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New Research: Antidepressants Can Cause Long-Term Depression - Posted: 11/16/2011

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New Research: Antidepressants Can Cause Long-Term Depression - Posted: 11/16/2011

New Research: Antidepressants Can Cause Long-Term Depression*|*Dr. Peter Breggin

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Remember/Warning -
Most psychiatric drugs can cause withdrawal reactions, sometimes including life-threatening emotional and physical withdrawal problems. In short, it is not only dangerous to start taking psychiatric drugs, it can also be dangerous to stop them. Withdrawal from psychiatric drugs should be done carefully under experienced clinical supervision. Methods for safely withdrawing from psychiatric drugs are discussed in Dr. Breggin's new book, Psychiatric Drug Withdrawal: A Guide for Prescribers, Therapists, Patients, and Their Families.
Shortly after Prozac became the best-selling drug in the world in the early 1990s, I proposed that there was little or no evidence for efficacy, but considerable evidence that the drug would worsen depression and cause severe behavioral abnormalities. I attributed much of the problem to "compensatory changes" in neurotransmitters as the brain resists the drug effect. Since then, in a series of books and articles, I've documented antidepressant-induced clinical worsening and some of its underlying physical causes. Now the idea has gained ground in the broader research community and has recently been named "tardive dysphoria."

It has been apparent for many years that chronic exposure to SSRI antidepressants frequently makes people feel apathetic or less engaged in their lives, and ultimately more depressed. In my clinical experience, this is a frequent reason that family members encourage patients to seek help in reducing or stopping their medication. SSRI-induced apathy occurs in adults and includes cognitive and frontal lobe function losses. (See Barnhart et al., 2004; Deakin et al., 2004; Hoehn-Saric et al., 1990). It has also been identified in children. Adults with dementia are particularly susceptible to antidepressant-induced apathy.

A recent scientific study by El-Mallakh and his colleagues reviewed the antidepressant literature and concluded that any initial improvements are often followed by treatment resistance and worsening depression. They compare this problem to tardive dyskinesia, caused by antipsychotic drugs, and call it tardive dysphoria, "an active process in which a depressive picture is caused by continued administration of the antidepressant." Based on rat studies, they hypothesize that "dendrite arborization" -- an increased branching growth of nerve cells -- caused by chronic antidepressant exposure, may be the cause.

In a meta-analysis of 46 studies, Andrews et al. (2011) found the relapse rate for antidepressant-treated patients (44.6 percent) was much higher than for placebo-treated patients (24.7 percent). Andrews also found that the more potent antidepressants caused an increased risk of relapse on drug discontinuation. A 2010 Minnesota evaluation of patient care in the state found that only 4.5 percent of more than 20,000 patients were in remission at 12 months, indicating that they had become chronically afflicted with depression during and probably as a result of their treatment.

Andrews et al. (2011), like El-Mallakh et al. (2011), stress what I had first described as compensatory mechanisms. SSRI antidepressants block the removal of serotonin from the synapses between neurons, in effect trying to flood these synapses with serotonin. Many studies confirm that the brain attempts to compensate for the impact of the SSRIs by reducing the brain's capacity to respond to serotonin. This leads to a loss of serotonin receptors that can reach 60 percent. Blockade of serotonin reuptake causes a potentially harmful adaptive response in the form of a persistent hypertrophy of the reuptake mechanism. Additional studies show persistent biochemical changes in the brain following exposure to SSRI antidepressants.

In addition, I have been describing direct toxic effects on the brain that can account for the emotional deterioration of these patients. Prolonged SSRI antidepressant use can produce abnormal cell growth in the rat brain (neurogenesis) and decreased thalamic volumes in children (tissue shrinkage from cell death). Thus far, most researchers have not yet begun to take into account or to face these more gross threats to the integrity of the patient's brain after prolonged exposure to antidepressants. Meanwhile, drug-induced changes in brain cell structure and number, when found as a result of taking illegal drugs, are always touted as a reason not to take these drugs.

Antidepressants are the second most prescribed group of drugs in America. Yet evidence continues to converge on the dangerousness of antidepressant drugs. Given the difficulty showing any effectiveness even in the short-term, the use of these drugs becomes more and more problematic. On top of that, the antidepressants produce serious withdrawal reactions, making it difficult and at times life-threatening to withdraw from them, even with the recommended clinical supervision and slow taper. Psychiatry has always been slow to respond to scientific evidence that its treatments are harmful. Often, as in this case, psychiatry flouts science. The public will have to develop its own resistance to taking antidepressant drugs.

Peter R. Breggin, M.D. is a Harvard-trained psychiatrist and former full-time consultant with NIMH who is in private practice in Ithaca, New York. Dr. Breggin is the author of more than twenty books including the bestseller Talking Back to Prozac and the medical book Brain-Disabling Treatments in Psychiatry, Second Edition. His most recent book is Medication Madness, the Role of Psychiatric Drugs in Cases of Violence, Suicide and Crime. He is also the author of dozens of peer-reviewed scientific articles, many in the field of psychopharmacology. On April 13-15, 2012 in Syracuse, New York, the annual conference of Dr. Breggin's 501c3 nonprofit international organization, The Center for the Study of Empathic Therapy, will present a panel of lawyers, experts, survivors and families concerning antidepressant-induced violence and crime. Conference information is available on Peter Breggin's Empathic Therapy Center.
 
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Peter Breggin is a bit of a quack in my opinion, he cherry picks his data that matches to his predilections. Yes it is true and possible for psychiatric drugs can be a hinderance and can impact negatively on your health. However certain variables need to be meet in order for this to happen. Let's break it down...

Serotonin and Norepinephrine are a balancing act in the body. If you naturally are not producing enough serotonin to meet an equilibrium which is what has been deduced in psychiatry then these drugs should help you. Excess serotonin is usually converted into melatonin within 3-4 hours assuming that the pineal gland is not calcified. The plasma level of course, is the variable part of the equation based upon the organisms surroundings and hormone status and their light levels.

The crazy thing though is that low serotonins don't cause depression, high serotonin levels also cause depression. when you don't sleep well you don't convert serotonin to melatonin so it builds up even more. The brain has to do alternative things with the serotonin. High levels of serotonin then are allowed to persist and it begins to fry your neurochemistry in many parts of your brain. The sympathetic nervous system is one of those systems among others. But that system requires nerve growth factor, and brain derived neurotropic factor. Both of these chemical replenish old worn out cells from our stem cell population. If those systems no longer work then high serotonin constantly makes cells stressed and drives cells into apoptosis (suicide) and there is less chemicals around that allow our stem cells to replace them. When cells are not replaced at appropriate times the synapse ages and the amount of serotonin in the nerve terminals seriously degrades. That means intracellular serotonin plummets. Then you now have the instance where serotonin levels are low but your plasma levels are high and this exacerbates the situation even further.

This might sound like a recipe for failure when you throw an SSRI or SNRI, but the fact is say you eat a lot of Carbs, and you don't sleep, this is a prime example where your serotonin goes from okay to high, and then plummets down. What I didn't mention is that if there serotonin cells are not recycled then that is also bad, so an SSRI makes sense to restore the levels, however we can not measure these levels, though studies have shown those with asperger's have lower dopamine levels. It could be quite natural to deduce that some people with depression have lower serotonin and norepinephrine levels.
 

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Peter Breggin is a bit of a quack in my opinion
A lot of people agree with you.

i think he makes some good points, & i'm glad he's out there to try & balance out the dominance of the big pharma/biomedical psychiatric Empire.

i don't agree with everything he says, & i think there is a very valid place/role for a wise use of psychiatric medications.

Would still be interested in reading his latest book.

With regards to brain chemistry & psychoactive drugs - i think the entire thing is Alchemy.
 
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Hi Thoth,
I'm not going to pretend to understand your post...it went over my head a little tbh.

I don't understand why serotonin is the target when the receptors are apparently most prolific in the gut and the heart....or do I have this wrong? You may know more than me.

I agree that the sympathetic nervous system is affected....these are the reflexes that we can't control aren't they....heart beat, tear/saliva production, peristalstis etc???? and also agree that the longer you take these drugs for the more damage they do.

My question is this....is the damage reversible?

I have an arrhythmia following 5 years on these drugs. 5 years later, and now off SSRIs, it's still there!

Is he cherry picking or is there a true threat to public health here?
 

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Is he cherry picking or is there a true threat to public health here?
i don't agree with Breggin on everything - But i think he's a voice of reason & sanity - as are,Joanna Moncrieff, David Healey, Bob Johnson, John Breeding, Lucy Johnstone, Robert Whitaker, & everyone else that has spoken out on all these issues.

A large part of the problem is that it isn't really up for debate - Not at an Establishment, nor wider social level, nor within the mental health community, it's just the same few people that speak out on it all, really against a massive Zeitgeist.

i think that part of the issues as well, is that for a percentage of people, psychiatric drugs are probably very helpful - in an ideal World with a comprehensive psychiatric system, i expect about 20% of people may well be best helped with medications. The mass drugging of society however, which is what we have, i think is outright insanity - But the whole of society is insane anyway with everything that goes on. & the system & majority of the population want it all the way it is.

i think before there can be systemic & meaningful change within all these areas, there needs to be a genuine, open & honest discussion on all of it - & the system/society isn't ready for such a debate - & it may take many more decades before society is ready for such an honest discussion.

i personally think it may well take another 200 years before there is a genuinely fit for purpose understanding & treatment of mental health, & for this civilisation to become more civilised - & God knows what kind of state this World will be in by then?

i think it's all very sad - But what really can anyone do about it all? The book sales & influence Breggin has, & he knows he can't change it all. & it doesn't take a lot to close down discussion on all these areas - generally all you have to do is bandy around accusations of anti-psychiatry.

i think society/people just need to be left to it all - it's not worth getting too bothered over.
 
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Hi Thoth,
I'm not going to pretend to understand your post...it went over my head a little tbh.

I don't understand why serotonin is the target when the receptors are apparently most prolific in the gut and the heart....or do I have this wrong? You may know more than me.
First off I will point out that I do not have the authority on this discussion. I just read books and peer-reviewed journals, so that I can understand and gain insight to depression and pharmacokinetics.

Firstly I think the Serotonin thing is a fallacy of composition I believe. Yes it is true that there is more serotonin in the stomach than anywhere else. However to target the serotonin pathways, and the receptors there is what the drugs do. The reason being is that the serotonin pathways in the brain have been linked to sleep, memory processing, cognition, and mood.

Before the advent of SSRI, SNRI, and Tricyclics, people were prescribed opiates, and amphetamines as anti-depressants. The other thing though is that the strongest Tricyclic (clomipramine) is very weak when compared to Sertraline, and Escitalopram. SSRI's and SNRI's are newer, more potent but only in select areas. So this is why doctors have a tendency to prescribe these first. Tricyclics though focus on both Norepinephrine, Serotonin, and some target the muscarinic, and alpha-1 adrenergic. That and the fact that Tricyclics are 'dirty' drugs, most of the side-effects on the substance though is only there while you take it, but it's almost definite you will get them.

Before we go on I should also mention that just because drugs target a certain receptor does not mean they activate it. They can be inverse agonist, antagonist, and agonist. Which is why Zyprexa is an antagonist to the muscarinic, and alpha-1 adrenergic receptors, which is supposed to knock you, and make you sleep (but it didn't for me).

My question is this....is the damage reversible?

I have an arrhythmia following 5 years on these drugs. 5 years later, and now off SSRIs, it's still there!
Sadly, I think that some side-effects are for life. These new atypical anti-psychotics which might slow down your thyroid and metabolism won't do it temporarily, it is often the case it will for life. I haven't heard many bad stories for SSRI's, and hence why GP's prefer to dole them out.

Is he cherry picking or is there a true threat to public health here?
There's a few things worth pointing out. USA is a completely different kettle of fish compared to the UK, Sweden and Australia. In the US you have pharmaceutical adverts on TV, GP's gaining commission for doling out certain brand name drugs. The fact that a Zyprexa in USA is $350 a pack, and a generic Olanzapine is $34 a pack highlights this. Also Pristiq is $290 a pack, yet the generic Venlafaxine is $75 a pack.

From my experience of the 4 countries the UK is the most conservative from handing out drugs. Australia is by far the most liberal of the 3 with prescriptions, while Sweden sits in the middle. But it's not just my experiences, the Havard Review of Psychiatry has stated that UK has a tendency to a conservative approach to medication use. In fact the words were this:

"Our findings are that, despite many similarities, the UK guidelines are generally more conservative in their recommendations for medication use, especially for children experiencing only moderate impairment."

However lets get to the crux of the issue. First Peter Breggin who claims to be an M.D. Well here's the case

  • Breggin is not certified by the American Board of Psychiatry and Neurology, which is the recognized agency for certifying psychiatrists.
  • Having completed three years of psychiatric training, Breggin is entitled to call himself a psychiatrist or a "specialist in psychiatry."
  • Until 1996, the Maryland Board of Quality Assurance maintained a list of "identified" specialists. Anyone who completed an approved training program was eligible for listing. No special examination or additional qualifications were required.
  • To become licensed in the United States, every physician must pass an examination given by the National Board of Medical Examiners or an equivalent examination by a state licensing board.
  • The American Board of Forensic Examiners is not recognised by the American Board of Medical Specialties (ABMS), which is the recognised standard-setting organisation. ABMS offers subspecialty certification in forensic psychiatry and forensic pathology, neither of which Breggin has achieved.
  • Only one of the six journals with which Breggin has been affiliated is significant enough to be listed in MEDLINE, the National Library of Medicine's principal online database.

And if that wasn't enough, the citations that Breggin has used to state anti-depressants are harmful, and should not be used; Only 28 of the citations were listed in MEDLINE, none of these publications appears to be a research report. Eight were letters to the editor, two were books, and most of the rest were expressions of his opinion on various psychiatric topics.

On pages 36-37 in his Ritalin Fact Book, Breggin stated the following. "A 1997 study published in Pediatrics confirms high rates of stimulant-induced depression in 125 children . . . who were given relatively small doses of Ritalin or Dexedrine. Two children on Ritalin and two on Dexedrine developed severe enough adverse effects to be terminated from the study. One eight-year-old became 'over-focused, extra sensitive, and increasingly anxious,' and a five-year old became 'extremely aggressive and tearful' . . . . Side effects from amphetamine (Dexedrine) were higher than those from Ritalin for 'trouble sleeping, irritability, prone to crying, anxiousness, sadness/unhappiness, and nightmares."

Breggin's description distorts what the study showed. The study, which lasted two weeks, was done to compare the side effects of Ritalin and Dexedrine and to identify which symptoms might be due to the underlying condition rather than to the drugs. The researcher's concluded that overall, both drugs "were well tolerated by most subjects" and that "many symptoms commonly attributed to stimulant medication are actually preexisting characteristics of children with ADHD and improve with stimulant treatment." A 3% dropout rate caused by temporary symptoms is certainly is not reason to avoid use of the medications. What do you think it means that Breggin uses data from a highly favourable study to argue that stimulant drugs should be avoided? (see the report here)

The problem for me is that Breggin intentionally has been quoting people out-of-context and uses faulty citations to argue his case. The fact that he cites his own opinion on psychiatric topics, and makes premises showing no data showing that this is a major problem or that it is likely to happen. I just find it all quite alarming.

Is it worth looking into his claims? Absolutely, but we shouldn't have to be alarmist and emotional in regards to it. Yes some antidepressants are worse than others, Paroxetine and Duloxetine come to mind.

As for medication use, I think it should be quite clear what you and your doctor should be treating. I personally don't think Serotonin is the answer, even though reports state that 5-7 in 10 people with moderate or severe depression have an improvement in symptoms within a few weeks of starting an SSRI anti-depressant. So there is a case for having them, and if that doesn't work then there's SNRI's which target more on the norepinephrine. And you're last resort is always the monoamine oxidase inhibitors which is a completely different animal to all the other anti-depressants. It's also the only type of anti-depressant that can send you into cardiac arrest for eating too much aged cheeses and cured meats.

I personally think that for me personally we should be focusing on increasing dopamine, I had so much success from dexamphetamine which is a heavy dopamine inhibitor, so I would personally like to have taken Bupropion or Phenelzine.
 
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Not aware of this guy or his research at all. But...Paroxetine (Seroxat) caused hallucinations upon withdrawal, Prozac caused me huge mood swings & alcohol cravings (as a very light drinker previously). Citalopram caused me to have racing thoughts, agitation & issues with spatial awareness / reality / co ordination and gurning like a street drug addict. After 10+ years on various anti depressents, now 'clean' my memory, co ordination & energy levels remain severely depleted / impaired. I am taking these issues up with my primary health care provider. All I needed was counselling, practical support and time to heal from the source of my trauma. As this was not available, I was drugged as a 'quick' fix with long term consequences.

I will hold my primary 'health care' providers accountable for the ongoing health issues that I have as a consequence of long term SSRI use without adequate supervision. All documented in writing.
 
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What about months/years later?
Protracted withdrawal is often misdiagnosed as relapse which is the reason for wrongly prescribing anti depressants to patients experiencing withdrawal side effects which are incorrectly identified as a further episode of anxiety / depression.

Source: experience.
 

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First off I will point out that I do not have the authority on this discussion. I just read books and peer-reviewed journals, so that I can understand and gain insight to depression and pharmacokinetics.
i've read a lot on the corruption & influence of big pharma on Journals, & within the Establishment. So what/who do you trust? What is genuinely objective & impartial?

Deadly Medicines and Organised Crime: a review
 
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What about months/years later?
I'm Just going to state that I'm really not in the mood to battle out something that I don't know as well as say economics. My whole argument has centred around looking into the drugs before you take them, and know what you are taking. Awareness definitely does need to be made for this, drugs definitely have their purpose, this is why we have vaccines.

Here's a journal from ScienceDirect you might find interesting. ScienceDirect has plenty of books and reviews available to read at your leisure.

European Journal of Neurology

British Journal of Psychiatry

General Hospital Psychiatry

Addictive Behaviours

Psychiatry Research

Journal of Psychiatric Research

Journal of Psychopharmacology

There's also some good books at JSTOR.
 

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drugs definitely have their purpose
Never said drugs don't. i just personally question the long term efficacy of the mass drugging of society, & the primary approach of psychopharmacology (often at the exclusion of a lot else) as being the best one?

50% of people in the UK are now on one or more drug long term for a variety of general &/or mental health complaint.
 
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I've only skimmed through this thread, so can't claim to have understood and taken in all the arguments, but it's a subject I've looked into before, and frankly it has worried me a lot the suggestion that taking anti-depressants long term might have the opposite effect to what you took them for in the first place, and that it might be irreversible. I've taken them for the best part of twenty-five years, and come off them and gone back on them many times, and had a long struggle with finally deciding that I wasn't going to give them any more chances, they really haven't done a lot for me. I've been on tricyclics, SSRI's and SNRI's.

Anyhow, Breggin did influence me a lot when I read Toxic Psychiatry back in the mid nineties, and I came off Lithium as a result of what I read, and I never looked back on that decision, it was the right one for me. However, it's interesting to read a critique of him and his ideas, and get a more balanced view of what he says, I think back then I took it all very straightforwardly and uncritically. More recently I've looked into the idea of treatment-resistant depression, and the idea that long-term anti-depressant use might actually make depression more entrenched. Very daunting idea to consider. But I felt for so long that anti-depressants weren't actually helping.

I came across the idea of 'oppositional tolerance', introduced by Giovanni Fava, which is to do with how long-term use of SSRI affects the serotonin processes in the brain. I came across it on McMannWeb here, which I find a fairly balanced site, in that he accepts the need for medication short-term, but thinks it wise to be cautious about how much it can be expected to do, and about whether there are dangers in taking it long term. More detail on the suggested/hypothesised long-term effects of anti-depressants, including work by Fava and others in this article Now Antidepressant-Induced Chronic Depression Has a Name: Tardive Dysphoria | Psychology Today

McMann's site also gave me more info on the idea that bipolar can manifest as a result of taking anti-depressants, where previously there was only depression and no mania/hypomania. I had felt for a long time that maybe I wouldn't have had any hypomania if I hadn't been on such high doses of tricyclic anti-depressant, but my psychiatrist was having none of it, and that was right at the outset, a good twenty plus years ago. The statistics that there has been a big increase in the diagnosis of bipolar since the use of anti-depressants has ballooned (if these are reliable, but it sounds likely to me) is very worrying indeed .

I think it is very hard to be balanced about this subject. My personal decision has been to stop taking anti-depressants now for a couple of years. But I think it has to be just that, a personal decision, what is right for one person, may not be right for another. Maybe my depression is more a feature of emotionally unstable personality traits, and therefore that is why I felt it was never responsive to anti-depressants, and of course this will not apply to most people. And how possible is it to tell how responsive you are to anti-depressants, there must be quite a bit of 'viewer bias'? I've had a GP tell me she thinks I do better when I stay on anti-depressants long term, but I don't agree with her. I now don't think I ever had bipolar, I think my symptoms were always more a reaction to complex trauma, and the bipolar was a red herring, perhaps mainly caused by the medication I was taking. I don't get (fingers crossed!) such huge sweeping swings of mood as I used to, and don't get the periods of hypomanic activity, or the huge crashes into blackness, I used to get when I was on anti-depressants. The idea that I have permanently f****ed up the natural functioning of the neurotransmitters in my brain by being on anti-depressants for so many years, and actually given myself a higher likelihood of permanent depression, well, I put that to the back of my mind, my current state of mind doesn't seem to be bearing that out to a terrible degree. I am less worried about it than I was when I first heard about this idea. Maybe other treatment approaches, therapy, CBT, DBT, mindfulnesss and so on, can help repair/reprogramme, the neural pathways, neuroplasticity I think it's called.

So, I feel very wary posting on this subject. I know people who have been helped enormously by the same anti-depressants that have either made no difference to me, or made me feel worse, and who certainly fare much worse when they stop taking them, and seem to do better by staying on them long-term. So it's not a one size fits all thing at all. And the research, well, how certain can we be about the workings of the brain and neuro-transmitter system? I don't know. I think there are questions over this as well (both in the direction of using research to support or question the use of these drugs). But I don't think it should be forgotten that the more anti-depressants are prescribed, the more money is made for someone, it's a factor in the equation.
 
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