Antidepressants Make Things Worse in the Long Term


In June 2011, Rif El-Mallakh, MD, et al. published an article, Tardive dysphoria: The role of long term antidepressant use in inducing chronic depression, in Medical Hypotheses.  The article is a thorough and wide-ranging study review.

Here are some quotes from the abstract:

“Treatment-resistant and chronic depression appear to be increasing.”

“Depressed patients who ultimately become treatment resistant frequently have had a positive initial response to antidepressants and invariably have received these agents for prolonged time periods at high doses.” [Emphasis added]

The authors propose the term “tardive dysphoria” to describe this condition.  Tardive means delayed; dysphoria means unhappy or depressed.  The idea is that just as prolonged ingestion of neuroleptics causes tardive dyskinesia, so the prolonged ingestion of antidepressants causes tardive dysphoria.  It’s a nice idea, but the name hasn’t caught on – at least not yet.

The paper by Dr. El-Mallakh et al. is very detailed, and cites 85 references.  The arguments are well-marshaled and compelling.  Here’s a brief summary.

Depression affects about 5% of the world’s population.  Risk of recurrence is high (about 50-80%).  Maintenance antidepressant therapy may reduce the risk of relapse in the first year after an episode.  The APA recommends maintenance therapy for recurrent major depression.  But recurrence of depression is common even among individuals on maintenance therapy.  Recurrences of this sort are called treatment-resistant depression (TRD), the prevalence of which among depressed individuals may be as high as 30-50%.  This prevalence has increased from about 10-15% in the early 1990’s to about 40% in 2006.  Various reasons have been suggested for this increase, but, there “…are reasons to believe that antidepressant treatment itself may contribute to a chronic depressive syndrome.”

The authors provide a great deal of evidence in support of this conclusion.

“Up to 80% of patients diagnosed with major depressive disorder will experience a recurrence of depressive episode despite constant maintenance dose of an antidepressant.”

“Attempts to treat these individuals frequently result in poor response and the rise of TRD.”

“…there have been several reports of the loss of antidepressant efficacy.”

And perhaps most telling:

“A long-term placebo-controlled, blinded maintenance study of fluoxetine [Prozac] in major depression, found no difference after 62 weeks in subjects who were still euthymic [i.e. not depressed] on fluoxetine (11%) or placebo (16%).”

Dr. El-Mallakh et al. point out that individuals who were not initially depressed, but were given antidepressants for other problems (e.g. anxiety), often became significantly depressed.

“In a recent study 27% of patients without any history of a mood disorder who had received antidepressants for an average of 29 months for panic disorders, developed a cyclothymic illness that persisted for 1 year after antidepressant discontinuation.” [Emphasis added]

Also, and perhaps most alarmingly, it is stated:

“In…patients who have developed TDp [tardive dysphoria], ongoing attempts to treat the depression with antidepressants perpetuate the TRD, and may ultimately make the chronic depression permanent.”

The article was published in 2011, and the authors conclude their paper by calling for

“…blinded, randomized antidepressant discontinuation/continuation trials in TRD patients, over at least 1 year.”

They also suggest that

“…clinical trials of antidepressant taper and discontinuation for 6-12 months in patients who have failed most other options appear reasonable.”

Despite this call, I have not been able to find any follow-up research on this matter.

The notion that long-term ingestion of antidepressants leads to chronic, severe depression is not new. The present authors attribute the introduction of the concept to Giovanni Fava, MD, in his editorial Do antidepressant and antianxiety drugs increase chronicity in affective disorders?, Psychotherapy and Psychosomatics, 1994.

They also mention a paper by Verinder Sharma, MD, Treatment resistance in unipolar depression: Is it an iatrogenic phenomenon caused by antidepressant treatment of patients with a bipolar diathesis? Medical Hypotheses, 2006.

Dr. El-Mallakh himself and two other authors, Courtney Waltrip and Christopher Peters, wrote:  Can Long-Term Antidepressant Use Be Depressogenic? as a letter to the editor in the Journal of Clinical Psychiatry in 1999. 

In Anatomy of an Epidemic (2010), Robert Whitaker also addresses this issue (Chapter 8 – An Episodic Illness Turns Chronic).  Robert’s summary on this matter is clear and straightforward:

“We can now see how the antidepressant story all fits together, and why the widespread use of these drugs would contribute to a rise in the number of disabled mentally ill in the United States.  Over the short term, those who take an antidepressant will likely see their symptoms lessen.  They will see this as proof that the drugs work, as will their doctors.  However, this short-term amelioration of symptoms is not markedly greater than what is seen in patients treated with a placebo, and this initial use also puts them onto a problematic long-term course.  If they stop taking the medications, they are at high risk of relapsing.  But if they stay on the drugs, they will also likely suffer recurrent episodes of depression, and this chronicity increases the risk that they will become disabled.  The SSRIs, to a certain extent, act like a trap in the same way that neuroleptics do.” (p 169-170)

So, since at least 1994 – twenty years ago – researchers and commentators have been adducing evidence and arguments that antidepressants, even though they may have been initially successful in altering feelings of depression, when taken for extended periods may actually lead to persistent, treatment-resistant depression.  Discontinuation of the drug sometimes produces a slow and gradual lightening of the mood, but in some cases this does not occur, and the chronic depression can become more or less permanent.

Amazingly, or perhaps I should say predictably, organized psychiatry has not launched a major investigation into this matter, and I can find no indication that any such investigation is in the works.

In fact, the current (2010) APA treatment guidelines for major depressive disorder state:

“During the maintenance phase, an antidepressant medication that produced symptom remission during the acute phase and maintained remission during the continuation phase should be continued at a full therapeutic dose.” [Emphasis added]

Of course, the APA’s guideline will generate more drug sales.  But surely that wouldn’t be a consideration.  Would it?

* * * * *

This article first appeared on Philip Hickey’s website, Behaviorism and Mental Health


Mad in America hosts blogs by a diverse group of writers. These posts are designed to serve as a public forum for a discussion—broadly speaking—of psychiatry and its treatments. The opinions expressed are the writers’ own.


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  1. Great. Life long, worsening depression, a life long customer of Psychiatry, Inc. and Big Pharma. Some will end up, I imagine, far, far worse off (both emotionally and in terms of quality of life and economic stuff) than they ever were before treatment.

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    • Don’t forget, the antidepressants also CAUSED the “mania” required for the bipolar misdiagnoses, in millions of patients, too. And that, of course, results in a “far, far worse off” result.

      And, Fiachra, you’re right, patients are only “blank checks” to the psychiatric, and mainstream medical industry, today. Medicine for profit does not work.

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        • Fiachra,
          That happened to me, too. It’s called lithium withdrawal induced super sensitivity manic psychosis, I believe. And in my case, as in most people’s, it was misdiagnosed as a return of “bipolar,” rather than properly being diagnosed as a withdrawal problem.

          My understanding is lithium is primarily a “bipolar” drug, what was the stigmatization they gave you to rationalize the lithium in the first place?

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          • Someone Else
            To be straight with you, I sought help at the London Maudsley hospital in 1980. I declined medication and asked for psychotherapy. The next two months involved me resisting medication and the Maudsley trying to get it into me. They transferred me to Galway, Ireland where I was overpumped, and Lithium was one of the drugs used. I had been diagnosed acute with poor prognosis in 1980, and later chronic with poor prognosis: with all the Big Labels combined.
            I tapered off strong meds in 1984, moved to Psychotherapy and have been well since.
            In 1980, I had been suffering from panic attacks and anxiety, the doctor treating me at the Maudsley was alcoholic, and he has since killed himself.

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    another awesome idea
    Ketamine, really?
    For those who are not familiar with the chemical in question: it’s a very strong anesthetic, used during surgery and in smaller doses as a pain killer. It’s also very dangerous, can cause hallucinations and sudden death from heart and/or respiratory failure (in addition to other side effects). That’s why people during surgeries have to be constantly monitored. Actually, some of my colleagues who work with mice models use it during operations done for research and they often experience the mice dying for these reasons. Tell me that antidepressants are anything more than sedatives…

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  3. Hey there,
    Developing depression while taking antidepressants does not necessarily mean you have ‘treatment-resistant depression”. Treating depression involves much more than taking medication – and what is involved in treating it varies from person to person. Psychotherapy, doing some sort of exercise you love, a strong social network, meditation, nutrition and many other activities could all play a role. Much like diabetes and high blood pressure, medication is only one potential aspect of treatment. You might still get depressed while taking meds, but in some cases the depression is less severe, and the medication makes it easier to learn about oneself when going through the depression, because the meds may help you maintain the ability to concentrate and sleep, allowing you to make progress in therapy and to continue all the other anti-depressant activities you pursue. While the questions you ask are important, I don’t see much evidence for your theory. It is trendy these days to say that antidepressants are nothing but placebos, or that they are harmful. But the reality is that a great many people are helped by them, and over the long term, not just for 6 months.

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    • The fact is that the so-called antidepressants don’t work any better than a placebo. This is proven with valid studies that were not carried out by the drug companies that produce them. While I was on heavy doses of them there was no way that I could “learn about myself” since they’d numbed my feelings and emotions. They didn’t help me concentrate or sleep, just the opposite. My house fell down around me while I just sat there and watched it all happen.

      Also, the so-called antidepressants can cause suicidal and homicidal thoughts. You can call this “trendy” all you want but I know how these damned toxic drugs affected me and I’ll never take them for any reason. I can only speak for myself and from my own experience but these drugs were toxic to me, even leading to the loss of many friendships and to not giving a damn about what happened to me or anything else in the world. If you want to take them that’s just fine; but I don’t think I will be joining you anytime soon.

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        • Right!

          My mother took Zoloft for one month. Sitting in her kitchen one afternoon she said she looked down at the floor and wondered how her kitchen floor had gotten so dirty. She prided herself on her clean house, especially her clean kitchen.

          The apathy had gotten hold of her but she was smart and realized what was happening. She said she jumped up, ran to the bathroom, and flushed those damned capsules down the commode! Then she got herself a bucket of soapy water and her mop and made up for lost time cleaning her kitchen floor!

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      • I also was adversely effected by an antidepressant (“safe smoking cessation med”). It made it so I was unable, as normal, to think through my problems and see the big picture. And my research shows this has been known to be an adverse effect of these drugs for decades.

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    • Do you realize that most anti-depressants are prescribed without concurrent therapy?

      I was on SSRI antidepressants and benzos for over a decade and my board certified so-called expert psychiatrist told me that I needed to be on both drugs “for life” and that I didn’t “need therapy because all you need are the drugs” for success. It was a series of manic episodes culminating in suicidal ideation and a real attempt to die that woke me up to the truth and it took me the better part of a year to wean off of those drugs that kept me chained to psychiatry. I fired my psychiatrist, who tried to increase my dosages after my hospital visit and I never looked back.

      On the “trendy” placebo thing- there was a recent, well publicized study which basically said that antidepressants are little better than placebo when it comes to treating depression. Nothing trendy about hard scientific facts. Feel free to do a search for it; there are many links out there and maybe someone will post one.

      Lucky you that you are getting therapy. That is probably benefiting you far more than what you are putting in your body and brain. Hope you never suffer from the many and very real and dangerous side effects of the brain-disabling drugs you are taking.

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    • marchwinds,

      Thanks for coming in.

      The fundamental difference in our perspectives, I believe, is that you consider depression to be an illness, whereas I, very emphatically do not. I have no quibble with people taking drugs to alter their emotional state. That’s a person’s own business. What I do quibble with is psychiatry’s promotion of the notion that depression is an illness and that the pills are the cure. With the help of pharma, they have promoted this Great Lie to such an extent that it is now widely accepted by their customers, by the general public, and by the political and legislative establishment. But it’s still the Great Lie.

      The various activities that you mention all have merit, and to some extent psychiatry pays lip service to this kind of approach. In practice, however, they just dish out the pills and tell people the lie that the pills will correct the “chemical imbalance” or “neural circuitry malfunction” or whatever fictional pathology they’re promoting at that time. The psychiatrists know that this is fiction, but a great many (perhaps most) of the customers believe it. Most of them don’t pursue the kinds of activities you mention. And why should they? After all, a “doctor” has told them that the drugs are the cure!

      Your notion that the pills can give people the motivation and the breathing room to make positive changes has been standard psychiatric-pharma promotion for 30 or 40 years. Perhaps it happens, but I haven’t seen much of it.

      You write: “…I don’t see much evidence for your theory.” Isn’t the study by El-Mallakh et al evidence?

      You write: “It is trendy these days to say that antidepressants are nothing but placebos, or that they are harmful.” This has nothing to do with trendiness! The evidence is extensive and compelling. Antidepressants have demonstrated very little superiority to placebos, and in the long term they are harmful. By dismissing these facts as trendiness, I think you are in effect dismissing the evidence. What evidence can you adduce to support your position?

      Best wishes.

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  4. The sad irony is that those of us suffering from depression and the public at large have been told ad nauseum that the recovery rate for treated depression is 80%. The presumption is that those who fail to recover are simply not taking prescribed medications. The fact that many of us take antidepressants knowing they are little or no better then placebos says much about the nature, timing, and extent of the treatments available to us.

    I’d trade my antidepressants for the therapies that are so often the subject of conferences, webinars, seminars and the like (ex. CBT, DBT) but neither is on the menu. The transformation of our mental health system which would allow the widespread use modalities other then medications may be an aspirational goal that has not and may never be achieved …. but this could be the depression talking.

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    • Joe,

      Thanks for coming in.

      Have you had any contact with the survivors’ movement? Here are some places to check: first, as you probably realize, many of the writers on Mad in America are survivors and/or run survivor sites. If you click on the Writers tab at the top of this page, then look through each biography, you will find them. Some have their own survivor websites as well as writing on this blog. There is also a Wikipedia article on the topic. Just put “psychiatric survivors movement + wiki” in the search bar, and it should be the first article at the top of the page.

      There are options.

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  5. Another excellent article, Philip…thank you! I don’t really know what the current stats are, but i have long suspected that the apparent resurgence of ECT in recent years is connected to the increasing prescription of antidepressant medications. This article you cite by Rif El-Mallakh strengthens that suspicion. Like psychotropic meds, i’ve heard ECT spoken of by local psychiatrists and others as if it’s the best thing since sliced bread! Of course we know ECT is primarily used for “treatment resistant depression”, although it is also used for “treatment resistant mania” (which is what they tried to coerce my daughter to take it for). In either case, it seems so typical of psychiatry’s woefully ham-handed approach to things: after your full bore chemical assault fails, you turn to shocking the brain and inducing convulsions. If it were as benign as they portray, why isn’t it the first line of “treatment” instead of a last resort?? And why do they give people anti-convulsives if it isn’t because convulsions cause brain damage? And why don’t they conduct pre- and post-ECT neuropsychological assessments, including follow-up at periodic time points? Surely such studies would dispel the concerns of nay-sayers like me, no? Of course, we hear about and from those for whom “ECT saved my life!” Well, i certainly wouldn’t want to take that away from anyone. However, what they may not realize is that the ones who “saved their life” pushed them off the cliff in the first place. Luckily, they landed on a ledge below and the “ECT rescue helicopter” didn’t drop them to the canyon floor below! (We don’t hear too much about those unfortunate victims.)

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  6. Russerford,

    Thanks for your comment.  Yes, despite the growing evidence of harm, psychiatry becomes increasingly cavalier in the administration of these “wonderful” treatments.  By the way, the Northwick Park ECT Trial found no difference in outcome between people who received ECT and a randomized placebo group who received preparations, but no shock.  In fact, at the 6 months follow-up mark, the “sham” ECT recipients were doing slightly better!

    Best wishes.

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  7. This is an intriguing theory. So much so that I am honestly irritated that this is the first time I have seen mention of it anywhere – and I have trawled through a lot of depression research in the past few years, in an attempt to understand my own situation.

    A brief background of my experience with antidepressants: I had my first episode of major depression when I was 18, and succumbed to my second at 21, despite having been on a constant dose of ‘maintenance’ meds in the intervening time. I expected it might last another 6 months, perhaps require treatment with a different class of antidepressant. I had no way of knowing what I was in for. Throughout the course of the next three years, I did trials of over a dozen medications in different doses and combinations. I submitted to this in a continuing downward spiral until my psychiatrist and I agreed that if anything was going to help me, more medication wasn’t it. It wasn’t until I ceased all of my psychiatric meds that I began to fight my way out of the terrible mess my mind was mired in.

    I am lucky that I had a doctor who was observant enough to recognize the harm that was being done, and to attribute it – correctly – to the medications I was taking. I recognize that not everyone can cease medication with their doctor’s support and approval – there is still a terrifying majority of medical professionals who wholeheartedly believe that an episode of depression can be successfully treated – and relapse successfully averted – with antidepressants.

    It’s been almost six years since I’ve been med-free, and I have yet to fully recover. I’m still not certain if the damage done is permanent. But I know that I will never willingly take another antidepressant again, and I am not shy about encouraging others to seek alternative options. This article gives me some tentative confidence that I have made the right decision, and that there is some hope for the future. Perhaps, if enough research is done, there will be a serious re-evaluation of how depression is currently treated.

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  8. I appreciate all that is written here. Instinctively, I have not liked anti-depressants and the few times in past I went on them for anxiety, they made me panic and I hated the experience. Despite what doctors dismissing my feelings on how they made me feel, my problems didn’t amount to enough to stay on them.

    I wish i could say that was the end of it but it was not. After a major life event (one that includes a life-ending disease), I had a major bout of depression. I tried to avoid anti-depressants and certainly cannot say I was “well” but I went to counselling and I went to a stop-smoking clinic and was trying to get well despite a pretty bad prognosis I would forever have to live with. I spoke with an NHS assessor and he suggested anti-depressants and as I wasn’t well, I thought I’d try them again. Big mistake – I think anyways. I panicked badly, was shaking and with a whole lot of real problems, it was pretty bad. I had to get off of that prescription and move to a lesser one. Which I did but the shock of that experience stayed with me and for an already depressed person, this was an event that put my vulnerable system through h*ll and, I feel, made my journey that much harder. During those first few stages of the 1st meds and getting onto the 2nd, all stop smoking well stopped, in point of fact I went from a 4 a day smoker, who was trying to quit…to someone who cleared about 400 cigarettes in about a month’s time…while I got on one, suffered on it, left it and then “acclimated” to another.

    They say anti-depressants make you worse before better and I certainly experienced that worse. I am not sure if that worse is good for everyone. Sometimes a person cannot take that last dose of really bad.

    Maybe that is indicative of something really wrong with me, but obviously, I read these articles and feel a kinship with those who have not found it good and who have not seen this as the path of all good things, because my experience was not good. However, in saying that what I feel most people, especially those who are depressed, would like to see is understanding of them and their feelings – not for doctors to see them as non compos mentis as depression makes you unable to assess anything and if you state the meds are making you feel this way, they see it as you probably are stressed and that is the reason, not the meds. This article is helpful in giving that understanding to those who don’t fit the medical box. The second is that they seek hope but that is a really difficult one to get. Most articles state how difficult it is once a major depression hits to not have a relapse. Articles about anti-depressants state going on meds is your best way to not have a relapse. Articles denying that state that anti-depressants will more than likely bring about a relapse.

    So for some meds are great but for those it isn’t so great for, what is the path? I am in agreement with the general sense of the article, I am just not sure for the depressed where it leaves them if they want hope for a future without depression. What alternatives are there? Of course counselling, exercise, nutrition but major depression is some pretty bad chemicals – so I guess I think that articles such as this should give some ideas of how to deal with something this terrible so that readers who feel an affinity with your message can also feel hope and not just a dark idea that because I’ve taken these drugs, I have committed my self to future of more problems than if I hadn’t.

    Also, I think that there should be guidance with counselors to not just promote anti-depressants. Maybe there should be some guides out there that help you through a depression through a series of different methods – like nutrition, like encouraging a little exercise, like vitamins or even herbal remedies before going to the strong stuff. All the first items are, are trials to see if there are good opportunities to get well without taking something that clearly states that it is common for those taking it to become more depressed in the beginning, can be prone to suicide…these are not good for someone who is anxious and depressed.

    So for those in the health field, please read about how a patient might want to be treated and take that into account. Secondly, for the author of this article…I agree with your sentiments that medicine (even ECT as I see in your comments) might not work but don’t give the message to depressed people that all venues and roads offered by doctors or ‘the professional medical members’ won’t work without proposing some hopeful and helpful alternatives. Spouting resonating feelings peppered with doom and gloom will not help depressed members reading this.

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