Dopamine and the Placebo Effect Could Impact the Success of Your SSRI

woman holding a glass and a pill


Key Takeaways

  • When treated with Escitalopram, a Selective Serotonin Reuptake Inhibitor (SSRI), the effect was 4 times higher for patients with high expectations, as compared to those with low expectations.
  • It was a surprising finding that improved outcomes were linked to dopamine, when SSRIs are meant to increase serotonin.
  • Understanding how expectations impact treatment outcomes has the potential to improve how mental health is addressed.

Individuals are often told thinking positively will benefit their mental health, but research in support of these claims is still evolving. A recent study in Translational Psychiatry found that patients with high expectations had better outcomes than those with low expectations when treated with Escitalopram.

This study was conducted with 27 individuals with Social Anxiety Disorder to see how expectations based on information provided impacted outcomes when treated with a Selective Serotonin Reuptake Inhibitor (SSRI).

If the verbal information provided can have such an effect on the treatment outcomes with an SSRI then healthcare providers can improve how they navigate those discussions to maximize the benefits of pharmacotherapy.

Understanding the Research

In this randomized clinical trial, participants underwent Positron Emission Tomography (PET) imaging before and after 9 weeks of Escitalopram treatment, with the experimental manipulation being their verbal instructions of whether or not medication was anticipated to be effective.

PET imaging showed that those who were told they would be treated with an effective medication to address anxiety symptoms demonstrated 4 times the improvement of those who were told they received an active placebo.

Based on this study conducted in Stockholm, Sweden, verbally-induced response expectations had a significant influence on the effectiveness of the SSRI and dopamine, but not serotonin, transporter availability. A limitation of this research was its relatively small sample size.

High Expectations May Improve Outcomes

A researcher for this study, Olof Hjorth, PhD, says, "The takeaway is that the dopamine system may be important for boosting the clinical effect of SSRIs. Doctors and psychiatrists that prescribe SSRIs should not present the medicine in an overly critical way as that may reduce its efficacy."

Hjorth explains that the findings need to be replicated, but PET-imaging is a very expensive technique and consequently, sample sizes are generally quite small while noting that they did not measure all parts of the dopamine and serotonin systems, just the transporter proteins.

Olof Hjorth, PhD

Here, the expectancy of treatment success might be seen as expectancy of reward, and the brain's reward system is by and large governed by dopamine.

— Olof Hjorth, PhD

Given how much remains unknown about how exactly SSRIs work, Hjorth highlights that these findings are important. "Since SSRIs selectively block the serotonin transporters, we earlier assumed that the increase of serotonin in the synaptic cleft was the cause of the clinical effect," he says.

Hjorth explains, "Our findings show there was no difference between the groups with regards to serotonin transporter binding while the overtly treated group had 4 times more patients that responded to treatment."

In this way, expectations may play a large role. "Here, the expectancy of treatment success might be seen as expectancy of reward, and the brain's reward system is by and large governed by dopamine," Hjorth says.

Therapeutic Alliance May Be Key

Adult and geriatric psychiatrist and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center at Providence Saint John’s Health Center, David A. Merrill, MD, PhD, says, “The key takeaway is that the doctor-patient relationship, also known as the ‘therapeutic alliance’, is a key factor in predicting positive responses to mental health treatments."

Merrill explains, "We’ve known this is the case for psychotherapy treatments, now we’re seeing the same may be true for drug treatments of anxiety and similar conditions like depression. A positive expectation about the impact of treatment has real consequences on brain-based biology."

By this, Merril highlights the power of expectations to change the outcomes of treatment. "Namely, levels of dopamine-based neurotransmitters are changed by how we think about a treatment’s effects," he says.

David A. Merrill, MD, PhD

We see in clinical practice that therapy plus medication yields the best outcomes when treating anxiety and depression. This finding reinforces that observation – knowing is half the battle.

— David A. Merrill, MD, PhD

Merrill notes, "As a patient, understanding that anti-depressants work by synergizing with our expectations of treatment outcomes is a new and important finding. We need to use that knowledge to our advantage."

Expectations are crucial, as Merrill highlights how they may result in a significantly higher likelihood of benefitting from the medication treatment. "Put another way, discussing accurate information with a prescribing physician about a drug is a form of education-based psychotherapy that augments drug response," he says.

Merrill further explains, "We see in clinical practice that therapy plus medication yields the best outcomes when treating anxiety and depression. This finding reinforces that observation – knowing is half the battle.”

What This Means For You

As this research demonstrates, the verbal instructions that accompany SSRI treatment may have a significant impact on its efficacy. When discussing pharmacotherapy, healthcare providers should be mindful of the stigma that can often accompany treatment with medication.

Especially if navigating such challenges, it may be particularly helpful for patients to also access psychotherapy to address distorted thinking, which may help to improve SSRI outcomes. If you or someone you love is trying an SSRI, managing expectations may assist with treatment.

1 Source
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  1. Hjorth O, Frick A, Gingnell M et al. Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder: a randomized clinical trialTransl Psychiatry. 2021;11(1). doi:10.1038/s41398-021-01682-3

By Krystal Jagoo
 Krystal Kavita Jagoo is a social worker, committed to anti-oppressive practice.