“That’s my nickname,” I answer, confused. “Who’s this?” It’s a police officer.
“We think we have your father here. He says he’s trying to get into your house.”
“I’m in my house. Where are you?” They’re outside, down the block. My mother and I run out to the street and approach the unforgettable scene: my father, old, grey and stiff, arms bleeding in handcuffs, is sobbing and yelling, surrounded by officers.
“You hurt me!” my father yells. “Why do you hurt me?” My mother and I, mortified and scared (please don’t shoot him, I pray to myself), run up to them.
“Does he have dementia?” an officer asks.
“Yes, I apologize for this.” I’m relieved to have an explanation. They take him out of the handcuffs and allow us to walk him home. My father tells me that he’s sorry, that he decided to take a walk but coming back he couldn’t discern which house was ours. So he started entering neighbors’ houses. We cry as we hold each other.
We had already warned him not to leave our house. We had already taken his car away. We were making plans to take away his cell phone. We were battling with the million little details of dementia. So we thought.
* * *
My father’s transition from being an independent person to one who could no longer care for himself was messy and prolonged. It took years for us to truly recognize his decline. We knew he was on antidepressants and anti-anxiety medications and that they didn’t seem to be successful. We supported his decision to sell his small business and go on disability because of debilitating stress and anxiety. He was nearing retirement age anyway. We agonized over his deteriorating driving skills and his increasing disorientation. We worried that he wasn’t taking his medications properly, or might even be over-medicating himself. But since he lived on his own — an hour away from family — we couldn’t be entirely sure what he was doing. To make matters worse, he was being sued by his downstairs neighbor for making excessive noise while walking in his home. We hired lawyers and acoustics experts and negotiated a settlement, but this is where my father seemed to spiral.
No one tells you when it’s time to take over for a parent’s care. You just realize that someone’s at the end of their rope, and they’re about to fall.
My realization came when my father’s housemate called us to let us know he had driven my father to his first electroshock treatment.
“Why is he getting electroshock treatments?”
“He says he’s depressed. He says he wants to die.”
When I called the clinic that was performing the “emergency” electroconvulsive therapy (ECT) on the advice of my father’s newest psychiatrist, it was clear to me that they did not know what medications he was taking, were expecting him to get himself to and from the clinic without driving (he planned to drive himself until we intervened and paid people to drive), believed he would actually follow their instructions (you’re not supposed to drive for at least a week after your last treatment), and believed he was on the brink of committing suicide. But my father was almost 70 and had never attempted suicide. I was alarmed.
Another important note: an MRI later revealed that my father suffered a mini-stroke (transient ischemic attack) some time before his psychiatrist signed him up for ECT.
“Do you know that my father is showing signs of memory loss and confusion?” I asked the clinician. “Are you sure electroconvulsive therapy won’t exacerbate this?”
“Although there can be mild memory loss from the ECT, your father is suffering from treatment-resistant depression, and the ECT can help him.”
I never believed my father was clinically depressed. To the contrary, my father was gregarious, energetic and hard-working. He was a born performer, playing guitar, singing, performing as Santa Claus, emceeing wedding receptions, or reciting one of thousands of memorized poems and jokes. He had a witty, if caustic, sense of humor and he was always “on” in the company of others. The term “bipolar” or “manic depressive” would more aptly describe him, though his highs well outweighed his lows. I featured some of my father’s antics and talents in a compilation of old home movies — an entertaining glimpse into his typical disposition.
As I grew up, I recognized my father’s personality in people like Robin Williams (I’ll return to this point later). Like him, and like so many creatives with “dangerous gifts,” my father had demons. His marriage to my mother was deeply dysfunctional. He was a serial adulterer. His drinking of alcohol was likely influenced by his Russian genetic and cultural heritage. (Alcohol, I should note, is one of the most potent depressants a human can ingest.) And, as someone who had a family to support after immigrating to America at almost 40 years old, he shouldered immense levels of stress. He worked constantly. And the career he fantasized about, one full of music, singing and poetry, never materialized.
My father’s first foray into psychiatric medications coincided, not surprisingly, with the collapse of his marriage. A therapist prescribed Zoloft for depression. This was twenty years ago, before the term “chemical imbalance” was in vogue.
Following the Zoloft, two strains of a pattern emerged. Either my father would feel better and stop the medication, or he would feel worse and a doctor would increase his dose or introduce new medications. Throughout this pattern, my father continued to drink and never went to any sort of therapy. This lasted for close to two decades. He altered his mental state with pills and alcohol, which resulted not only in no improvement to his mental or emotional well-being, but ended with him abandoning his business and feeling worse than he ever had.
For me, there are a few clues that my father was misdiagnosed and mistreated. Medical professionals were probably rarely, if ever, exposed to the reality of my father’s bipolar personality, because when he was manically “happy” he was not making doctor’s appointments. It’s doubtful he confided in them about his level of drinking, partying and dysfunctional relationships with young women. Additionally, there was a language barrier. It was easier for my father to make simple statements, like “I’m depressed” and “I don’t want to live,” rather than try to find the appropriate English words to delve into his mental state and his manic lifestyle. He also probably became unable to differentiate between what might have been a side effect of one of the multiple prescriptions he was on, and what was his own self-diagnosed mental health issue. Most people, including doctors, don’t really know what the behavior they are seeing indicates. Unhappiness, sadness, boredom, stress, these can all come across to a doctor or patient as “depression.”
When he signed himself up for the ECT because he “wanted to die” and could hardly move his limbs, I’m betting his doctors and nurses didn’t stop to consider that a recent stroke and his self-medicating with alcohol and multiple psychiatric drugs might be contributing to his psychosis, or at least to cognitive impairment that could have led to the emotional devastation and anxiety he felt at the time.
One other thing I’m sure of: my father was a hedonistic pleasure-seeker. With his doctors, he found a high that could dull his senses and lift his mood. Although medical professionals may believe they are treating someone’s illness, my father, by ignoring things like therapy or sobriety, was enjoying the drug effect and sedation, the chemical fix for the unhappiness that came with the collision of his dreams and his reality. Meanwhile, the drugs wreaked continuous havoc to his brain.
Over the course of twenty years, my father was treated by or consulted with at least 16 different medical professionals who prescribed him a total of at least 21 psychotropic medications. He was frequently taking more than one medication at one time. Eventually, the antidepressants and anti-anxiety medications were not strong enough for him. His prescriptions were increasingly for antipsychotics, drugs that are used to treat schizophrenia and other psychoses, as well as anticonvulsants that are typically prescribed for mania.
And, this is the hardest part for me to accept: It’s well-understood that SSRIs, along with several other drugs, increase the risk of a stroke. This is particularly true if a person has been on blood thinners, which my father had been. I’m still a bit enraged when I think about the fact that doctors didn’t warn my father that he could increase his chances of a stroke by being on blood thinners and antidepressants, especially considering that his blood pressure and cholesterol levels already made him a stroke risk.
* * *
Upon completing a whopping 11 ECT treatments, my father only became more disoriented, more forgetful and less coherent. We could no longer let him drive, so we sold his car and asked his doctor to notify the DMV that his driving was impaired. Having evidence of my father‘s recent mini-stroke and memory loss, the doctor surmised that it looked like he was beginning to suffer the early stages of dementia.
From then on, my father was ping-ponging between my sister, my mother and me as his caregivers. We prepared every meal, eliminated his access to alcohol, supervised nearly everything he did and dutifully took him to his medical appointments. This included an almost monthly visit with a psychiatrist. By 2018, my father was taking lithium for depression/bipolar disorder, lamotrigine for bipolar disorder, clonazepam for anxiety and sleep, donepezil for dementia, plus his statin and other medications.
Meanwhile, I became more and more alarmed by my father’s mental and physical decline. After reading a well-known tome about caring for someone with dementia — “The 36 Hour Day” — and joining a 20,000-member Facebook group for caregivers of people with dementia and Alzheimer’s, I was introduced to many symptoms that I recognized in my dad. He was emotionally volatile, frequently sobbing for no reason. His physical movements were impaired: he had trouble moving his limbs or bending his body in any way, which meant he never wanted to change his clothes, nor shower. His mental decline was staggering. He no longer understood basic facts, or people’s names, ages and relation to him. He had no ability to read, play guitar, or even watch television. All technology became a frustration to him. He had hand tremors. His writing ability regressed to the point that he couldn’t spell basic words and would write painstakingly and slowly, like a child. He asked the same questions over and over, compulsively agonizing about small facts. He had trouble seeing. He did damaging things on accident, like pour liquid soap into a cup and drink it, or leave a faucet on.
Worst of all, he developed extreme combativeness and aggression, even physically lashing out, and yelling angrily at the top of his lungs, often in public. We began to fear him and the increasing frequency of “catastrophic reactions” that are well-known in the world of dementia.
One thing “The 36 Hour Day” and all medical professionals seemed to agree on was the obligation to treat a patient’s depression, even if (and maybe especially if) the patient has dementia. But this did not make sense to me. His treatment for depression had all but failed for 20 years; I couldn’t understand why medical professionals pursued this unicorn of a cure. While they were busy experimenting with his brain, my father was becoming a monster, and it agonized us that he was behaving so wildly and dangerously with everyone who cared for him (and in front of my small children — who hated being around him). The only reprieve we got was when he slept, which was often. After all, the majority of the drugs he was on had major sedating effects. But when he was awake, it was like dealing with an aggressive, 200-pound zombie. We were nearing the end of our ability to manage him. We considered two end-of-the-road options: a memory care facility and/or much heavier medications. We toured some facilities and asked the psychiatrist for Seroquel. Seroquel is a “black box” drug, which means it comes with the FDA’s most serious warning for serious or life-threatening risks. It also increases the mortality rate for dementia patients. Even though it’s specifically not approved for dementia, it’s well known as an off-label treatment. To my shock, after all the hand-wringing we did about the Seroquel, I found out that my father had already had a prescription for it several years earlier, before the dementia diagnosis.
Between all the appointments, medications and terror in our home, a thought continued to nag at me: how could this man suffer such a massive decline? He was barely 70 years old. The people at the memory care facilities were wheelchair-bound and decades older than him. There was no way he could sit alongside them. He never wanted to sit. He stood and paced frantically, he could walk for hours. If he went to a facility, they would only sedate him more, because he would be a combative nuisance.
When we took my father to a neurologist to see if there was anything new to report on his latest MRI, we learned that nothing had changed. There was nothing more going on in his brain than his original scan showed two years earlier.
“Can you at least test him? Find out how bad his dementia is? We don’t understand why he’s behaving this way,” I said. But the neurologist said my father seemed to be past the point of being capable of sitting through testing. He couldn’t sit at the appointment, he was complaining and yelling from the moment we entered the room, to the moment we exited.
“You know, the dose of Seroquel you have him on is not that high. You might consider increasing it,” the neurologist offered. I felt so defeated. Not a single drug was improving his condition.
“Okay, but can we at least take him off some of these other pills? They’re clearly not helping.”
“That’s a conversation you need to have with his psychiatrist.”
We’d already had that conversation. Her response was to replace lamotrigine with Trileptal. She didn’t even know, and then was fairly unconcerned, about his dementia diagnosis. She asked him how he felt, he talked through his mental fog about how depressed he was and how it was the worst day of his life, and she typed on her tablet and tweaked his prescriptions. It was a textbook case of what I later learned is referred to as the “15 minute med check.” After a few of these appointments, it was clear to me that my father’s brain was a problem no one could solve and no pill had ever seemed to solve. Not only that, the fact that he was making life in our home impossible seemed not to register with anyone.
I came to the conclusion that because doctors are always going to aim for “treatment,” it’s very difficult for them to accept the concept that drugs are doing more harm than good and that abandoning them might be warranted. They are not thinking about discontinuation, tapering and the complicated nature of a body’s and brain’s withdrawal symptoms. When the medical professionals had seemingly no interest in my father’s completely “insane” behavior, I looked more closely at his medications. The side effects were staggering: blurred vision, tooth pain, memory loss, muscle stiffness, depression(!), suicidal thoughts, drowsiness, insomnia, aggression. I read about the tragic misuse of sedating medications on people with dementia and small efforts to end the practice. I read about the use of these incredibly strong psychotropic drugs on children in the foster care system, on prisoners, on migrants. I read in the caregiver Facebook group how many caregivers were sedating their loved ones with hardcore drugs, and treating them for depression and anxiety, and yet still experiencing agitation and violence, just like we were. A study even shows that long-term use of benzodiazepines leads to a significantly higher risk of developing Alzheimer’s. “Unwarranted long term use of these drugs should be considered as a public health concern,” the study concludes.
What are we participating in, I wondered? Why aren’t the doctors who are seeing my father get worse and worse scrutinizing the medications more closely?
I’m going to cut to the chase here:
My father now uses Skype on his own to talk to friends. He has a tablet to watch YouTube. He reads. He plays guitar. He’s memorizing new poems. He recently transcribed, quickly and with perfect spelling, the song he sings in the YouTube video. He plays with my children almost daily and laughs uproariously. We got him a dog and he walks her and loves her. He rarely sobs. He almost never yells. He changes his clothes and can shower by himself. He can walk to the neighborhood pool by himself, swim, and walk himself back without getting lost. His memory has markedly improved. And his severe muscle stiffness is gone. Hand tremors, gone. He can hop, skip, even sprint. He does push-ups and sit-ups in his room every day without prompting.
How did this happen?
Well, three months ago—without any medical professional’s knowledge or assistance — we eliminated his last psychotropic prescription (please note: abrupt discontinuation is not recommended). We have him on a healthy diet and a routine of physical activity. And no alcohol. And a little THC.
It was as if my father, the one I knew, came back from the dead. As the months go by and I watch him emerge from his chemical stupor, I am in disbelief that such a profound change can happen in a person simply by removing the side effects of medications (by removing the medications themselves). It occurs to me that for so long what we thought was his declining mental state could actually have been a state of disinhibition, the way one might feel when they’re high or drunk. His wild and impulsive behaviors, his disorientation, the loud and combative aggression — in hindsight they seem like that of a person who spent his waking hours inebriated. And now, in a matter of months, he’s sober.
Just imagine if we had let my father stay on the medications, as doctors prescribed. We would have assumed, for example, that his inability to write was a symptom of his dementia. If we had told his psychiatrist “he’s no longer able to write,” she would have chalked it up to the recent dementia diagnosis we told her about, and would have continued right on keeping him in the chemical cage that took away his fine motor skills. He would have spent years in the stupor, unable to write his poems and songs. How many other people, I wonder, are stuck in a chemical cage, not realizing that their mental and physical well-being has deteriorated because of side effects? A mere six months ago, we were considering memory care facilities for my father, and would have put him on more sedatives to manage him, which now seems truly absurd.
Now the flip side: He did have a mini-stroke and we do think there is some mental fallout from that. He is, and will always be, a drug-seeker, looking for the magic fix. He tells us often how terrible he feels, how depressed he is. The more coherent he becomes, the more aware he is of his loneliness, his sadness, and his boredom. A pill — I’m convinced — won’t fix that. It never did. As his voluntary caregivers, we do what we can to keep him active and stimulated, as well as safe and healthy. We’re not going to let him drive, and we still supervise him almost everywhere. But — and I’m not exaggerating — all of the monster-like qualities that we thought were severe symptoms of his dementia have practically disappeared. The spectrum of his emotional volatility narrowed substantially. We’ve found ourselves questioning whether he has dementia at all.
* * *
So, a word about Robin Williams:
When Robin Williams committed suicide in August of 2014, within days the world began talking yet again about the need to treat depression. Everyone seemed to gloss over the fact that Williams was misdiagnosed with Parkinson’s disease. His wife wrote about “chemical warfare” in his brain, the symptoms of which went far beyond depression and into confusion, memory loss, paranoia, intense anxiety and insomnia. She was keen to pinpoint the final diagnosis — Lewy Body Dementia — as the culprit responsible for his suicide. Few talked about Williams’ multiple medications as a potential issue. Like the fact that he had taken two medications for Parkinson’s, which not only can lead to psychosis, but are specifically flagged as inappropriate for people with psychiatric disorders because they can lead to psychosis.
On top of the Parkinson’s drugs, Williams was also taking an antidepressant called mirtazapine, a “black box” drug with noted suicide risk. Additionally, Williams had taken out a prescription for Seroquel mere days before his suicide. Williams did indeed have “chemical warfare” in his brain. But we can never truly know how much of the culprit was his dementia, and how much was the number of psychosis-inducing, sedating, debilitating chemicals that the doctor who was “treating” him prescribed.
Susan Schneider, Williams’ wife, made clear that Robin Williams was being treated for depression. He was, after all, a star with the best medical resources and treatments available to him. It’s not like they weren’t going to treatment. Schneider described at least a year of doctor’s appointments, of trial and error with medications, of worsening symptoms, of a “terrorist” inside her husband’s brain. It was as if she was speaking about my father. But my father got better. He may still call himself depressed, but he’s sober, stable and coherent, the value of which he will probably never admit nor appreciate, because he doesn’t remember what the monster in him was like.
Having had this experience, the way I look at psychiatry and psychotropic medications has completely changed. Of course, I understand that they work for some people (though time and life changes also work). I know stories of people who have had specific mental conditions and behaviors that certain medications helped alleviate, usually in combination with self-care, psychotherapy and eventual discontinuation. Antidepressants might be an important tool in certain situations, though the benefits have repeatedly been shown to be small, especially when compared to a placebo.
However, I can say with certainty that doctors and psychiatrists often don’t really know if they’ve got the diagnosis, the treatment, or the symptoms right when it comes to mental health. They often aren’t taking time to understand the brain they are altering. They are often unaware of what other medications the patient might be taking. They don’t know if they’re treating the patient, or the patient’s side effects. And they can’t be sure that the cure isn’t worse than the disease.
If you are being treated with psychiatric medications, please consider my warning:
They are experimenting.
Every time.
On you.
At the end of the day, the psychiatric drugs you or your loved one are on are sedatives and chemicals. Some go so far as to call them neurotoxins. The longer you use them, the weaker your brain gets at being able to regulate itself on its own. The higher your risk of deleterious effects. And the harder it is to get off them. But sometimes that’s exactly what needs to happen.
A few months ago I was surprised to receive a request from an obscure journal of consciousness studies to review a paper. I was surprised because, although it was not immediately obvious from the title, the paper contained the first reports of the primary outcome measure of the massive and notorious STAR-D study, 14 years after the study was finished.
What in the world were the main findings of the world’s largest ever antidepressant trial doing being presented now in a little known journal? The answer may lie in the fact that they show how miserably poor the results of standard medical treatment for depression really are!
With 4041 participants, the STAR-D study is by far the largest and most expensive study of antidepressants ever conducted. The intention of the study was to see how antidepressant treatment combined with high quality care performed in usual clinical conditions. It did not involve a placebo or any sort of control. All treatment was provided free for the duration of the study to maximise engagement.
The paper I was asked to review, which is now published in Psychology of Consciousness: Theory, Research and Practice, is written by a group led by Irving Kirsch and based on the original data obtained through the NIMH.1Shannon Peters describes its findings in detail.
Kirsch’s group point out that the paper that describes the design of the STAR-D trial clearly identifies the Hamilton Rating Scale for Depression (HRSD) as the primary outcome.2 This makes sense since the HRSD is one of the most commonly used rating scales in trials of treatment of depression, especially trials of antidepressants. As the STAR-D authors note in the study protocol “the HAM-D17 (HRSD), the primary outcome, allows comparison to the vast RCT literature” (cited in (1)).
Yet the outcome that was presented in almost all the study papers was the QIDS (Quick Inventory of Depressive Symptomatology), a measure made up especially for the STAR-D study, with no prior or subsequent credentials. In fact, as the authors of the present paper point out, this measure was devised not as an outcome measure, but as a way of tracking symptoms during the course of treatment, and the original study protocol explicitly stated that it should not be used as an outcome measure.
The analysis found that over the first 12 weeks of antidepressant treatment, people in the STAR-D study showed an improvement of 6.6 points on the HRSD. This level of change fails to reach the threshold required to indicate a ‘minimal improvement’ according to the Clinical Global Impressions scale (a global rating scale), which would be 7 points. It is also below average placebo improvement in placebo-controlled trials of antidepressants. A meta-analysis of paroxetine trials, for example, found that the average improvement in placebo-treated patients was 8.4 points on the HRSD.3 A meta-analysis of trials of fluoxetine and venlafaxine reported average levels of improvement on placebo of 9.3 points over just 6 weeks.4 Another meta-analysis found placebo improvement levels of between 6.7 and 8.9 points in placebo groups across trials involving a variety of antidepressants.5
The proportion of people classified as showing a ‘response’ (using the arbitrary but commonly used definition of a 50% decrease in HRSD score as per the original protocol) was 32.5% in the STAR-D study, and the proportion classified as showing remission (HRSD score ≤7) was 25.6%. The meta-analysis of placebo-controlled trials of fluoxetine and venlafaxine reported response rates of 39.9% among people allocated to placebo, and remission rates of 29.3%. In another antidepressant meta-analysis, the response rate on placebo was just above the STAR-D level at 34.7%,6 and in another it was just below at 30.0%.7
The authors of the current paper point out, however, that improvement is lower in placebo-controlled trials, even in the people treated with antidepressants, than it is in trials that compare one antidepressant against another without placebo controls. This is presumably because people in placebo controlled trials are told that there is a chance that they will receive a dummy tablet, while in comparative trials, they know they will receive some sort of active drug. Therefore they compare the results of the STAR-D study to the results of a large meta-analysis of comparative trials (cited in (6)). These find average HRSD improvement levels of 14.8 points; response rates of 65.2% and remission rates of 48.4%. Therefore the STAR-D results are approximately half the magnitude of those obtained in standard comparative drug trials.
The authors propose that the reasons for this poor performance of antidepressants in the STAR-D study is due to the selection of more complex patients. Industry studies in particular exclude people with ‘co-morbid’ conditions and symptoms or history of self-harm, and often recruit people via advertisements. It may also be due to the intensive attention and assessment procedures people undergo in industry-funded studies, and the added placebo effect of being in a trial of a ‘new’ treatment, which most trials involve.
Whatever the reason, STAR-D suggests that in real life situations (which the STAR-D mimicked better than other trials) people taking antidepressants do not do very well. In fact, given that for the vast majority of people depression is a naturally remitting condition, it is difficult to believe that people treated with antidepressants do any better than people who are offered no treatment at all.
It seems this may be the reason why the results of the main outcome of the STAR-D study have remained buried for so long. Instead, a measure was selected that showed results in a slightly better light. Incidentally, even then results were pretty poor, especially over the long-term, as Piggott et al have showed in a previous analysis.8
Whether this was deliberate on the part of the original STAR-D authors or not, it was certainly not made explicit. There should surely be uproar about the withholding of information about one of the world’s most widely prescribed class of drugs. We must be grateful to Kirsch and his co-authors for finally putting this data in the public domain.
Mad In America Robert Whitaker Aug 6, 2016 In June, the Centers for Disease Control reported that the suicide rate in the United States had increased 30% from 1999 to 2016, with more Americans killing themselves “than ever before.”
The CDC has been sounding this alarm for several years now, stirring
headlines—each time it issues its annual report—of a “public health
crisis.”
Here are just a few of the headlines that have appeared:
Although the media reports may tell of social factors that can
contribute to suicide, such as unemployment, the language in the
articles often tell of a medical crisis. “Mental health experts
say mental health screening would help people get into treatment before
their depression becomes severe,” Voice of America News wrote, in an article
on the CDC report. “Other recommendations include reducing the social
stigma associated with mental illness and making treatment more widely
available.”
The American Foundation for Suicide Prevention, which has been
promoting suicide awareness programs since the late 1980s, similarly
tells of how “ninety percent of people
who die by suicide have a mental disorder at the time of their deaths.”
The most common disorder associated with suicide, the Foundation
states, is “depression, an illness that goes undiagnosed and untreated far too often.” It advises reporters to “convey that suicidal thoughts and behaviors can be reduced with the proper mental health support and treatment.”
This rise in suicide certainly deserves societal attention. But given
that it has occurred during a time when an ever greater number of
people are getting mental health treatment, there are obvious questions
to investigate, with the thought that perhaps our societal approach to
“suicide prevention” needs to change. Specifically:
Is suicide in the United States really at an “epidemic” level? Or is there a bit of “disease mongering” present in such claims?
What do we know about societal risk factors that could account for changes in the suicide rate during the past forty years?
Are there guild and commercial interests present in “suicide prevention” campaigns?
Is there evidence that suicide prevention campaigns work? Does more
access to mental health treatment lead to a reduction in suicide?
Do antidepressants reduce the risk of suicide?
In short, we need a scientific fact-check on suicide in the Prozac
era. The hope is that doing so might help our society respond to this
suicide crisis in a more “evidence based” way.
madinamerica Martin Plöderl, PhD & Michael P. Hengartner, PhD Suicide rates decreased steadily from the mid-eighties until the new
millennium in the USA and, on average, in Organisation for Economic
Cooperation and Development (OECD) countries.1 In Europe, suicide rates decreased until around 2007 in most countries.2
Parallel to this drop of suicides, prescriptions of SSRI’s, the new
generations of “antidepressants,” gradually increased. This led to
numerous publications arguing that the negative correlations between
antidepressant prescription rates and suicide rates was evidence that
antidepressants are likely helpful in reducing suicide because they can
alleviate symptoms of depression, one of the major risk factor for
suicide. Authors of these papers often had financial or other ties to the
pharmaceutical industry (e.g., Ulrich Hegerl, Göran Isacsson, John Mann,
Zoltan Rihmer). In 2004, a kind of shock wave hit mainstream psychiatry when the FDA
released the black box warning about prescribing antidepressants to
children and youth. Not long after, Robert Gibbons and others published a
now widely cited paper, based on data from 2003 to 2005, reporting that
the black-box warning led to a reduction in the prescribing of
antidepressants which was associated with an increase of suicides among
young people.3 However, although the article was published in the high-ranked, peer-reviewed American Journal of Psychiatry,
the statistical analysis and the related conclusions by Gibbons were
quickly shown to be in error; there simply was no increase of suicides
associated with the decrease of antidepressant prescriptions (see
Jureidini, 20074 and Stone, 20145; see also Robert Whitaker’s report). From 2000 onwards, suicide rates in the USA started to rise again
(among youth around 2007). In most countries in Europe, suicide rates
stopped declining or even increased again starting around 2007. However,
antidepressant prescription rates steadily increased from the
mid-eighties until today. As a result, the association between increased
antidepressant rates and reduced suicide rates has faded with each
passing year. Even worse for mainstream psychiatry, if you look at the
past 10 years, antidepressant rates are associated with increased
suicide rates. Yet, as this has occurred, there has been, in our opinion, a strange
silence. There has been a lack of research updates on the trend of
increases in suicide rates as prescriptions of antidepressants have
risen. And what about research reports on the long-term outcomes of the
FDA black box warnings? Two papers pointed out that suicide rates did
not increase as a result of the black box warnings in the United States
and in Canada (Rhodes, Skinner, McFaull, & Katz, 20136
and Stone, 2014), but these papers were also “silenced” in psychiatry,
since they were much less cited (9 and 36 times, respectively) than the
Gibbons et al. paper that was cited 569 times (citation-frequency
assessed via Google Scholar on August 12, 2018). Other attempts to show that the FDA warnings led to increased suicides (Lu et al., 2014,7 cited 115 times) have also been debunked (see comments to the Lu article and Philip Hickey’s blog “Suicidal Behavior After FDA Warnings” here on MIA). This silence about increasing suicide and antidepressant rates, and
the silencing of studies that disproved harmful effects of the FDA
warnings, was interrupted by at least two noteworthy incidents that
demonstrate some deep-seated form of “evidence-resistance.” First,
Robert Gibbons simply kept on claiming that the black box warning led to an increase of suicides (LA Times,
Feb. 06/2012). Second, a research group around Zoltan Rihmer published a
paper in 2015 about suicide trends and antidepressant prescription
rates in Hungary, but only used data up until 2006, excluding the time
span afterwards when suicide rates increased again (Otuyelu et al., 20158).
This way, they of course could prove that increased antidepressant
prescriptions came along with reduced suicide rates. No word about the
restricted time frame or the increase of suicides in recent years in the
limitation section of the paper. They even claimed that their results
were an indirect proof of the harms of the FDA warnings (of course
citing the debunked 2007 Gibbons et al. paper). They said that, since
there was no related warning in Hungary, antidepressant prescriptions
kept on rising in young people whereas suicides kept on falling. Otuyelu
also cited another paper that “proved” the harms of the black box
warning (Katz et al., 20089), despite opposing evidence available at that time (Rhodes et al., 2013). All of this is the background to our recent research on this topic.
Recently, when we became aware of a newly published paper in the Journal of the American Academy of Child & Adolescent Psychiatry
that analyzed trends of suicidality and mental health utilization of
young people in the US, we wondered why the authors did not also include
the results for prescriptions rates, despite that data being available.10
However, since the data was in the public domain, we were able to
investigate the association of the suicide attempt rate with drug
prescriptions for mood disorders (most likely antidepressants) among
adolescents for the years 2004 to 2016. Our analysis was rejected for publication by the Journal of the American Academy of Child & Adolescent Psychiatry and by JAMA Psychiatry. We were finally able to publish the paper in Epidemiology and Psychiatric Sciences (Plöderl & Hengartner, 201811). Unfortunately, variables for years prior to 2004 could not be
compared to later years, but with the available data we could still
explore changes in the rate of prescriptions and suicide attempt rates
following the FDA warning. The data is based on the annual National
Survey on Drug Use and Health, a nationally representative survey among
the US population. Past year major depression was assessed with a
structured interview, and participants were asked if they had taken
prescribed medication for their mood problems in the past year. We used
this as a proxy for use of antidepressant medication. Prior suicide
attempts were also assessed. This suicide attempt variable seemed to be a
valid indicator of past year suicide risk, since it correlated high
with the yearly suicide rates of the same age group (r = 0.75, p <
.05). Our analysis revealed that the rates of prescriptions, suicide attempts, and suicides decreased
in the years following the FDA warning in 2004 but started to rise
again in recent years. This is also confirmed by large and statistically
significant correlation coefficients. Obviously, this contrasts with
the assumption that the FDA warning led to an increase of suicidal
behavior. On the contrary, it seems that reduced prescriptions lead to a
reduction in suicidal behavior. It also indicates that the FDA
warning had no enduring effect, since prescriptions to youth are on the
rise again. The usual interpretation by mainstream psychiatry is that our
findings are an artefact: young people attempting suicide are more
likely to receive mental health treatment, and this produces the found
association. This explanation, however, does not fit with the fact that
our findings apply both to adolescents with and without a major
depression diagnosis. Persons without major depression are rarely
suicidal; therefore, in these youths, the strong correlation between
suicide attempts and antidepressant prescriptions is hardly explained by
diagnosis alone. Also, antidepressant prescription rates increased before the suicide attempt rates did, as indicated via a statistical technique called changepoint-analysis.
Given the limitations of our study, it is important to look for
replications. Indeed, our findings are similar to that of a study by
Gupta, Gersing, Erkanli, & Burt (2016).12
By using patient data from psychiatric settings, Gupta et al. found
that antidepressant prescriptions decreased from 79 to 60% from the
period before the black box warning (2000-2003) relative to the period
afterwards (2004-2009). The relative risk for suicidality decreased
substantially by around 60-70% as well. Of note, the relative risk for homicidality and other violent events
was also reduced around 60-70%. These findings are exactly what would be
predicted by the outcomes of randomized controlled clinical trials. In
these trials, young people using antidepressants had higher rates of
both suicidality and aggression, compared to those taking placebo. With our study results, as with all such correlational data, it must
be mentioned that causality cannot be inferred, and there are other
strong arguments regarding why such data must be interpreted with
caution. However, as stated above, our findings are in line with those
from randomized controlled trials, where young people taking
antidepressants indeed had higher rates of suicide attempts and other
forms of suicidality (Healy, Le Noury, & Jureidini, 2018;13 Sharma et al., 2016;14 Stone et al., 200915). Put together, these data strongly suggest that antidepressants can cause suicides and aggressive behavior. Disturbingly, our study and others reveal that the black box warning
is now ignored in many countries, since antidepressant prescription
rates for children and youth are on the rise again (Bachmann et al.,
2016;16
Otuyelu et al., 2015). This increase is happening despite increasing
certainty that antidepressants are rather ineffective and most likely
cause suicidal behavior in young people. It seems that the current strategy in mainstream psychiatry to deal
with the problematic evidence base is to recommend fluoxetine, because
it was reported as being the most effective drug with no increase of
suicidality (Brent, Gibbons, Wilkinson, & Dubicka, 2018;17 Cipriani et al., 201618).
Again, problems with these studies and the excess of suicidal events
under fluoxetine in the trials continue to be ignored. As with other
reports critical of antidepressant prescriptions, these inconvenient
findings are not properly acknowledged. As a result, mainstream
psychiatry will continue to claim that antidepressants effectively
reduce suicide risk, despite compelling evidence to the contrary. Show 18 footnotes
They're not happy because it takes away one more leg of their Virtue Signaling stool in order to make children safer from people who've been poisoned with mind control drugs.
dailycaller rob shimshock education reporter 7/19/18
A school district voted unanimously to become the first Virginia county to permit armed teachers, but Virginia government officials are not pleased.
The Lee County School Board decided earlier in July to arm teachers in its 11-school, 3,200-student school district, but face backlash from Virginia’s Department of Education and attorney general, according to The Washington Post Wednesday.
“[There are] one or two people out in the community that are not for it, and I think it’s probably from an anti-gun standpoint, really,” Lee County School Board member Rob Hines said. “But people can have concerns about it. We have concerns about it. We just think that, financially, it’s our best option and we have to do something.”
The board believes 50 out of Lee County’s 700 school employees will be responsible for concealed weapons in September after going through psychological evaluations, background checks and summer training. Virginia state law forbids the presence of firearms on school property, but the Lee County School Board will attempt to classify the armed employees as “conservators of the peace” to gain exemption. (RELATED: Alabama Superintendent: Metal Detectors Weren’t In Use On Day Of School Shooting)
“We recently found out about this scheme, and we’re looking into it,” Virginia Attorney General Mark Herring’s spokesman, Michael Kelly, told WaPo. “It’s troubling to learn that people are putting so much time and effort into getting around the law and getting more guns into schools when the focus should clearly be on creating a safe, welcoming learning environment.”
Kelly said that Virginia “clearly prohibits guns in schools” barring a few small exceptions.
“Lee County did not approach the department for guidance or technical assistance before the local school board took this action,” Virginia Department of Education spokesman Charles Pyle said. His department is examining the school district’s decision in light of “relevant statutes.”
Fourteen states have armed teachers and 16 more states give school boards discretion over arming teachers as of March, according to VICE News. Virginia is not listed as one of those states.
1: ‘Antidepressants and Violence; Prof. David Healy et al, here or download here. 2. ‘Suicidality, Violence and Mania Caused by SSRIs; Dr Peter R Breggin here. 3. Drugs associated with violence.Here. 4. The Systemic Correlation Between Psychiatric Medications and Unprovoked Mass Murder in America. Jeanne M. StolzerHere. 5.Case Histories As Evidence. David Healy et al. Here. 6. SSRIs and Involuntary Intoxication Defense.Wade C. Myers et al. Here. 7. Fort Hood Shooters. Donald J Farber, Attorney at Law. Here. 8. Prescribed drugs and violence: a case/noncase study in the French PharmacoVigilance Database. Rouve et al. Here. 9. Antidepressant-induced
akathisia-related homicides associated with diminishing mutations in
metabolizing genes of the CYP450 family. Lucire et al. Here. 10. Precursors to suicidality
and violence on antidepressants: systematic review of trials in adult
healthy volunteers. Bielefeldt et al.Here. 11. Suicidality and aggression
during antidepressant treatment: systematic review and meta-analyses
based on clinical study reports. Sharma et al. Here. 12. Selective serotonin
reuptake inhibitors versus placebo in patients with major depressive
disorder. A systematic review with meta-analysis and Trial Sequential
Analysis. Jakobsen et al.Here. 13. Antidepressants and suicide among young women in Sweden 1999–2013. Janne Larsson.Here.
A new study conducted by Jeffrey Vittengl at Truman University has found that taking antidepressant medications resulted in more severe depression symptoms after nine years.
The study, published in Psychotherapy and Psychosomatics, examined outcomes over a nine-year period and included initial depression severity as well as other factors. Vittengl divided treatment into categories and compared them to those who received no treatment: inadequate treatment without medication (fewer than eight sessions of therapy) inadequate treatment including medication (fewer than four appointments with prescriber) adequate treatment without medication (at least eight sessions of therapy) adequate treatment with medication (at least four appointments with prescriber)
Of participants with depression, 38.1% received no treatment, 25.2% received inadequate treatment with medication, while 13.5% received adequate treatment with medication. 19.2% received inadequate treatment without medication, and only 4.1% received adequate treatment without medication.
The results were startling. Even after controlling for depression severity, participants who took medication had significantly more severe symptoms at the nine-year follow-up than participants who did not. In fact, even people who received no treatment at all did better than those who received medication. “Adequacy” of treatment did not appear to make much of a difference. Photo Credit: Philippa Willitts, “A is for antidepressants,” Flickr
These results add to a body of research that indicates that antidepressants worsen long-term outcomes. In an article published in 1994, the psychiatrist Giovanni Fava wrote that “Psychotropic drugs actually worsen, at least in some cases, the progression of the illness which they are supposed to treat.” In a 2003 article, he wrote: “A statistical trend suggested that the longer the drug treatment, the higher the likelihood of relapse.”
Previous research has also found that antidepressants are no more effective than placebo for mild-to-moderate depression, and other studies have questioned whether such medications are effective even for severe depression. Concerns have also been raised about the health risks of taking antidepressants—such as a recent study which found that taking antidepressants increases one’s risk of death by 33% (see MIA report).
In fact, studies have demonstrated that as many as 85% of people recover spontaneously from depression. In a recent example, researchers found that only 35% of people who experienced depression had a second episode within 15 years. That means that 65% of people who have a bout of depression are likely never to experience it again.
Critics of previous findings have argued that it is not fair to compare those receiving antidepressants with those who do not. They argue that initial depression severity confounds the results—those with more severe symptoms may be more likely to be treated with antidepressants. Thus, according to some researchers, even if antidepressants worked as well as psychotherapy or receiving no treatment, those treated with antidepressants would still show worse outcomes—because they had more severe symptoms in the first place.
That is why, in the current study, Vittengl included initial and follow-up depression severity in his analysis, as well as other variables that might provide alternate explanations for the results. This provides a direct counterargument to those who argue that initial severity confounds the results.
To this end, he used data from the Midlife Development in the United States Survey, which tracked depression severity as well as types of treatment utilized over the course of nine years. The data were collected in three waves (1995-1996, 2004-2006, and 2013-2014), and 3,294 participants remained in the study by the third wave.
The survey collected data on depression, generalized anxiety disorder, panic disorder, as well as other medical conditions, family history of mental health conditions, and childhood trauma. Additional data included personality factors, social support, daily functioning, and alcohol use. Because all of this information was included in the survey, Vittengl was able to add it in his analysis.
He found that although these factors impacted depressive symptoms, they did so equally between the groups. That is, initial depression severity does predict lack of improvement—but it does so whether the person is taking medication or not. Therefore, it does not explain how outcomes could be worse with medication.
Perhaps the most notable limitation of Vittengl’s study is his distinction between “adequate” or “inadequate” treatment based solely on the number of sessions (because that was tracked in the survey). This may not be the best indicator of whether participants were receiving sufficient care. However, this does not impact his general findings comparing treatment with medication to treatment without medication and to the group that received no treatment.
Although Vittengl writes that antidepressants may have an immediate, short-term benefit, he argues that long-term use appears to be detrimental. His results suggest that in general, people actually fare better over the long-term if they seek no treatment at all than if they take antidepressant medications. Psychotherapy, on the other hand, appeared to have no detrimental effects. However, even doing nothing was more successful at reducing symptoms after nine years than medication use.
****
Vittengl, J. R. (2017). Poorer long-term outcomes among persons with major depressive disorder treated with medication. Psychotherapy and Psychosomatics, 86, 302-304. doi: 10.1159/000479162 (Link)
Human antidepressants are building up in the brains of bass, walleye and several other fish common to the Great Lakes region, scientists say.
In a new study, researchers detected high concentrations of these drugs and their metabolized remnants in the brain tissue of 10 fish species found in the Niagara River.
This vital conduit connects two of the Great Lakes, Lake Erie and Lake Ontario, via Niagara Falls. The discovery of antidepressants in aquatic life in the river raises serious environmental concerns, says lead scientist Diana Aga, PhD, the Henry M. Woodburn Professor of Chemistry in the University at Buffalo College of Arts and Sciences.
"These active ingredients from antidepressants, which are coming out from wastewater treatment plants, are accumulating in fish brains," Aga says. "It is a threat to biodiversity, and we should be very concerned.
"These drugs could affect fish behavior. We didn't look at behavior in our study, but other research teams have shown that antidepressants can affect the feeding behavior of fish or their survival instincts. Some fish won't acknowledge the presence of predators as much."
If changes like these occur in the wild, they have the potential to disrupt the delicate balance between species that helps to keep the ecosystem stable, says study co-author Randolph Singh, PhD, a recent UB graduate from Aga's lab.
"The levels of antidepressants found do not pose a danger to humans who eat the fish, especially in the U.S., where most people do not eat organs like the brain," Singh says. "However, the risk that the drugs pose to biodiversity is real, and scientists are just beginning to understand what the consequences might be."
The research team included other scientists from UB, Ramkhamhaeng University and Khon Kaen University, both in Thailand, and SUNY Buffalo State. The study was published on Aug. 16 in the journal Environmental Science and Technology.
By Peter Breggin, MD May 24, 2017 Doctors often tell patients that antidepressants can only cause suicidal behavior in children and not in adults. Many publications also make the same claim. The false claim is based on the FDA-approved Black Box Warning for antidepressants that warns about an increased rate of suicidality in children, youth and young adults taking antidepressants, but not in adults over age 24. The Black Box Warning specifically summarizes, “Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24.”
The studies that the FDA relied upon for adults over age 24 were dismally flawed and untrustworthy compared to the ones used for children. According to the FDA at the 2006 hearings:
“Due to the large number of subjects in the adult analysis, almost 100,000 patients, the adjudication process was left as the responsibility of the sponsors [the drug companies] and was not overseen or otherwise verified by the FDA. This is in contrast to the pediatric suicidality analysis in which the FDA was actively involved in the adjudication (p. 14).”
In addition, the FDA also announced at the 2006 hearings on antidepressant-induced adult suicidality that it did not require a uniform method of analysis by each drug company and an independent evaluator as required with the pediatric sample.
Thus, the FDA was comparing somewhat good apples (the pediatric studies) to rotten apples (the adult studies), while making them seem comparable. The child studies showed that antidepressants can cause suicidality — the adult studies (after age 24) showed nothing other than FDA collusion with the self-serving drug companies. As I have described in my books and scientific articles, drug companies routinely manipulate their data on suicide to avoid any causal connection to their drug (see for example my 2006 paper about GSK and Paxil).
In the case of Eli Lilly, here are two memos by employee Claude Bouchey (pages 2 & 3 of document) written to the hierarchy of the company in which he expresses guilt and shame about changing official investigator reports of Prozac-induced suicide attempt to misleading terms like “overdose” or “depression.”
Ironically, the FDA controlled and monitored the original pediatric studies precisely because the drug companies on their own failed to find any risk of antidepressant-induced suicidality in any age group. Why would the FDA assume these same self-serving drug companies, left on their own again, would spontaneously begin for the first time to conduct honest studies on the capacity of their products to cause adult suicidality?
Furthermore, even in the rotten-apple adult studies, despite the drug company’s manipulations, Paxil (paroxetine) turned out to be causally associated with increased suicidality in depressed adults in an internal FDA review of the data. As a result, in 2006 the FDA then forced the maker of Paxil, GlaxoSmithKline (GSK), to write a “Dear Doctor” letter to all healthcare providers confirming the Paxil/suicidality causal link in adults.
In April 2006, the FDA also made the drug company put a warning in its Full Prescribing Information (label or package insert) about the risk of Paxil causing suicidality in adults with depression; but GSK convinced them to drop it in subsequent years. The warning appeared in the Physician’s Desk Reference (PDR) only once in 2007.
Meanwhile, there are many studies showing that antidepressants do cause suicidality and suicide in adults.
Next time you hear someone say that the FDA studies only showed increased suicidality in children and young adults as opposed to adults, remember that the adult studies, unlike the pediatric studies, were not controlled, monitored or validated by the FDA. This is one more example of the extremes the FDA will go to in order to protect drug companies and their often lethal products.
It was bad enough to find out that antidepressants cause suicidality in children. The drug companies and their minions complained mightily. The FDA and the drug companies were not going to allow a repetition of sufficiently unbiased studies that might conclude that adults are also vulnerable to antidepressant-induced suicide.
Editor’s note: We know that our reviews of the withdrawal literature are incomplete, and we urge readers to help us add to these withdrawal reviews. Please send study citations that are relevant to the withdrawal literature for antidepressants to rwhitaker@madinamerica.com. Introduction
Selective Serotonin Reuptake Inhibitors (SSRIs) have been used in the treatment of depression since the late 1980s. Serotonin–norepinephrine reuptake inhibitors (SNRIs) were introduced in the 1990s. It is proposed that SSRIs work by increasing serotonin activity in the brain, and that SNRIs work by increasing both serotonin and norepinephrine. These are chemicals that have been linked to the regulation of mood.
Although these drugs were initially indicated for depression, they have also been FDA approved for other conditions, including anxiety disorders, posttraumatic stress disorder, premenstrual dysphoric disorder and fibromyalgia. Antidepressant medication (ADM) use has dramatically increased over the last few years in the United States; about 1 in 10 Americans aged 12 and over take an ADM. This document reviews drugs classified as SSRIs or SNRIs, although a bulk of the research focuses on SSRIs. Mechanism of Action
1) Moncrieff J, Cohen D. Do antidepressants cure or create abnormal brain states? Plos Medicine. 2006;3(7):e240-e. Link
The authors provide evidence against the “disease model” of depression which states that depression is the result of a biochemical abnormality that ADM corrects. They argue for the adoption of a “drug-centred model” which posits that ADM lead to the creation of an abnormal brain that can have an effect on certain symptoms of depression. Treatment decisions should be based on the short-term, known effects of the drug according to this view.
2) Fava GA. Can long-term treatment with antidepressant drugs worsen the course of depression? Journal Of Clinical Psychiatry. 2003;64(2):123-33. Pubmed link
This literature review summarizes research supporting the oppositional tolerance hypothesis, that is continued treatment with ADM may activate processes that go against the initial effects of the drug and lead to a loss of clinical effect. At worse these processes can continue even when the drug is discontinued and increase vulnerability to relapse. The author proposes that withdrawal symptoms that occur after an ADM is discontinued may be clinical evidence of the oppositional tolerance hypothesis.
3) Andrews P, Kornstein S, Halberstadt L, Gardner C, Neale M. Blue Again: Perturbational Effects of Antidepressants Suggest Monoaminergic Homeostasis in Major Depression. Full Text Link
This meta-analysis tests the “oppositional tolerance” hypothesis – that is patients whose symptoms lessen with ADM treatment will have a higher risk of relapse after treatment stops than patients whose symptoms improve without ADM. It further tests the hypothesis that greater oppositional tolerance is linked to the greater disturbance of the monoamine neurotransmitter system in the brain. Both hypotheses were supported – over time ADM use leads to an increased risk of relapse, and this risk is even greater when the drug has more of an impact on the monoamine system. The authors compare these findings to the mechanism of action of of a spring – the further a spring is pulled away from it’s equilibrium or original position, the greater will be the force produced by this spring when it is released. Animal Studies: Long-term Effects of Exposure to ADMs
4) Kepser L-J, Homberg JR. The neurodevelopmental effects of serotonin: A behavioural perspective. Behavioural Brain Research. 2015 1/15/;277:3-13. Pubmed link
This is a review of animal studies which summarizes the behavioral effects of early exposure to SSRIs. The authors conclude that serotonin disturbances during the prenatal and postnatal phases are linked to an increased risk for mood disorders whereas the risk for autism-like behaviors and sexual abnormalities is linked to increased serotonin levels in the postnatal period. These findings in rats are discussed in relation to similar findings on the role of serotonin exposure in human studies.
5) Maciag D, Simpson KL, Coppinger D, et al. Neonatal antidepressant exposure has lasting effects on behavior and serotonin circuitry. Neuropsychopharmacology: Official Publication Of The American College Of Neuropsychopharmacology. 2006;31(1):47-57. Pubmed link
This study provides evidence that rats exposed to an SSRI very early in life displayed disruptions in behavior as adult rats, long after the medications had been discontinued. This cluster of behavior changes called the “neonatal antidepressant exposure syndrome” are discussed in light of the implications of exposure to ssris at critical phases of brain development. Similar changes were not seen in rats exposed to ssris as adults.
6) Hilakivi LA, Hilakivi I. Increased adult behavioral ‘despair’ in rats neonatally exposed to desipramine or zimeldine: an animal model of depression? Pharmacology, Biochemistry, And Behavior. 1987;28(3):367-369. Pubmed link
In this study rats were exposed to a tricyclic ADM and an SSRI from 7-18 days after they were born. ADM was stopped after this period. The adult rats were assessed at 2 months and 5 months and it was found that early ADM exposure had negative emotional effects, which was observed in their behavioral responses to a stressful situation. These findings are explained as a cause of a reduction of neurotransmitters like serotonin and dopamine in the forebrain because of early exposure to ADM that cause changes that do not renormalize.
7) de Jong TR, Snaphaan LJAE, Pattij T, et al. Effects of chronic treatment with fluvoxamine and paroxetine during adolescence on serotonin-related behavior in adult male rats. European Neuropsychopharmacology: 2006;16(1):39-48. Pubmed link
Results of this study indicate that there are some effects on adult sexual activity and anxiety behaviors after adolescent SSRI exposure. However, the authors are unclear about whether these findings are limited to adolescent exposure, whether serotonin receptors play a role and did not investigate whether these effects are temporary or permanent.
8) Gouvêa TS, Morimoto HK, de Faria MJSS, Moreira EG, Gerardin DCC. Maternal exposure to the antidepressant fluoxetine impairs sexual motivation in adult male mice. Pharmacology, Biochemistry, And Behavior. 2008;90(3):416-9. Pubmed link
Exposure to SSRIs in utero is associated with impaired sexual motivation in adult male mice.
9) Iñiguez SD, Warren BL, Bolaños-Guzmán CA. Short- and Long-Term Functional Consequences of Fluoxetine Exposure During Adolescence in Male Rats. Biological Psychiatry. 2010;67(11):1057-66. Pubmed Link
The results of this study suggest that adolescent exposure to fluoxetine leads to lower levels of a behavioral response to a stressful situation in adulthood in male rats. This anxiety response reduced when the same rats were given fluoxetine for a few days as adults. The same long-term pattern was not observed in adult rats after their ADM was discontinued. Similarly, fluoxetine exposed adolescent rats showed signs of sexual dysfunction as adults. The authors conclude that exposure to the drug in adolescence can impact behavioral responses in adulthood.
10) Bosker FJ, Tanke MAC, Jongsma ME, et al. Biochemical and behavioral effects of long-term citalopram administration and discontinuation in rats: role of serotonin synthesis. Neurochemistry International. 2010;57(8):948-57. Pubmed link
The results of this study suggest that treatment with citalopram increased the number of serotonin receptors in the brain. The two treatment conditions were divided into a drug washout (abrupt discontinuation) and non-drug washout group (continuation). There were differences observed in these two groups on the turnover and synthesis of serotonin with an increase of both processes in the discontinuation group. There were also behavioral changes observed in the discontinuation but not the continuation or control groups. The authors conclude that chronic SSRI treatment does not impair brain serotonin function, but it may lead to an increased vulnerability fluctuations in its synthesis.
11) Raap DK, Garcia F, Muma NA, Wolf WA, Battaglia G, van de Kar LD. Sustained desensitization of hypothalamic 5-Hydroxytryptamine1A receptors after discontinuation of fluoxetine: inhibited neuroendocrine responses to 8-hydroxy-2-(Dipropylamino)Tetralin in the absence of changes in Gi/o/z proteins. The Journal Of Pharmacology And Experimental Therapeutics. 1999;288(2):561-7. Link
The authors report a continued desensitization of a type of serotonin receptor (the 5-HT1A receptor) 60 days after discontinuation of fluoxetine, an SSRI, indicating that the receptors did not renormalize much after the medication had left the brain tissue. The authors conclude that mechanism of desensitization of receptors when the drugs are being used versus when they are discontinued are likely to be different. The implications of these results for humans are discussed. Discontinuation Syndromes
12) Fava, M. . “Prospective Studies of Adverse Events Related to Antidepressant Discontinuation.” Journal of Clinical Psychiatry (2006); 67, suppl. 4, 14-21. Pubmed link
Though varying in frequency and intensity, nearly all classes of antidepressants have been linked with discontinuation reactions and the associated psychological, physical, and somatic discomfort. Spontaneous reports have been typically used to gauge the risks of discontinuation reactions. Judging from a number of prospective studies, spontaneous reports very likely underestimate the occurrence of discontinuation reactions. The author provides a review of studies dealing with discontinuation-related adverse events.
13) Shelton, R. “The Nature of the Discontinuation Syndrome Associated With Antidepressant Drugs. Journal of Clinical Psychiatry (2006); 67, suppl. 4, 3-7.
A common phenomenon accompanying treatment with nearly every major class of antidepressant is the emergence of the discontinuation syndrome. The term withdrawal has been used in the past; however, the distinctions between discontinuation symptoms and drug withdrawal are clear. In addition, awareness of the unique nature of discontinuation effects and a grasp of the typical time frame of their emergence can assist in distinguishing between discontinuation syndrome and relapse. As a result, it is vital that both patients and their relatives be provided with adequate education and a realistic and objective appraisal of expected outcomes upon initiation of antidepressant treatment, which may include experiencing discontinuation adverse events upon cessation of the drug treatment. Pubmed link
14) Smith, P. F. and C. L. Darlington. “A possible explanation for dizziness following SSRI discontinuation.” Acta Oto-Laryngologica 2010; 130(9): 981-983. Pubmed link
The authors provide an explanation for the often experienced symptom of dizziness upon SSRI discontinuation. They link to a reduction in a region of the brain that has an abundance of serotonin receptors. The implications of this finding are discussed.
15) Renoir T. Selective Serotonin Reuptake Inhibitor Antidepressant Treatment Discontinuation Syndrome: A Review of the Clinical Evidence and the Possible Mechanisms Involved. Frontiers in Pharmacology. 2013; April 16, 4:45. Pubmed link
In this review the author examines the evidence for the phenomenon of a discontinuation syndrome and notes that even though it is clear that it exists, there are several limitations of existing studies. These include the absence of studies comparing drugs with similar half-lives but that have different effects upon discontinuation, the short durations of treatment interruptions and the lack of studies designed to take into account the pharmacokinetics of the drug and the role of its metabolite. He also summarizes the preclinical animal studies examining the effects of treatment discontinuation as well the limitations of this body of literature. For instance, they were designed to study the mechanism of action of SSRIs rather than the effects of discontinuation, and they used “normal” animals instead of animal models of depression. Potential directions for future studies that can shed light on our current limited understandings of the mechanism of discontinuation syndrome are discussed.
16) Michelson D, Fava M, Amsterdam J, et al. Interruption of selective serotonin reuptake inhibitor treatment. Double-blind, placebo-controlled trial. Br J Psychiatry. 2000 Apr;176:363-8. Pubmed link
In this controlled study half the patients who had been taking SSRIs were assigned to continue their medication and the other half were given a placebo. The authors found that the effect of stopping the drug was associated with the drug’s half-life – the shorter the half-life, the more severe the adverse effects and functional impairment. The effects were most severe with paroxetine, followed by sertraline whereas no significant effects were observed upon discontinuing fluoxetine. The predominance of physical effects upon discontinuation were hypothesized as representing a drug induced reaction rather than a return of depression.
17) Rosenbaum JF, Fava M, Hoog SL, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry. 1998;44. Pubmed link
This study was conducted to understand the effects of ADM interruption for a brief period in light of “patient noncompliance” or missing doses. After being on a maintenance dose of ADM for anywhere between 4-24 months, 83% (192) patients were given a placebo instead of their ADM for 5-8 days. After this phase ADM was reintroduced. The frequency of psychological and somatic symptoms upon ADM interruption was greatest for paroxetine, followed by sertraline and lastly fluoxetine. Patients treated with sertraline and paroxetine but not fluoxetine also experienced a return of depressive symptoms. When the medication was reintroduced there was a rapid reduction of somatic symptoms and depression scores. Thus the results are hypothesized to reflect a response to the stopping of SSRIs rather than a relapse or return of depression.
18) Judge R, Parry MG, Quail D, et al. Discontinuation symptoms: comparison of brief interruption in fluoxetine and paroxetine treatment. International Clinical Psychopharmacology. 2002;17(5):217-225. Pubmed link
This study was conducted to understand the effects of a shorter treatment interruption of SSRIs (fluoxetine and paroxetine), that is 3-5 days, which has implications for when patients miss taking their medication. Results indicate that there was a significant increase in adverse events (as measured by the Discontinuation Emergent Signs and Symptoms (DESS) scale) reported by the paroxetine but not the fluoxetine group. Stopping ADM also had negative clinical (return of depression) and quality of life implication for the paroxetine but not the fluoxetine group. The depression scores increased as a result of an increase in somatic symptoms upon ADM interruption.
19) Viguera AC, Baldessarini RJ, Friedberg J. Discontinuing antidepressant treatment in major depression. Harvard Review Of Psychiatry. 1998;5(6):293-306. Pubmed link
This literature review summarizes the results of 27 studies on long-term ADM use and effects after discontinuation of the medication. Results indicate that discontinuing treatment leads to higher rates of monthly relapse rates, shorter time to relapse and higher risk of relapse on a yearly basis. Also slower rates of discontinuation did not lead to a lower relapse risk. Lastly being on a maintenance dose for longer after being stabilized with ADM did not protect participants from a lower relapse rate one ADM was discontinued. This goes against the conventional wisdom that patients need to be on a maintenance dose for several months after acute symptoms have remitted.
20) Verbeek-Heida PM, Mathot EF. Better safe than sorry–why patients prefer to stop using selective serotonin reuptake inhibitor (SSRI) antidepressants but are afraid to do so: results of a qualitative study. Chronic Illness. 2006;2(2):133-142. Pubmed link
In this qualitative study the authors interviewed 16 SSRI users (range of use: 6 months to 10 years) to understand their decision making around continuing or stopping their medication. A subset of 9 patients had attempted to discontinue their medication in consultation with their physician, but all had been unsuccessful (the experience upon stopping is not described) and had re-started the drugs. Another relevant theme was that patients received conflicting advice from physicians which made them err toward continuing rather than discontinuing the medication.
21) Bahrick AS. Persistence of sexual dysfunction side effects after discontinuation of antidepressant medications: Emerging evidence. The Open Psychology Journal. 2008;1.
The author summarizes evidence from the literature on the occurrence of sexual side effects that persist long after stopping SSRIs. She notes that a great deal of evidence on this phenomenon emerged outside the professional community, from consumer reports on internet communities. Implications for prescribing and non-prescribing psychologists are discussed.
22) Valuck RJ, Orton HD, Libby AM. Antidepressant discontinuation and risk of suicide attempt: a retrospective, nested case-control study. Journal Of Clinical Psychiatry. 2009;70(8):1069-77. Pubmed link
This study compared a group of individuals who had been diagnosed with depression to a group of individuals who had been diagnosed with depression and attempted suicide. Relevant to discontinuation, the authors found that the first 2 weeks after stopping an ADM is a time for increased risk for suicide as well, whereas using AD was found to be a protective factor. Initiation of AD therapy was associated with the highest rate of suicide attempt, followed by phases where doses were reduced or increased. Also individuals who attempted suicide were more likely to use ADM and have multiple occurrences of depressive episodes.
23) Csoka AB, Shipko S. Persistent sexual side effects after SSRI discontinuation. Psychotherapy And Psychosomatics. 2006;75(3):187-188. Pubmed link
In this paper the authors present 3 cases where patients experienced persistent sexual dysfunction several years after discontinuing their ADM. Some potential hypotheses to explain this phenomenon are discussed.
24) Csoka AB, Bahrick A, Mehtonen O-P. Persistent sexual dysfunction after discontinuation of selective serotonin reuptake inhibitors. Journal Of Sexual Medicine. 2008;5(1):227-233. Pubmed link
In this paper the authors present 3 cases where patients experienced persistent sexual dysfunction several years after discontinuing their ADM. These 3 were chosen out of 1300 individuals who self-identified as having sexual problems post SSRI discontinuation. The findings are discussed in light of the changes that SSRIs produce in various systems that do not seem to renormalize upon discontinuing the medication.
This brief report described four patients on SSRIs who all suffered prolonged neurological symptoms for months after discontinuing their medication. All patients were on drugs that affect the reuptake of serotonin despite being structurally dissimilar and having different mechanisms of action. The authors speculate that this may be responsible for the persistent neurological symptoms observed despite stopping the medication.
26) Bolton JM, Sareen J, Reiss JP. Genital anaesthesia persisting six years after sertraline discontinuation. Journal Of Sex & Marital Therapy. 2006;32(4):327-30 Pubmed link
This paper describes a case study of a 26-year-old man who experienced a sexual side-effect during active use and 6 years after discontinuation of the ADM sertraline, even as his mood remained stable. The authors hypothesize the cause of this persistent dysfunction a) may be related to psychological reasons or b) the sertraline led to long-term functional changes in the brain that did not reverse. The patient believed that his symptoms were an effect of the sertraline.
27) Kauffman, RP Murdock, A. Prolonged post-treatment genital anesthesia and sexual dysfunction following discontinuation of citalopram and the atypical antidepressant nefazodone. The Open Women’s Health Journal. 2007, 1: 1-3.
This paper describes a case of a 32-year-old woman who experienced sexual side effects during 4 weeks of treatment with an SSRI, citalopram which led to switching to nefazodone. Even though her depression symptoms remained in remission, the sexual side effects persisted even after a year of stopping all medication. Possible reasons for this phenomenon are discussed.
Abrupt venlafaxine discontinuation involves a high risk of withdrawal syndrome. Mechanism of its development is similar to that of selective serotonin reuptake inhibitors (SSRIs), but of higher intensity. Venlafaxine withdrawal symptoms may include several somatic symptoms as well as several psychiatric symptoms. In some cases, symptoms may look like a stroke. A treatment option is re-inclusion of venlafaxine or a SSRI antidepressant.
29) Wang J, Greenberg H. Status cataplecticus precipitated by abrupt withdrawal of venlafaxine. Journal Of Clinical Sleep Medicine. 2013;9(7):715-6. Pubmed link
A case study of a narcoleptic patient who developed status cataplecticus after abrupt withdrawal of venlafaxine.
A case study of six patients who developed withdrawal syndromes after discontinuing venlafaxine.
31) Rosenbaum J, Zajecka J. Clinical Management of Antidepressant Discontinuation. Journal of Clinical Psychiatry 1997; 58, suppl. 7, 37-40. Pubmed link
To minimize the symptoms of antidepressant discontinuation, gradual tapering is necessary for all serotonin reuptake inhibitors (SRIs) except fluoxetine, which has an extended half-life. Discontinuation symptoms, which frequently emerge after abrupt discontinuation or intermittent non-compliance and, less frequently, during dose reduction, are generally mild, short-lived, and self-limiting but can be distressing and may lead to missed work days and decreased productivity. The symptoms may be somatic (e.g., dizziness and light-headedness; nausea and vomiting; fatigue, lethargy, myalgia, chills, and other flu-like symptoms; sensory and sleep disturbances) or psychological (anxiety and/or agitation, crying spells, irritability).
32) El-Mallakh RS, Gao Y, Jeannie Roberts R. Tardive dysphoria: the role of long term antidepressant use in-inducing chronic depression. Medical Hypotheses. 2011;76(6):769-773. Pubmed link
The authors propose a model of tardive dysphoria, which is a potentially chronic depressive state that develops in some individuals who have been using ADM over a longer period of time. Discontinuation of ADM may lead to a gradual improvement in symptoms some people, but in others the chronic state of depression may be permanent and irreversible. A genetic explanation linked to a serotonin transporter gene for this phenomenon is provided. The authors conclude by stating the need for randomized control trials to test the existence of tardive dysphoria. They state that discontinuation may be more likely to be beneficial for those who have had briefer exposure to ADM, have greater brain neuroplasticity and have the long form on the serotonin transporter gene.
33) El-Mallakh RS, Karippot A. Antidepressant-associated chronic irritable dysphoria (ACID) in bipolar disorder: a case series. J Affect Disord 2005;84:267–72. Pubmed link
A case study of six bipolar patients who developed a chronic dysphoric mood, irritability and middle insomnia, which is associated with occupational and social dysfunction, after receiving antidepressants for three years. Discontinuation of antidepressants was associated with a slow and gradual improvement in these symptoms over the ensuing year.
34) Fava GA, Gotti A, Belaise C, Guidi J, Offidani E. Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review. Psychotherapy and Psychosomatics 2015;84 (2):72-81. Full Text.
A systematic review of the research literature for studies that reported on SSRI withdrawal symptoms. These studies showed that discontinuation symptoms typically occur within a few days following discontinuation and last a few weeks. This occurs with gradual tapering too. However, patient experiences are variable, and some may experience late onset of discontinuation symptoms, or disturbances that persist. Such withdrawal symptoms are often misidentified as signs of impending relapse. Relapse Upon Discontinuation
35) Baldessarini RJ, Tondo L, Ghiani C, et al. Illness Risk Following Rapid Versus Gradual Discontinuation of Antidepressants. American Journal of Psychiatry. 2010;167(8):934-941. Pubmed link
In this naturalistic study patients on ADM were taken off their medication either rapidly (1-7 days) or gradually (over 14 days or more). Results indicate that rapid discontinuation leads not only to early withdrawal or physiological symptoms, but also to a quicker return of a new episode of depression or panic. They also found a link between a drug’s half life and recurrence of illness. They conclude that gradual dose tapering may be especially beneficial when discontinuing older antidepressants and those with shorter half-lives. However, since physiological discontinuation reactions are linked with drugs that act on the serotonin system, they recommend gradual dose tapering for all ADMs.
Tapering Speed
Tapering to be customized for a patient depending on the half life of the ADM being used as well as the dose. The general rule is that drugs with shorter half lives need a longer taper period. Another factor that impacts speed of taper is the dose the patient has been taking. Most guideline documents say “reduce dose gradually” over a certain number of weeks depending on the ADM but do tend not to specify exactly what gradual means.
36) Keks N, Hope J, Keogh S. Switching and stopping antidepressants. Australian Prescriber. 2016;39(3):76-83. Pubmed link
The authors recommend stopping ADMs over 4 weeks at least, but mention other factors that need to be taken into consideration when making this decision. They provide tables listing the approximate half-lives of ADMs, general techniques for switching between ADMs and guidelines for switching between specific ADMs.
37) Khan A, Musgnung J, Ramey T, et al. Abrupt discontinuation compared with a 1-week taper regimen in depressed outpatients treated for 24 weeks with desvenlafaxine 50 mg/d. Journal Of Clinical Psychopharmacology. 2014;34(3):365-368. Pubmed link
This controlled clinical trial was conducted to assess if there were any differences in the emergence of discontinuations symptoms with an abrupt versus a taper protocol. The control group continued taking the medication as usual. The taper protocol switched patients to 25 mg/d for one week after 24 weeks of treatment with 50 mg/d, followed by a placebo for 3 weeks. Symptoms or adverse events after stopping the medication were measured using the Discontinuation Emergent Signs and Symptoms (DESS) scale. The authors conclude that even though there were more absolute adverse events reported by patients in the abrupt taper group compared to the taper group, this difference was not statistically significant.
38) Ogle NR, Akkerman SR. Guidance for the discontinuation or switching of antidepressant therapies in adults. Journal Of Pharmacy Practice. 2013;26(4):389-396. Pubmed link
This is a guidance document based on evaluation of the literature and is intended as a guide for clinicians or other healthcare professionals in their management of patients who want to stop or switch their ADM (see Tables 1 and 2). They note that package inserts for ADMs warn of withdrawal risk but do not provide details about how to taper. They also mention that there is very little evaluation of the data presented and the source documents provide varied information.
39) Phelps J. Tapering antidepressants: is 3 months slow enough? Medical Hypotheses. 2011;77(6):1006-1008. Pubmed link
This study was designed to test a new drug for the treatment of cataplexy (a sleep-related disorder) which has a history of being treated with ADM. This necessitated stopping the ADM patients were taking. Control participants were patients who had never taken ADM. The author concluded based on the higher number of weekly cataplexy attacks for the ADM group that longer taper rates for ADM may be warranted. He proposes discontinuing over 4 months at a rate of 25% reduction per month or 12.5% every 2 weeks. However, he says, this needs further systematic study.
40) Fava M, Rosenbaum JF, Hoog SL, et al. A comparison of symptoms following treatment interruption: Evidence from a randomized, double-blind trial with fluoxetine, sertraline, and paroxetine. European Neuropsychopharmacology 8:S171-S172
This controlled trial followed a protocol where ADM was stopped for 4-6 day periods in a group of patients who had responded to 4-10 weeks of treatment. Adverse events measured using checklists and spontaneous reporting by patients. Results indicate that brief interruption of SSRI treatment results in new or worse adverse events. The frequency of adverse events was greatest for paroxetine, followed by sertraline and lastly fluoxetine.
41) Pringsheim T, Kelly M, Barbui C. Stopping antidepressants following depression. BMJ 2016;352. Pubmed link
This is a 10-minute consultation guide for practitioners. It follows NICE guidelines in recommending ADM to be taperered over 4 weeks if the patient has been well for 6-12 months. If discontinuation symptoms occur they recommend tapering over a longer period, but do not specify how much longer.
42) Tint A, Haddad PM, Anderson IM. The effect of rate of antidepressant tapering on the incidence of discontinuation symptoms: a randomised study. Journal Of Psychopharmacology (Oxford, England). 2008;22(3):330-332. Pubmed link
This study compared the emergence of SSRI discontinuation on tapering the medication over 3 versus 14 days. Results indicate that there were more adverse events reported upon quicker taper, but these results were not significant. However, the half-life of the drug is an important consideration – drugs with shorter half lives need to be tapered more slowly, especially because of the possibility of increased depressive and suicidal symptoms when SSRIs are discontinued.
43) Kaymaz, N., et al. (2008). Evidence that patients with single versus recurrent depressive episodes are differentially sensitive to treatment discontinuation: a meta-analysis of placebo-controlled randomized trials. The Journal Of Clinical Psychiatry 69(9): 1423-1436. Pubmed link
This review of 30 trials (4890 patients) was conducted to understand what moderates the effect of the finding that ADM prevents the occurrence of relapse after remission from an episode of depression. Relapse rates were found to be greater in patients with recurring episodes of depression. The mode of discontinuation of ADM had an effect on this group, but not single episode patients. The authors found that acute withdrawal was more likely to lead to relapse in recurrent episode patients. Acute withdrawal was not as relevant for single episode patients. The authors conclude that the recommendation that patients should be treated for at least 6 months after achieving remission or that patients with more frequent episodes should receive maintenance treatment is not supported based on these findings. They recommend gradual discontinuation of ADM in general, to manage withdrawal symptoms.
44) Rothschild, Anthony J. Selective Serotonin Reuptake Inhibitor-Induced Sexual Dysfunction: Efficacy of a Drug Holiday. The American Journal of Psychiatry 152.10 (1995): 1514-6. ProQuest. Web. 2 Sep. 2016. Pubmed link
This study was conducted on a group of 30 outpatients who experienced sexual dysfunction upon taking SSRIs to assess whether a “drug holiday” or brief break from medication would lead to improved sexual functioning. ADM was stopped for 4 weekends from Thursday to Sunday. Results indicate that sexual functioning improved in patients taking sertraline and paroxetine, but not fluoxetine. The authors presume this is because of the shorter half lives of sertraline and paroxetine compared to fluoxetine. There were no statistically significant increases in depression scores across all patients.
44) Fava GA, Bernardi M, Tomba E, Rafanelli C. Effects of gradual discontinuation of selective serotonin reuptake inhibitors in panic disorder with agoraphobia. Int J Neuropsychopharmacol 2007;10:835–8. Pubmed link
In a study of 20 remitted patients, antidepressants were tapered at the slowest possible pace and with appropriate patient education. Nine of the 20 patients (45%) experienced a discontinuation syndrome, which subsided within a month in all but three patients who had been taking paroxetine for a long time. Discontinuation syndromes appeared to be fairly common even when performed with slow tapering and during clinical remission. In some cases disturbances persisted for months after discontinuation.
One other thing I’m sure of: my father was a hedonistic pleasure-seeker. With his doctors, he found a high that could dull his senses and lift his mood. Although medical professionals may believe they are treating someone’s illness, my father, by ignoring things like therapy or sobriety, was enjoying the drug effect and sedation, the chemical fix for the unhappiness that came with the collision of his dreams and his reality. Meanwhile, the drugs wreaked continuous havoc to his brain. 
