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Depression

5 Surprising Facts About Treating Depression

3. Serotonin levels may actually be higher during depression, not lower.

Key points

  • Cognitive-behavioral therapy works as well as a similar "dose" of depression medication in the short term, and better in the long term.
  • Serotonin levels may very well be higher during depression, not lower as commonly believed.
  • Depression may be an evolved adaptation to help a person solve complex social problems.

If you’ve been depressed, clinical psychologist Dr. Steve Hollon can relate. “It’s an absolutely miserable thing to go through,” said Hollon, who experienced multiple depressive episodes in his 20s. Since that time, he has published many groundbreaking research studies on effective treatment for depression, with a focus on cognitive-behavioral therapy (CBT). Perhaps not coincidentally, Hollon has not experienced depression since he started treating patients with CBT.

I recently spoke with Hollon on the Think Act Be podcast and had my mind blown multiple times. The latest developments in depression research contradict society-wide assumptions about what causes depression and the best way to treat it.

1. Cognitive-behavioral therapy works as well as medication.

Medications like selective serotonin reuptake inhibitors (SSRIs) are typically seen as the “gold standard” for depression treatment. However, multiple studies have shown that “in acute response—getting someone over depression—cognitive behavioral therapy and medication are comparably efficacious, on average,” said Hollon. “Neither is a panacea,” he cautioned, “since not everybody responds to either one.” But those who don’t get better with one treatment may benefit from the other.

So what makes CBT highly effective? Two things, said Hollon:

  1. Behavior change: Doing activities that bring enjoyment and a sense of accomplishment is a proven antidepressant. “Aim to do whatever you would do if you weren’t depressed,” advised Hollon, though he is quick to add that the behavioral part of CBT is not simply advice to “get moving.” The power of CBT comes from the leverage it offers when energy and motivation are low, through tools like breaking down bigger tasks into smaller steps and carefully scheduling manageable goals. “Don’t wait to be motivated,” said Hollon. “You need to ‘prime the pump’ in terms of the underlying motivational systems. Start doing stuff and the motivation will come.”
  2. Cognitive change: When someone is depressed, their thinking becomes “much more negative and pessimistic,” said Hollon. “They tend to get down on themselves, think things won’t work out, that they can’t get anything accomplished, and that they won’t enjoy anything.” Those kinds of beliefs stop a person from trying to do the things that make life enjoyable and rewarding—“and then they blame themselves for not getting anything done.” The solution, according to Hollon: “Don’t believe everything you think. Just because you think something is true doesn’t mean it is.” The cognitive part of cognitive-behavioral therapy for depression focuses on helping us to think more clearly and accurately so we can see through the false beliefs that contribute to low mood.

2. CBT Is better than medication for preventing relapse.

Part of the beauty of CBT is that it doesn’t just relieve depression—it prevents it from returning. “If somebody gets better on CBT, you cut the risk for relapse by about half” after treatment ends, said Hollon, compared to those who get better with medication and then taper off of it. “It’s a pretty well-established phenomenon,” Hollon continued, noting that seven of eight studies show this effect. “Twelve to sixteen weeks of cognitive therapy does as well as keeping somebody on medication for up to two years.”

The limitations of depression medication are no fault of the medications themselves. “The antidepressant medications are good psychiatric medications,” said Hollon, “You don’t get tolerance and withdrawal in the classic sense, and they’re relatively safe and efficacious. But it’s like aspirin—you take an aspirin today to get rid of a headache, but it doesn’t mean it’s going to keep you from getting a headache next week unless you keep taking aspirin on a continuous basis.”

3. Serotonin levels may be higher during depression.

So how does CBT do as well as medication in the short term (and better in the long term) if it’s not directly treating the underlying “chemical imbalance”—the low serotonin that causes depression? As it turns out, low serotonin in depression is a myth. But the real link between serotonin and depression is even more surprising.

“The evidence is pretty clear,” said Hollon. “There’s not a deficit—there’s an excess.” He described findings from a study that measured metabolite levels from blood in the brain, which indicate how much serotonin the brain is using. Results from this study revealed that serotonin levels were elevated among those with clinical depression, and returned to normal levels following medication treatment. Other studies (e.g., Gjerris et al., 1987, and Sulllivan et al., 2006) using different methods have found similar results.

These findings sound paradoxical, given that depression medications tend to increase the amount of serotonin in the synapse, at least initially. But Hollon explained that “within a week to ten days, you increase the amount of serotonin so high that the regulatory mechanisms push back.” As a result, serotonin levels fall. “It’s like holding a match up to a thermostat to turn the furnace down,” said Hollon. “You’re tricking the system into kicking back in and regulating” serotonin levels.

High levels of serotonin in depression make more sense when we realize that serotonin is not the “feel-good neurotransmitter,” as has often been claimed based on its involvement in depression; that role is played by the endogenous opioids (as the name suggests) like endorphins. According to Hollon, “Serotonin is the energy transfer regulator. It moves you back and forth between approach and avoidance behavior.”

4. Depression may be an evolutionary adaptation.

Despite the misery that depression entails, there are good reasons to believe that it was shaped through evolutionary pressures because it helped our ancestors solve a specific problem. Hollon points out that “all negative affective states serve a survival function.” Fear causes us to flee from danger; anger drives us to attack a potential threat; pain motivates us to avoid future harm. “There’s no reason to think of depression any differently,” said Hollon.

So what might have been the survival function of depression in our evolutionary history? The Analytical Rumination Hypothesis (ARH) offers a possible explanation. Social problems had serious survival implications for our ancestors; for example, broken relationships could result in death at a time when being “thrown out of the troop was a ticket to being picked off by predators,” said Hollon, “or starving.” Accordingly, depression directs energy to the brain to “keep you in your head and make you ruminate” about complex social problems; if you’ve experienced depression, you’re probably very familiar with this process.

As frustrating as it can be to feel like you’re stuck in your head, it may very well have a purpose, according to the ARH: to help you engage in “very careful thinking where you’re focused on analyzing what the source of the problem is, and coming up with a solution,” said Hollon. A corollary of this theory is that the tools of CBT are exquisitely well matched for the actual problem in depression—namely, to think more effectively.

5. Depression tends to resolve on its own.

There is a common belief that depression sticks around indefinitely unless it’s treated; however, research shows that most episodes are time-limited even without treatment. “Nobody knows for sure [how long an average episode lasts],” Hollon said, “but it looks like it’s about six to nine months.” This spontaneous remission may be a result of the rumination processes described above, to the extent that they lead to effective solutions. Nevertheless, Hollon points out that helping depression to resolve in “three to six weeks” through an effective treatment like CBT “is much better than six to nine months.”

If you or someone you love has been struggling with depression, consider finding a therapist who specializes in depression treatment through the Psychology Today Find a Therapist search function.

LinkedIn image: Prostock-studio/Shutterstock. Facebook image: Branislav Nenin/Shutterstock

References

Barton, D. A., Esler, M. D., Dawood, T., Lambert, E. A., Haikerwal, D., Brenchley, C., ... & Lambert, G. W. (2008). Elevated brain serotonin turnover in patients with depression: Effect of genotype and therapy. Archives of General Psychiatry, 65, 38-46.

Gjerris, A., Stub, A., Rafaelsen, O. J., Werdelin, L., Alling, C., & Linnoila, M. (1987). 5-HT and 5-HIAA in cerebrospinal fluid in depression. Journal of Affective Disorders, 12, 13-22.

Hollon, S. D. (2020). Is cognitive therapy enduring or antidepressant medications iatrogenic? Depression as an evolved adaptation. American Psychologist, 75, 1207-1218.

Sullivan, G. M., Oquendo, M. A., Huang, Y. Y., & Mann, J. J. (2006). Elevated cerebrospinal fluid 5-hydroxyindoleacetic acid levels in women with comorbid depression and panic disorder. International Journal of Neuropsychopharmacology, 9, 547-556.

Andrews, P. W., & Thomson Jr, J. A. (2009). The bright side of being blue: Depression as an adaptation for analyzing complex problems. Psychological Review, 116, 620-654.

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