First-line treatment for a diagnosis of depression is psychotherapy and/or antidepressant medications, of which there are four main classes: monoamine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors and atypical antipsychotics. (According to Up To Date, a physicians standard-of-care database, psychotherapy OR medication, or psychotherapy PLUS medication are equally valuable options depending on patient preference.)
Most of the antidepressants prescribed today work on the monoamine neurotransmitter system –serotonin, norepinephrine and dopamine. In the last 30 years we have become fixated on this theory of depression, a theory that is just that: theory.
It has never been proven that lack of or an imbalance in these neurotransmitters cause depression.
And yet, prescriptions written for antidepressant medications help pharmaceutical companies pull profits in the billions year after year. In fact, antidepressants are the second most commonly prescribed drugs in the US. But do they work? For some. And for some time.
At least 50% of patients on antidepressants see no improvement after 4-6 weeks of consistent use. And a large number of people fail to make it to the 4-6 week mark due to side effects.
Because of our fixation on these neurotransmitters, before ketamine came on the scene in the early 2000's, there had not been a new drug for depression in over 30 years.
Ketamine ushered in a new paradigm... kind of.
Ketamine works on an entirely different neurotransmitter system: the glutamate system. It also causes significant shifts in consciousness, commonly referred to in research as a "non-ordinary state of consciousness" or NOSC. Taking ketamine is kind of like taking valium, drinking alcohol and tripping on a psychedelic, but it doesn't really belong in any of these drug classes. (Chemist used to call it "promiscuous" because of all it's varied receptor functions.)
But one thing we know for sure, it's a pretty reliable antidepressant.
Even if one is open to trying a conventional treatment – such as a daily antidepressant medication– there are often unbearable side effects and long-term consequences that providers are generally unable to shield the patient from. One may not feel satisfied with the lack of certainty around questions, like:
How long do I have to take this?
If I experience side effects, will they go away if I stop?
How and when can I come off?
Are there withdrawal symptoms?
Are there long-term negative effects if I stay on them long-term?
Will I be depressed again if I stop?
Might I be more depressed when I want to go off?
Despite the uncertainty, side effects and other downsides of antidepressants (ADs), the CDC estimates that 13% of adult Americans – that’s 40 million people – are taking a daily antidepressant.
As I mentioned previously, SSRI's and SNRI's will work for approximately a third of patients – but that is only when considering them in the short term. The STAR*D trail – the largest study ever conducted looking at the effectiveness of antidepressants – showed that one fourth of patients respond to first line antidepressants. If the first line doesn’t work, another medication is trialed, resulting in another quarter who will respond to that second agent. As you keep trailing medications, the numbers stayed consistent: about a fourth will keep responding.
However, there are approximately one third of people at the end of STAR*D who will fail conventional antidepressant therapy altogether – no matter how many mediations they try, it doesn’t work for them. These patients are given a special diagnosis: treatment resistant depression.
But what if they aren’t treatment resistant, they are just monoamine and atypical medication resistant? In other words, this definition of "treatment" is extremely narrow.
We should also ask ourselves: what does it mean for a drug to “work”?
The term is a little misleading. A large percentage of patents who report a decrease in depressive symptoms also report a decrease in positive feelings.
Patients also commonly reported sexual disfunction, apathy, decreased ability to feel positive emotions, weight gain, fatigue, and just "not feeling like themselves."
Sometimes these side effects are significant enough that even though depression is gone, patients will choose to go off the medication.
That being said, antidepressant medications can and do work for thousands, probably millions, of people. They can and have saved lives by decreasing suicidal ideation and in many other ways. Further, so many suffering with mental health disorders do not have access to anything better, either because they can’t find a doctor who will offer anything else, or they cannot afford any other treatment.
In other words, sometimes it’s the exact right medicine, and sometimes it’s just the best we’ve got.
However, just to be clear: no doctor can tell you for certain that you have a serotonin deficiency and any doctor that tells you that is full of it.
There is no test that has ever been proven to test the hypothesis that depression is caused by low serotonin, even 30+ years after the advent of Prozac.
The way a doctor discovers you have a "serotonin deficiency" is to give you a serotonin medication and see if it helps.
Even that is a leap, considering we still don’t know if this is how SSRIs work. For example, they’ve also been shown to be anti-inflammatory. Might this be how they effect mood?
We are left guessing, after all these years. Depending on your paradigm, world view, and cultural bias it is truly just as valid to believe that depression is the result of demonic possession, and Ayahuasca is the best medicine for that. We truly do not have evidence to the contrary.
In my practice I see patients at the end of their rope; they’ve seen every specialist, tried many medications and are hopeless for a cure. Finding right diagnosis where conventional docs won’t look – neuroinflammation, SIBO, or a stealth infection, can help some.
But for those for whom no physical cause is found, ketamine is for all intents and purposes, a wonder drug.
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