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Study: Do Antidepressants Work Long-Term?

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Our team recently came across a study demonstrating that antidepressants are not presenting a measurable and significant improvement to patients over the long term. This lends itself to a rabbit hole of research! Consolidated with sources at the end, we present to you our findings on depression rates and the topic of antidepressants working over a long period of time.

Depression has been around for as long as written history.

Illustration of the story of Hippocrates refusing the presents of the Achaemenid Emperor Artaxerxes, who was asking for his services. 1792.

By Anne-Louis Girodet de Roussy-Trioson, Public Domain

Considered the “Father of Medicine,” Hippocrates (460 – 370 BCE) was an ancient Greek physician who saw all bodily mechanisms as caused by the relative amount of four internal fluids, called humors: blood, black bile, yellow bile, and phlegm. He believed that a balance between the four brought on good health, while an extreme deficiency or excess of one caused physical ailments.

Greek physician and philosopher Galen (129AD – c. 200/c. 216) expanded upon Hippocrates’ theory, by stating that personality types were also derived from an excess of one of the four humors.

Physicians in the Persian and then the Muslim world developed ideas about melancholia during the Islamic Golden Age. Ishaq ibn Imran combined the concepts of melancholia and phrenitis. The 11th-century Persian physician Avicenna described melancholia as a depressive type of mood disorder in which the person may become suspicious and develop certain types of phobias.

According to the humors theory, the melancholic personality type was created by an excess of black bile. Melancholics were accordingly seen as introverted, deep thinkers, who typically related more to the sadder part of the emotional spectrum. It is from this perception of melancholia that our current concept of depression eventually evolved.


65% of those with depression seek and receive treatment.

What happens to the 35% of those who suffer from Depression and do not receive treatment?

Depression is widespread and should cause no shame.

Global estimates conclude that 8.7% of women and 5.3% of men currently have depression.

Famous figures who experienced depression.

The 1700s

Ludwig van Beethoven.

The 1800s

Abraham Lincoln. Edgar Allan Poe. Charles Dickens.

The 1900s

Virginia Woolf. Sylvia Plath. Ernest Hemingway. Martin Luther King, Jr. Pablo Picasso. Princess Diana of Wales.

The 2000s

Buzz Aldrin. Heath Ledger. Robin Williams. Jim Carrey.


How does the current rate of those with depression compare to history?

This is difficult to determine and quantify accurately. Luckily for us, researchers have been able to shed light on the matter by analyzing long-term studies.

Three samples over a 40-year period showed a stable current prevalence of depression and cast doubt on the interpretation that depression is generally increasing. Within the overall steady rate observed in this study, historical change was a matter of redistribution by sex and age, with a higher rate among younger women being of recent origin.

The portion of the population who suffer from depression seems to remain consistent at about 5% throughout history.

What is Depression and how does it impact your life?

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines a major depressive episode as at least two weeks of a depressed mood or loss of interest or pleasure in almost all activities, as well as at least five other symptoms, such as

  • Sleep issues on an almost daily basis (either difficulty sleeping or sleeping too much)
  • Changes in appetite and weight (change of more than 5% body weight in a month) or a decrease or increase in appetite nearly every day
  • Decreased energy or fatigue almost every day
  • Difficulty concentrating, making decisions, and thinking clearly
  • Psychomotor agitation or change that is observable by others (slow physical movements or unintentional or purposeless motions)
  • Recurrent thoughts of death or suicide, a suicide attempt, or a specific plan for suicide

There’s no single cause of depression. Brain chemistry, hormones, genetics, life experiences, and physical health can all play a role.


Let’s get to the study and the data.

Long-term antidepressant use did not improve physical or mental health in patients with depression according to a new study published in the journal PLOS ONE.

Among people with depression, those using antidepressants had no better quality of life in the long run.

Over time, using antidepressants is not associated with significantly better health-related quality of life, compared to people with depression who do not take the drugs. These are the findings of a new study published on April 20, 2022, in the open-access journal PLOS ONE by Omar Almohammed of King Saud University, Saudi Arabia, and colleagues.

It is widely acknowledged that depressive illness has a major impact on a patient’s health-related quality of life (HRQoL). While studies have demonstrated the usefulness of antidepressant drugs in the treatment of depressive disorder, the effect of these medications on patients’ general well-being and HRQoL remains debatable.

In the new study, the researchers used data from the 2005-2015 United States Medical Expenditures Panel Survey (MEPS), a large longitudinal study that tracks the health services that Americans use. Any person with a diagnosis of depressive disorder was identified in the MEPS files. Over the course of the study, 17.47 million adult patients were diagnosed with depression on average each year, with two years of follow-up, and 57.6% of these were treated with antidepressant medicines.

The use of antidepressants was associated with some improvement in the mental component of SF-12—the survey tracking health-related quality of life. However, when this positive change was compared to the change in a group of people who were diagnosed with a depressive disorder but did not take antidepressants, there was no statistically significant association of antidepressants with either the physical (p=0.9595) or mental (p=0.6405) component of SF-12.

In other words, the change in the quality of life seen among those on antidepressants over two years was not significantly different from that seen among those not taking the drugs.

The study was not able to separately analyze any subtypes or varying severities of depression. The authors say that future studies should investigate the use of non-pharmacological depression interventions used in combination with antidepressants.

The authors add: “Although we still need our patients with depression to continue using their antidepressant medications, long-term studies evaluating the actual impact of pharmacological and non-pharmacological interventions on these patients’ quality of life is needed. With that being said, the role of cognitive and behavioral interventions in the long term-management of depression needs to be further evaluated in an effort to improve the ultimate goal of care for these patients; improving their overall quality of life.”


Despite the empirical literature demonstrating the efficacy of antidepressant medications for the treatment of a depressive disorder, these medications’ effect on patients’ overall well-being and health-related quality of life (HRQoL) remains controversial. This study investigates the effect of antidepressant medication use on patient-reported HRQoL for patients who have depression.

On average, 17.5 million adults were diagnosed with depression disorder each year during the period 2005 to 2016. The majority were female (67.9%), a larger proportion of whom received antidepressant medications (60.5% vs. 51.5% of males). Although the use of antidepressants was associated with some improvement on the MCS, D-I-D univariate analysis revealed no significant difference between the two cohorts in PCS (–0.35 vs. –0.34, p = 0.9595) or MCS (1.28 vs. 1.13, p = 0.6405). The multivariate D-I-D analyses ensured the robustness of these results.

The ultimate goal of using antidepressant medications or psychotherapy is to improve patients’ important outcomes, such as HRQoL. The real-world effect of using antidepressant medications does not continue to improve patients’ HRQoL over time, as the change in HRQoL was comparable to patients who did not use any antidepressant medications. Future studies should not focus on the use of pharmacotherapy only, it should rather investigate the long-term impact of pharmacological and non-pharmacological interventions, such as behavioral therapy, psychotherapy, social support sessions, education, or combined interventions, on these patients’ HRQoL.

It is more important that you know what your body is doing.

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Source one. Source two. Source three. Source four. Source five. Source six. Source seven. Original study.


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