Do antidepressants really work? The short answer is no. Antidepressants do not work for the majority of people who use them. Do you suffer from depression? Better yet, do you use antidepressants? If so, then you might want to read this article.
If you use an antidepressant, did your doctor tell you that it was unlikely to work? Did he/she say that even if we try another antidepressant after the first one fails, it too is unlikely to be effective. It gets worse. Do you know that even a third or a fourth antidepressant is still unlikely to cure your depression?
Millions and millions of people use antidepressant medication. Despite this, clinical evidence that shows the benefits of antidepressant medication is remarkably thin. Read on to learn more.
Antidepressants vs Smarties
We need to be clear on the question. The question is “Do antidepressants really work?” I’m not asking if antidepressants are better than Smarties or placebo.
A 2018 meta-analysis published in the Lancet concluded that all 21 antidepressants they investigated are more effective than placebo. Whoopee!
In contrast, the following year a more powerful analysis appeared in the British Medical Journal. They came to the astounding conclusion that a firm statement is not possible. In their opinion, we cannot say if antidepressants are any better than placebo!
As a consumer of healthcare products, you should be be wary of such comparisons. Think about it! The critical question is not antidepressants vs placebo. Nor is it about one antidepressant versus another. Instead, we should be asking if using antidepressants makes you feel better. That’s the issue, isn’t it?
Does their use result in what we call remission of symptoms? In other words, do antidepressants really work and cure or fix or stop depression? The scary part is that the overwhelming weight of evidence tells us to the contrary. At best, only a tiny percentage of severely depressed individuals have meaningful improvements from using antidepressants. It’s bizarre that the side effects are so bad that most sufferers would be better off without the medication.
You’re Kidding, Right?
Wow, these statements are so at odds with conventional wisdom! Social conditioning makes us believe that we should use antidepressants when we’re feeling down. Right? So how come I am making such strong statements about the use of antidepressants? It’s simple, really. This is an issue of great importance to me. Depression has a terrible effect on many of my patients. Hey, it even affects me too at times.
I work in rehab, helping people recover from brain injuries, strokes and the like. I witness emotional blunting in my patients and it bothers me. Antidepressants make people emotionally numb. They kill drive and lead to passive acceptance of deficits. I want my patients to fight to recover. It’s very unhelpful when medication makes them flat.
So, I look to science for answers. I read a lot on the topic. What I am telling you here distils a large amount of scientific information. For those who would like the fine grain details, I’ve provided links to key papers below.
Okay, so let’s be clear. I am a caring clinician and scientist. I’m not a fruitcake extremist. Nor am I anti medication. I use prescription medication every day of my life. (No, not antidepressants). I certainly have patients who have benefited from antidepressant medication. Still, most patients that I encounter are unhappy with their antidepressants. They often get unpleasant side-effects. Furthermore, they report that the medication has not helped them.
The Depression Industry
Let’s not lose sight of the vested interests at play. Some players have a major investment in antidepressants, like the pharmaceutical companies, of course. Then, there are the doctors who make money prescribing antidepressants.
And the profits are astronomical! Astonishingly, the value of the antidepressant market was approximately $16.6 billion in 2023. Projections are that it will reach $25.52 billion in 2027. To put that into context, the country of Malawi’s GDP for 2023 was $15 billion.
There are substantial vested interests in selling antidepressants. Some people will be very angry about this article. No doubt I’ll be accused of bias, ignorance and lack of objectivity.
Do antidepressants really work?: The STAR*D Trial
In my universe, a drug trial often referred to in support of the use of antidepressants is the STAR*D drug trial. This is the largest and longest trial ever conducted to evaluate antidepressants. It ran from 2001 to 2006. A crucial issue is that these guys investigated the question of symptom remission. As we’ve seen, this is the crunch clinical issue.
The US National Institute of Mental Health funded STAR*D at huge cost. The study represents an attempt to optimize treatment with antidepressants. STAR*D is an acronym for “sequenced treatment alternatives to relieve depression.” It was a worthy project that included 4041 major depressive disorder (MDD) patients. The primary objective was to assess the effectiveness of treatment combinations for MDD, particularly for patients who did not achieve remission with the first antidepressant they used.
When a patient did not respond to first-line treatment (step 1), the good doctors tried again with up to three alternative antidepressants (steps 2-4). Careful thought went into dosage and type of antidepressant. This huge project resulted in 120 scientific papers that dealt with the many findings. Helpfully, they produced a summary of their findings. Go on, and have a look for yourself.
Do antidepressants really work? No: Check the numbers
In answer to the question of “do antidepressants really work?” the investigators report a remission rate of 36.8% in patients after step 1. That’s startling! In other words, as a first line treatment for depression, antidepressants failed for 63.2% of patients!
Furthermore, STAR*D found that the rate of side effects increased with each change in treatment. Each time you tweak the meds, the side-effects get worse! Also, the dropout rate increased from 28% in step 1 to 42% by step 3. Keep in mind that people drop out because they’re unhappy with the medication.
Playing with Numbers
Concerningly, the figures presented in the STAR*D summary statement significantly overstate the benefits of antidepressant medication. The extent of the misrepresentation is staggering and other scientists have raised serious concerns. If fact, when correctly interpreted, the stats shows a remission rate of only 17.8%. In other words, the initial failure rate was an astonishing 82.2%.
The STAR*D investigators claim a “theoretical” overall success rate of 67%. The figure is gobbledygook because, by their own admission, it assumes that no-one dropped out of the study. However, scrutiny shows that by step 4 only 35% of patients had achieved remission and had not relapsed or dropped out.
Now, my intention here is not to criticise the STAR*D trial; others have done that. So, let’s use the official STAR*D statistics. As noted, even on their own terms, remission occurred in only 36.8% of patients after starting on their first antidepressant. That’s a spectacularly high failure rate (63.2%). It seriously makes one wonder, do antidepressants really work?
One wonders how many patients would agree to using antidepressant medication if they knew the likely failure rate was so high. Imagine if your toilet was leaking. What if your plumber said that there was a 63% chance that it would still be leaking after his repair? Would you tell him to go ahead? I doubt it.
Why agree to such bad odds when it comes to your health?
Bias and Vested Interests
Vested interests feature strongly in discussion about antidepressants. Many papers are biased. Inaccurate reporting of drug trials is a huge problem. It makes it difficult to gauge the value of the medication. For instance, an important study compared published data to the data that by law had to be submitted to the FDA. They found that 94% of the drug trials were considered positive in the published literature, whereas the FDA data showed that only 51% were positive. Clear evidence of serious bias.
A metanalytic review concluded that a high chance of bias characterised all the research they investigated. Those authors considered the clinical benefits of antidepressants to be questionable. They also found that antidepressants significantly increased the risk of minor and major side effects. They concluded that “the potential small beneficial effects seem to be outweighed by harmful effects.”
Other Perspectives on Efficacy
The Journal of the American Medical Association published a major meta-analysis comparing antidepressants to placebo. Effectively, they addressed the question of “Do antidepressants really work?” They concluded that the benefits of antidepressants “may be minimal or non-existent, on average, in patients with mild or moderate symptoms.” It was only for patients with very severe depression that they reckoned that the benefit of antidepressants over placebo is substantial.
A task force appointed by the International College of Neuropsychopharmacology reviewed the use of antidepressants. The authors noted that “despite sufficient dosage, 25-50% of patients do not respond sufficiently to the initial treatment selection.” This echoes the STAR*D finding that that odds are that an antidepressant will not work first time round.
A nuanced meta-analytic study obtained data from the FDA on all clinical trials for four new generation antidepressant drugs. They specifically investigated the relationship between initial severity of depression and improvements due to drugs or placebo. There was virtually no difference in the improvement scores for drug and placebo in patients with moderate depression and only a small and clinically insignificant difference among patients with very severe depression. Additional analyses showed that the apparent clinical effectiveness of antidepressants among the most severely depressed patients reflected decreased responsiveness to placebo rather than an increased responsiveness to antidepressants. In short, the drugs were useless.
Other Considerations on Do Antidepressants Really Work?
Dose-response is a basic measure of the effectiveness of a drug. It turns out that there is no clinically meaningful dose-response relationship of SSRIs (the most common type of antidepressant) to symptoms of depression. On the contrary, for a few SSRIs, higher doses were associated with worse response!
This is telling us that there is not a direct link between symptoms and antidepressants. That’s important. It has been suggested that antidepressants create abnormal brain states that coincidentally relieve psychiatric symptoms.
Another study asked if antidepressants do more harm than good. They considered that antidepressants were modestly effective in reducing symptoms but increased the brain’s susceptibility to future episodes of depression. When all the adverse side effects were factored into the picture, they concluded that antidepressants do more harm than good.
Conspiracy Theory?
Is there a conspiracy between big Pharma and medical doctors to hoodwink depressed people into using antidepressant medication? No, it is not that simple. Still, there are uncomfortable facts. For instance, the US Department of Justice charged GlaxoSmithKline (GSK) for misrepresentation and other offences. The GSK antidepressant Paxil is not certified for paediatric use, yet they promoted Paxil for treating depression in children. GSK paid US$ 3 billion to settle the case.
According to Wikipedia, GSK documents from 1998 show that they intentionally chose to suppress unfavourable data showing a lack of efficacy because if was “commercially unacceptable.” In 2001, GSK “ghost wrote” an article that misrepresented clinical trial results.
Astonishingly, in 2013 GSK announced that they would no longer pay kickbacks to doctors to promote their products. At least in my country, it is a serious offence for a healthcare practitioner to receive kickbacks.
The Antidepressants Tsunami
More and more people are using antidepressants. In the USA, antidepressant use increased from 32.7 million people in 2013 to 37.3 million in 2018. In England, in the decade from 1998 to 2018, antidepressant prescriptions more than tripled. Get this, these increases are greater than the population growth. So, antidepressants are becoming increasingly popular. In the United States, monthly antidepressant prescriptions jumped by more than 66% between January 2016 and December 2022.
So, do antidepressants really work?
In this article we’ve addressed the question of “Do antidepressants really work?” We’ve seen that there simply isn’t decent evidece to support their use. At best, they might help very seriously depressed people, but even that evidence is thin. It’s astonishing that this vast industry is based on such flimsy evidence.
What are the Alternatives?
If not antidepressants, then what? This takes us off topic, but briefly there are alternatives. Talk therapy is popular. Programmes that target brain health, like our Neuroharmonics treatment can be beneficial. Vagal nerve stimulation (VNS) is a new and exciting FDA approved treatment for depression. The great thing about VNS is that it does not cause serious side effects. However, it’s new and at this stage we can’t say how effective it is.
Depression is a complex topic. We will be saying more about the issue. Antidepressant side effects deserve comment. Importantly, at least in my view, there is a lot we can do to improve symptoms and treat depression. It’s just that antidepressants are not the solution. Watch this space! Keep an eye on our website. Love our Facebook page. That way, you’ll see when there is an update.
