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Why Antidepressants Don’t Always Work – And What Can Make a Difference

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Why Antidepressants Don't Always Work - And What Can Make a Difference

The presence of hope can be just as powerful as its absence. Just ask anyone with depression. Depression is a devastating illness that thrives on hopelessness. This sense of hopelessness can be worsened when medication, often taken as a last resort, fails to deliver any relief. New research finds clues as to why antidepressants don’t work for everyone.

There are a number of treatments for depression, and amongst the most common are SSRI’s (Selective Serotonin Reuptake Inhibitors). About 50% of people who take SSRI’s find that their depressive symptoms are halved within 8 weeks of taking the medication. Then there are the other 50%. For those people, antidepressants just don’t work. 

Out of the people who do find relief, half of them will see a return of the symptoms, taking the actual recovery rate to 25%.

The way we think about depression is changing. 

Though SSRIs are a lifeline for many people, their sketchy levels of effectiveness have put pressure on the idea that depression is caused by a lack of serotonin. The way we think about depression is changing. More recently, there has been a dramatic shift away from the serotonin theory of depression. There are a number of reasons for this:

  • If depression was caused by low serotonin, it would be expected that medication which increases serotonin would be more effective than the 50% strike rate of SSRIs.
  • A number of studies (including here and here) have found that in some depressed people, serotonin is elevated.
  • There are other treatments for depression, including therapy, a combination of meditation and exercise, and medication that has little effect on levels of SSRI, that can reduce depression as much as SSRI’s do.
  • The key argument in the serotonin theory of depression was the observation that increasing serotonin relieved depression. However, in the same way that a headache is not caused by low levels of paracetamol, the effectiveness of SSRI’s does not necessarily mean that depression is caused by low serotonin.
  • Recent research points to the possible role of oxidative stress in depression. 

SSRI’s seem to have some capacity to heal, but not reliably, and only in around half of the people who take them. Clearly something is missing. New research seems to have found some pieces that can start to fill out the picture.

Why Antidepressants Don’t Always Work – Let’s talk about the research. 

In a study published in the journal, ‘Brain, Behavior and Immunity,’ researchers found important clues about how SSRI’s work, and more importantly, what can be done to increase their effectiveness.

 ‘There is no doubt that antidepressants work for many people, but for between 30 and 50% of depressed people, antidepressants don’t work. No-one knows why. This work may explain part of the reason.’ – Silvia Poggini, researcher, Intituto Superiore di Sanita, Rome.

From the research, it seems that the effectiveness of SSRIs doesn’t happen directly by increasing serotonin. What seems more likely, it that SSRIs facilitate recovery by increasing the plasticity of the brain so it can be changed, healed and strengthened by environmental and lifestyle factors. (Plasticity refers to the brain’s capacity to change.)

‘In a certain way it seems that the SSRIs open the brain to being moved from a fixed state of unhappiness, to a condition where other circumstances can determine whether or not you recover’ – Silvia Poggini. 

The research was conducted in mice. (Mice are often used in research in place of humans because of their biological and genetic similarity to humans.) After the mice had been stressed for two weeks, they were all given SSRIs. They were then split into two groups. Half the mice continued to be exposed to stress while the other half were put in a calmer, less stressful environment.

The mice that were treated with SSRIs and put into the more comfortable environment showed an improvement in their depression symptoms. In contrast, the ones who were treated with the SSRIs and put into the stressful environment showed a distinct worsening of their symptoms.

What makes a difference?

When someone takes SSRIs, the environment and the things that person does, play a critical role in whether he or she will get better, stay the same, or get worse.

The research suggests that the effects of the SSRIs aren’t necessarily on serotonin, but on the brain’s capacity for change. The medication conditions the brain for recovery, and the environment drives the recovery – for better or worse. The environment has a heavy influence on how the person will respond to the antidepressants.  

‘This work indicates that simply taking an SSRI is probably not enough. To use an analogy, the SSRIs put you in the boat, but a rough sea can determine whether you will enjoy the trip. For an SSRI to work well, you may need to be in a favourable environment. This may mean that we have to consider how we can adapt our circumstances, and that antidepressant treatment would only be one tool to use against depression.’ –Silvia Poggini. 

What can help?

Environment seems to be key. Environments that are nurturing and supportive of healing are more likely to change and strengthen the brain in a positive way. This might be enhanced if SSRIs have prepared the brain for this. On the other hand, environments that are stressful and unsupportive, and a lifestyle that doesn’t nurture the body and the brain, will potentially fail to make the most of any benefits of SSRIs.

The research is in its early days, and more will be needed before we have a clearer picture. 

In the meantime, an abundance of research has found strong evidence for the effectiveness of various lifestyle and behavioral factors in easing the symptoms of depression. These include meditation, exercise, reduced stress, diet, sleep, and the company we keep. These have been found to change the structure and function of the brain in ways that promote a healthy brain.

The idea that healing is more likely through a combination of environment and medication is nothing new, but this research gives us evidence of the importance of environment and lifestyle in healing from depression.

And finally …

The hopelessness that is so characteristic of depression can be worsened when medication fails to bring any sort of relief. For at least 50% of people, medication makes no dent at all in their symptoms. From the research, it seems that the effect of antidepressants may be more indirect than once thought. More importantly, it seems that they might not be as effective on their own, as they can be when lifestyle and environmental factors are able to support the healing.

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21 Comments

Frances

Great article! This is timely as my son *who has anxiety has asked me a lot of questions about medication. I take an SSRI as does my daughter and we find that it is not a cure for depression, but prevents us from slipping into the depths. Medication is just one tool in our toolbox that also includes a walking, running, gym classes (good for social support), healthy diet, sleep, gratitude, and prayer.

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Monique

This is so true. I have been taking antidepressants before, with no effect, apart from feeling an un-emotional shell of a person.
It appears I lived with a person who triggers my depression, and the first time I was truly happy and ALL signs of depression have lifted, was when I was so far away from her that there was no way she could follow me.
Now planning for a new life away, feeling more hopeful than ever before. All my other relationships improved nearly instantly. I’m still undergoing psychotherapy, but of course it will take time to be fully recovered.
Thank you for such a timely article – it strengthens my resolve not to take antidepressants.

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Carole Lyden

Hey Karan, I just love this site, when I have time to sit down to read. Always such sensible information. Depression is so unique and complex to each sufferer. It’s great to read a balanced article for a change.

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SharonH

I sometimes say that I was born depressed. Actually, it kicked in big time as I entered my teens and have been wrestling with it since. My opinion is that mine is half genetic, half situational.

That said, anti-depressants can lift my mood. My experience showed St. John’s Wort to have the exact same effect as the pharmaceuticals, though now I can’t take it due to a medication interaction. So they do work, but not all that much. Hardly worth the effort of taking them.

Because the situational part is so stressful and shows little hope of being resolved, I’ve found that my “escape” is medication and visualization. My mind can be taken to a much nicer place. Also, writing my feelings down helps quite a bit.

Perhaps the SSRI I’m taking does help my brain do these things better. Showing this article to my husband as he decided to stop his anti-depressant due to making him feel like a zombie.

Another very pertinent and informative article. Much appreciated.

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Amanda

What if taking an SSRI makes you feel worse? That happened to me 8 years ago, then as a result I was diagnosed with Bipolar 2 and set off on a road that ultimately led to taking a LOT of strong medications. Finally in the last year I have been able to take a wean off most of them and at last discovered how to be more mindful and grateful. I still don’t know how to make sense of that initial event where the SSRI made me feel worse and what else could have been done or how else it could have been interpreted.

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Karen - Hey Sigmund

A worsening of symptoms is definitely a potential side effect of SSRI’s, which is why finding the right medication can sometimes take a bit of experimenting. It’s not clear why this is, but one explanation according to this new research, is because SSRI’s work by making the brain more plastic, which means more open to change. The problem is that sometimes the conditions or the environment you are in might not necessarily support the change happening in a positive direction. In this study, the mice that were used showed a worsening of symptoms when they were put in the stressful environment. This is just one theory as to why SSRI’s lead to a worsening of symptoms. There are no definitive answers for this, just that it’s clear that it happens. It’s difficult to say what else could have been done because we don’t know exactly why it happens. It might just be something to do with the way the medication interacted with your particular chemistry. It’s like any side-effect – we don’t always know someone is going to have a reaction until they’re actually having the reaction.

It sounds like you’ve worked hard to get to where you are now. That can’t have been easy but you’re doing it. All the best to you.

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aamlewis16

I don’t know why they jumped to the conclusion that it was bipolar with not a lot of other evidence. 8 years of serious meds and still weaning. Yes I was in therapy before the SSRI and 7 years after but somehow never got the message that moods are normal and not to panic and keep asking for more meds. Oh well, like you said I am on a really good path now and need to be grateful!!

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Mary

Thanks for sharing your story. I was also given the diagnosis of “soft bipolar” after 8 years on Cipralex (medication made me a bit hypomanic until I reduced my dose). Now the psychiatrist wants to start me on another round of stronger medications to stabilize my mood. Like you I am using visualization, yoga, meditation and social support to stay on track.

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Riza Sukman

I think the importance of increasing the range of someones ability to handle and be present with over-whelming “bad” emotions needs to be mentioned as relevant for curing depression. As is mentioned in Theodore I. Rubin’s book “The Angry Book” unacknowledged and unfelt anger is often a big player in the cause of depression and symptoms. Often times avoiding the “bad” emotions in order to feel better can prolong and worsen the condition. I think that medication can help us get out of the depth of depression but then we need to do work to get in touch with all of the suppressed emotional pain that we really don’t want to feel which will help to release stuck energies that create depressive symptoms.

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Simba

That’s because the reason for depression isn’t due to Serotonin.

Mine was a lack of Dopamine. They offered me wellbutrin (it’s like an SSRI but works on another pathway and doesn’t make you gain weight).

I decided to use a natural adaptogenic from iherb (or any vitamin shop) and it fixed it. I no longer have depression. I dont even have PMS anymore. It’s called Vitex and it stops prolactin, increases dopamine and progesterone.

Who would have thought my depression was caused by my female hormones? It was by fluke I stumbled upon an article on the internet that saved me. I still love this website even though I’ve fully recovered (in just 3 months!)

NB if you’re male then this is not an option for you, it will dampen your testosterone making your situation worse. It’s also not recommended for women who are menopausal.

I truly hope you stumble upon your answer. I know where you are. It’s painful, scary and dark! If you are reading this then you are still better off than many and you still have hope of finding the light. It’s there waiting for you. You may have forgotten what happiness feels like just ask for help. Whatever is out there is watching over you. It’s a kind beautiful spirit.

It’s real, joy after depression.

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tom

why aren’t companies forced by government to reveal true results of drug tests ? this is such a major issue , peoples well being and even lives may be at stake , depression is not a game , our damaged minds are not footballs to be kicked around , were being treated appallingly when companies are allowed to manipulate results and keep results secret then put ineffective drugs on the market .I gave up so called ‘ therapy, ‘ talking was such a humiliation but I did it but simply repeating myself week after week was humiliating and a complete waste of time , anti depressants also . one type of tablet after the other , and when you ask why none of them work its always the same reply , ‘ not everyone responds . ‘ but reading articles like this and others such as in new scientist etc it seems a lot more people are aware that these so called anti depressants are a con and a waste of money as they are actually ineffective , and as the government will not force companies to reveal honestly the real test results , it appears as though depression is being treated as just game by a lot of people in the know , and those that have the illness are being treated as mugs as were the ones who have to go through this charade and pay for these drugs which actually are simply a waste of money as they are not going to help at all , but no one will admit it

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Karen Young

Antidepressants can be useful and they can provide relief, but not for everyone. Whether medication is used or not, for anyone struggling with depression it is important to also put other strategies in place to strengthen and protect the brain against depression. This includes meditation, exercise etc. There are still a lot of unanswered questions about depression, but the research is happening and hopefully there will be more answers soon.

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tom

” anti depressants don’t work for everyone ” seems to be drug companies stock answer whenever the question is asked as to why I’m not getting any benefit from taking them. I have tried so many types of so called anti depressant over more than 30 years and have not had any benefit what so ever .talking ” therapy ” is humiliating and a complete waste of time , all the depressive is doing week after week after week is repeating themselves .we keep getting these new fads from America as if we must follow because its from America and we are constantly told of the benefits and the difference these new fads from America will have on our mental state , until the next fad .whether its positive thinking , well being meditation , exercise ” therapy ” , music ” therapy, ” cbt , etc , etc , I have even known someone whos parents wasted their money and paid for him to attend the priory clinic to try to cure his depression, and when I asked him what he got for his parents money , ” I repeated myself week after week ” was his reply . theres been a lot in the media lately about mental health care , I just wish someone in government would just take a look at the so called therapies and treatments and ask whether drug companies are delivering drugs that actually work by fully analizing the true data from tests and make sure that money is spent where real and positive results are independently verified .

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Kara

I have tried various antidepressants and while I can function I still feel depressed most days. It’s situational. I am stuck in a marriage that I want to leave after 28 years. However I will have no means of support I have two. I have 2 daughters in college. One has some learning issues. I have tried therapy. Etc. I exercise daily etc

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Dara

For 20 years I have been taking 75mg of Effexor XR, which is an SNRI – raising both serotonin and norepenephrines. I tried 2 SSRI before that – both made me feel worse. But the Effexor was the ticket. My boyfriend is in a deep depression with a lot of anxiety – the SSRIs didn’t help and neither did the SNRI. Now they are trying Wellbutrin and he’s off the wall with the anxiety. I keep telling him he has to see a psychiatrist for a true diagnosis and blood work to determine what neutransmittor isn’t too low. Hopefully he’s not one of the people that is medicine resistant. He does exercise every day. But he was fine for years before this bout of depression and exercises more now than he did when he was happy. And he is seeing a psychologist to talk. Thanks for an interesting article.

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Stephen

I’m sure no one is going to love my comment. I’m a realist , and just tell it like it is……. I’ve tried 7 antidepressants, none of them worked on me at all. I did them all the proper length of time. No results. I was no happier, and Everyone I know noticed no change whatsoever, if anything worse.
This whole idea of serotonin and depression being caused by a ” chemical imbalance ” is absurd and totally wrong..
I’ve never been an up person ” high on life” looking back now at 46 , I loved my old life and would give anything to have it back….. but that is impossible for me and thousands of others. I’ve always been a medium or low person. The reason for that is life itself. We were not meant to be happy all of the time. Some of us get slapped really hard in the face very early in life , others late and they are lucky for getting it later in life. It’s inevitable that we will all get it though.
I talked with a psychiatrist several times. He put me in my first antidepressant. His exact words were ” we know very little about the brain or how it works. We just know that increasing serotonin causes these tiny hairlike particles in your brain to move more and that is common in happier people. Now , first and foremost, would any of you let someone work on your car that admitted they had no idea how it worked??
Again , its no chemical imbalance. Take my life for example. I met a woman I truly loved . We had a great life together, 3 children along the way….. and no , it was not always perfect. But, we both loved each other and our children . We made it well through everything. Good times , bad …. you name it. In 2008 the economy got bad and my business went down with it , we lost our home , had to move into a smaller rental home. Through all of our financial problems, we actually got closer. We both have great faith in God and finances are something that can be recovered. At the time we thought it was horrible. That was only because we didn’t truly know horrible…. yet.
We moved into a second rental home and a month later she was diagnosed with the worst of the worst type of breast cancer there is at 37 years old, at 39 me and our 3 children had to watch her suffer and die in our den.
How is it possible for any of us to be “happy” anymore? Our children have coped a little better than me. But still nothing like they were. I will never be the same person again and I knew it the day it happened. I would never do anything stupid, I wNt to be here for our children as long as possible. But as far as myself, I went from being afraid of death to actually looking forward to it one day. I can’t stand this world and there are so many that go through the same and worse. There is no amount of therapy or pill I can take that will make me feel one bit better about my life now. It has NOTHING to do with a chemical imbalance.
I’m 46 with 3 children ( 9, 15 and 18) It happened 4 years ago and time makes nothing better.
And there are those that tell me , find someone else and make the best of it. There’s not too much to choose from at this age and I don’t want a woman with 2 or 3 children pulling me away from ours. I also really don’t care to be going on first dates at 46 years old. I was ready for us to raise our children and grow old together. But we didn’t have that luxury. That is why myself and millions of others are depressed. Life throws you things you don’t want and can’t cope with. I tried dating in spite of not wanting too, she was actually good with the kids, had nine if her own and was the first girlfriend I ever had, in the 5th grade. Most people thought it was perfect…… but I wanted nothing to do with her, ended it in 2 months. I just have no interest there anymore. Just want to raise our children and go , because I hope to see my wife again.
Aside from my “terrific life? ” Let’s just take someone with an average good life. I don’t understand how ANYONE can wake up….. do the same things over, and over, and over for 75-80 years without being bored and depressed. There’s just nothing here that can keep you happy. People let you down even when they don’t want to , they have no choice. I look forward to the next world and God . I’m sure some will laugh at this , with all the atheists out there now…… but I really never cared what anyone thought of me, and really don’t now. God is our only hope, and better than any medication for depression.
On another note , I was also told that doctors were making tremendous strides with breast cancer. After, watching everything they did, and seeing what it did to her. I really believe they just killed her faster. She would have had a longer, better quality life had she never set foot in a hospital.

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Karen Young

I wish I could take your pain away. It sounds as though you shared the deepest, purest, most beautiful love for each other and I’m so sorry she’s gone. I can hear how the absence of her has left such a deep and profound pain in you and I’m not surprised that medication isn’t taking away the pain you’re feeling. The vastness of the pain that comes with losing the people we love could swallow us up if we let it, and I know it can be a constant, daily fight to stop that from happening. I wish you much love and strength.

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