A new study has found that antidepressant resistance is more common than was thought: 48% of people with depression have tried at least two medications without effect, while 37% have tried four or more. It suggests the need for an urgent rethink of the current approach to treating depression.
Depression is a debilitating condition that pervades all aspects of a person’s life. But when antidepressants, the first-line treatment for depression, don’t effectively relieve the symptoms of the condition, then an additional layer of hopelessness gets added to the mix.
A recent study led by the University of Birmingham in the UK has highlighted just how common the issue of treatment resistance is in people with depression. And the findings are, frankly, concerning.
“This paper highlights how widespread treatment-resistance depression is among those who are diagnosed with depression,” said Kiranpreet Gill, a PhD candidate from the University’s School of Psychology and the study’s lead and corresponding author. “With nearly half of all patients not responding to multiple drug options, we need better treatment options to be able to support patients for whom first-line antidepressant medications don’t make a difference.
“Furthermore, the experiences of patients who took part in this study shows that more awareness and options for treating depression when first-line antidepressant medications don’t work well is urgently needed.”
The present study is the first to adopt a mixed-methods approach to understanding the prevalence of treatment resistance in people with depression. This means that both quantitative (numbers, statistics, measurable data) and qualitative (interviews, surveys) research methods were used to provide a fuller, more well-rounded overview of the issue.
Electronic health records maintained by the UK National Health Service (NHS) were used to identify current adult patients with a diagnosis of major depressive disorder (MDD). Current patients were chosen so that the researchers could better understand the ongoing treatment challenges in this population. The Maudsley Prescribing Guidelines, or MPG, were used to classify people with treatment-resistant depression (TRD). The MPG is a set of evidence-based guidelines used by healthcare professionals, particularly in psychiatry, to support the safe and effective prescribing of medications for mental health conditions. TRD was defined as “failure to respond to at least two antidepressants prescribed at a therapeutic dose for 4-6 weeks within the current depressive episode, without treatment progressing to a third antidepressant and/or an augmenting agent (e.g. lithium) following two failed trials.” If patients met this definition, they were classified as having TRD. If not, they were classified as having MDD.
Of the 5,136 patients diagnosed with MDD, nearly half (47.92%) met the criteria for TRD, with the remaining 52.08% classified as having MDD. According to the definition of TRD adopted by the researchers, that means that 47.92% had trialed at least two antidepressants without effect. Somewhat concerning was the finding that 36.93% had unsuccessfully trialed four or more antidepressant treatments.
Although both groups experienced single episodes of MDD, people with TRD exhibited a significantly higher prevalence of recurrent depression than those with MDD: 31.76% vs 26.62%. People with TRD who died were, on average, about five years younger at the time of death than those with MDD. Compared to those with MDD, people with TRD had significantly higher rates of substance use (20.85% vs 18.17%), anxiety disorders (30.80% vs 24.50%), personality disorders (16.54% vs 11.18%), self-harm (2.70% vs 0.90%), and psychosis (15.03% vs 8.30%).
“There is an irony that the experience of struggling to treat depression is in itself a risk factor for a worsening sense of ‘hopelessness’ as one patient described it,” Gill said. “This should be a clarion call to recognize that treatment-resistant depression needs to be factored into clinical decision making and the ongoing support that patients are offered.”
In addition to the effect of TRD on other mental health conditions, compared to those with MDD, individuals with TRD had a higher prevalence of physical health concerns, including smoking-related diagnoses, cardiovascular, respiratory, and gastrointestinal disease, as well as higher rates of both type 1 and type 2 diabetes.
The study’s qualitative data came from interviews with clinicians and people with TRD. One patient stated, “I’ve taken that many antidepressants that my synapses are just frazzled.” And a clinician commented, “I have seen patients who have been on like every single antidepressant under the sun. And when you go back and look at the records … they might have had some sort of response, but then it wasn’t titrated up.” Both patients and clinicians acknowledged that the ‘one-size-fits-all’ approach that relied heavily on medication was inadequate.
The study has limitations. Because it was based on data from electronic health records that focused on psychiatric ICD-10 codes, physical health conditions may have been underreported. Additionally, self-harm incidents are often recorded as free-text notes rather than ICD-10 codes, making them harder to capture. So, the self-harm figures reported in the study may underestimate the issue. However, it also had strengths, including its mixed-methods approach and the fact that its findings were based on a large, diverse dataset.
“This study is important as the data demonstrates people with TRD are at a higher risk of a range of poorer outcomes, and that we need better-defined care pathways for helping this population, and are in urgent need of developing and testing new treatments for this group,” said study co-author Professor Steven Marwaha, a consultant psychiatrist at Birmingham and Solihull Mental Health NHS Foundation.
The study was published in The British Journal of Psychiatry.
Source: University of Birmingham
