Drugs That Boost Mood: Do You Even Have a Mood Disorder?

Source: Tom Varco / Wikipedia Commons

A brand new systematic review and meta-analysis evaluating over 500 previous research studies on the effectiveness of antidepressants determined that they work. The effects aren’t always very large, and psychotherapy is often equally effective—but nonetheless, these drugs improve mood, the study’s authors concluded.

As with a lot of research studies on controversial topics, those inclined toward antidepressants lauded the study, while those skeptical of them pointed out what they saw as the study’s flaws—which in turn produced critiques of the study’s critiques! So, why do mental health professionals disagree so strongly over the issue of antidepressant effectiveness? What is their disagreement about?

Let’s start with a basic, if often overlooked, truth: Mental health professionals (and the general public more broadly) don’t agree on whether depression is primarily endogenous or exogenous. This is a fancy way of saying that some people see depression as emanating from within the individual (i.e., endogenous) and others see it as produced by social circumstances (i.e., exogenous). These views make very different assumptions about the origins of depressed mood.

In the endogenous view, depression is a bodily illness that afflicts the individual, no different than cancer or diabetes. Depressed people are sick, plain and simple. Antidepressants, if not a total cure, are at least an effective biological intervention that helps depressed individuals manage their illness. Those coming from an endogenous view often interpret the “antidepressants work” research results as supporting their biological orientation.

The exogenous perspective offers a different outlook, seeing depression as much more tied to situational factors than biological ones. Life circumstances such as job status, economic and social inequality, relationship satisfaction, and social standing are what primarily determines mood. From this point of view, depressed people aren’t sick; they are unhappy because of things going on in their lives. Those operating from an exogenous perspective might question the veracity of research indicating antidepressants alone can correct the factors fostering sadness.

Of course, some clinicians see depression as combining exogenous and endogenous factors, while other clinicians see some cases as endogenous and others as exogenous. Thus, much of the disagreement over the effectiveness of antidepressants occurs within the context of broader debates over whether the causes of depression in a specific instance are mainly endogenous or exogenous. The endogenous view finds support for its “brain disease” model whenever research finds antidepressants help improve depressed people’s moods. Similarly, the exogenous perspective is buoyed whenever studies find antidepressants are ineffective, only mildly effective, or no better than placebo—especially when such results simultaneously highlight the value of talk therapy as an equal or better alternative to drug treatments.

The endogenous-exogenous debate is unlikely to subside anytime soon (impressive studies like the aforementioned meta-analysis notwithstanding). Thus, nothing I can say is likely to promote détente on the issue. However, allow me to make a few observations (which you’ll likely find either provocative or half-baked—maybe a bit of both!):

• Drugs can change mood. Just ask your pot-smoking friends. Marijuana often results in worried people worrying less! This doesn’t mean that cannabis “cures” anxiety or that those who smoke weed and feel calmer had anxiety disorders to begin with. It just means that drugs can alter mood. Thus, even if antidepressants can elevate sad people’s moods (and there is ample evidence suggesting they might, at least somewhat), this doesn’t necessarily indicate that the original depressed mood was a product of neurological illness. So, feeling better when on antidepressants isn’t automatically indicative that you suffered from a mental disorder before you started taking them. It just means that some drugs can improve mood.
• Life events can improve mood too, as anyone who has ever encountered good fortune knows. Getting a raise, having someone admire your work, or meeting someone you like and having them reciprocate the feelings are all examples of life events that usually make people feel good. Of course, whenever a life event provokes improved mood, there are corresponding changes in your brain. After all, we are biological organisms and therefore every experience we have has biological correlates. Thus, just as antidepressants can improve mood by promoting biological changes in the brain, effective psychotherapy probably elicits the same kinds of brain changes, but in a different way. It would have to if your mood shifts because, as already noted, every human experience has biological correlates.
• Antidepressants are used for a lot of presenting problems other than depression—including anxiety, obsessions and compulsions, eating problems, trauma, dissociation, and grief. This might mean that all these problems have the same or similar underlying biological correlates, but it doesn’t necessarily answer whether those correlates are products of internal biological malfunctions or expected biological responses to environmental occurrences.
• We don’t know how much of this or that neurotransmitter you’re “supposed” to have. One of the biggest problems mental health professionals face is that they cannot diagnose depression or other presenting problems using biological tests. Therefore, even though we like to conceptually distinguish endogenous from exogenous forms of depression, we lack “biomarkers” to differentiate whether someone’s mood originates “from within” or “from without.” Further, even if we could measure whether a person’s sadness had an endogenous component (such as too little serotonin in the brain), how would we know whether this serotonin problem originated from the person’s biology or from exogenous events that affected the person’s biology?
• Echoing and amplifying the previous bullet-point: If some cases of depression are truly endogenous and others exogenous, we still face a major problem—namely that clinicians don't have a clear way to distinguish them other than by clinical judgment; there are currently no biomarkers we can reliably use to diagnostically make the distinction.

So, even if we all come to a consensus (however unlikely!) and conclude that antidepressants “work” (and by that, we mean “improve mood”), we still haven’t sorted out complicated and vexing questions about the origins of the puzzling and often debilitating human experience called depression. Figuring out whether antidepressants elevate mood, while difficult in its own right, does not really address (and pales in comparison) to broader issues about environment, biology, and mood. For better or worse, it’s complicated!

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Note (3/17/2018): Thanks to Felix Yu for translating this post into Chinese.