Doubts about antidepressants

Antidepressants are the mainstay for treating depression, but their use is clouded by doubts about their short-, medium- and long-term efficacy. This is not to say that we should not use them, as these drugs save lives in many cases, but a recent review reinforces these questions as it sees little difference in the quality of life of people who have taken antidepressant drugs versus those who have not.

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A research team led by pharmacoepidemiologist Omar Almohammed of King Saud University (Saudi Arabia) has analyzed data from the U.S. Medical Expenditure Panel Survey, a national registry that tracks the health services used by Americans 1. This database shows that, on average, between 2005 and 2016 approximately 17.5 million adults were diagnosed with depression each year, a striking figure that exceeds the sum of inhabitants of Andalusia and Catalonia, the two most populous regions in Spain.

Health-related quality of life (HRQoL) was measured using the SF-12 and the physical and mental components (PCS and MCS) were analyzed separately. The PCS focuses mainly on physical functioning, limitations due to physical health problems, bodily pain, general health and vitality (energy/fatigue). The MCS focuses on social functioning, limitations of function due to emotional problems, and mental health (psychological distress and psychological well-being). The study compared a cohort of patients who used antidepressant medications with a cohort of patients who did not. Univariate and multivariate difference-in-differences (D-I-D) analyses were used to assess the significance of the mean difference from baseline to follow-up two years later.

The study also found that about two-thirds (67.9%) of people in the 11-year data set were women, reflecting gender disparities in mental health, and nearly 60% of depressed people were treated with antidepressants, a somewhat higher percentage in whites than in other ethnic groups. Married patients accounted for the largest proportion of the study sample (47.6%), followed by patients who had never been married (23.3%), with the latter receiving the least antidepressants compared with the others. Most of the patients (62.9%) were from middle- and high-income households. In addition, most patients (64.4%) had private insurance, and uninsured subjects were less likely to receive antidepressant treatment (47.6%) compared with those with private (58.8%) or public (58.0%) insurance.

Among patients with depression, the use of psychotherapy and pharmacotherapy are effective in improving patients’ symptoms and quality of life. However, it is better to use the combination of the two treatment options, as it has a better effect than using each option separately. Although psychotherapy appears to be slightly more effective than pharmacotherapy, there is no strong evidence that one of the two treatment options is better than the other. However, American Psychiatric Association (APA) guideline recommendations include the use of psychotherapy or second-generation antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs), for adult patients as initial therapy. For patients who have partial or no response to initial therapy, the guidelines recommend switching from pharmacotherapy alone to cognitive therapy alone or switching from one antidepressant medication to another antidepressant medication.

The main conclusion is that although antidepressant use was associated with some improvement in the mental component, univariate analysis revealed no significant differences between the two cohorts in the physical component. This means that people tended to report that their psychological distress improved with antidepressants, but their physical health problems, body pain and lack of vitality tended to remain. The team conducting the study believes that physicians and health professionals should consider including people in psychotherapy or social support sessions before turning to antidepressants “mainly because there was no persistent impact of these medications.”

This study may support the experiences of people who feel let down by antidepressants. For some, these medications barely relieve depression and can have unwanted side effects, such as weight gain, insomnia, loss of sexual desire, and even some withdrawal syndrome if stopped abruptly 2.

The ultimate goal of antidepressant therapy is to improve people’s overall well-being, especially their quality of life, for years and not just a few months, but whether antidepressants help achieve this goal is questionable to say the least. Antidepressants have a chequered history, plagued by undue influence from the pharmaceutical industry which, as we now know, has long hidden trial data whose outcome was that antidepressants showed no difference with placebo, presenting only the favorable results and thereby inflating the apparent effects of the lucrative drugs. Although this publication bias seems to have diminished in recent years, the fact remains that antidepressants leave many people desperate for better treatments, while the global burden of depression continues to grow. Moreover, many studies compound the problem by focusing on some variable of purely professional interest and failing to take into account the aspects that matter most to patients, such as quality of life.

Among the limitations of the study, the first is that it did not distinguish between newly diagnosed cases of depression and people who had lived with the mood disorder for many years; people were included in the analysis as long as they had a diagnosis of depression and two years of follow-up data 3. This means that we cannot rule out the hypothesis that, for some, these drugs had different effects depending on how long they had been taking them or how long their depression had evolved.

A second limitation is that the researchers were also unable to control for the severity of depression because this was not recorded in the survey data. Third, the two groups analyzed, with antidepressants and without antidepressants, also differed to some extent in terms of age, gender, ethnicity, and their experience of poverty, so the comparison was not perfect. Finally, we also cannot extrapolate the findings of this U.S.-focused study to the whole world, as there are significant differences between countries, but it fits with the growing evidence from other countries that modern antidepressants fall short in many respects.

This does not mean that we should eliminate antidepressants altogether. Rather, as this study underscores, clinicians need to rethink how antidepressants are best used and whether the drugs bring significant and lasting benefits to people. For example, last year other researchers asserted that mental health experts should review to whom and how antidepressants are prescribed, that the drugs should be prescribed for shorter periods and only for people with severe depression, not mild symptoms. Moreover, pairing antidepressants with the support of a psychotherapist seems key to improving people’s quality of life, rather than drugs or psychotherapy in isolation.

According to the research team, “although we still need our patients with depression to continue using their antidepressant medications, long-term studies are needed that evaluate the real impact of pharmacological and non-pharmacological interventions on the quality of life of these patients”.


  1. [Almohammed OA, Alsalem AA, Almangour AA, Alotaibi LH, Al Yami MS, Lai L. (2022) Antidepressants and health-related quality of life (HRQoL) for patients with depression: analysis of the medical expenditure panel survey from the United States. PLoS One 17(4): e0265928.
  2. Horowitz M, Wilcock M. (2022) Newer generation antidepressants and withdrawal effects: reconsidering the role of antidepressants and helping patients to stop. Drug Ther Bull 60(1): 7-12. doi: 10.1136/dtb.2020.000080
  3. Watson C (2022) Massive Study Finds We Need Better Therapies Than Antidepressants. Here’s Why. Science Alert April 23.

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