In September of 2019, Jakobsen, Gluud and Kirsch published a review in the British Medical Journal: Evidence-Based Medicine entitled “Should antidepressants be used for major depressive disorder?” (1)
Their conclusion was this:
“Antidepressants should not be used for adults with major depressive disorder before valid evidence has shown that the potential beneficial effects outweigh the harmful effects.”
Now, before we move on with what drove them to make this seemingly radical conclusion, I want to be clear:
I am not stigmatizing medication.
All of those who take medication for depression have asked for help.
Asking for help is important.
Asking for help is brave.
And, whatever help works for you is the right kind of help.
But imagine this; imagine you are a pretty decent swimmer.
You’ve practiced swimming all your life. You’ve gotten lots of experience swimming in pools, lakes, and oceans. You know how to swim, just like you know how to cope with turmoil. But, despite your strength, one day you find yourself drowning.
“No, I’m not drowning,” you might say at first. “I can’t be drowning. I know how to swim! If I’m drowning, it means I’m a failure…
“What will everyone think?”
And so you continue to splash around a bit, until it becomes undeniable. You gasp some water-filled air. Your head submerges and you think, indeed, “I’m drowning.”
When you get your head above water you call for help.
This takes a lot.
It’s not easy to admit that you need help.
It’s not easy to overcome that little voice that tells you that asking for help is troubling other people, admitting defeat, showing weakness—and whatever else that darned little voice thinks it means.
“HELP!” You exclaim, louder this time—little voice be damned.
“HEEELP!”
And someone on shore sees you. They have a life-preserver in their hands and they throw it your way.
Your shame is peppered with relief—and gratitude: there’s an answer to all this suffering. You thrust your hand towards the life preserver, grasping it with a firm bravery.
Only, it starts to sink. It’s full of holes.
“What’s the matter?” The person waiting on the shore exclaims, as you continue to struggle, “Don’t you want help?”
The shame returns. Hopelessness joins it.
I advocate for mental health awareness. I advocate for perpetuating the message that it’s ok to talk about mental illness. It ok to admit you need help.
I believe the following:
Depression is not a a sign of weakness.
It’s not a sign that you are defective.
It’s not a sign that you haven’t learned proper coping skills, or that your coping skills are defective, or that you’re fragile.
It’s also not fixed by simple solutions like eating salad, running or putting “mind over matter”.
Depression happens to a lot of us.
It affects 300 million people globally. It is the leading cause of disability world-wide, with a lifetime prevalence of 10 to 20%. This means that 1 in 5 people will experience depression in their lifetimes.
We all know someone who suffers. Maybe you suffer.
And a lot of people ask for help. The National Health and Nutrition Examine Survey (NHANES) in 2017 found that 1 in 8 people over the age of 12 are taking an anti-depressant, a 65% increase over the last 15 years.
This means that 65% more of us are asking for help.
That’s a lot of life preservers.
So, just how effective is this help?
First, we need to understand how the efficacy of anti-depressants are measured.
The symptoms of depression are subjective. This means they are not observable. There is no imaging that shows if someone is depressed. There are no blood tests for depression. There are no physical exams.
Therefore, to assess the presence and severity of depression, clinicians use questionnaires. The most commonly used depression questionnaire is The Hamilton Depression and Rating Scale (HDRS), a 52-point checklist that assesses various symptoms of depression and rates them on a scale of no-depression to severe.
When patients with depression first see a family doctor or psychiatrist they are often issued the HDRS and given a score.
Let’s use Janet’s story as an example. Janet first came to see her psychiatrist two years ago. She wasn’t sleeping and yet felt sleepy all the time. She’d gained weight but had no appetite. Her entire body was sore, as if she had the flu. She’d lost interest in all of the activities that used to fire her up. She’d lost interest in everything.
After a few weeks of feeling progressively worse, Janet began to be plagued by thoughts of suicide. This scared her. She went to her family doctor, who referred her to a psychiatrist.
Janet’s HDRS score was 25. This meant she was moderately to severely depressed.
Janet was given an anti-depressant, a Selective Serotonin Re-uptake Inhibitor (SSRI). She was told it would correct her “brain imbalance”, and treat the cause of her symptoms. Janet was relieved that there was a solution.
If an anti-depressant can decrease the HDRS by 3 points, then the medication “works”. Or at least the results are statistically significant.
However, if Janet’s symptoms improve by 3 points, from a score of 25 to, say, a score of 22, how does she feel?
Not much different, it turns out.
To experience “minimal improvement”, a decrease in symptoms that someone with depression would notice, say an increase in energy, an improvement in sleep, or a change in mood, a patient’s HDRS score would need to decrease by at least 7 points.
This means the Janet would need to bring her HDRS down to 18 or lower before she starts to feel noticeably better.
Studies show that anti-depressants, on average, don’t do this.
Some randomized control trials do show that anti-depressants decrease the HDRS score by at least 3 points, which is still registered by patients as having no perceptible effect, but the results are mixed.
A large 2017 systematic review showed that anti-depressants only decreased patients’ HDRS by about 1.94 points (2) and another large study published in the Lancet (3) also failed to show that anti-depressants produce a statistically significant effect, let alone a clinically significant one.
In addition to the minimal changes in symptoms, anti-depressant research is also polluted with for-profit bias. Most studies are conducted or funded by the drug companies.
This makes a difference: an analysis showed a study was 22 times less likely to make negative statements about a drug if the scientists worked for the company that manufactured it (4).
Studies at high-risk of for-profit bias were also more likely to show positive effects of a drug (5).
Another limitation of anti-depressant trials is the lack of active placebo control. In Randomized Control Trials, participants are sorted into two groups: an active group, in which they receive the medication, and a placebo group, in which they receive an inert pill.
The goal of this process is to control for something called the “meaning response”, or “placebo effect” where our expectations and beliefs about a therapy have the potential to affect our response to it.
Remember that depression, as I mentioned before, is a condition made up of subjective symptoms.
If I asked you to rate your energy on a scale of 1 to 10, how would you rate it? What if I asked you tomorrow? What if I asked you after giving you a drink of something that tastes suspiciously like coffee?
Because of its subjective nature, and the subjective questionnaires, like the HDRS, that measure it, depression is very susceptible to the placebo response.
Therefore, it’s important to control for the placebo response in every trial assessing anti-depressants.
But it might not be enough to just take a sugar pill that looks like an anti-depressant.
SSRI medication produces obvious side effects: gastrointestinal issues, headaches, changes in energy, and sleep disturbances, to name a few.
When a patient taking a pill (either placebo or active treatment) starts to feel these side effects, they immediately know which group they have been randomized to, and they are no longer blinded.
This can be solved by giving an “active placebo”: a placebo that produces similar side effects to the active medication. Unfortunately anti-depressant trials that use active placebo are lacking.
But what about the people who DO benefit from anti-depressants?
Janet knew a few. She had a cousin who also suffered from depression. He took medication to manage his symptoms. He’d told her many times that he just wasn’t the same without it.
Perhaps you, reading this article have found benefit from an anti-depressant medication. Perhaps you know someone who has: a family member, or a friend. Maybe it was their lifeline. Maybe it’s yours.
According to Jakobson et al., there are indeed some people who benefit from anti-depressants. Anecdotally we know this to be true. However, the results of large studies show minimal to no benefit from medication, on average.
This means that some people might benefit; we know that some do. It also means that an equal number of people are harmed.
In order for the net effect of anti-depressant medication to be close to zero, an equal number of people experience negative effects that outweigh the positive effects seen in others.
So, while some may have already tried medication and benefited from it, those considering medication won’t know if they’ll be in the group who benefits, or the group who is harmed.
The side effects of anti-depressant medication are often underrepresented. In the Lancet study, adverse effects were neither recorded nor assessed (3).
The most common side effects include gastrointestinal problems, sleep disturbances, and sexual dysfunction. More serious side effects, like increased risk of suicide, are also possible. Some of these effects may persist even after the medication is stopped.
Anti-depressant trials are short-term. Most trials assess patients for 4 to 8 weeks, while most people take anti-depressants for 2 years or longer.
Anti-depressants also put people at risk of physiological dependence and withdrawal.
Withdrawal symptoms can occur a few days, or even weeks, after tapering anti-depressant medication. They sometimes last months.
Withdrawal symptoms are often mistaken for depressive relapse. This can make it difficult, or even impossible, for patients to come off medication. This is worrisome considering the lack of research on long-term medication use.
It is sometimes argued that anti-depressants are more effective, or even essential, for severe depression, however the evidence for this is lacking (4).
In their paper, Jakobson, Gluud and Kirsch conclude that, based on the evidence, anti-depressants show a high risk of harm with minimal benefit.
Before prescribing them, Jakobson et al recommend more non-biased, long-term studies that use active placebo, and honestly assess the negative effects of the medications.
They recommend that studies use improved quality of life and clinically meaningful symptom reduction, not just statistical significance, as standards for treatment success.
Despite these conclusions, SSRIs remain a first-line treatment for major depressive disorder. They are also prescribed for conditions like severe PMS, IBS, anxiety, grief, and fibromyalgia, or other pain conditions. 1 in 8 adults in North America are taking them.
As a clinician who focuses in mental health, I am not against medication.
I have seen patients benefit from SSRI or SNRI medications. Sometimes finding relief with medication when nothing else worked.
My clinical practice keeps me humble.
If a patient comes into my practice on medication, or considering medication, I listen. I ask how I can support them. I answer questions to the best of my ability. I trust my patients.
Patient experience trumps clinical papers.
However, for every patient who benefits from medication, just as many experience negative side effects, or no effect. I trust their experiences too.
I also trust the experiences of the patients who have been trying for months, or years, to wean off medications.
Let me repeat it again: depression is real. Asking for help is hard. And it’s important.
Depression is a multi-factorial condition.
This means that it stems from hundreds of complex causes. This is why it’s so difficult to treat. This is why so many people suffer.
Let me also repeat: depression is not easily fixed.
There is no one solution, and there are certainly no ONE-SIZE-FITS-ALL solutions.
So, if you or someone you care about is suffering from depression, what can you do?
First, get help. This is not something you can get through alone.
Second, seek lots of help: gather together a team of professionals, family and friends. You can start with one person: your family doctor or a naturopathic doctor, and then assemble your support network.
Choose people you trust: people who listen, provide you with options, and seek your full informed consent.
It is important to work with a healthcare team who take into account the factors that may be contributing to your symptoms: brain health, gut health, life stressors, nutrition, inflammation levels, presence of other health conditions, sleep hygiene, family history, contributing life circumstances, such as grief, trauma, or poverty, and who lay out various treatment options while filling you in on the risks, benefits and alternate therapies of each.
Medication may be part of this comprehensive treatment plan, or it may not.
It is brave to ask for help.
And I believe that bravery should be rewarded with the best standard of care—with the best help.
References:
- Jakobsen JC, Gluud C, Kirsch IShould antidepressants be used for major depressive disorder?BMJ Evidence-Based Medicine Published Online First: 25 September 2019. doi: 10.1136/bmjebm-2019-111238
- Jakobsen JC, Katakam KK, Schou A, et al. Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and trial sequential analysis. BMC Psychiatr2017;17:58
- Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. The Lancet2018;391:1357–66
- Kirsch I, Deacon BJ, Huedo-Medina TB, et al. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the food and drug administration. PLoS Med2008;5:e45.doi:10.1371/journal.pmed.0050045
- Ebrahim S, Bance S, Athale A, et al. Meta-Analyses with industry involvement are massively published and report no caveats for antidepressants. J Clin Epidemiol2016;70:155–63.doi:10.1016/j.jclinepi.2015.08.021
