Our modern conception of the link between depression and chemicals in the brain was sparked quite by accident in the middle of the last century. In the autumn of 1951, doctors treating tubercular patients at Sea View Hospital on Staten Island with a new drug — iproniazid — observed sudden transformations in their patients’ moods and behaviors. The wards — typically glum and silent, with lethargic patients — were “bright last week with the happy faces of men and women,” a journalist wrote. Patients laughed and joked in the dining hall, as if a dark veil of grief had lifted. Energy flooded back and appetites returned. Many, ill for months, demanded five eggs for breakfast and then consumed them with gusto. When Life magazine sent a photographer to the hospital to investigate, the patients could no longer be found lying numbly in their beds: they were playing cards or dancing in the corridors. If the men and women at Sea View were experiencing an awakening, then a few hundred miles south, others at Duke’s hospital encountered its reverse. In 1954, a 28-year-old woman was prescribed Raudixin to control her blood pressure. A few months later, she returned to the hospital, complaining of crying spells, dullness and lethargy. She felt futile, guilty and hopeless, she told her doctors. A few months later, when she returned, the sense of futility had turned into hostility. A 42-year-old woman prescribed Raudixin told her doctor that “God would cause her to become insane” before she could repent. The “feeling blue,” as another patient described it, persisted until the drug was discontinued. Psychiatrists and pharmacologists were quick to note these bizarre case reports. How, they wondered, could simple, seemingly unrelated chemicals like Raudixin or iproniazid produce such profound and opposite effects on mood? It was around this same time that scientists were learning that the brain itself was immersed in a soup of chemicals. In the early part of the century, scientists wondered how nerve cells talked to one another. By the late 1960s, evidence suggested that signals between neurons were carried by several chemicals, including the neurotransmitter serotonin. Might iproniazid and Raudixin have altered the levels of some neurotransmitters in the brain, thereby changing brain signaling and affecting mood? Strikingly so, scientists found. Raudixin — the “feeling blue” drug — drastically lowered the concentration of serotonin and closely related neurotransmitters in the brain. Conversely, drugs known to increase euphoria, like iproniazid, increased those levels. These early findings led psychiatrists to propose a radical new hypothesis about the cause and treatment of depression. Depression, they argued, was a result of a “chemical imbalance” of neurotransmitters in the brain. In the normal brain, serotonin shuttled between mood-maintaining neurons, signaling their appropriate function. In the depressed brain, this signal had somehow gone wrong. The writer Andrew Solomon once evocatively described depression as a “flaw in love” — and certainly, the doctors using Raudixin at Duke had seen that flaw emerge grimly in real time: flaws in self-love (guilt, shame, suicidal thoughts), love for others (blame, aggression, accusation), even the extinction of a desire for love (lethargy, withdrawal, dullness). But these were merely the outer symptoms of a deeper failure of neurotransmitters. The “flaw in love” was a flaw in chemicals. Powerful vindication for this theory came from the discovery of new medicines that specifically elevated serotonin concentrations. The first such drug, Zimelidine, was created by a Swedish researcher, Arvid Carlsson. Following Carlsson’s lead, pharmaceutical chemists threw their efforts and finances into finding serotonin-enhancing drugs, and the new giants of the antidepressant world were born in rapid succession. Prozac was created in 1974. Paxil appeared in 1975, Zoloft in 1977 (the trade names were introduced years later). PROZAC - THE STAR/VILLAIN OF THE SHOW In 1987, the antidepressant fluoxetine (Prozac) was introduced. It had been tested by the FDA and found to be an effective antidepressant with fewer than usual side effects. Doctors began to prescribe it to depressed patients. The results were astonishing. Patients reported feeling "better than well." It not only eased their depression, but seemed to give them a new look at themselves. Prozac users felt they were discovering their own true personalities for the first time. It seemed to make cautious people more spontaneous, the introverted more outgoing, the timid more confident. In short, it seened to improve people's personalities, at least in making them more socially attractive. Within two years, pharmacies were filling 65,000 Prozac prescriptions per month -- in the United States alone. Within five years, 4.5 million Americans had taken it. This was the fastest acceptance ever for a psychiatric drug. And because it seemed to go beyond treating illness and actually improve people, to be a facelift for the character, it gained the status of a celebrity. As Peter Kramer wrote in Listening to Prozac, "Prozac enjoyed the career of a true celebrity -- renown, followed by rumors, then notoriety, scandal, and lawsuits, and finally a quiet rehabilitation." Reports emerged that some patients felt more suicidal on Prozac. Lawyers began to defend murder suspects by saying that whatever they did, it was under the influence of a drug -- Prozac. There was a backlash to the use of the drug, followed by a smaller backlash to the backlash, until Prozac left the front pages and returned to the pharmacist's formulary. Still, it had opened a new window on an old question about personality and mental health -- how much of it is biological, and how much experiential? CHANGES IN APPROACH Depression was traditionally viewed as a chemical imbalance: a deficiency in a single chemical messenger in the gaps (or synapses) between nerve cells was believed to disrupt communication between these cells. However, studies in the 1980s and beyond found some patients with depression had increased rather than decreased levels of these chemical messengers (or neurotransmitters). In addition, some effective depression medications decreased the level of a chemical messenger rather than increasing it. Finally, many treated with medications that enhanced serotonin didn't show an improvement in mood. It was clear that depression wasn't related to a simple, single chemical deficiency. Instead, scientists designing new treatments began to understand that people with depression had widespread alterations in the function of neurotransmitters, structural changes in brain regions that regulated their mood and emotions, and changes in the brain's wiring or connectivity. The next step was to find a drug that worked on the wider circuits and connections of the brain. That drug turned out to be one that had been used in operating theaters and on battlefields for decades. . Ketamine: An Anesthetic Repurposed
Ketamine has been used as an anesthetic since the 1960s. In an influential study in 2000, a single injection of ketamine exerted a rapid antidepressant effect within 72 hours. This benefit lasted for several weeks. A nasal spray version called Spravato (esketamine) received FDA approval in 2019 as an add-on therapy for treatment-resistant depression. The exciting story of ketamine has highlighted the need to think beyond a single chemical messenger when developing modern antidepressants. Ketamine triggers positive changes in the function of brain circuits and stimulates the regrowth of synapses, restoring connections between brain cells. That said, there are drawbacks. Ketamine side effects include dissociative symptoms (out-of-body experiences and hallucinations), and it carries the potential for abuse. Response rates may be lower in older patients . It must be administered in a doctors' office or clinic. Adapted from: https://www.greenbrooktms.com/blog/the-history-of-antidepressants https://www.nytimes.com/2012/04/22/magazine/the-science-and-history-of-treating-depression.html
0 Comments
|
Archives
December 2023
Categories
All
|