Antidepressants are among the most frequently prescribed medications, yet they do not yield positive results for everyone. A significant real-world study published in the journal Psychological Medicine has pinpointed specific demographics that are less likely to benefit from these medications, including men and older adults. This research utilized data from the ongoing UK Biobank health study, where participants were asked whether they had ever taken a type of antidepressant known as SSRIs (selective serotonin reuptake inhibitors), such as Prozac, and whether they found these medications effective. The study encompassed nearly 20,000 individuals.
Approximately three-quarters of the participants reported that antidepressants had provided them with some degree of relief, “at least a little.” However, the findings indicated that certain groups were less likely to experience benefits. Specifically, men and older individuals were found to be less responsive to these medications. Additionally, the study highlighted that “non-responders” were more likely to have lower incomes, resort to alcohol or illegal drugs as mood enhancers, and have experienced depression for over two years.
Factors Influencing Mood Improvement
Another notable risk factor linked to a diminished likelihood of benefiting from antidepressants was the absence of mood elevation in response to positive events. On the flip side, individuals were more likely to report improvement from antidepressants if they were women, younger, had higher incomes, did not use alcohol or illegal drugs for mood enhancement, and had not been grappling with depression for an extended period.
However, the study did not delve into the reasons behind these associations, and it should not be assumed that these factors directly caused the differences in response rates. Professor Cathryn Lewis, a geneticist at King’s College London (KCL), emphasized, “We don’t know whether this is cause or effect.”
Moreover, individuals who consume excessive alcohol or engage in illegal drug use may miss doses of their antidepressants, potentially diminishing their effectiveness. It is also worth noting that while many believe alcohol can uplift their mood, it often exacerbates feelings of depression.
Another risk factor for a poor response to antidepressants identified in the study was a genetic variant that impairs the liver’s ability to metabolize these medications. This could lead to elevated levels of antidepressants in the body, increasing the risk of side effects.
The relatively high proportion of individuals reporting positive outcomes from antidepressants was welcomed by Professor Peter Tyrer, a psychiatry researcher at Imperial College London who did not participate in the study. “A 75 percent positive response is a very significant finding,” he remarked. These results align with previous smaller randomized trials, although such trials typically involve participants who are in better overall health and have less complex mental health issues. “Trials don’t account for the variations within the population. A major advantage of these large-scale studies is that they can,” he added.
Antidepressants have faced scrutiny in recent years, with independent analyses of pharmaceutical company trial outcomes suggesting that their effect on mood may be minimal compared to placebo groups. Dr. Michelle Kamp, a postdoctoral research associate at KCL, stated, “The usage of antidepressants, and how frequently they are prescribed in the UK, has been a topic of much debate. This research offers reassuring evidence that many individuals feel this common type of medication helps them manage what can be a debilitating illness.”
The Placebo Effect
However, Professor Joanna Moncrieff, a psychiatrist at University College London who has previously expressed concerns about the increasing reliance on antidepressants, pointed out that depression is particularly sensitive to the “placebo effect.” This phenomenon occurs when symptoms improve simply due to patients’ expectations of improvement. “This study was not an evaluation of the actual response to antidepressants. It was an assessment of how people perceive their antidepressants,” she clarified. “We know that most individuals who respond to an antidepressant will also respond to a placebo.”
Professor Moncrieff suggested that some of the identified “risk factors” for non-response might merely indicate markers of more severe conditions, such as lower income. “Individuals with milder conditions tend to improve on their own and may therefore attribute their recovery to the antidepressant. In contrast, those with more severe conditions may not experience improvement and thus feel that the medication has failed them,” she explained.
A spokesperson for the Royal College of Psychiatrists noted, “Most patients will benefit from antidepressants, but, as with all medications, some individuals may experience side effects or have negative experiences. Hence, their usage should be carefully monitored and regularly reviewed. We advise anyone considering discontinuation of their antidepressant to consult their doctor first, as these medications should not be stopped abruptly.”
