Anti-depressants. No more effective than a placebo?

By looking at the evidence surrounding anti-depressants for depression, this post will hopefully stimulate some useful dialogue to maybe rethink the way we approach this complex and debilitating disease.

What is depression?

Depression is a debilitating disease that is becoming ever so prevalent in our modern world.

Most of us either know someone with depression or have experienced it first hand ourselves.

If we think about this disease critically, it is hard to neatly define and categorize depression. This is because it involves a vast array of symptoms and causes that differ from person to person, however they all come under the umbrella of depression.

Basically, depression is a blanket term for a wide variety of cognitive, behaviour and mood disorders that also have physical symptoms.

Despite the heterogeneity of what is classified as depression, the current approach to its treatment is very much uniform, which is the prescription of anti-depressants.

There are currently 4 classes of drugs that are classified as anti-depressants.

These include:

  1. SSRI’s (selective serotonin re-uptake inhibitors)
  2. SNRI’s (selective noradrenaline re-uptake inhibitors)
  3. TCA’s (tricyclic amines)
  4. MAO (monoamine oxidase inhibitors)

SSRI’s are the most commonly used anti-depressants and are the first line of treatment for depression these days. Therefore, in this post, I will focus my discussion mainly around SSRI’s, however many of the concepts we address can be generalized to all of the types of anti-depressants.

SSRI’s contain the active ingredient sertraline, which is believed to exert the anti-depressant effects of SSRI’s, which are sold on the market under names such as Zoloft, Prozac, Lexapro, Celexa and Paxil.

As their name implies, SSRI’s have a mechanism in the brain whereby they inhibit the re-uptake of serotonin (a neurotransmitter) into pre-synaptic neurons in order to increase the bioavailability of serotonin in the brain.

Basically, they increase the amount of serotonin in the brain by inhibiting its re-uptake of it into neurons. Serotonin is a neurotransmitter, which are chemical messengers in the brain and nervous system that play various roles in digestive function as well as cognition, mood, memory and behaviour.

Most of the drugs used to treat depression have actions in which they alter the activity of and increase the amounts of various neurotransmitters in the brain, mainly being serotonin, dopamine and noradrenaline, as low levels and imbalances of these are supposedly implicated in the cause of depression. However, this idea of a  “chemical imbalance” in the pathology of depression will be addressed later on.

Like all drugs, SSRI’s and anti-depressants in general, come with a cocktail of side effects and potential adverse reactions. These include:

– Weight loss and appetite changes

– Sleep disturbances

– Nausea

– Diarrhoea

– Rash/hypersensitivity

– Agitation

– Anxiety

– Nervousness

– Restlessness

– Sexual dysfunction

– Headache

– Dry mouth

– Changes in mood, memory and cognitive function

– Increased blood pressure

– Increased suicide risk

– Impaired vision

– Movement disorders

– They have also been known to increase suicide risk (especially in children and teenagers), and result in the worsening of depressive symptoms like:

– Sleep disturbances

– Anxiety

– Panic

– Irritability

– Restlessness

– Hyperactivity

– Impulsivity

– Aggression

They also have the potential to alter brain chemistry permanently, predisposing a person to future depressive episodes and increasing the chronicity of depression.

Anti-depressants are no more effective than placebo

With a side effect rap sheet like that, you would hope these drugs are effective at treating depression right? However, the current evidence is starting to cast doubt on the effectiveness of anti-depressants in treating depression.

Which is clearly demonstrated in the fact that despite the increased use of anti-depressants, the depression rates are still rising.

In any one year, around 1 million Australian adults have depression. On average, 1 in 6 people – 1 in 5 women and 1 in 8 men – will experience depression at some stage of their lives.

Australia is second in the world for anti-depressant prescriptions and prescriptions in Australia appear to have doubled between 2000 and 2011. Eighty-nine Australians in every 1,000 are now prescribed some form of daily anti-depressant.

The potential explanation for these statistics is probably due to the fact that anti-depressants have been shown to be NO MORE EFFECTIVE than placebo in treating depression and decreasing suicide risk.

This was clearly demonstrated in the ever so controversial meta-analyses of Irving Kirsch.

Now people often say that anti-depressants are useful and necessary for severely depressed patients, however, the patients in the trials analyzed by Kirsch had a mean baseline severity rating that was in the ‘very severe’ range of depression for all but one of the trials. This rating was done using the American Psychiatric Association classification scheme. The one exception was a clinical trial involving moderately depressed patients, in which the response to a drug was virtually identical to the response to placebo.

These studies also make us realise the power of the placebo effect, which is likely to be the main driving factor behind anti-depressants working in clinical settings, because people believe they will work (which is influenced by the media and health practitioners), rather than having an actual effect, solely due to their chemical composition.

Placebo effects have been tested in clinical trials and can reverse the effects of powerful medications. They can affect the body as well as the mind. They produce side effects as well as beneficial effects. They can produce symptoms and also alleviate them.

Kirsch points out that there is good reason to believe that the placebo effect should be even greater on depression, which is why clinical trials display the results that they do. This is because hopelessness is a core feature of depression, and one of the presumed effects of a placebo is to instil hope.

Kirsch also mentions that it is feasible that there are other subgroups of patients for which antidepressants are more effective. This also points towards the fact that there are probably many different types of depression with differing causes and pathologies, hence anti-depressants only work for certain types and we are yet to define the different sub-types of depression.

This is important to note because there is no doubt that they work in some people with depression, however this is likely to be because the people that they do work in, have a certain type of depression for which anti-depressants can be useful. Depression can be caused by multiple factors that are a complex interaction between diet, lifestyle, genes and environmental factors. This is why a uniform treatment may not be effective. In my opinion, I believe anti-depressants may work in patients who have clinical signs of depression but have no situational basis for the way they are feeling. Meaning they don’t know why they feel depressed, as everything in their life is going well. These people may have some kind of neurotransmitter imbalance in their brain, being created by physiological causes that may be linked back to their diet, lifestyle or even a physical health issue. Anti-depressants help to correct this imbalance. This is unlike many other people who have internal (i.e. emotional issues) and external (i.e. life stressors) factors that can drive and exacerbate their depression. Their depressed state also increases poor diet and lifestyle choices, which further exacerbates their mental health issues, leading to a vicious cycle. For these people, anti-depressants are unlikely to work effectively because the underlying causes of the depression need to be addressed.

Lastly, another criticism of the studies done on anti-depressants is that they usually use participants who only have depression and no other health conditions or previous health issues. This is to reduce confounding variables. Therefore people with other medical conditions are excluded, however in the real world, most depressed patients have other concurrent conditions.

Overall, in conclusion, it can be said that both clinical studies and clinical experience shows that antidepressant drugs work, in the sense that patients get better when given medication. However, the same can be said for placebo drugs in depression. Patients given antidepressants in the clinical trials showed substantial and clinically significant improvement, as did those given placebo.

But if anti-depressants are no more effective than placebo, it makes me wonder why are they still on the market? This is an issue to address because they are not harmless to our health.

In my next post, I will explore a likely explanation as to why anti-depressants have been shown to be no more effective than placebo, by looking at the potential underlying drivers of depression.

If you suffer from depression, call Oak Health today or book an appointment online to find out how practical and evidence based diet and lifestyle changes, as well as herbal and nutritional supplementation can be used to address the underlying causes of your mental health issues. 

You may also want to enquire about the 6 week mental health treatment program.

Note: If you are currently taking anti-depressants, DO NOT stop taking them as a result of reading this article. Please consult your doctor first.