The list of approved antidepressant medications for the FAA has expanded dramatically since May 21, 2023. The four original SSRI antidepressants were approved for use by the FAA on April 5, 2010. A dopamine/norepinephrine reuptake inhibitor (DNRI) antidepressant was added to the four original selective serotonin reuptake inhibitors (SSRIs) in 2023. I am happy (pun intended) to wholeheartedly agree with the addition of three conditionally acceptable antidepressants for depression/anxiety and other psychiatric diagnoses by the FAA. My decision process for the prescribing of antidepressants in aviation has always been on randomized controlled trial data, efficacy in post-marketing studies, safety, and how to get over the stigma of the depression diagnosis. Embry Riddle Aeronautical University conducted a study of participants who were presented with various scenarios about a pilot taking one of four types of medications (or no medication at all) at a low or high dosage.
Participants were asked to rate their willingness to fly as passengers on the pilot’s flight. Eighty-eight (34 females) participants from the United States participated. An example of the scenario-based question is, “Imagine a situation where you will fly on a commercial aircraft from one major city to another. The captain (pilot) in charge of the aircraft is not taking any medications. Given this information, please respond to each of the following questions below.” In eight separate experimental conditions, participants were told that the pilot had been taking a low or high dosage of either Prozac (antidepressant), Claritin (antihistamine), ibuprofen (anti-inflammatory), or Catapres (antihypertensive) for the past two months for depression, allergies, arthritis, or high blood pressure, respectively. Fluoxetine (Prozacâ), the SSRI antidepressant, had the lowest willingness to fly with both low and high doses. The study found that consumers were less willing to fly when pilots took medications than when they were not (Review of European Studies; Vol. 7, No. 11; 2015).
A further study was conducted to determine airplane pilot’s mental health and suicidal thoughts. One thousand eight hundred thirty-seven (52.7%) of the 3,485 pilots completed the survey. One thousand eight hundred and sixty-six pilots (53.5%) achieving at least half, 233 (12.6%) of 1,848 airline pilots, responded to the Patient Health Questionnaire 9 (PHQ-9) for depression, and 193 (13.5%) of 1,430 pilots reported working as an airline pilot in the last seven days at the time of the survey. The study found that 233 (12.6%) of airline pilots met the depression threshold, and 75 (4.1%) pilots reported having suicidal thoughts. There was a significant number of active pilots suffering from depressive symptoms (Wu et al. Environmental Health (2016) 15:121).
The pharmacodynamic properties of antidepressants began with the “monoamine hypothesis.” Monoamine neurotransmitters in the brain affect neuronal activity in brain signaling. The monoamine hypothesis suggested that depression may be due to imbalances and deficiencies in three brain chemicals: serotonin, norepinephrine, and dopamine. The research on monoamines has continued for over fifty years.
Serotonin affects memory, impulse, compulsion, mood, anxiety, appetite, and irritability. Norepinephrine affects alertness, energy, concentration, attention, motivation, mood, irritability, and anxiety. Dopamine affects mood, pleasure, reward, drive, attention, motivation, anxiety, and irritability. It is clear where these neurotransmitters intersect. The answer is mood. Each of these monoamines is stored in specific axons. The axons communicate with receptor sites on other axons. In between the axons are spaces called synapses. The neurotransmitters get released from their axon storage areas called vesicles. The transmitters first go to the presynaptic axon and move through the synapse. The next step of the journey is to the postsynaptic axon, where neurotransmitter receptor sites await the arrival of the specific neurotransmitters.
Each of the monoamines has a specific axon. The crux of the monoamine hypothesis is that if you inhibit reuptake back into the axon, there will be higher levels of dopamine, norepinephrine, and serotonin in the brain. Higher levels lead to better mood control.
There has been a change in the research and thoughts on the deficiency and low levels of serotonin being the main reason for depression in patients. Serotonin levels were measured in healthy and depressed patients, and there was little or no difference between the two groups. Recent research indicates that high stress levels cause changes in the axons and affect the hippocampus section of the brain. Animal models suggest that the neural architecture of the brain atrophies, which impairs the function of the brain, leading to depression. Stay tuned for future changes in this theory.
The first approved antidepressants for pilots were the serotonin reuptake inhibitors. The four SSRIs are fluoxetine (Prozacâ), sertraline (Zoloftâ), citalopram (Celexaâ), and escitalopram (Lexaproâ). The facts of SSRI use are safety and efficacy. For most patients with depression, it may take 4 to 8 weeks to start seeing an effect. The theory behind this long-onset effect is a lipid raft (cholesterol) that may absorb and release the SSRI very slowly or due to the time it may take serotonin to make positive changes to axons. I have spoken to multiple patients on SSRIs who expected immediate effects. Generally, the patient will experience anti-anxiety effects in the first two weeks and then proceed to be seen by their healthcare provider in a month. The patient will complain that the SSRI prescribed is not working and stop taking their prescribed medication. The most common side effects are sexual dysfunction in males, and women may have decreased orgasms, insomnia, irritability, suicidal ideations, and long-term use weight gain. An adverse effect that is rarely seen is serotonin syndrome (high levels of serotonin). Symptoms seen with serotonin syndrome are rigidity, severe sweating, cardiac arrhythmias, seizures, and hyperthermia.
Bupropion extended-release (Wellbutrin SR/ERâ) is a dopamine/norepinephrine reuptake inhibitor (DNRI). Bupropion extended-release blocks dopamine reuptake in the dopaminergic axon, causing a higher level of dopamine and norepinephrine in the brain. Side effects include drowsiness, anxiety, excitement, difficulty falling asleep, dry mouth, dizziness, headache, and nausea. Bupropion immediate-release tablet has also been prescribed for smoking cessation. For those of you who are smokers, bupropion immediate release is a NO for use by pilots.
The three antidepressants that were added in April are duloxetine (Cymbaltaâ), venlafaxine (Effexorâ), and desvenlafaxine (Pristiqâ), which are serotonin and norepinephrine reuptake inhibitors (SNRIs). The FDA-approved indication for duloxetine is major depressive disorder (MDD), generalized anxiety disorder (GAD), diabetic peripheral neuropathic pain (DPNP), fibromyalgia, and chronic musculoskeletal pain. The FDA-approved indication for venlafaxine is for the treatment of major depressive disorder (MDD). The extended-release form of venlafaxine is FDA-approved for generalized anxiety disorder. Efficacy was established in three short-term (4, 8, and 12 weeks) and two long-term maintenance trials. The FDA-approved indication for desvenlafaxine is for major depressive disorder. The side effect profile for all of the SNRIs is hypertension, dizziness, nausea, dry mouth, sweating, tiredness, insomnia, anxiety or agitation, constipation, and modest weight gain.
I am glad that there are now eight antidepressant medications on the FAA antidepression list. Each category of antidepressant has different characteristics that could be a better choice for a depressed patient. The advantages of having in the toolbox eight medications for depression may lead to benefits that far outweigh the risks. It has taken forever for the public to understand that a combination of cognitive behavior therapy and an antidepressant for a pilot and the general patient population can have positive outcomes and lead to living a fulfilling life.
Be well and fly safe.
