About the author : victoriafenton

Last week I had four separate patients ask me whether they should ‘give up’ their anti-depressant medications.  All of these were on some form of Selective Serotonin Reuptake Inhibitor: Citalopram, Escitalopram or Sertraline.

Obviously, my response to all of them was, “I am not a doctor, and I am not your prescribing clinician.  I personally have a biochemical understanding of anti-depressant medications which makes me both sceptical of their benefit, and immensely wary of their side effects.  That said, titration off anti-depressants is nuanced and must be done gently, with effective support.”

I then went on to recommend different approaches for each client, either offering support to titrate off them – or recommending that they stay on them until the rest of their health (gut health/toxicity load/stress levels) was more balanced.

Whilst recommending the fourth, different iteration of a potential route forward I caught myself with a shock, and realised the idiocy of what I was dealing with.

Conventional medicine carries the opinion that depression arises out a combination of factors, a key one of which is neurotransmitter imbalance – most notably a lack of serotonin.  Therefore the default treatment option for depression (without checking any neurotransmitter levels, it must be said) is to prescribe a selective serotonin reuptake inhibitor (SSRI) which works by preventing the receptors in the brain from ‘taking up’ the serotonin released by certain neurons.  This increases the presence of serotonin at the location of the synapses in the brain and, theoretically, the depression is alleviated – because obviously depression is due to the lack of serotonin.  Fix the deficiency, fix the problem – right?

Well not only was this actually not working for at least 3 of my 4 clients last week, but as I was discussing this for the fourth time with my last client I realised that nobody I had spoken to that week was alike, and yet in the eyes of conventional medicine, all depression is just one and the same thing.

It is not separated into subgroups of different presentations, of different neurotransmitter balances, or different physiological states.  Instead, it is segmented by length of time or severity of symptoms, with dysthymia being persistent mild depression, whereas major depressive disorder, or clinical depression, is a severe and life-changing depression which affects mood and energy for most of the day.

As I thought further around this, and reflected on the patients for whom their treatment was, at best, woefully inadequate and, at worst, damaging, I contemplated how treatment for depression is largely experimental – with one drug being tried for efficacy, and its dosage increased until it becomes clear that it is not working (or has intolerable side effects).  Then another, more potent drug is tried in an attempt to ‘fix’ the problem.  This is based on a central belief that depression is the result of low activity of serotonin at the receptors in the brain.  All of these drugs are designed to change the neurotransmitter concentration at the synapses… the hope is that the psychiatrists just pick the right manipulating chemical.

However in truth, and as is borne out by my clinic just last week, depression is an umbrella term describing a mood state.  It is a catch-all term for a number of what I (and a lot of Functional Medicine Practitioners) view as completely different disorders.

The patients I dealt with in my clinic last week were all different people, and a little digging into their history, genetics and functional biochemistry showed me that their depression was emerging from different combinations of biochemical and emotional situations.

Is Every Depression Different?

Because we are straying here into mood disorders or dysregulation, I want to take a moment to acknowledge something that I firmly believe: that the emotional and mental thought fields contribute greatly to our overall health.  I do genuinely know, from personal and professional experience, that the frames we create with our mind and the perspective we have on life has the power to be the limiting factor in our illness and healing journeys.

However, there is always a chicken and egg question when it comes to brain and mind.

Biology affects mental chemistry and therefore thought potential.  Mental perspective has the power to radically change physiological reactivity, immune function and the digestive state, but digestive state can also change clarity of thought, immune reactivity and mental abilities.

It is clear that the relationship between body and mind is symbiotic and bi-directional.  So, when it comes to depression, as a clinician I recognise the value of both talking and counselling therapies AND chemical, biological and nutritional interventions.

I think that it is cognitively impossible to think that the thoughts we have are independent from either our biochemistry OR our experiential memory.  They are the product of both.  Thinking is a chemical process where the biology of our overall vehicle (our body) influences the synaptic and neurotransmitter activity.  These neurotransmitters provide the mood and feeling sensations (serotonin is the happy chemical, dopamine the reward chemical, GABA releases feel good sensations, oxytocin is chemical for love and connection etc.).

However, the specific thoughts which which we populate and associate those chemically-determined ‘moods’ are shaped by our history, our conditioning (from childhood and adulthood), our prejudices and our societal norms.

Therefore, we think in the colour of our neurotransmitter activity, but we paint the detail using the infrastructure of our experiential memories.

This means that every depression is different in terms of the thoughts that are entered into.

But after that slight segue, is every depression also chemically different?

The 5 Subtypes or Subtypes of Depression

In Functional Medicine we recognise that catch-all terms that describe a set of symptoms are often non-descriptive of the cause of those symptoms.  It is clear that there are myriad different routes to a person becoming depressed – and justifying them as a lack of serotonin is woefully inaccurate.  Even if it were true, it doesn’t go anywhere near explaining ‘why’.  So for the rest of this article I want to explain the 5 different subgroups or biotypes of depression and mental health/behavioural issues.  Some of this may surprise you.  It is long, it is a bit geeky on the science – but it lifts the lid on the chemistry behind the colours of our minds.


If you read my previous blog on the MTHFR gene, you will know that the title “undermethylator” doesn’t automatically apply to everyone with a SNP that’s been picked up by 23andme within the MTHFR gene – even the big ones like A1298C and C677T.  For reasons explained in that post, commercially available genetic testing is not specific or accurate enough (yet) to give us all the information.

Instead, this name applies to someone who has been clinically evaluated to be poor at methylation (i.e testing the conversion of SAMe to SAH, or checking whole blood histamine) and demonstrates the psychological tendencies common in those who undermethylate (see below).

Lack of methylation activity creates a higher incidence of certain reuptake proteins (called SERTs) which thereby take back up too much serotonin, too quickly.  The net effect is a lack of serotonin activity at the synapses in the brain because it is too rapidly removed.  Therefore the depression theory of low serotonin holds true within this biotype, and undermethylation is the biochemical reason behind the lack of available serotonin.

Typical undermethylator characteristics are as follows:

  • wilful and determined – competitive, particularly in sports etc.
  • OCD tendencies, with high needs for perfectionism
  • calm, almost cold, exterior masking high inner tension
  • addictive tendencies
  • seasonal allergies
  • low libido

This personality description, combined with accurate testing, will give a clinician a solid picture of whether the lack of methylation is what is affecting serotonin concentrations in the brain.  In someone who is depressed due to undermethylation, a doctor’s choice of SSRI medication is likely to actually help the situation because it basically increases the availability of serotonin, albeit unnaturally and without asking why serotonin is low in the first place.

The side effects of such medication is often why I have clients in my clinic begging to get off their drugs – not because they aren’t changing their neurotransmitters and giving them a psychological relief, of sorts, but because they are doing so with far too many consequences.

Treatment for undermethylating depressives, from an holistic point of view, requires working alongside a practitioner on nutrient intake to support methylation.  PLEASE NOTE THAT THIS IS NOT ABOUT SUPPLEMENTING WITH FOLATES – and this is one of the reasons I wrote my previous post on proper analysis of methylation status.

In someone who has impaired methylation and low serotonin, adding folates into the mix will further activate the serotonin reuptake proteins and this is precisely what you don’t want to happen.

All of the hype about supplementing with methylcobalamin and 5-MTHF if you have an MTHFR SNP means that I have clients that come to me with serotonin issues who have been made much worse by misunderstandings perpetrated by their previous practitioners who were attempting to treat based on genetics alone.

That said, the correct, targeted nutrient therapy is capable of assisting the patient with methylation and, when methylation status is improved, the wilful, addictive, obsessive tendencies dissipate and the fog of this depression lifts.

Pyrrole Disorder

This is not a commonly recognised disorder, but this is a genetic issue which creates several nutrient deficiencies which affect neurotransmitters.  Every human being produces pyrroles as a biproduct of chemical reactions in the spleen and bone marrow.  However, pyrrole disorder is when too many of these pyrroles are produced.  This is a problem because the pyrrole molecule has an affinity for any chemical that is an aldehyde.  The most available aldehyde within the body is actually Vitamin B6.  An excess of pyrroles strips the B6 from the body and causes alarming and profound B6 deficiencies, along with accompanying deficiencies in Zinc and Magnesium – all vital nutrients in multiple physical systems, including in brain health.

All neurotransmitters require B6 and Zinc.  In terms of this concept of a ‘lack of serotonin’ causing depression is technically true because serotonin requires B6 for production.  However in someone with pyrrole disorder there is a fall in serotonin levels but also in levels of GABA, 5-hydroxytryptophan and dopamine.

This disorder simultaneously leads to a chronic lack of endogenous antioxidant production such as glutathione, metallothionein, cysteine, superoxide dysmutase and catalase.  All of these are vital to the detoxification systems of the body, and an inability to detoxify can also contribute to depressive biochemistry (see “Toxin Overload” below).  Therefore pyrrole disorder is really a double whammy: lack of essential nutrients to make the neurotransmitters and lack of ability to detoxify so extra stress on the whole system.

Some characteristics of this disorder include wild and uncontrollable mood swings, occasionally violent outbursts with extreme fears and anger.  Patients usually have both light sensitivity and occasionally poor memory or lack of dream recall.  They demonstrate a rather characteristic resentful depression.

In patients with pyrrole-disorder-associated depression SSRI medication can also work to some degree.  However, in this population the side effects may be even greater.  The chemical load of this foreign substance must be processed (and detoxified) by the liver and these patients have a down regulated antioxidant production.  It is often these patients who are tried on several different antidepressants with varying degrees of success in alleviating depressive symptoms but many tolerance issues.

Again, working with a practitioner who can conduct a pyrroles test and then treat the patient in accordance with the restoration of zinc and B6 levels whilst supporting antioxidant production can dramatically, almost unrecognisably transform the lives of these patients.  With the right level of baseline nutrients patients’ levels of violence, aggression and extreme mood swings – even frank schizophrenic episodes – can be put into complete remission.

Copper Overload

Copper overload is much rarer than the above two subtypes.  However, it is vitally important in perhaps one of the most poorly discussed and misunderstood topics in mental health: postpartum depression and psychosis.

Please note: copper overload does not only occur postpartum, but does typically arise after hormonal incidents. Symptoms included, alongside the psychological effects detailed below, oestrogen intolerance, occasionally intolerance to progesterone creams, tinnitus and sensitive skin with an intolerance to cheap metals (in jewellery, cookware and some perfumes/self care products).

Copper overload occurs especially after giving birth because during pregnancy a mother’s copper levels double to help build her baby, with copper being involved in angiogenesis (or the making of blood vessels etc.)  After pregnancy these copper levels are supposed to fall quite naturally as a mother’s next phase of caring for a newborn begins.  However, metabolising metals is a genetically determined function (to do with the production of certain antioxidants in the gut) and some people cannot metabolise this high level of copper out of their system.

Copper has a direct impact in neurotransmitter metabolism because a form of copper is required for changing dopamine into norepinephrine (noradrenaline).  With too much copper in her system a new mother’s dopamine (a relaxing and reward chemical) is rapidly converted to noradrenaline – an activating and mobilising chemical which primes the fight or flight response of the sympathetic nervous system.  Instead of relaxing into the pleasure of being a new mother, excess copper can drive a mother into agitation, paranoia, anxiety and depression.  At worst, postpartum psychosis and mania can result.

Supplementing here with an SSRI typically has almost no effect whatsoever.  Prescription medication is not a wise choice for either mother or baby if the mum is breastfeeding.  Whilst some psycho-pharmaceuticals are supposedly safe during breastfeeding, the reality is that if even coffee is too much for a newborn then psychoactive substances are hardly benign.  Regrettably, many new mothers with postpartum depression are tried on many different medications in an attempt to try and regulate something that simply cannot be fixed by trying to change neurotransmitter levels directly.

The naturopathic approach would, again, focus on the real issue: the overload of copper.  Here, working closely with a practitioner, the aim is to enable to body to adequately metabolise this copper.  This requires boosting the production of substances like metallothionien, and again can be done using nutrients rather than medication.

Toxin Overload

Sometimes toxicity overload in general is a major part of depression.  The brain’s protection mechanisms revolve around antioxidants which are largely derived from nutrients, yet again.  Therefore a lack of these essential nutrients can cause an inability to produce the protective antioxidants.  Sometimes these processes are also genetically determined, and the inability to produce antioxidants is more permanent, but in both cases the characteristics of someone whose neurotransmitter production is being impacted by neurotransmitter imbalances looks very different to the depression above.

Toxin overload depression manifests as a more permanent, all-consuming blackness of mood, with addictive tendencies and often without any discernible ’cause’ or trigger.  Toxin overload affects the NMDA production, which is a neurotransmitter not at all like serotonin, and has entirely different pathways of production and metabolism.  It is becoming more widely researched within the context of bipolar disorder, obsessions and addictions.  With toxin overload, irritability is more frequent than violence or outbursts and this depression is often accompanied by abdominal issues, a nasty taste in the mouth and food sensitivities.

Obviously the supplementation of SSRIs in this instance do nothing because they’re not impacting the correct neurotransmitter pathway.  In an holistic and naturopathic approach to some presenting with toxin overload, the obvious course of action is to support detoxification, to supplement with the cofactors which can help produce antioxidants, but also simply to supplement with a broad spectrum of antioxidant nutrients and vitamins themselves.  Sometimes this is for a short time to clear a toxicity that is temporary and due to intense or prolonged exposure that has now passed.  Sometimes, however, the genetic ability to detoxify must be supported for life.  It is the skill of a qualified practitioner who can identify which of these may be relevant for their patients and to offer the correct nutritional support accordingly.

Low Folate or Overmethylated Depression

This is where treating depression as one disorder with serotonin issues at its heart gets worrying.  Depression occurs in patients who have low levels of folate in the body.

The characteristics of someone exhibiting depression alongside low folate are as follows:

  • high anxiety levels, tendency to panic
  • uncompetitive and with a tendency to underachieve
  • musical ability and artistic but not pushing to achieve more within these fields
  • sleep issues or disorder, low libido
  • food and multiple chemical sensitivities (though not inhalant allergies)

These patients experience an adverse effect from taking prescription SSRIs.

The reason for this lies in the chemistry of folates – as briefly touched on above.  Folate status, and methylfolate status, affects brain chemistry profoundly.

A lack of folate equals a lack of serotonin reuptake proteins.  The problem isn’t underproduction or lack of serotonin, the problem is that this serotonin is not being taken up, which effectively means that messages are being sent, but not received.  The signalling is broken.  In the low folate category, overmethylation means that there are too many neurotransmitters: too much dopamine, too much serotonin – and an ensuing complete neurotransmitter imbalance.  Supplementing with SSRIs in these patients can cause further turmoil because it keeps flooding the brain with serotonin, of which it already has plenty.  This, in the worst cases, can potentially lead to destructive, suicidal ideation and delusions.

The holistic and Functional Medicine approach to low folate, overmethylating individuals with depression is to balance the methylation cycle by enhancing the activity of a process called acetylation.  The exact description of this is beyond the scope of this article, but acetylation is the counterbalance to the process of methylation.  And in the brain acetylation enhances the activity of the reuptake proteins and allows the synaptic activity to re-regulate, normalising the neurotransmitter chemical levels within the brain.  Understanding what is happening biochemically, and why, empowers a clinician to actually help such patients using relatively benign therapies.

Each of these subtypes requires a different nutrient approach for support and, ultimately, healing.  And each of these subtypes has a different reaction to the medication that is being used as a blanket front-line defence, supposed to benefit all.  The treatment of mental health conditions by conventional medicine – with judgement, drugs which dull symptoms rather than treat causes, or frankly make you worse, and no answers as to the ‘why’ behind the development of symptoms – is one of the main reasons why I became involved in Functional Medicine to begin with.

So you’re on an SSRI medication but you’ve no idea which subtype you are… What Do You Do?

The truth is that some people don’t easily fall into just one of these subtypes.  Sometimes there are two things happening, like overmethylating and pyrrole disorder.  Even though our brains like categorising, it is not a simple and clean-cut process to just delineate and label.

Which is why I do not want you to use any of this information to make your decision about the way forward with your treatment and/or therapy for depression, or any other mental health or behavioural disorder.

I told each of my clients this week slightly different things about their SSRI medication, but I began in the same way.

Firstly, you don’t do any of this alone.  Secondly, you don’t do any of this quickly.  My recommendation would be to find a practitioner who can work with you to understand the biochemical origin of your neurotransmitter imbalances.  Countless times, as if often promoted in the work of Kelly Brogan MD, mental symptoms are the result of digestive issues, detoxification issues, blood sugar dysregulation and undiagnosed food intolerances.  When this is the case, healing from mental illness requires putting in place solid foundations of diet and lifestyle to drastically improve health and then working closely with a professional to titrate off depression medications which should no longer be necessary if good, nourishing food and lifestyle habits were all that were required to heal the mental imbalances.

But I sometimes object to the clinicians who promote the paleo or autoimmune diet like it is the resolution for every issue.  As you will see above, genetics play a role and nutrient sufficiency is not always guaranteed – even on the perfect diet and with impeccable digestive systems.  Sometimes, therefore, nutrient imbalances need to be fixed using an approach similar to the ones detailed in the breakdowns above.  And this must be done with the assistance of someone in Functional Medicine or naturopathy and at least knowledgeable about neurotransmitters and mental health.  Do not play in this area yourself, please ask for help.  If you want help knowing who to look for and how to select your practitioner, please contact me and ask me for help.

The Thoughts Piece of Mental Health

I just want to skip back at the end of this very long article about chemistry to the point I made first in this article.

It is my belief that if your brain chemistry has been to a place where negative, depressive thoughts have flitted across your mind then a therapeutic approach may begin in the chemistry, but it should also take into account the places and thinking that you have been to as a result of that chemistry.  Even if the chemistry becomes fixed, sometimes we can’t un-think the thoughts we had when we were broken.

It is for this reason that I am a supportive counsellor for my clients, along with being a Functional Medicine Practitioner.  It goes back to the fact that the colour of your mind is neurotransmitter dependent, but the detail of your mental pictures comes from your life’s experiences.  Anyone who has been to a dark place in their mind comes out of it with some residue, and some thoughts about themselves (shame, guilt, fear, paranoia, distress) that must mentally be faced and accepted.

And even if the mind is the result of chemistry, that mind that results is our personality and characteristics and who we relate to as ‘us’.  Changing the underlying biochemistry can therefore alter our sense of who we think we are, and this process deserves to be supported by someone who grasps the enormity of having nutrient levels corrected – and can help you navigate the process of clearing off the debris of any depressive states.

If you’d like to talk to me more about depression, medication or any of the subtypes or tendencies mentioned in this article, just email me directly or submit an enquiry here.  And please, don’t forget to share this article with those you know and those you care about if they have mental health issues or you think they may benefit from understanding their psychology through the lens of their biochemistry.

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