You are probably familiar with the idea that depression, anxiety, and other mental health conditions are caused by a "chemical imbalance" or a deficiency of certain neurotransmitters in the brain. This causal explanation became popular in the late 1980s and early 1990s, coinciding with the development of a new set of drugs that treat depression, selective serotonin reuptake inhibitors or SSRIs. The first of these was fluoxetine (aka Prozac or Sarafem: sold by Eli Lilly & Co.). Other drugs in the same class are sertraline (Zoloft: Pfizer), paroxetine (Paxil: GlaxoSmithKline), citalopram (Celexa: Lundbeck), escitalopram (Lexapro: Lundbeck & Forest Labs), and fluvoxamine* (Luvox: Solvay). It became convenient for providers to explain the benefits of antidepressant medication by talking about how they modified brain chemistry: These drugs increase the availability of naturally occurring serotonin neurotransmitter molecules in the brain, by slowing down a process in which the neuron that originally released the serotonin molecules then scoops them back up for re-use. If drugs help the brain's neurotransmitters to have their desired effect, then it means the brain was initially under-utilizing them or not functioning at full efficiency, right? This leads to the idea that brain chemicals cause depression.
I have written previously about the challenge of specifying causal pathways in research. Although it's relatively easy for us to think about physiological changes and subjective symptoms as being the result of biological factors like genes or neurochemicals, the "shape shifters" symptom model suggests that a given symptom experience can be either the result or the cause of a biological shift. For example, let's say that you wake up one morning feeling particularly depressed. We don't yet have ambulatory monitoring technology that could detect changes in your neurotransmitters the way a CGM device detects minute-by-minute shifts in your blood sugar levels, so we don't know if your neurotransmitters were "off" in some way already by the time you woke up. But during the day, you mostly stay home because you feel depressed, you cancel some appointments, you have a hard time focusing, you sit around thinking depressing thoughts, and you maybe don't exercise or eat well. By the end of the day, perhaps your neurotransmitters truly are different from their usual levels. But was that a pre-existing problem, or did it result from your atypical behavior? Even if there was a small change in neurotransmitter levels from the start of the day, was it maybe because of how you slept? Or something that happened to you the previous evening? What point do we declare to have been the "start" of this causal sequence? In reality, neurotransmitters probably shift gradually to a new level, as the result of a complex interplay between biology and behavior.
Antidepressant treatment effects show that interpreting depression as a brain-chemistry problem can only take us so far. First, although a large meta-analysis of clinical trials confirmed that antidepressants do more than a placebo, it also showed relatively weak average effects. This also leaves out the large percentage of people who drop out of clinical studies: In the well-regarded STAR*D study that provided a sequence of treatment options to patients who didn’t initially respond to treatment, 90% of the patients who stayed in the study did experience improvement in their depression after a year. But by then two-thirds of them had dropped out, and 10% of those who stayed in the study still didn’t improve, despite multiple attempts to give them a range of different empirically supported medications. These results are statistically reliable - meaning that the medications work better than nothing - but they are certainly not impressive.
The success of other interventions like talk therapy also can’t be easily explained by the chemical imbalance metaphor: meta-analytic results show that a variety of brief psychotherapy approaches work just as well as antidepressant medication, and that a combination of medication and psychotherapy produces a small but statistically reliable gain over either one alone, a finding that suggests the two approaches might reduce depression by different mechanisms.
A range of other nonpharmacological approaches have also shown benefit for depression, including weaker but still significant effects for mindfulness meditation. There is also evidence supporting light therapy for seasonal depression, electromagnetic methods that include transcranial magnetic stimulation as well as electroconvulsive therapy, and even psychedelic drugs. But the strongest antidepressant effects for any intervention — even greater than those of medication — come from aerobic exercise. None of these approaches’ effects are consistent with the chemical-deficiency model of depression.
Even pharmaceutical companies now admit that brain chemistry was never more than a metaphor. And this metaphor can have negative effects, such as making depressed people feel that something is intrinsically wrong with them, or taking away their sense of control over the problem. It might also lead people to think that medication is the only thing that can help them, when the reviews noted above suggest that it is certainly not the only possible approach or even necessarily the most effective one.
——————
* Side Note: The history of Luvox is interesting. It was withdrawn from the U.S. market as an antidepressant in 2002, as a direct result of the 2000 Columbine school shooting. One of the shooters was taking that medication at the time, and it was posited that the antidepressant had made him suicidal. (The pattern of school shooters killing others and then killing themselves was relatively unknown at that time, although now it is disturbingly familiar). All of the SSRI antidepressants now carry a black-box warning that they might increase suicidality among adolescents and young adults, in part because of the Columbine incident. But the severity of this possible side effect has been disputed, it's apparently no greater with Luvox than with any other SSRI, and a recent meta-analysis found that there is more suicide risk associated with not treating adolescents' depression than with treatment using SSRIs. Regardless, Luvox remains on the U.S. market only as a treatment for obsessive-compulsive disorder and not for depression, even though chemically it's very similar to the other SSRI antidepressants. This is just one example of the interplay of politics or popular opinion with medical science, all of which are factors that have strong effects on people's decisions to use or not use antidepressant drugs.
Comments
Post a Comment