Kevin Majeres MD | Aquinas, Adrenaline, and the Dangers of Antidepressants
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Aquinas, Adrenaline, and the Dangers of Antidepressants

22 Oct Aquinas, Adrenaline, and the Dangers of Antidepressants

A recent study in Neuropsychopharmacology by West et (2010 July; 35; 1653) has suggested a possible mechanism for the increase in suicidality, anxiety, and/or irritability sometimes seen when starting antidepressants. Using rats, the researchers measured the activity of the part of the brain that releases noradrenaline, called the locus ceruleus (LC), and correlated this activity with their behavior.

In humans we observe that LC activity grows calmer when patients are successfully treated with antidepressants. In this study of rats, the antidepressant had the same results. Early in treatment, however, there was a paradoxical increase in LC activity seen in younger rats. Simultaneously, these rats displayed increased depression-like behaviors during the “forced swim test” (the name says it all).

So what does this have to do with humans — and with Aquinas?

Plato was the first to divide emotions into two major categories, the “spirited” and the “appetitive.” Receiving this distinction via Aristotle, Aquinas elaborated on it in the Summa Theologiae, renaming the spirited part as the “irascible,” after anger, and the appetitive part as “concupiscible,” after desire (clearly, he wrote in Latin!). All the emotions in their essence are responses toward sensible things. The emotions that generally correspond to evil things (not necessarily moral evil — a flat tire is also an “evil” suffered by the driver) are hate, aversion, and sadness; but when these evils immediately invoke the fight-or-flight-or-freeze response, the list includes anger (fight), fear (flight), and despair (freeze).

According to Aquinas, these irascible “fight-flight-freeze” emotions all intrinsically involve a surge in energy; according to neuroscience, we know that this energy surge involves an increase in LC activity. A Thomistic neuroscientist would have predicted that anything that causes an increase in the activity of the LC will likewise cause an increase in the irascible emotions.

And this is exactly what happens. As the young rats LC activity increased, their despairing behavior (giving up on the forced swim test) increased; in those rats who did not have despairing behaviors, their LC activity remained normal.

Assuming that the response in humans mirrors that of the animals studied — and in this branch of neuroscience, it typically does — it is likely that the surge in LC activity soon after starting an antidepressant underlies the emotional dangers seen in this time period. For reasons still unknown and un-theorized, some patients experience this surge more in anger, and they become noticeably irritable; others seem to shunt the surge into anxiety, often to the point of having panic attacks (which is why many psychiatrists prescribe Xanax, Klonopin or Ativan during the start-up phase); and others, of greatest concern, experience a surge in despair, leading to suicidal thoughts and actions. Unfortunately, these emotions are not mutually exclusive: in the most serious cases, anger, fear, and despair all surge together.

In fairness to the antidepressants, it must be said that the LC adrenaline surge does not present problems for the majority of patients. If an antidepressant is prescribed, there are strategies for navigating the surge to prevent it from being disruptive.

The first thing a psychiatrist must do is inform patients of the irritability, anxiety, and despair (suicidality) that they may experience. People need to understand what is happening to their emotions. The very act of taking antidepressants can lead someone to second-guess the meaning of their emotional lives; having them go unexpectedly into fight-flight-freeze would only make things more confusing. If the emotional surge is expected, however, it is normalized and made understandable. Warning the patient makes it more likely that the patient will be mindful of the emotional surge when it occurs and then tell his or her doctor.

Starting the medicines at low doses and gradually titrating to higher ones has been key, in my experience, to avoiding this irascible surge. This approach is at variance with the findings in the study, however; when the rats were given doses two or four times higher, the LC surge didn’t occur. This is one finding from research that I am not willing to attempt replicating — starting low and going slow has been working fine. Patients who previously had bad experiences with antidepressants (e.g., had an irascible emotion surge) have almost always done very well on re-attempts when the starting dose was sufficiently small. I tell my patients that start antidepressants that if they have an increase in irritability or anxiety, they should cut the dose in half. (If they have an increase in despair, I have them call me directly.)

A third thing psychiatrists can do is to offer their patients cognitive-behavioral therapy for their depression, rather than using medicines. This is my first choice in most cases, and the research supporting CBT as a first-line treatment is excellent. Other non-medical interventions, such as more frequent exercise (read “Spark,” by John Ratey) can also help patients improve without medications.