Crushing symptoms day after day for years. Is it any wonder some of us want a permanent out? Assisted dying for patients with psychiatric disorders – psychiatric euthanasia. You okay with it?
’A few days ago, a 30-year-old patient with very treatable mental illness asked me to end her life. Her distraught parents came to the appointment with her…’
Buckle up, we’re going to discuss a gut-wrenching and controversial topic that will continue to attract major attention.
Some of you may find it troubling, even triggering. If you’re one of them, please feel free to close the piece.
We laid a solid informational foundation in part one of our two-part series on assisted dying for patients with psychiatric disorders – psychiatric euthanasia. If you haven’t already, be sure to give it a read.
By the way, I shared the inspiration for writing about the contentious subject in that piece – the heartbreaking Shanti De Corte story.
Well, part two – ethics and opinions. Let’s get after it…
Assisted dying: Ethics and opinions
“…to do good or to do no harm.” Hippocrates c. 400 BC
First, a quick heads-up. The terminology associated with assisted dying can be confusing – euthanasia, medical aid in dying, legal suicide, physician-assisted dying, physician-assisted suicide, and more.
Don’t lose the forest for the trees over semantics.
Okay, let’s take a look at how several healthcare professional organizations feel about assisted suicide…
American Medical Association
The AMA has a Code of Medical Ethics Opinion for physicians who oppose assisted suicide and for those who are neutral or support it.
Opinion 5.7 states that allowing physicians to engage in assisted suicide would ultimately cause more harm than good. Among other negative consequences, it’s incompatible with a physician’s role as a healer.
Opinion 1.1.7 declarers physicians need to have the opportunity to act (or not) in accordance with the dictates of their beliefs and conscience.
British Medical Association
In September of 2021, the BMA changed their policy from opposition to assisted dying to a position of neutrality.
American Psychological Association
The APA takes a position of neither endorsing or opposing assisted dying.
Assisted dying for patients with psychiatric disorders: A psychiatrist’s opinion
Dr. Mark S. Komrad is a practicing and teaching psychiatrist, as well as a medical ethicist. His commentary, “Oh, Canada! Your New Law Will Provide, Not Prevent, Suicide for Some Psychiatric Patients,” appeared on Psychiatric Times in June of 2021.
Dr. Komrad put a lot of thought and feeling – and, yes, opinion – into his piece. I’d like to run with some highlights.
Context is crucial. Dr. Komrad’s comments were motivated by the development and passage of a Canadian law, and its expansion, that permit what they refer to as medical aid in dying (MAID). We reviewed it in part one.
The door’s wide open
As he begins, Komrad untangles some of that terminology confusion we just talked about. He defines euthanasia as allowing suicidal patients to receive death by lethal injection. It’s assisted suicide when the lethal medication is self-administered.
Komrad points out that Belgium, the Netherlands, and Luxembourg legalized both in 2002. As he puts it, laws in those countries permit voluntary death for patients whose physical or psychological suffering is unbearable and can’t be effectively treated by means that are acceptable to them.
A terminal condition is not a necessary criterion.
Komrad believes these developments opened the door for some patients with psychiatric illness having suicide provided for them, rather than prevented.
He observes that these laws are now being passed around the world, which could profoundly change the practice of psychiatry.
The Canadian spark
Now to what lit Dr. Komrad’s fuse. Canada is the latest nation to legalize voluntary death for psychiatric conditions.
In 2016, Canada passed a law permitting medical euthanasia and physician-assisted suicide, together labeled medical aid in dying (MAID).
A key eligibility criterion was a prediction that a patient’s natural death is “reasonably foreseeable.” Since death from mental disorders wasn’t seen as strongly predictable, mental illnesses were not considered eligible conditions.
Superior Court intervenes
In 2019, a Quebec Superior Court ruling led to the introduction of a new federal bill extending euthanasia eligibility, without limiting it to the end of life. It also removed the prior exclusion of those who have non-terminal chronic illnesses.
And because of accusations of discrimination against those with mental illnesses, the Canadian Psychiatric Association being one of the accusers, euthanasia was permitted for those whose psychological or physical suffering is deemed “intolerable and untreatable.”
A vote was forced and on March 17, 2021 the expansion of euthanasia became the law of the land in Canada.
It’s interesting that the mental illness piece was put on a two-year hold. The idea was to give an expert panel time to establish standards for evaluating patients and procedures.
Without a protocol, there would be no way to determine if suicide for someone with a psychiatric disorder should be prevented or allowed.
A psychiatrist’s bottom-line
Komrad provides this statement by Canadian psychiatrist, Dr. John Maher…
A few days ago, a 30-year-old patient with very treatable mental illness asked me to end her life. Her distraught parents came to the appointment with her because they were afraid that I might support her request and that they would be helpless to do anything about it. It’s horrific they have to worry that by going to a psychiatrist, their daughter might be killed by that very psychiatrist.
What are your feelings?
Objections to physician-assisted dying
Pentobarbital is typically the choice for physician-assisted dying. It’s usually secobarbital capsules for self-administered.
According to Dr. Komrad, countries that have allowed physician-assisted dying have quickly found themselves descending a slippery slope.
He quotes attorney Wesley J. Smith, a prominent critic of such policies…
Once a society embraces doctor prescribed death as an acceptable answer to human suffering or as some kind of fundamental liberty right, there are no brakes.
Indeed, Komrad points out that in Belgium and the Netherlands, policy makers and legislators are debating extending euthanasia beyond medical conditions to include those who feel they have a completed life and are tired of living.
There’s even discussion of demedicalizing euthanasia by providing lethal pills over-the-counter.
And then there’s Pegasos Swiss Association, which will take an application for voluntary assisted death (VAD) at their clinic in Basel. You have to be a “Pegasos Supporter” to apply.
Primary objections
Using the Canadian law as reference, Dr. Komrad shared his primary objections to physician-assisted dying…
There’s no requirement that additional, evidenced-based treatments be implemented, although patients are urged to give all treatments serious consideration.
Physicians are allowed to end the life of people with disabilities or chronic illnesses at their request and will require the system to ensure it happens – even when physicians are convinced, based on their expert knowledge, that medicine offers options and even when the patient may have years or decades to live.
Assisted dying laws would represent a terrible shift in the deep ethos of psychiatry. Psychiatrists would have to decide which suicides should be prevented and which should be abetted.
Do you think his objections are legit?
Assisted dying – psychiatric euthanasia: You okay with it?
If I’m going to ask, “You okay with it?” regarding assisted dying – psychiatric euthanasia, It’s only fair that I respond first.
As a former clinician and 50-year mood and anxiety disorder warrior, I’m not okay with it – as a matter of law for the masses.
My concern is the potentially lethal impact of a tired and hopeless mind, a lack of resources and alternatives, cognitive distortions, impulsivity – and rubber-stamped approvals.
What if I did it?
I know what it’s like to endure life-interrupting symptoms day after dreaded day. And I have no doubt my circumstances would qualify for assisted dying wherever it’s legal.
Thing is though, what if I did it? And don’t think checking out hasn’t crossed my mind a time or two over the decades.
What’s my family supposed to do with it? What about my readers? How do I account for it with my maker?
But you know what? Maybe most important of all is my belief there’s a living purpose for my suffering. And I sure can’t fulfill it if I’m dead.
So now it’s your turn. You okay with it?
If you or someone you care about are in immediate danger call 988 in the U.S. And here’s a list of international suicide hotlines.
Again, if you haven’t already, give part one a look-see. You’ll find lots of interesting details.
Have you ever wanted to die when your symptoms were at their worst? I have. So how do you feel about assisted dying for patients with psychiatric disorders – psychiatric euthanasia? You okay with it?
Shanti made a decision and requested to be euthanized because of ‘unbearable psychiatric suffering.’
This won’t be the first, or last, time I open by saying we don’t back away from controversy here on Chipur.
And it doesn’t get more controversial than discussing assisted dying for patients with psychiatric disorders – psychiatric euthanasia.
In fact, some may find the topic troubling, even triggering. If you’re one of them, please feel free to close the piece.
We have tons to cover, and to ensure we get to it all we’ll roll with two parts.
Information will lay the foundation in this piece. And we’ll come back with an ethics and opinions chat in part two.
Let’s get busy…
The Shanti De Corte story
It was March 22, 2016. Waiting for a flight to Italy with classmates, 17-year-old Shanti De Corte was strolling through Brussels Airport.
It was more than she could absorb.
Suddenly, all hell broke loose as a terrorist-placed bomb exploded.
Mortally wounded
Shanti came through physically unscathed; however, what she saw, heard, and felt left her mortally wounded – emotionally and mentally.
It was more than she could absorb.
She was already troubled by depression and anxiety. But after the cataclysm, episodes of dark depression and non-stop panic attacks dominated her life.
Shanti was admitted to a psychiatric hospital where she was administered a variety of antidepressants. She claimed up to 11 a day.
Her decision to die
There was no response to the meds and she went on to attempt suicide in 2018 and 2020.
Shanti made a decision and requested to be euthanized because of “unbearable psychiatric suffering.”
After two of three physicians approved her request, surrounded by family, Shanti De Corte died in Brussels, Belgium on May 7, 2022 at the age of 23.
Her final social media post…
I was laughing and crying. Until the last day. I loved and was allowed to feel what true love is. Now I will go away in peace. Know that I miss you already.
Hits hard, doesn’t it.
The dissenting opinion
Though Shanti’s earthly life was over, legalities weren’t.
A neurologist at the CHU Brugmann academic clinical hospital was the physician who denied Shanti’s request.
After she died, he made it known that he believed the decision “was made prematurely,” as other care proposals had been made.
In response to his objection, Antwerp prosecutors opened an investigation. But it was closed in fairly short order.
Assisted dying protocol
A quick note before we continue. The terminology associated with assisted dying is varied and can be confusing – euthanasia, medical assistance in dying, legal suicide, physician-assisted suicide, and more.
To simplify matters, I go with “assisted dying”: voluntary active euthanasia and physician-assisted dying when a patient’s life is ended at their request.
Okay, in discussing protocol we’re not going to get into by-country or state lists of where assisted dying is legal. The information is easily found.
We’ll stick with what procedure protocol looks like, referencing Shanti’s home country, Belgium, and Canada.
(Alright, sort of a list: assisted dying is legal in some form in 10 U.S states and the District of Columbia, as well as seven countries.)
The Belgian protocol
Within the context of our discussion, what do you feel when you look at the image?
Belgium has by far the most permissive assisted dying laws. Adults, minors, psychiatric patients – all can make a request.
A physician is required to consult with the patient for a period of time to establish that they’re aware of the decision and process.
No diagnosis is required for adults. However, a terminal diagnosis from a physician with agreement from a guardian or legal representative is mandated for minors.
In some cases, if death isn’t imminent, a pathologist or psychiatrist may be asked to assess a patient’s condition.
If a physician is responding to a patient’s medical directive (e.g., a living will), the patient must be permanently unconscious and suffering from an incurable condition.
Finally, the life-ending drug can be self-administered orally or by infusion or injection by a physician.
The two most common drugs used are the barbiturates, secobarbital (Seconal), which comes in a capsule, and pentobarbital (Nembutal), a liquid.
By the way, it’s free.
Medical assistance in dying: Canada
Canada passed a law in 2016 that permitted what they called medical assistance in dying (MAID).
The primary criterion of the law was a patient’s natural death is predicted to be “reasonably foreseeable.” Psychiatric illnesses were excluded.
Some four years later, in excess of 19,000 individuals had been voluntarily euthanized.
A new law
As a result of a Superior Court ruling, a new federal bill was introduced that extended assistance in dying by removing the prior exclusion of those who have non-terminal chronic illnesses.
It also permitted euthanasia for those whose psychological or physical suffering is deemed “intolerable and untreatable.”
On March 17, 2021, the euthanasia expansion became the law of the land.
The criteria: 18 years of age, mentally competent, a grievous and irredeemable medical condition,” assessed by two independent practitioners, if a psychiatric illness is the only medical condition the patient must wait until March 17, 2023.
On to part two
I have to ask. How are you feeling about all this? My mind has been somewhat unsettled and troubled since I began working on the piece. Hmm.
The coroner ruled it was “…an act of self-harm while suffering from depression and the negative effects of online content.” The truth about social media and teenage suicide – the heartbreaking, yet hopeful, Molly Russell story…
’If you’re struggling, please speak to someone you trust or one of the many support organizations, rather than engage with online content that may be harmful.’ Molly’s father, Ian Russell
Molly Rose Russell was 14-years-old when she died on November 21, 2017.
The inquest – judicial inquiry – at North London Coroner’s Court ended this past Friday.
Coroner Andrew Walker attributed Molly’s death to…
…an act of self-harm while suffering from depression and the negative effects of online content.
He went on to say the online material Molly viewed on platforms, including Pinterest and Instagram, “was not safe” and “should not have been available for a child to see.”
The Molly Russell story
Molly Russell lived in Harrow, a northwest suburb of London. According to her father, she showed no obvious signs of severe emotional or mental illness until a year before her death.
It was then that the family noticed major changes, including feelings of worthlessness, a deepened sense of helplessness, and social withdrawal.
Still, to her family, Molly’s life appeared to be normal.
Her mother’s statement
During the inquiry, a statement was read to the court on behalf of Molly’s mother, detailing the discovery of her daughter’s body.
Mrs. Russell said she was doing household chores on the morning of Molly’s death. After sending one of her other daughters off to school, she began searching the house for Molly – but couldn’t find her.
Then the shock and heartbreak…
I knew then something wasn’t right. I saw a load of her clothes on the floor (of her bedroom). For some reason I thought Molly had run away.
As I looked in her room, I found her…I had no doubt it was her.
I can’t even imagine.
Social media and teenage suicide
Molly Russell
Mr. Walker’s ruling – “…an act of self-harm while suffering from depression and the negative effects of online content.” – was unprecedented.
It was the first of its kind to directly and officially blame a child’s death on social media.
Also unprecedented was requiring the in person, under oath testimony of representatives of the two platforms involved.
Jud Hoffman, Global Head of Community Operations, stood for Pinterest. Meta, owner of Instagram, sent Head of Health & Well-Being Policy, Elizabeth Lagone.
We’ll get into some telling cross-examination details in just a bit.
Molly’s online activity
In her father’s words, Molly’s online environment was “the bleakest of worlds.”
During the inquiry he stated a lot of the content Molly was viewing seemed to “normalise” self-harm and suicide, while discouraging people from pursuing mental health care.
When Mr. Russell looked at Molly’s YouTube account he saw numerous normal teenage “likes” and “follows.” And there were a similar high number of disturbing posts pertaining to anxiety, depression, self-harm, and suicide.
Molly had accounts with Instagram, Pinterest, YouTube, and two with Twitter (one secret).
She used her Instagram account up to 120 times a day.
Of the 16,300 posts she saved, shared, or liked on Instagram in the six-month period before her death, 2,100 were depression, self-harm, or suicide-related.
Mr. Russell expressed shock when he saw the subject lines of the emails were clearly promoting depression-related content.
Trapped by algorithms
Perhaps most exasperating of all, some of the emails were selected and provided without a request from Molly.
How horrific was the material? A testifying child psychiatrist said even he found it disturbing and distressing. After the inquiry, he said there were times over several weeks that he was unable to sleep well.
And given that a depressed 14-year-old viewed the material over a period of months, there could be no doubt Molly was affected.
Even after her death, the disturbing content continued to be delivered.
John Naughton of The Guardian nailed it when he wrote, “Molly Russell was trapped by the cruel algorithms of Pinterest and Instagram.”
Pinterest and Meta respond
During the inquiry, cross-examination of the two company representatives spoke volumes.
The Russell family’s lawyer, Oliver Sanders KC, walked Mr. Hoffman of Pinterest through the last 100 posts Molly had seen before she died.
Hoffman expressed deep regret that she was able to access some of the content.
He even admitted that recommendation emails sent by Pinterest to Molly, such as “10 depression pins you might like,” contained disturbing content and images he wouldn’t show his children.
Meta’s turn
It was a little different with Ms. Lagone of Meta. Evidence was presented showing that, as said earlier, of the 16,300 posts Molly saved, shared, or liked on Instagram in the six-month period before her death, 2,100 were depression, self-harm, or suicide-related.
Sanders then asked if she believed the material is safe for children.
Lagone’s first reply was it’s safe for people to be able to express themselves. Not satisfied, he asked again. Lagone said she didn’t find it a binary question.
Sanders was relentless. He asked, “So you are saying yes, it is safe or no, it isn’t safe?”
Lagone replied, “Yes, it is safe.”
The aftermath
Advocate for health and peace for our young people.
Instagram already announced in 2019 that it will ban all graphic self-harm images and drawings as part of a series of changes made in response to Molly’s death.
Mr. Hoffman admitted Pinterest was “not safe” in 2017, when Molly died. And they have since introduced measures to limit access to dangerous content.
However, when the co-founder of Pinterest, Ben Silbermann – a father of two, was asked at his home if he believed his platform is dangerous for kids, he replied, “I don’t have any comment.”
Her father’s grace and vision
In response to the coroner’s ruling, Molly’s father had the grace and vision to say “there is always hope” no matter how “dark it seems.”
More of his wisdom and love…
If you’re struggling, please speak to someone you trust or one of the many support organizations, rather than engage with online content that may be harmful.
Thank you, Molly, for being my daughter. Thank you.
We should not be sitting here. This should not happen because it does not need to happen. We told this story in the hope that change would come about.
During the inquiry Mr. Russell emphasized “It’s OK not to be OK.”
International attention
The coroner’s ruling received well-deserved international attention. Here’s what Prince William tweeted from the official Prince and Princess of Wales account…
No parent should ever have to endure what Ian Russell and his family have been through. They have been so incredibly brave. Online safety for our children and young people needs to be a prerequisite, not an afterthought.
Well said.
No more denial and ignorance
The coroner ruled “…an act of self-harm while suffering from depression and the negative effects of online content” killed Molly Russell.
And we all know she isn’t the only one.
Molly’s story is heartbreaking, but now hopeful. Social media’s deadly impact upon our youth can no longer be denied – ignored.
Let’s advocate for health and peace for our young people – and continue to monitor the work of Silicon Valley.
Be sure to connect with the Molly Rose Foundation. Established in Molly’s memory by family members and friends, its mission is to reach out to those under the age of 25 who are at risk of suicide. The foundation provides a ton of help, support, and practical advice.
If you or someone you care about needs help or are in immediate danger, the Foundation has incredible resources. Go to their Find Help page and tap on the green box: “To use the Find a Helpline service click here.” There are other resources available as well.
On our bellies, we scratch and claw, looking for the light at the end of the tunnel. In time, we become convinced there’s no hope for depression and anxiety. And we thought we’d never give up.
But you quit – gave up. And now all hope is truly gone.
If you’ve lived with a mood or anxiety disorder for any length of time, you likely deeply felt the opening.
Family members and friends can say, “Never give up.” ‘til the cows come home. But doing so can remain an attractive option.
Among the many reasons for never giving up…
Hope for depression and anxiety: Never give up too soon
What if we give up too soon? I mean, for all we know there really is hope for depression and anxiety – hope for all sorts of good things in our lives.
And a load of it was about to be delivered.
Heather’s story
Heather is 27 years old and has done her best to manage depression and anxiety since she was a kid.
As an adult, they’ve cost her plenty vocationally, as well as in relationships.
Two years ago, Heather met Marty and decided to give dating one more go. They were a great match; however, when it came to Heather’s symptoms, Marty struggled with empathy and tolerance.
That was hurtful to Heather. And as a result, she became tense and cautious around him.
Fact was, though, they were in love. So much so that Marty proposed. And with his commitment to work hard on his attitude and behavior, Heather accepted. They were to be married in nine months.
The dinner
Marty did the best he could, but then came the dinner with his family. Heather had a major panic attack and dashed out of the restaurant.
Marty went after her and found her pacing in the parking lot. He proceeded to go off on her, shouting some horrible things.
It was more than Heather chose to take. In tears, she told Marty she didn’t want to see or talk with him again. Marty knew she meant it and honored her wishes.
And that’s the way it was, at least for several months.
Lesson learned
What Heather didn’t know was Marty did some serious soul-searching after his tantrum. He knew he loved Heather. He also knew he had a lot of learning and maturing to do.
So he decided to work with a counselor. And it wasn’t long before he was a changed man. Wanting to put the past – the pain – behind him, Marty moved – far away.
After several months of reflection and a good bit of healing, Heather wanted to try again. She reached out to Marty, but he was gone. She had given up – too soon.
But you know what? Heather learned a life lesson, and began working even harder on becoming comfortable in her own skin.
She’ll be fine.
That close to success
“This is hard. I want to give up, yet I know I can’t – I won’t.”
Consider the words of Thomas Edison…
Many of life’s failures are people who did not realize how close they were to success when they gave up.
Edison’s observation has meant a lot to me over the many years. By the way, replacing “are” with “happen to” works better for me.
I remember the utter hopelessness and helplessness I felt as I was enduring – battling – panic, anxiety, depression, and alcoholism.
I mean, I’d work and work and work some more; however, I just couldn’t seem to see the light at the end of the tunnel.
Throwing in the towel
And you’d better know I thought about throwing in the towel plenty of times. But some sort of stupid blind faith well beyond my conscious awareness kept my nose to the grindstone.
And it’s the same with Chipur. I devote so much time and energy to the project and (unrealistically) can’t imagine why I don’t have 1,000,000 hits a day.
I mean, there have been times when I post an article and say to myself, “Okay, so who’s even going to read this?”
But give up? Nah.
Do you have hope for depression and anxiety?
So what about you? Whether it has to do with a mood, anxiety, or substance abuse issue – or something else entirely – have you ever felt like giving up?
Maybe you do right now. Perhaps you already have. Yes, in spite of your emotional, mental, physical, relational, and financial investment, cashing out seems to be the only option.
But consider this. Sure, you may not be getting the results you long for. Heck, you may not be seeing any positive results whatsoever.
What if?
We so often use “what if’s” to express our catastrophic thinking. How ‘bout we use them for purposes of strength and hope.
What if all this time something incredibly positive and powerful was building way down deep inside – again, well beyond your conscious awareness?
And what if it all was about to blossom within days, taking you to a wonderful place you could never have imagined?
But you quit – gave up. And now all hope is truly gone.
We can never give up
On our bellies, we scratch and claw, looking for the light at the end of the tunnel. And as episodic as our suffering can be, it could be a frequent activity.
But as convinced as we may be there’s no hope for depression and anxiety, we have to intervene and strongly refute the myth.
Absolutely, we can never give up.
Hundreds of Chipur mood and anxiety disorder inspiration and info articles await. Just peruse the titles.
Antidepressants work. Antidepressants don’t work. Which is it? Let’s check-in with two academic psychiatrists who believe they do, even if scientists don’t know exactly why.
…psychiatrists have never explained clinical depression solely in terms of reduced serotonin or any specific neurotransmitter.
Here we are, smack-dab in the middle of the “Do antidepressants work?” donnybrook.
Two weeks ago I posted “Serotonin and Depression: Is there really a relationship?.”
It’s a discussion of a recent University College London (UCL) news release entitled “No evidence that depression is caused by low serotonin levels, finds comprehensive review.”
That comprehensive review was conducted by a team of UCL researchers and published in Molecular Psychiatry.
Not serotonin, not a chemicalimbalance
The team’s bottom-line is summed up in the title of the release. And we can add depression isn’t likely caused by a chemical imbalance.
That’s right, so why bother with antidepressants?
I didn’t question the accuracy of the data used in the review. However, I sensed an “agenda-driven bias” and “unyielding bite” that made me uneasy.
For the record, two of the team members published a follow up article in which they more directly attacked antidepressants.
Up front, this is a long article. But it has to be, given the abundance of interesting and need-to-know information.
So get comfy, take breaks, read it over a couple of days, whatever – you don’t want to miss this.
Serotonin or not, antidepressants work
Seems I wasn’t the only one uncomfortable with the review.
Bumped into an article on Psychiatric Times entitled, “Serotonin or Not, Antidepressants Work,” written by academic psychiatrists and psychopharmacologists Ronald W. Pies, MD and George Dawson, MD.
The byline: “The latest claim that antidepressants don’t work: refuted.”
Dr. Pies and Dr. Dawson get right down to it…
In our view, the credulous, media-driven narrative generated by the review and the follow-up article amounts to well-worn rhetoric – and the review itself is little more than old wine in new bottles.
Furthermore, we find at least 7 serious problems with the review’s claims, each of which undermine the review’s thesis, as we will elaborate.
We’re going to dig in to those “serious problems.” And to bring them to you I’ve had to do some pretty intense condensing and editing. The docs were on a mission.
7 serious problems with the review’s claims
“Psychiatry” has never proposed a theory of depression asserting it’s caused by one or more neurotransmitters. Dr. Dawson conducted a detailed review and found no references to a “chemical imbalance theory” of mental illness in any standard psychopharmacology textbook or peer-reviewed literature over the past 30 years.
Psychiatrists have known for decades that the cause of depression and other mood disorders can’t be explained solely in terms of a single neurotransmitter. Furthermore, in the period of 1990 to 2010, psychiatrists and neuroscientists proposed at least 17 other hypotheses regarding depression, with eight additional ideas since then.
The complexity of serotonergic (having to do with serotonin) systems and signaling in the brain is not captured in the review. Recent work in this area reveals that although serotonin systems are now much better characterized, additional work needs to be done. The review’s claim that psychiatric research on serotonin has yielded no useful information – and that this whole area of research should be brought to a close – does not accurately reflect the current scientific research program.
Information in the review wasn’t news to psychiatrists. At least four investigations of the 5-HT (serotonin) hypothesis found inconclusive or inconsistent evidence. The most recent review (2017) concluded that additional evidence was needed to support the model and resolve inconsistencies. These authors also proposed several new 5-HT receptor-based hypotheses.
The brain contains about 50 to 100 neurotransmitters. Hypotheses regarding depression have extended far beyond serotonin – indeed, far beyond biogenic amines (e.g., the monoamine neurotransmitters: norepinephrine, histamine, dopamine, etc.). The review is focused narrowly on serotonin and does not address other small molecule or neuropeptide neurotransmitters (e.g., galanin) that may figure in antidepressant action. Furthermore, the review does not address effective nonserotonergic antidepressants like bupropion (Wellbutrin) or antidepressants like vortioxetine (Trintellix), which have very complex serotonergic effects.
In the area of drug development, there has been active debate about whether a specific mechanism of action and/or drug target is necessary for a medication to be approved. Dr. Dawson recently reviewed the package inserts of drugs that were FDA approved as disease-modifying drugs for multiple sclerosis. Eighteen drugs have been approved since 1993, yet the mechanism of action for 17 of the 18 medications is listed as unknown.
The techniques described in the review were not designed to determine antidepressant efficacy, which is determined by randomized controlled clinical trials. Thus, no conclusions can be drawn from the review regarding antidepressant efficacy, or the “good versus harm” associated with antidepressant treatment.
Told you they were on a mission.
Clinical approach to depression
“Okay, I’ve examined both sides. Now I can work on an informed decision.”
Pies and Dawson weren’t finished.
They go on to say that in response to the UCL review, several neuroscientists and researchers have pointed out that the role of serotonin in mood disorders isn’t settled science.
There may well be some role for it in some types of depression.
They quote psychiatrist and researcher Michael Bloomfield, MD…
I don’t think I’ve met any serious scientists or psychiatrists who think that all [cases] of depression are caused by a simple chemical imbalance in serotonin. What remains possible is that for some people with certain types of depression…changes in the serotonin system may be contributing to their symptoms. The problem with the review is that…it has lumped together depression as if it is a single disorder, which from a biological perspective does not make any sense.
Pies and Dawson point out that the review doesn’t in any way impugn the overall safety and effectiveness of serotonergic antidepressants in the acute treatment of moderate-to-severe major depression. They’re concerned the public may be led to believe otherwise.
That said, they believe antidepressant treatment should be undertaken conservatively, monitored closely, and regarded as only a single component of a comprehensive, biopsychosocial approach to depression, generally including talk therapy.
As such, patients should be educated regarding all three components of mood disorders: biological, psychological, and sociocultural.
Finally, the risk/benefit discussion concerning antidepressants (and other biological treatments in psychiatry) should be approached in the same way as the physician would approach any other serious medical intervention.
Dr. Pies and Dr. Dawson conclude
Dr. Pies and Dr. Dawson wrap up their article by referring to depression as a complex, heterogeneous disorder with biological, psychological, and sociocultural determinants and risk factors.
They go on to submit that few, if any, US psychopharmacologists and academic psychiatrists have ever endorsed a sweeping chemical imbalance theory of mood disorders.
Historically, psychiatrists have never explained clinical depression solely in terms of reduced serotonin or any specific neurotransmitter.
Perhaps most important of all, Pies and Dawson hope that patients and clinicians are not deterred from the use of antidepressants by the review, or by the fact that the SSRIs’ mechanism of action is complex and not completely understood.
An informed decision
Antidepressants work. Antidepressants don’t work. Which is it? Well, you’ve gotten a full dose of “they do.” Two weeks ago you got “they don’t.”
Depression and despair can be best friends. And that’s why millions keep an eye on the meds pipeline. A new antidepressant has been approved by the U.S. FDA. Let’s see what’s up with Auvelity.
’…the first and only rapid-acting oral medicine approved for the treatment of MDD with labeling of statistically significant antidepressant efficacy compared to placebo starting at one week.’
Hope emerges in our neck of the woods when a new antidepressant makes the scene.
Even if we’ve taken major hits in the meds crapshoot over the years, we imagine “Maybe this is the one.”
Our friend above sure looks excited. Does he have reason to be?
Auvelity: A new antidepressant
Axsome Therapeutics has announced U.S. Food and Drug Administration (FDA) approval for Auvelity for the treatment of adult major depressive disorder (MDD).
It was developed with FDA Breakthrough Therapy designation and evaluated by the FDA under Priority Review.
Frankly, if Auvelity’s primary target were monoamine neurotransmitters – specifically serotonin, norepinephrine, and dopamine – I’d have to work hard to hold back a yawn.
However, such isn’t the case, as you’ll see in a moment.
From Axsome’s press release…
AUVELITY is the first and only rapid-acting oral medicine approved for the treatment of MDD with labeling of statistically significant antidepressant efficacy compared to placebo starting at one week.
That’ll grab one’s attention, won’t it?
Auvelity: The action
Auvelity is a dextromethorphan and bupropion combo delivered in an extended-release tablet. You’re familiar with both, aren’t you?
Yep, dextromethorphan is used as an over-the-counter cough suppressant. And bupropion is the generic for Wellbutrin, Zyban, Elontril, used to treat MDD and to aid in smoking cessation.
Dextromethorphan
The dextromethorphan component serves as an antagonist (works to inhibit action) of the NMDA (N-methyl-D-aspartate) receptor of our most excitatory neurotransmitter, glutamate. It’s also a sigma-1 receptor agonist, which modulates glutamate and monoamine neurotransmitter signaling. Yes, some serotonin reuptake inhibitor action is involved.
“I know the meds crapshoot well, so I’m skeptical. Still, I’m glad the research wheels continue to turn.”
Keep in mind, dextromethorphan is in the morphinan class of medications. That means it has sedative, dissociative, and low dose stimulant properties.
By the way, there’s another rapid-acting NMDA receptor antagonist approved for the treatment of MDD, as well as treatment-resistant depression. That would be esketamine (Spravato), which is administered via infusion or nasal spray.
Bupropion
The bupropion component of Auvelity provides inhibition of the enzyme CYP2D6, which increases blood levels of dextromethorphan by preventing rapid metabolism. And bupropion’s dopamine/norepinephrine reuptake inhibiting action is a bonus.
Hey, if you’re a bupropion user you may be thinking “Heck, I’ll buy some cough medicine and make my own.” Seriously, I wouldn’t.
The necessities
As with most any psychotropic med, Axsome says, “The exact mechanism of action of AUVELITY in the treatment of MDD is unclear.”
And the warning is issued that antidepressants increase the risk of suicidal thoughts and behaviors in pediatric and young adult patients. Again, Auvelity is not approved for use in children.
Finally, contraindications, warnings and precautions, adverse reactions/side effects, drug interactions, and more have to be taken into account. Be sure to review the package insert/prescribing information.
Almost forgot, Auvelity is expected to be commercially available in the fourth quarter of this year.
Final thoughts and close
A novel, rapid-acting antidepressant is ready to go. How do you feel about it? Perhaps you’re imagining “Maybe this is the one.”
In my opinion, the arrival of Auvelity is great news for two major reasons. Its primary target is glutamate’s NMDA receptor, not monoamine neurotransmitters. And it’s a sign that the research and development wheels continue to turn.
So if you ask me, our friend really does have reason to be excited.
But you know what? Meds may come and meds may go. Therapy, spiritual practices, and healthy lifestyle habits are mainstays.
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