Frozen Progress: What’s Holding Back the Evolution of Depression Treatment?
It’s been over 50 years since antidepressants like Prozac revolutionised the treatment of depression. And yet, for millions of people dealing with this condition, the landscape of treatment hasn’t changed much. Most still rely on selective serotonin reuptake inhibitors (SSRIs), even though many question just how effective these medications really are — especially for mild to moderate depression. So, have we hit a wall in treating depression with medication alone, or is there a new way forward?
Globally, depression affects over 280 million people, making it one of the leading causes of disability. Yet, despite the growing burden of this condition, treatments have made little progress over the past few decades. In this article, we’ll explore why depression treatment seems to have stagnated, consider new alternatives on the horizon, and argue for a more personalised, whole-person approach to addressing this complex disorder.
A Quick History of Depression Treatment
A century ago, the options for treating depression were limited and often bordering on barbaric by modern sensibilities. Psychoanalysis, inspired by Freud’s theories, was the go-to treatment. For those with severe symptoms, institutionalisation was common, though conditions in these facilities often did more harm than good.
Things changed dramatically in the 1950s with the introduction of the first antidepressants: monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). These medications were groundbreaking but came with serious side effects, making them difficult for many patients to use long-term.
Then came SSRIs like Prozac, introduced in the 1980s. These drugs, which work by preventing the brain from reabsorbing serotonin too quickly, were considered safer with fewer side effects than older antidepressants. And thus, the “chemical imbalance” theory of depression gained traction. The idea was simple: low serotonin levels caused depression, and SSRIs would fix that.
But decades later, many are wondering if that theory is too simplistic. SSRIs remain the most common treatment, but their limitations are becoming clearer.
Why Antidepressants Aren’t Always Enough
For people with severe depression, SSRIs can be life-changing. But for many with mild to moderate depression, the difference between taking an antidepressant and a placebo is surprisingly small. Research by Irving Kirsch in 2008 showed that in these cases, the impact of SSRIs is often barely better than a sugar pill.
One reason could be the placebo effect, which has grown stronger in antidepressant trials over the years, with placebo effects ranging from 30% to 50%. Some studies even suggest that 80% of the benefit from antidepressants may be due to placebo.
On top of this, SSRIs can have significant downsides. Common side effects include sexual dysfunction, weight gain, and emotional blunting. Worse, many people struggle to stop taking them due to antidepressant discontinuation syndrome, which can cause withdrawal-like symptoms such as dizziness, irritability, and a return of depressive symptoms. A 2022 review estimated that up to 56% of patients experience withdrawal when discontinuing SSRIs.
Rethinking the “Chemical Imbalance” Theory
For decades, the “chemical imbalance” theory dominated how we understood depression. But recent research, such as a 2022 review by Joanna Moncrieff, has shown that there is no solid evidence linking serotonin levels directly to depression. While serotonin may play a role, it’s not the whole story.
So, if low serotonin isn’t the main cause of depression, what is? It turns out that depression is far more complex than we once thought. Genetics, stress, trauma, inflammation in the brain, and even environmental factors all contribute to the disorder. Simply boosting serotonin with medication isn’t enough.
This oversimplified narrative has left many patients frustrated, searching for something more than what SSRIs can offer.
The Need for a Holistic Approach
Too often, treatment for depression has focused on fixing what’s wrong with brain chemistry while overlooking other factors that contribute to the disorder. The biopsychosocial model, which considers biological, psychological, and social factors, offers a more complete understanding of depression.
For example, Cognitive Behavioural Therapy (CBT) has been shown to be just as effective as medication for many people with mild to moderate depression. It helps individuals recognise and change negative thought patterns that contribute to their symptoms. Unlike medication, which often needs to be taken indefinitely, the benefits of CBT frequently last well after treatment ends.
Lifestyle changes also play a key role. Exercise, for instance, can reduce symptoms of depression by 48%, according to a meta-analysis. Improving sleep and diet, practising mindfulness, and addressing stress through social connections or therapy can all make a significant difference. But despite this evidence, many people still rely on medication alone — largely because it’s easier to get a prescription than access therapy or other non-medication treatments.
The Unseen Power Players Behind Stagnant Depression Care
Despite all the talk about advancing depression treatment, insurance companies and Big Pharma are two major forces keeping things stagnant. Insurance companies prioritise quick, cost-effective solutions, making medication the default option. Therapy and holistic approaches, while proven effective, are often too expensive to cover consistently. Studies show therapy can cost 3–5 times more than a year’s worth of medication, so patients are steered toward prescriptions, even if long-term results are lacking.
Meanwhile, Big Pharma has spent billions marketing antidepressants, reinforcing the now outdated chemical imbalance theory. This narrative helped make SSRIs the most common treatment for decades, but the focus on medication limits other promising therapies. Pharmaceutical companies have also heavily funded medical research and education, which has kept antidepressants at the forefront of treatment strategies. As a result, patients often feel trapped, cycling through medications while alternative treatments, such as CBT or lifestyle changes, remain underused.
Together, these forces have shaped the mental health landscape, ensuring that medications dominate, even when more personalised, holistic treatments could offer better long-term relief. Until we confront these influences, meaningful progress will continue to lag.
New Treatments: Promising or Overhyped?
As the limitations of SSRIs become clearer, new treatments are emerging. Ketamine, once used only as an anaesthetic, has shown rapid antidepressant effects, particularly for people with treatment-resistant depression. In one study, 71% of patients responded to a single infusion of ketamine within 24 hours.
Then there are psychedelics, like psilocybin (the active ingredient in magic mushrooms). A recent study found that 57% of patients treated with psilocybin experienced a significant reduction in their depression, compared to 28% in the group taking escitalopram (an SSRI).
Non-drug therapies like transcranial magnetic stimulation (TMS), which uses magnetic fields to stimulate parts of the brain involved in mood regulation, are also showing promise. These therapies are particularly helpful for people who haven’t responded to traditional treatments.
However, these new approaches aren’t without risks or limitations. Ketamine, for example, has the potential for abuse, and psychedelics remain illegal in many places. While these treatments offer hope, they also come with challenges around cost, accessibility, and the need for more research.
A Path Forward: Personalised Care
Looking to the future, precision medicine could be the key to moving past stagnation in depression treatment. Just as cancer treatment has been revolutionised by personalised therapies tailored to an individual’s genetic makeup, depression care could follow suit by addressing each patient’s unique biological, psychological, and social profile.
Digital therapeutics, such as AI-based mental health apps like Woebot, are also expanding access to care. These platforms offer real-time support, using techniques like Cognitive Behavioural Therapy (CBT) to help people manage their mental health between sessions. This could be a game-changer for those who may not have access to traditional therapy.
But ultimately, the future of depression treatment must be patient-centred. Each person’s experience of depression is unique, and treatment plans need to reflect that. By integrating medication, therapy, lifestyle changes, and social support, we can finally begin to move forward in breaking the stalemate in depression care.
Conclusion
Depression is too complex to be treated with a “one-size-fits-all” approach. While antidepressants like SSRIs help some people, they are not the solution for everyone. Emerging treatments like ketamine and psychedelics offer hope, but they’re not without risks. The key to moving beyond stagnation lies in a holistic, personalised approach — one that treats the whole person, not just their symptoms.
It’s time to rethink how we treat depression. We need more research into emerging therapies, increased access to non-medication treatments, and better education on the benefits of holistic care. Only then can we offer meaningful, lasting relief to the millions of people affected by this debilitating condition.
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References:
- Kirsch, I. (2008)
“Antidepressant Drug Effects and Depression Severity: A Patient-Level Meta-Analysis”
Published in: PLOS Medicine
Summary: This meta-analysis reviewed data from clinical trials submitted to the FDA, concluding that for individuals with mild to moderate depression, the difference between antidepressants and placebos was minimal. - Kirsch, I. (2014)
“The Emperor’s New Drugs: Exploding the Antidepressant Myth”
Published by: Basic Books
Summary: In this book, Kirsch argues that much of the benefit attributed to antidepressants can be explained by placebo effects, questioning their true efficacy. - Moncrieff, J. et al. (2022)
“The Serotonin Theory of Depression: A Systematic Umbrella Review of the Evidence”
Published in: Molecular Psychiatry
Summary: This review found no clear evidence supporting the serotonin imbalance theory of depression, challenging the long-held view that low serotonin levels cause the disorder. - Global Burden of Disease Study (2015)
“Global, Regional, and National Incidence, Prevalence, and Years Lived with Disability for 310 Diseases and Injuries, 1990–2015”
Published in: The Lancet
Summary: The study ranked depression as the single largest contributor to disability worldwide, accounting for 7.5% of all years lived with disability. - STAR*D Trial (2006)
“Acute and Longer-Term Outcomes in Depression with and Without Treatment-Resistant Features: A STARD Report”
Published in: American Journal of Psychiatry
Summary: The STARD trial, the largest study on treatment-resistant depression, showed that only about one-third of patients achieved remission after their first treatment attempt with an SSRI. - Zarate Jr., C. et al. (2006)
“A Randomized Trial of an N-Methyl-D-Aspartate Antagonist in Treatment-Resistant Major Depression”
Published in: Archives of General Psychiatry
Summary: This study demonstrated the rapid antidepressant effects of ketamine, with 71% of treatment-resistant patients responding to a single infusion within 24 hours. - Carhart-Harris, R. et al. (2021)
“Trial of Psilocybin versus Escitalopram for Depression”
Published in: New England Journal of Medicine
Summary: This trial showed that psilocybin was more effective than escitalopram (an SSRI), with 57% of patients in the psilocybin group showing a significant reduction in depressive symptoms. - Exercise and Depression Meta-Analysis (2013)
“The Effects of Exercise on Depression: A Meta-Analysis of Randomized Controlled Trials”
Published in: Journal of Psychiatric Research
Summary: This meta-analysis found that exercise could reduce depressive symptoms by up to 48%, highlighting its value as a non-pharmacological treatment option. - Woebot: AI-Driven Mental Health Support
Website: Woebot Health
Summary: Woebot is an AI-based chatbot that uses CBT techniques to provide real-time mental health support, offering patients assistance between therapy sessions.
