The Mystery of Reserpine: High Blood Pressure Medication and Depression Risk. Written lay summary

Medicine and Health Sciences: Clinical Psychology

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The Mystery of Reserpine: High Blood Pressure Medication and Depression Risk


Reserpine, originally a traditional Indian remedy for mental illnesses, was adopted in Western medicine in 1952. It was widely prescribed for high blood pressure and specific mental health illnesses.

However, there were reports that some people who took reserpine for high blood pressure became depressed (e.g., sad, tired, hopeless) and had thoughts of suicide. Similar stories came from people with mental illness problems who took reserpine.

Past studies found that reserpine could lower the level of a group of brain chemicals called “monoamines” like serotonin, norepinephrine, and dopamine. When these chemicals decreased, some people who took reserpine felt depressed. Now, the medication is rarely given.

Studies suggesting reserpine’s potential to cause depression influenced our current understanding of how chemical imbalances in the brain relate to depression (i.e., a medical illness where a person feels very sad, hopeless, and unmotivated for a long time). This idea suggested that fixing this balance might help improve depression, and later led to developing medications to correct these chemical imbalances.

However, some researchers questioned whether reserpine truly caused depression, arguing that the previous reports may have been incorrect. There were also concerns that drug companies might not want to promote reserpine because it could not be easily turned into a more profitable medication.


Considering the significant and long-standing impact of the connection between reserpine and depression, Strawbridge and colleagues found it surprising that there had not been a comprehensive review of past studies. So, in a paper published in 2022, they provided an in-depth examination of existing research on how reserpine affects depression. The aim of the paper was to understand how often and how severe instances of depression occurred. They also collected information about presence of other problems like feeling worried (anxiety) and thoughts of self-harm (suicidal thoughts) that may be linked to depression.

Strawbridge and colleagues made sure to include all possible evidence to thoroughly examine how reserpine might affect depression. They did require that the studies they reviewed had at least 10 adult human participants, but did not place any other requirements such as their age, gender, type of illness, or what types of treatment the participants received. From these studies, they compared the results of participants who took reserpine to those who did not take it to measure the occurrence of depression. The review further analysed information about how the studies were done, who was in them, how reserpine was given, what these studies measured, and what they found. They also looked at whether people stuck with taking reserpine, how many people dropped out of the studies, if there were side effects that made people feel worse, and if reserpine helped with problems with anxiety or suicidal thoughts.


Strawbridge and colleagues reviewed 35 studies that met their requirements. Of the 35 studies reviewed, 9 of them were “randomized controlled trials” which randomly assigned the participants into two groups for those that received reserpine and those that did not. Meaning, only 9 studies addressed the potential risk of bias for the participants. After looking at the 35 studies, they discovered that the occurrence of depression after reserpine treatment varied widely, ranging from 3% to 87%, and the studies had different outcomes. In 11 studies, reserpine was linked to making depression worse, 13 studies showed no change, and in 11 studies it showed it improved depression. In studies where reserpine made depression worse, participants did not originally have any mental illness, used it for a longer period, and received smaller doses than in studies where depression improved.

The study with the highest depression rate (87%) included a mix of participants, with 38% who were already depressed before starting reserpine. This suggests that reserpine might make depression worse in people who are vulnerable to it, challenging the idea that reserpine could improve feelings of depression. On the other hand, when the reviewers looked at all the studies together, there was only a 3% difference in occurrence of depression after being on reserpine when comparing between those that had a mental illness and those that did not. But there was a 7% difference after taking a placebo (fake reserpine). This might be because in certain instances, participants were mistakenly recorded as having depression when they actually had a side effect that resembled depression. This side effect is common in individuals with high blood pressure who don’t have a mental illness.

Even though the review found signs that reserpine might cause depression depending on the amount and period the medication is given, it could not clearly show how it works in the body.


The review had limitations which included not having enough good evidence, a wide range of differences in the studies, and majority of the studies lacked objectivity. These challenges made it hard to see clear patterns in how reserpine and depression are related. Strawbridge and colleagues had to account for many varying factors such as differences in types of people that participated in the studies, amount of medication and the length of time that a participant was prescribed to take, and the different techniques used in these studies to measure the outcomes. Moreover, many of the studies were very outdated and most of the studies did not meet today’s research standards. Therefore, the credibility of the studies reviewed are in question. Finally, some of the data could not be accessed by the reviewers due to missing reports and some authors of the studies could not be reached for more information.


There has been a long debate about whether reserpine causes or helps with depression. While this review does not give a clear answer it is the first in-depth look at this topic. Some studies that reported reserpine made people feel depressed were not entirely fair and accurate. Participants also used reserpine for a long time with low doses, including people without mental health issues. We need more research to see if taking reserpine for a short time, in moderate amounts, along with common medications, would improve depression.

Reserpine’s effects are complex, not simple. The studies’ outcome on reserpine are uncertain, and this review also raises questions about the idea that depression is only about certain brain chemicals. People react differently to reserpine, so we need a careful approach to understanding how it affects depression.


Title of lay summary The Mystery of Reserpine: High Blood Pressure Medication and Depression Risk. Written lay summary
Lay Summary Author(s)

Ann Yom Steel

Vetting Professional Naghmeh Nikkheslat, PhD.
Vetting Professional Affiliation(s) / participating organisation(s) King's College London, Institute of Psychiatry, Psychology & Neuroscience: Applied Neuroscience MSc PG Dip (online)
Science Area Subject
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high blood pressure



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Title of the original peer-reviewed published article: The effects of reserpine on depression: A systematic review.
Journal Name: Journal of psychopharmacology
Issue (if applicable): 3
Page numbers (if applicable): 248–260
Year of publication: 2023

Strawbridge, R.

Javed, R. R.

Cave, J.

Jauhar, S

Young, A. H

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Original Article language: English
Article Type: Systematic review of non-randomised or observational studies with meta-analyses
What licence permission does the original e-print have? For more information on this please see our permissions video): Attribution 4.0 International (CC BY 4.0)

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