Do Antidepressants Really Work?

by Paul Cullen, Ph.D. on February 14, 2013

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Whether or not antidepressants work has been hotly debated by mental health professionals over the last three years. In this article I want to put forward a balanced opinion about how effective antidepressants may or may not be. Before I begin, I can’t emphasise strongly enough that you always consult your physician before making any changes to your medication regimen.

What are antidepressants?

The most commonly prescribed antidepressants at the moment are a class of medications called Selective Serotonin Reuptake Inhibitors (SSRIs). As you almost certainly already know the brain is made of nerve cells that transmit messages to each other. These messages are transmitted along nerve cells by electrical impulses. When one nerve cell needs to transmit a message to another nerve cell chemicals are sent across the gap between the two nerve cells. The different chemicals released send different kinds of messages from one nerve cell to another. The SSRI medications function by causing an accumulation of a chemical called serotonin in the gaps between nerves and therefore increasing the strength of the message.

Serotonin is involved in regulating mood, sleep, muscle contraction and learning. So far so good, but this theory has some serious holes in it. Research so far has been unable to find convincing evidence that people experiencing depression have decreased serotonin (or any of the other molecules that send messages across the gaps in nerve cells). You also cannot make people depressed by reducing their amount of serotonin.

Who says they work?

Drug companies tell us they work. Now I’m certainly not against drug companies; they’ve developed thousands of effective medicines that help reduce suffering and prevent deaths. It costs millions of dollars to do the research needed for drug development and millions more to demonstrate the drugs are effective and get them approved by government bodies. With that said there is a big financial incentive for the pharmaceutical companies to produce drugs that recover their costs and make a profit for their shareholders. They call these ‘blockbuster’ drugs and SSRIs have certainly been blockbusters for the drug companies. They are now the most commonly prescribed type of medication in the USA with 11% of americans age 12 and over taking antidepressants. Antidepressant sales are estimated at 20 billion dollars a year.

Since the introduction of SSRI antidepressants the diagnosis of depression has increased 500-1000 fold. Sound fishy that since these drugs came out a hell of a lot more people have depression.

How effective are antidepressants claimed to be? According to the president of the American Psychiatric Association, Dr. Jeffery Liberman:

“As a class, antidepressant medications are highly effective. They alleviate substantial amounts, if not complete symptoms, in 50 to as high as 80% of patients treated who suffer from major depression”.

Who says antidepressants don’t work?

Many researchers and clinicians are skeptical that antidepressants are as effective as the studies conducted by the drug companies would have us believe. Their skepticism is based on several factors. Firstly, there are the results of what researchers call meta-analyses. Meta-analysis is a process where the results from many clinical trials are combined to provide a more accurate measure of how effective a treatment is. A landmark meta-analysis of antidepressant clinical trials was published in the Journal of the American Medical Association in 2010 the results of which shocked professionals the world over.

In these studies, people are included in clinical trials who are not given medication but unbeknownst to them are given a sugar pill (placebo) instead. The meta-analysis showed that 82% of the effect of the medication was attributed to the placebo effect, which is largely caused by the expectation that the medicine will make you better. The mind is powerful, isn’t it? This conclusion of the study was as follows:

“The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.”

Another reason researchers are skeptical is that drug companies have been withholding clinical trials that produce results that their drugs aren’t effective. Of 74 registered clinical trials only 37 with positive results were published. The remainder were either not published or presented in a way that made it seem the drugs were effective.

Some researchers and practitioners are also asking the question “What is depression anyway?” The diagnosis for depression is based on a checklist that people came up with; it’s not like diabetes where you can measure blood sugar levels. It may be that not all the people being diagnosed with depression are suffering from the same thing. Hence, we’re probably comparing apples with oranges, which makes trying to figure out whether a medication is effective considerably difficult.

My opinion

My personal opinion based on the drug company trials, the researchers’ meta-analysis and my clinical experience is as follows:

  • Depression is over-diagnosed and consequently many patients are inappropriately treated with antidepressants
  • Antidepressants are likely to be ineffective for the majority of people diagnosed with depression (being mild to moderate depression)
  • A fraction of people, especially those with severe depression, may benefit tremendously from treatment with antidepressants

I want to emphasise that the response to antidepressants is highly variable depending on the person. This is best illustrated by the words of one of my clients, “I may as well have been swallowing Tic Tacs for all the good they did me”, whilst there are other clients I see who are generally doing well, but find that their depression returns each time they try to go off antidepressants.

What to do?

I recently had a couple contact my practice who wanted to know if there was a pill I could prescribe them that would fix their marriage. This is how far we’ve come that we believe we can take a pill to fix about any problem. Many of the people that come to see me have depressing life situations and if I transposed myself into their situation I would feel depressed or anxious too. It is worth evaluating what you might need to change in your life before trying to fix the way you feel with a pill. In my opinion anyone who is taking any kind of psychiatric medication should have a course of psychotherapy and check in with his or her therapist at regular intervals. Psychotherapy has been shown to be highly effective for the treatment of depression without medication or in combination with medication. A meta-analysis of the effectiveness of psychotherapy was published in 2008 in the Journal of The American Medical Association showing that after psychotherapy treatment 96% of patients were better off than the comparison groups.

I’d be interested to hear your personal experiences with antidepressants in the comments section below. Were they helpful, ineffective, or harmful?

The team at Paul the Counsellor provides confidential, supportive, non-judgemental counselling and psychotherapy to individuals and couples in the Melbourne CBD.

0458 090 687
253 Lonsdale St, Melbourne VIC 3000

{ 15 comments… read them below or add one }

tash February 14, 2013 at 10:58 AM

extremely well explained and fairly presented. food for thought…thank you.


Torsten Seemann February 14, 2013 at 11:15 PM

Good article.
Now if you could define serious versus very serious depression that would be helpful.
Also I think you mean 1000 times not 1000 fold. A fold is a doubling.


Paul Cullen, Ph.D. February 15, 2013 at 12:23 PM

As usual Torsten a fine critical analysis. Prior to the introduction of SSRIs, depression was considered to affect only 100 people per million. Since the introduction of SSRIs, prevalence rates for depression are now considered to be in the range of 50,000 to 100,000 cases per million. By my calculations that is a 500 to 1,000 fold increase. Re measuring severity ‘instruments’ such as the Hamilton Depression Rating Scale are used. However, I agree these are subject to some degree of subjectivity. Thanks for reading.


Lisa Carlton April 23, 2013 at 1:35 PM

I would just like to say as someone who has been diagnosed with mild to moderate anxiety/depression, I am pro-meds at least in this situation. I was diagnosed in 2009, and my doctor was very reluctant to do so (because, I was fairly young at the time). I actually went back two or three times before he finally prescribed me something. I am a completely different person when I am on my meds than when I am off. They help me HUGELY in my daily life to stay balanced and to feel “normal.” When I am off of them I turn in to a “monster” I hate my self and I am not an easy person to be around. My only complaint is that there is no fool-proof method for finding the “right one” for you at least according to my doctor. I swear I have been on like at least 7 different ones, before, I found one that worked for me and then after a while that one stopped working and I had to switch, but I will say I am much “happier” or at least a lot easier to get a long with when am on them, just ask my husband.


Paul Cullen, Ph.D. April 26, 2013 at 4:23 PM

Hello Lisa. Thanks for stopping by and reading the blog. It’s great to hear that meds have been helpful for you despite having moderate anxiety/depression. Although describing yourself as a monster sounds more than moderate. I think this shows how variable the response can be. Also if you’re looking at 82% of the effect being placebo it’s quite possible this is at play here too. If you’re feeling good and the rest of your life is in check then keep doing what you’re doing.


Larus S Gudmundsson May 17, 2013 at 1:02 AM

Thank you for a good explanation on topic that is not easily explained.
We need more balanced discussions like the one here above.
As a researcher who studies people who suffer from migraine headaches where depression is often involved, I hope we can increase awareness about both conditions and reduce the ignorance and the stigma that is still present.
We need more well conducted population based studies were we collect information prospectively on health status and what treatments pharmacological and non-pharmacological people are receiving. We also need to collect information about what people are doing on there own with out any help from others and how they feel from day to day.
Then we can start go get an idea what really works and maybe find out why different treatment strategies are needed and which strategy is best in each case.
Regarding the clinical trials, the registry of trials and demand for reporting the results is good. What we need is a better structure on how the date will be gathered, analyzed and reported before the trial is accepted. We should still let the pharmaceutical companies do their secondary or tertiary analysis (which often is not in their original protocol) but results like that have to be taken with a grain of salt, and more looked at as a exploratory analysis.


Paul Cullen, Ph.D. May 18, 2013 at 8:21 PM

Hello Larus. Thanks for stopping by. Great comment.


Mackenzie May 24, 2013 at 11:34 AM

I’ve been seriously wondering if antidepressants would be a good idea for me. I’m a terrible judge at how depressed I am, though. I’ve been going to a therapist for a few months and it doesn’t seem to help much. And I have this idea in my mind that if this one event in my future doesn’t turn out the way it needs to, I’d almost be better off dead. I’m thinking that even if a medication’s effectiveness would be mostly the placebo effect, it might be worth it anyway.


Lisa Carlton May 24, 2013 at 10:32 PM

I’m no dr. But in my experience, it would be worth a try. When I am on my meds I feel better over all, saying you would almost rather be dead, seems pretty severe to me, I think it would be worth a visit to your PCP


Paul Cullen, Ph.D. May 24, 2013 at 10:54 PM

Hi Lisa. Thanks for your comment. Sage advice. Much appreciated.


Paul Cullen, Ph.D. May 24, 2013 at 10:54 PM

Hello Mackenzie. Thanks for stopping by. You’re clearly doing the research to see what will work best for your situation. I wouldn’t rule medication off the list either. If you haven’t already it’s critically important to let your therapist know that you’re feeling you’d almost be better off dead. Feel free to get in touch and remember there is help out there. Take care.


Claire August 14, 2013 at 3:50 PM

Thank you for the interesting article. I have just come home from hospital after being treated for depression. In my case I would have struggled without an antidepressant to take. For me I needed a combination of a pill to take and intensive therapy just to begin to feel better.


counselling in northampton July 11, 2014 at 9:23 PM

Interesting stuff. I’m not a massive fan of antidepressants but I have clients who swear they need them. As a counsellor, I don’t prescribe medication of course, but its my job to help my clients with depression so I suggest alternatives. Just going to a walk every day has massive benefits. Not only does it lift the soul (on a nice day!) but it also stimulates production of Serotonin therefore providing natural medication. I guess its hard to work out which approach works best if a doctor has already prescribed something.


Graham M March 24, 2016 at 5:51 AM

I have been on all most every antidepressants made and have been abusing drugs along the way for almost 5 years. It was not until 6 months age I was placed on 225 mg of Venlafaxine also know at Effexor within 3 weeks after starting the new drug my mood went for a 1 to a 9 and I stopped using Crack and never picked it up again or no craving at all. Effexor has been like a blessing from God. I have never been happier or a brighter out look on life before.


Tahlia C June 20, 2016 at 6:14 PM

Hi Paul,
Just read this now…very open discussion and good to hear the different perspectives on this topic. On a personal note…anti depressants did not work for me in the year that I took them – looking back in hindsight, I really feel there is so much more I could have done for myself before taking daily pharmaceuticals. Last year I found Amen Clinics by Dr Daniel G. Amen MD did his online brain test, and bought and took a course of his Brain MD products. What a difference this made to my mental state and wellbeing. Now I’m onto his books to further educate myself on this topic (brain health and brain types particularly) but even the website has a lot of information there on the blogs which creates a lot more awareness even for someone with perhaps a limited understanding – it can provide you with more options in that perhaps not everyone will do well on anti depressants, and that there is no “pill” to fix a problem, most things like the laws of nature take a bit of time.
Kindest Regards,


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