Empowerment Through Learning about Medication
When faced with a confusing or concerning medical issue, we often rely upon the knowledge and expertise of medical professionals. When it comes to treatment options, we trust that they are making choices in our best interests. However, personal due diligence is also important when it comes to medication. In the rush toward getting relief, sometimes one may fail to explore any alternative solutions. 
As it turns out, there’s more to learn about many of the drugs on the market today — that even prescribers may not be aware of.
While fluoxetine is classed as an antidepressant, it is more specifically an SSRI, or selective serotonin reuptake inhibitor. The aim of SSRIs is to help increase the level of serotonin active in the brain. Serotonin is a natural chemical — a neurotransmitter — that is designed to buffer the impact of outside stimulation, and in this way, is thought to have a softening effect on mood. Serotonin is associated with feelings of relaxation and ease. Serotonin also regulates thousands of other functions of the body, including digestion, sleep, blood sugar levels, metabolism, growth, gastrointestinal motility, and a very wide range of other vital functions.6
It’s important to know that no drug can create serotonin. Serotonin (and many other natural chemicals) are produced mainly in the gut, and distributed along the body’s highly refined system of nerve channels. Drugs like fluoxetine can manipulate the transmission of serotonin, but cannot create more.7
In addition, the idea of specifically targeting serotonin in the treatment of depression has been under robust debate for some time. Recent research has begun to question whether there is any relationship between low serotonin and depression. And certainly, the mechanics of how SSRIs are thought to work may be more nuanced than was previously believed.2-4
How Do Issues With Serotonin Production Affect the Human Body?
Interest in serotonin seems to have centered on two categories: issues that arise when there’s a scarcity of serotonin and issues that occur when there’s too much serotonin. The former is the narrative often cited as a contributor to anxiety and depression, although the evidence for that has become a matter of debate. Prozac was originally marketed to correct a “serotonin imbalance.”
The theory was that Prozac could correct an imbalance of serotonin and relieve feelings of unhappiness, hopelessness, and even suicidal ideation. This is an area of debate, as more researchers such as Moncrieff, Horowitz, and others, have begun to question this narrative that has been in play for decades.2-4
Ironically, fluoxetine carries a black box warning for suicide.12
You can find more on the marketing of fluoxetine further below.
What is Serotonin Syndrome?
Elevated levels of serotonin can be problematic and even life-threatening. Instances where there is too much serotonin activated may lead to serotonin syndrome. This is a state of drug-induced toxicity where medication has caused too much serotonin to become activated.
Some cases of SS occur after a single dose of a serotonergic medication, and other cases occur where 2 or more serotonergic agents have been taken concurrently. For example, St. John’s Wort should not be taken concurrently with an SSRI medication, due to their combined effects. Multiple serotonergic drugs taken simultaneously, such as taking Prozac and Celexa together, should be avoided.
The condition is potentially life threatening and needs immediate treatment to save the patient’s life. It’s one of the rare scenarios where abrupt cessation of the drug is necessary. Since serotonin regulates so many systems in the body, many negative presentations can arise with serotonin toxicity. Some of the clinical abnormalities that are signs and symptoms of serotonin syndrome are listed below. Doctors should not only be aware of these symptoms, but should inform their patients before prescribing SSRIs like Prozac, and especially in cases of combining prescriptions drugs and in cases of polypharmacy (5 or more prescription drugs being taken). 5,15,17
Signs and symptoms of serotonin syndrome:
- Elevated heart rate (tachycardia)
- Unstable heart rate
- Seizures
- Increased or unstable blood pressure
- Hyperthermia (overheating due to loss of internal regulation)
- Profuse sweating (diaphoresis)
- Confusion
- Agitation
- Dilated pupils
- Akathisia
- Tremors (rhythmic involuntary muscle movements)
- Sudden, brief, involuntary jerky muscle spasms (myoclonus)
- Increased or overactive reflex responses (hyperreflexia)
- Coma, unresponsiveness
- Muscle rigidity
- Flushed skin
- Sweating
- Increased bowel activity
If these sign present, one should seek immediate medical attention. Call 911 or have someone arrange transport to the nearest ER unit without delay. Early recognition and treatment, such as giving the patient a serotonin agonist before complete shutdown occurs, are vital for the patient to survive.5,15
What Does an SSRI Do?
SSRIs are compounds that specifically target serotonin molecules. Serotonin is a natural neurotransmitter, a messenger molecule. The messenger’s job is to carry signals throughout the central nervous system, telling other cells what to do, or what not to do. SSRIs block this pathway, so the messenger molecules become suspended, instead of continuing to travel along their normal relay line, on to the next receptor in the the nerve pathway. Chronic use of SSRIs can trigger what is called downregulation. Downregulation of serotonin receptors occurs over time, which means they become less responsive, and less in number.10
You might think of the central nervous system as a giant switchboard consisting of lines, receivers, transmitters, and of course, messages. Neurotransmitters such as serotonin have the task of sending communication between various parts of your body, transmitting signals between neurons to other cells. After delivering the message, the serotonin molecules are normally reabsorbed into the vesicles (storage sacs) of the nerve cells in your body. There they remain protected, ready to be used again, and again, as the need arises.
However, an SSRI disables this process. The serotonin molecules can’t be stored in the vesicles, and they remain suspended, and now subject to deterioration via nearby enzymes. So over time, these serotonin molecules can deteriorate and become waste material. Whether or not one had a serious serotonin deficiency before antidepressant use, after SSRI use this is certainly a possibility. Animal studies have shown this to be true.8,9
The History of Fluoxetine
We have a lot of rats to thank for the development of fluoxetine, according to the American-based Institute of Science History.10 Chemists employed by Eli Lily borrowed a method introduced to them by a John’s Hopkins chemist named Solomon Snyder. Snyder showed them how he first drugged rats with chlorpromazine, an antipsychotic, ground up their brains, and took extracts of those rat brains. Snyder found that these rat-brain-extracts responded to other experiments just the same way live nerve endings responded.
So, many chemists at Eli Lily experimented with drugging rats with other chemicals, grinding up their brains, and using the rat-brain-extracts as Snyder had showed them. They found one compound in particular had the effect of stopping serotonin reuptake in ground-up-rat-brains.
That was the birth of fluoxetine.10
The other part of the story was the narrative about natural transmitter deficiencies leading to depression, and the idea that Prozac and other SSRIs could correct such a deficiency. Since 1987, this theory has come under scrutiny.2-4
The Marketing of Prozac
The efforts dedicated to marketing Prozac cannot be understated. Prior to Prozac’s release, antidepressants in general and ECT as another treatment for depression, had become unpopular mainly due to their dangerous side effects. Prozac was touted as the super-drug that was going to change all that.
Everything from the promotional language surrounding its release, to the materials given to medical professionals, to the very name of the drug, was intentionally chosen to maximize its positive reception. The name Prozac was chosen to appear both professional and snappy, remaining in line with the overall messaging of fluoxetine serving as a “one-pill-fits-all” solution.
The main angle of the promotional materials advertising Prozac used the guise of teaching vital information about depression to consumers, cautioning the public about the dangers of remaining depressed — while extolling the benefits of Prozac. This came at a time where previous negative experiences with the side effects of antidepressants weighed heavily upon the populace, making the promise of an exciting, effective new drug even more enticing. Prozac became a trendy choice, recommended by celebrities, best-selling books like “Prozac Nation,” and “Listening to Prozac,” and the name “Prozac” saturated all media.
In addition to targeting those with depression, Prozac was promoted towards increasingly larger groups of people to continue capitalizing on the drug’s popularity. Not only was it recommended to those with diagnosed depression and anxiety, but it was also offered as a potential cure for those who simply struggled with shyness or those looking for an easy way to feel happier. Over time Prozac was even marketed towards children. In fact, the FDA approved it for children age 7 with OCD, and age 8 for children diagnosed with MDD (major depressive disorder.)11,12
The biggest challenge fluoxetine faces is the lack of evidence on its effectiveness. A marketing formula was heavily promoted: low serotonin equals depression, so a drug that helps you increase serotonin should cure it. Even a child could understand the concept. What could possibly be missing in this equation? In fact, the conversation about the hype surrounding Prozac is often missing facts about side effects, efficacy, managing Prozac withdrawal safely, as well as nuance and individual contexts of the persons who are prescribed such a drug. 2,3,6,9,20-22
In addition to questions about its value as an antidepressant, Prozac also presents some significant risks. First, common negative side effects include nausea, increased anxiety, trouble sleeping, and fatigue. Some patients also report significant side effects like agitation, akathisia, rage, hostility, and other extreme changes to their mood. Also reported are uncontrollable muscle spasms, tremors, decreased libido, and sexual dysfunction even after withdrawal from the drug. One of the most serious possible side effects is increased thoughts of suicide.
