Antidepressants Explained part I

Disclaimer: This post contains information about medications. I will not be citing references (mainly because I am typing away quickly) but the information is based on research evidence. Please discuss all health-related decisions with your doctor. 

One of the commonest topics I get asked about are antidepressants. The topics of the questions are numerous and I will not cover all of them here. However I did want to address some of the commonest recurring questions, comments and misconceptions. I will break this post into several parts and address any reader comments that come up as we go along. 

Question I: Why are antidepressants over-prescribed and why don't they work well for many people?

I decided to combine these two questions because they partly answer each other. The first part is why are antidepressants over-prescribed? This is a complex issue because the answer depends on the premise of the question, namely that anti-depressants ARE over-prescribed. My response to this premise is yes anti-depressants are over-prescribed but they are also under-prescribed. That doesn't make any sense, right? Actually it does. 

You see the research demonstrates that anti-depressant prescription rates in the developed world having been sky-rocketing over the last decade. This can be partially (but not completely) explained by an increasing recognition of depression especially at the primary care levels of the health care system. In fact, when you consider the amount of people whose depression went unrecognized for many years you begin to realize that for many individuals antidepressants are under-prescribed. After all, these are potentially life-saving medications for people who really need them. And the research clearly shows that many people who  need antidepressants do not receive them either due to decreased access to or poor quality of care. So we need to do a better job for this under-prescribed group who need antidepressants. 

Herein lies the problem of over-prescription though. How do we recognize those who really need an antidepressant? Well, we make sure the person getting the prescription has depression. Depression the illness, not just the feeling of sadness (more on this in a future post). This brings us back to why antidepressants are over-prescribed. Well there are many reasons. I'm sure some readers of this blog will point all the fingers of blame at Big Pharma stating that they have driven this trend both through patient demand and prescriber practice. And while there may be some kernels of truth to any position in any debate including this one, I think that pinning ALL the blame on Pharma is naive. A large driver of over-prescription is the fact that in a zeal to "capture" all cases of depression practitioners have "cast the net to wide". In other words many people who have mild sadness related to life circumstances or even mild depression that would have responded to talk therapy and behavioural modification alone are instead prescribed an antidepressant and sent on their way. This leads to a poor response to the medication because you are treating something that doesn't exist (at least not in the form that the medication would treat) and you are not addressing the underlying causes. 

The evidence of antidepressant response rates from clinical trials is compelling. For example in a recent (non-pharmaceutical funded) large-scale clinical trial of antidepressants only about 25% of patients responded to the first go on an anti-depressant. This is appallingly low! However if that same data is reanalyzed to examine only those patients whose depression was ranked severe then the antidepressant response rates jump to around 80%! What does that mean? Well it means that once we "lock in" on the form of depression which appears to be an almost purely biologically disease entity then the response to a chemical agent (antidepressant) is great. But this data also demonstrates the perennial problem in modern day psychiatry. Getting the diagnosis right is very hard compared to other fields of medicine that have the benefit of biomarkers (diagnostic lab or imaging tests). 

So in summary I believe that antidepressants are over-relied upon and often don't work well in "normal" human sadness or even in mild cases of depression. In these cases talk therapy, physical exercise (see previous blog posts) and lifestyle/behavioral modification should be tried first before going for an antidepressant. However antidepressants are life-saving drugs that are unfortunately still under-prescribed in moderate-severe depression. These types of depression often present with manifestations such as inability to function, suicidal thoughts or actions or psychosis (loss of touch with reality). Of course there is no perfect solution or template especially in a field as nascent as mental health. I use the above opinion as a "compass" to guide my thinking and practice but I think we should still treat patients on a case-by-case basis working with them to tailor treatment to their specific needs. 

STAY TUNED: In the next part of this series I will address the question - Will I become addicted to or dependent on the antidepressant?

Note as a disclosure of impartiality: I have not mentioned any specific antidepressant neither by proprietary or non-proprietary (generic) name in this post. I do not have and have never had any affiliation with any pharmaceutical company; neither in the form of a "consultant" or being on a "speakers' bureau" or otherwise. I have done research and clinical trials with pharmaceutical agents but have not received any reimbursement for doing this by any pharmaceutical manufacturer. Full disclosure: I have owned a small amount of equity in a pharmaceutical company (sanofi-aventis) but this was as part of an investment fund rather than an outright purchase or being granted stocks. 

Creativity or “Craziness”?

Originally published Thursday March 10, 2011
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Around this time of year, 123 years ago, a young painter entered a psychiatric hospital in Saint-Rémy-de-Provence in Southern France. He was known by his neighbors in the town as “fou roux" (the crazy redhead). Having been troubled with mental illness throughout his life, a few months prior he had reached a crisis point and during his breakdown rushed to a brothel. There he handed his friend - a prostitute named Rachel - a small wrapping of newspaper telling her to “keep this object carefully.” Unwrapping it she was shocked to find the freshly cut and still bloody lower portion of his left ear!

Vincent van Gogh holds legendary status in Art and his influence has crossed cultures and eras. To gaze onto the vivid colors and hypnotic swirls in his work is to be transported into another world - a morphed view of reality that can only be seen through his eyes. There is a tendency to romanticize van Gogh’s mental illness, which most respected psycho-biographers believe was bipolar disorder. The notion, however, that there is a fine line between creative genius and “craziness” is not new and has existed since ancient times. Most of this has focused on Bipolar Disorder (previously called Manic-Depression) and many famous figures have been speculated to have suffered it: Beethoven, Edgar Allan Poe, Emily Dickinson, Victor Hugo, Charles Dickens, Edvard Munch and many more. Today we see this pattern with an established diagnosis in many celebrated actors, poets, painters, musicians and others of artistic temperament. Yet, despite our modern methods illuminating the “line” or “link” between mental illness and creativity remains elusive. 

The famous theory in popular culture (illustrated above and known in neuroscience as the Hemispheric Lateralization Theory) that so called right-brained individuals are more artistic and creative while left-brained people are logical and better at the sciences and maths has been disproven. Not least because it is possible to be profoundly creative in the maths and sciences. New theories are now being studied and several are promising. Read more here if interested in the neurobiology.

One theory I have found useful comes from the elegant scientific work of one of my mentors Dr. Terence Ketter and his group at Stanford University. They demonstrated that individuals with bipolar disorder when tested with rating scales of simple and abstract images tended to like abstract images more than the average individual. Seems intuitive enough right? Well here is what surprised Dr. Ketter and his team: When looking at the “dislike” ratings, people with bipolar disorder DISLIKED the simple images drastically more than the average individual. So then that DISCONTENT with the simple may actually be the “mother of invention” or the drive to creativity. Unfortunately this negative emotion may also underlie some of the symptoms seen in this disorder. 

The message to mental health is clear in my mind: we should attempt to treat highly-creative individuals with mood disorders with all the latest advancements including medications. BUT we should listen carefully and work with our patients to understand what effect treatment is having on their creative drive. Perhaps some individuals need some degree of discontent to “kindle the creative fire” and we should step up to the challenge of helping them achieve a tolerable and productive balance. 

At the young age of 37, after a fit of creative production of many paintings, Vincent van Gogh walked into an empty field outside the home where he was staying, aimed a loaded revolver into his own chest and pulled the trigger. His famous last words as he lay dying in his brother Theo’s arms were "La tristesse durera toujours" (the sadness will last forever). 

Perhaps had he not suffered some degree of sadness you and I would have never heard of van Gogh. Perhaps if he had lived longer his influence would have been greater. Perhaps the next van Gogh or Beethoven or Poe will walk into my clinic next week suffocated by their sadness yet possessed by creative inspiration. The questions are complex scientifically, ethically and philosophically. But I believe that a balance can and should be reached (or at least approached) and that tragic endings can be re-written. 

The Social Environment - Expanding the target of healing

Originally published Tuesday, February 8, 2011
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*The first three paragraphs of this post contain graphic themes. Please skip to paragraph four if you prefer not to read them. 

As you are reading these lines, a smart and pretty young woman seeking a better job in a country not infested with corruption like her own, is being abducted by modern day slave-masters that will make her body into a commodity to be bought, used and discarded. And as she lays stunned beyond tears after her first night in the basement of a brothel, the fear and vigilance regions of her brain are “short-circuiting” and she begins to develop post-traumatic stress disorder. 

Right now in a dark cell, on a cold, damp floor, bitter with the smell of urine, a man is slowly oozing blood from where his two front teeth were before the police club of an abusive regime knocked them out. His attempt to give voice to the voiceless has been blocked and his hope fades with the last of his happy memories as clinical depression sets in. 

At this moment a teen living in a poor corner of a wealthy cosmopolitan city has been kicked out of his overcrowded classroom for ‘daydreaming’ because his ADHD has gone unrecognized. Heading to the local gang hangout he can already feel the coming cool bite of a needle pushing into a vein in his left forearm sedating his fears and murdering the memory centers of his brain. His reward for selling the same drug to his friends.

I beg you do not misread my intentions for I am not affiliated with a political agenda or party. I am a doctor and the healing of humanity is my creed. In mental health the modern mantra is that psychiatric illness is caused by an interplay between biological, psychological and social factors. Yet when assessing social factors we are often focused on the immediate and personal: financial difficulties,  rocky relationships, migration and immigration. But what of larger ingrained social injustice across our world? Racism overt and hidden. Sexual enslavement of women and minors. Systematic suppression of basic human rights and its proponents. Stigma and mistreatment of the mentally ill, physically impaired and developmentally delayed. 

Psychiatry has made tremendous progress in the understanding and healing of depression and other mental illness. Our patients have a far better chance of recovery then they did 100 years ago. Yet there remains much to improve upon. Less than a third of depressed patients improve with the first try of an antidepressant medication. Only about 60% recover after four different trials with medications. So many medications cause side effects that are harmful or difficult to bear. I am not against medications. I prescribe them all the time and have seen lives change with their help. But mental health professionals can no longer afford to focus all efforts on the same targets of treatment. We must expand our sights from the individual to the society and from chemicals to injustice. 

When we do that we can actualize that noble motto: Saving lives.. Millions at a time

Exercise & Mood Part III - From Science to Action

Originally published Tuesday, February 1, 2011
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There is probably no one word that can sum up what people want in terms of emotional or mental health. Whether it be clients I meet in the clinic with a mood or anxiety disorder or a friend or acquaintance asking for an opinion in a social setting, the theme of the question is common but each one is different. However I think there is one common thread that joins the questions and ONE word that captures 99% of what is ideally sought STABILITY.

Those with recurring depressive episodes or mood swings want mood stability. Others with anxiety, nervousness or worry want calm stability. The frazzled, stressed, workaholics want relaxed stability. For many achieving stability would make them happier, more productive, more sociable and have a better quality of life. I don’t claim that exercise is the only way to achieve stability. There is no panacea. The correct treatment of all of the above situations is an individually tailored combination that could include medications, talk-therapy, lifestyle changes and other components but should ALWAYS include exercise.

Now let’s make the leap from the science we reviewed in the previous blog posts to action. How do we “dose” exercise? What kind of exercise? What time should I exercise? For how long? How do I start and how do keep going?

For an easy reference I will summarize the answer in one sentence then explain the details and the fine tuning will come later. Remember here we are talking about the ‘dosing’ of exercise that changes the biology of the brain and not the number of packs in your Abs! Although that might be a welcome side effect - if you are trying to achieve that talk to a personal trainer. Here we are treating the brain and going after STABILITY. 

Exercise for 30 minutes 6 days a week at a high-impact level. 

That’s it simple, right? Ok ok I know it is not that easy. So let me explain further by breaking it down into 3 rules.

Rule #1 - Exercise: For brain health exercise can be any type that suits you. It does NOT have to be weight-lifting or running on a treadmill. You do NOT have to go to a gym or use a workout DVD. Do any exercise that you enjoy. Swim, run, hike, climb, lift weights, tennis, basketball, soccer, yoga, cycling and on and on. Adapt the exercise to your body if your capacity is limited by physical needs or injuries, but anyone can do some sort of exercise unless you are fully paralyzed. 

Rule #2 - 30 minutes 6 days a week: The bottom-line is that the research shows this is the average of the dose needed for the brain to adapt. Now let’s break this rule down. First reactions are usually - 6 days?! That’s a lot! Yes it is, but we are only asking for 30 minutes. Think about it, how many hours a day do you sit at the internet or TV? 30 minutes is very short. In fact, DON’T do more than 30 minutes (unless you have a routine and have been doing this for years). Doing more will lead to inconsistency and skipping workout days. The science shows it is far better (at least for the brain) to be consistent in exercising most days of the week rather than spending an hour exercising 2 or 3 days a week. In fact, for you gym-goers if you think about it (and research also supports this) if you are spending more than 30 minutes at the gym then your are chatting and resting too much. Thirty minutes makes it harder to come up with excuses such as: There is no time! or I’m too busy! If you work a lot or travel find 30 minutes to do some stretches, pushups, air-squats, jumping jacks etc. 30 focused minutes is all you need, Done! Six days too much? Fine five days is the absolute minimum, but better to aim for 6 so that if you fall short then you have a day to save for later.

Rule # 3 - High Impact: For the scientists reading this that is 16 kcal/kg/week. What?? English please! Ok so here is how I explain high-impact to people: For most of the 30 minutes you are exercising you should be sweating and it should be difficult to speak in complete sentences without needing to catch your breath. This means you work hard for 30 minutes then you are done. Walking doesn’t count unless it meets the criteria above. Commuting does not count! That is your normal energy expenditure. Remember we are trying to change the brain and you can’t do that without effort. 

Last few tips:

• You can exercise anytime in the day that fits your schedule. I find first thing in the morning works best because it is the time of day with the least demands on your schedule. Plus there is evidence this timing may have a more efficient effect than other timings. If it means you have to wake up 30 minutes earlier then do it and just sleep 30 minutes earlier at night. No big deal. But if it doesn’t work just exercise at any time that’s the most important thing. Get it done. 

• You can either start slow and build up to 6 days a week over a number of weeks or just pick a week and start. If you have started and stopped exercise routines in the past you will find this one is easier to maintain because it is more flexible. You can do anything as long as you break a sweat. Jumping rope is great if you don’t have a lot of equipment and can’t go to a gym. Keep telling yourself it’s only 30 minutes and just get up and do it. 

• If you skip days and don’t exercise at least 5 days in a week don’t be discouraged and go back down to zero. Just start again. It is normal to stumble. I do all the time. The important thing is to keep the 30 minutes 6 days a week in your head and keep as close to that as you can. But the closer you are to that ‘dose’ the better the result will be.

Exercise & Mood Part II - New Science

Originally posted Tuesday, January 25, 2011
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The human brain is a complex marvel. There are more than 15 times the number of cells in your brain as there are people on this planet. Every moment of your life countless electro-chemical messages are being sent in your brain (see image) to regulate everything from your hands picking up a coffee to your feet walking out the door; and from your lungs unconsciously drawing in the crisp morning air to your hopes and worries about the coming day.

When patients or acquaintances used to ask me, “What causes mental illness?” I used to give a standard answer that many doctors give today, “There is a chemical imbalance in your brain and that’s what we need to correct with medication.” But as I learned more about the secrets of the brain and realized how little, in fact, we know I changed my answer. “I’m not sure what causes mental illness. It is probably a unique interaction between your genetics, brain chemicals, life experience and other factors.” 

Although this second answer sounds less certain and may seem like it is not instilling hope, I believe that being honest about the complexity of the problem leads to a better acceptance of the need for a variety of treatments. This diversity often means needing an individually-tailored combination of more than one medication rather than the myth (as the research now shows) that using less medications is always better. But it also means that medications alone are NOT enough. Talk-therapy is also essential even if in the simplest of supportive listening techniques. But even using both medications and talk-therapy is NOT enough. Other health-promoting treatments are needed and in the field of mental health, physical exercise is often overlooked or given passing praise. 

The truth is that exercise CHANGES the brain. It causes surges of brain chemicals linked to the treatment of depression and other mental illnesses. Brain messengers like noradrenaline, serotonin and dopamine. It promotes a sense of well-being and relaxation through stimulating cannabinoid-like brain receptors. That’s right for those of you who are re-reading that last sentence this is the brain’s “natural cannabis” without the ill effects of marijuana! (of course it is a little more complicated than that but that’s the short version). If you have heard of the ‘runner’s high’ it may be linked to this cannabis-like signalling system. Exercise also strengths the body’s anti-oxidant and anti-inflammation system. This is important because new research is linking several mental illnesses to inflammation and oxidative stress. Finally exercise can promote the health of brain cells so that they can live longer, stay healthier and regenerate. Of course beyond the biological effects physical exercise is a form of activation behaviourally and socially- both important in treatment. 

So I hope you are now thinking, “I’m convinced tell me what to do!” I will discuss the dosing, timing and type of exercise in the next post.

Exercise & Mood Part I - Tears and Smiles

Originally published Tuesday, January 18, 2011
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“I can’t remember the last time I felt..” I looked up from my notes as she paused over the word as if expecting a mirage to fade into the desert, “You felt?” I said. “..happy,” she said, “.. it feels weird to say that word you know?” I took in the gravity of what she was telling me for a moment and returned her gaze quietly. Then I smiled and for the first time since I had met Alicia about nine months ago she smiled back. Not the half-smile that came with a greeting, fading away no sooner than having appeared, but a full, sustained, toothy smile. A smile that humbled me. 

I had first met Alicia last March when she had been referred by her family doctor. She described a life-long struggle with episodes of deep and disabling sadness and sorrow with no clear relation to any ‘triggering’ events in her life such as a break-up or financial troubles. Over the years the recurrence and length of these depressive spells had become faster and longer; so that now she had been living with a two year long depression that was unbroken by more than a few hours of normalcy. She had become overweight and despite perceiving herself as attractive in the past she now saw herself as unappealing and ugly. As a consequence of her depression she had socially isolated herself and lost touch with many of her friends. In short she was feeling miserable and hopeless. 

“Well,” I said to her at that time, “You have come to the right place!” You see I was feeling emboldened and self-righteous  because I had picked up on a clue in her history that previous health-care providers had missed. When Alicia was younger and she felt ‘better’ in between storms of depression she was in fact doing ‘too better’. She had what we call hypomania - mini episodes of over-the-top happiness bordering on irritability accompanied by faster pace of thoughts and speech and by impulsive pleasure-seeking behavior. Alicia had not improved in the past when doctors gave her anti-depressants because she did NOT have depression! She had Bipolar Disorder (previously known as Manic-Depression). And so armed with this new knowledge I put together a plan with her to start treatment with ‘mood-stabilizing’ rather than anti-depressant medications. Little did I know that I had already missed part of her treatment.

Over the next 3 months Alicia gradually began to improve. Her crying spells subsided, she started eating more regularly and her sleeping improved, and she felt she could concentrate better on her tasks. Overall she described a 60-70% improvement. But the remaining percentage was a big deal because Alicia still did not feel ‘happy’ and she wondered aloud if the best she could get to was to feel ‘not sad’. I kept trying different strategies over the next few months with medications and talk-therapy but we could not break across that elusive happiness barrier. 

At this point it occurred to me that in my zeal for helping her get better I had taken on all the work myself and she had become a passive player in her recovery. In fact, that was just the tip of the iceberg because as an extension I had relied solely on the miracles of modern medicine and had not helped her enable her own body’s natural healing potential. I was ashamed I had let pride get to my head but better late then never I thought.

The next time Alicia came in to see me I shared with her this line of thinking. She was a little confused, “..I’m not a psychiatrist.. How can I treat myself?” I then explained how certain “doses” of physical exercise can change the brain (more on this in next blog entry) and lead to healing. She had her doubts, but we put together a plan, she would take up an exercise routine for 30 minutes 5 days a week and I would follow up with her every on her progress. We didn’t change her medications and stayed with the ones that had gotten her 2/3 of the way to full recovery.

It was hard to get started those first few weeks, but once she had exercised for 5 days in a row she was hooked. She reported little incremental changes - her energy improving, her sleep cycle becoming more regular, her concentration better than it had been for years. And after about 4 months of this, in a small office on the 9th floor of Toronto Western Hospital with miserable freezing rain outside, she smiled and her eyes welled with tears. Happy ones.

-- More on the biological effects of exercise on the brain and using the right ‘dose’ of exercise in an upcoming post. 

*Alicia is a pseudonym and a character drawn from a compound of multiple patients that have allowed me to serve them.