that Siddhartha Mukherjee didn’t have predecessors who wrote captivatingly about illnesses and their science, evolution, ecology and tryst with humans.

There were many physicians who wrote arresting prose before his Emperor of All Maladies, a “biography of cancer”, there were many who obsessively followed catastrophic illnesses and epidemics with a trained clinical mind and kind heart.

Instead of morbidity and fear, whether it is about tuberculosis, AIDS or cancer, they fascinated us with the revelation that human life is very complex, and living is an exceptional privilege.

A year since his best-selling Emperor of Maladies, that decoded cancer for us in all its complexity, Mukherjee is back examining another common illness through his unique and piercing perspective: depression, a medical condition that affects millions of people all over the world.

Many, mostly in rich countries, get treated while many more, mostly in poor countries, languish in anxiety, pain and fatalistic thoughts.

In a 5,000-plus word essay in the New York Times magazine titled Post-Prozac Nation, that evidently owes its title to Elizabeth Wurtzel’s 1994 best-seller Prozac Nation, he seeks to deconstruct depression and its most common treatment through different hypothesis, brain chemistry, clinical evidence and the science of drugs.

“Wonder drugs” such as Prozac, Paxil and Zoloft that transformed the lives of millions of people are also at the centre of his inquiries and exposition.

As in his Emperor of Maladies, Mukherjee is rigorous in his research on the science and clinical evidence of depression and quite masterly in piecing them together. Diverse hypotheses, scientific evidence, analogies, case studies and his own personal experience as a physician are the tools for his argument.

He looks at the basic premises of brain chemistry that once explained depression while presenting more evidence to show that it is still inadequate or incomplete, including the working of drugs such as Prozac and Paxil. It makes sense in a lot of cases, but is completely confounding in may others.

Interesting clinical evidence into the working of the brain, in the realm of depression, makes for captivating reading. For example that in the 1950s, a tuberculosis drug dramatically enhanced the mood of the patients creating a minor sensation, while a blood pressure drug drove many to a highly depressed mental states. In another case, he narrates his personal experience of how a cancer patient on chemotherapy drowning in self-abandonment resurrected herself on depression-medication.

Although millions pop Prozac, Paxil and Zoloft, the science behind depression and the efficacy of the drugs is not black and white.

Here is an interesting sentence from the essay:

The latest research suggests that serotonin is, in fact, central to the functioning of mood, although its mechanism of action is vastly more subtle and more magnificent that we ever imagined.

What is serotonin and its connection to depression and how does Prozac work on that? Here’s what his essay explains.

In a scientific sense too, the chemical hypothesis of depression has moved from static to dynamic — from “state” to “process.” An antidepressant like Paxil or Prozac, these new studies suggest, is most likely not acting as a passive signal-strengthener. It does not, as previously suspected, simply increase serotonin or send more current down a brain’s mood-maintaining wire." he says.

There is more:

There are, undeniably, important gaps in this theory — and by no means can it claim to be universal. Depression is a complex, diverse illness, with different antecedent causes and manifestations. As the clinical trials show unequivocally, only a fraction of the most severely depressed patients respond to serotonin-enhancing antidepressants. Do these patients respond to Prozac because their depression involves cellular death in the hippocampus? And does the drug fail to work in mild to moderate depression because the cause of that illness is different?

He sums up his essay and the technical limitations in probing the realm of mood and emotions so insightfully:

We possess far fewer devices to look into the unknown cosmos of mood and emotion. We can only mix chemicals and spark electrical circuits and hope, indirectly, to understand the brain’s structure and function through their effects. In time, the insights generated by these new theories of depression will most likely lead to new antidepressants: chemicals that directly initiate nerve growth in the hippocampus or stimulate the subcallosal cingulate. These drugs may make Prozac and Paxil obsolete — but any new treatment will owe a deep intellectual debt to our thinking about serotonin in the brain. Our current antidepressants are thus best conceived not as medical breakthroughs but as technological breakthroughs. They are chemical tools that have allowed us early glimpse into our brains and into the biology of one of the most mysterious diseases known to humans.

Read the complete essay here .