It has been noted in these annals that I haven’t felt quite myself recently. However, last night, after having endured several days that I wouldn’t recommend to anyone, not even as an adventure holiday, I flipped 30mg of mirtazapine, took a nap, and woke up quite conscious that I was my ‘old self’ again, quite distinct from the person I’d been for the past week or so. So, now I understand that when people say that they don’t feel that they are ‘quite themselves’, I know exactly how that feels. Exactly. And it’s weird. But what does it all mean?
For those that are hard of reading, let me reprise the story so far. I’m an experienced depressive, a true Veteran of the Psychic Wars. It’s all down to a chemical in the brain called 5-hydroxytryptamine, or serotonin to its friends.

A molecule of serotonin, recently.
This is a molecule that an estate agent would probably describe as Deceptively Spacious. Though small, it has a lot going for it. It’s derived from the amino-acid tryptophan, which is found in dairy products, as this T-shirt from Zazzle (not one of mine - though I have since put matters straight) makes clear.
I count myself as a particular friend of serotonin, as I can’t get enough of the stuff. Perhaps that’s why I like cheese sandwiches before bedtime. Indeed, in my resting state there’s probably not as much of it around as there should be, which is why the antidepressants I’ve taken fall into a class called serotonin re-uptake inhibitors (SRIs). That is, serotonin having been squirted across my transom, they inhibit the biochemical hoopla that soaks it up again, ensuring that there’s always enough of it sloshing around to make me feel happy. Or at least ‘normal’.
When I was a graduate student I ran into a sticky patch (I used to be a fly) but was helped out by an SRI called mianserin, which is known as a tricyclic, on account of its having three cycles. It has the curious property of extending lifespan in the roundworm Caenorhabditis elegans, though news of any effects it might have on the ability of giraffes to ride unicycles has yet to reach Cromer.

A molecule of mianserin. Just count the cycles.
Time passed, as it does, and I came off these, but many decades later when I was once again in Slough the Slough of Despond I was prescribed a different sort of SRI called citalopram.
Well, as I reported earlier, after many happy years of using citalopram my body started taking it for granted and its effects started to wear off, so I went back to my general practitioner who prescribed another tricyclic, mirtazapine.
The astute reader will note that this looks very similar to mianserin. I can only spot five three five differences between them.
(1) The molecule of mirtazapine is upside down;
(2) where mianserin has a regular -CH- in one of its mickey-mouse ears, mirtazapine has an N;
(3) <geek> whereas both molecules are chiral, the sinistral form of mianserin is 200-300 times as effective as the dextral version, whereas mirtazepam is offered as a racemic mixture </geek>.
(4) … er …
(5) That’s it.
Now, I don’t know this, but I suspect that difference #4 is the most significant. So far, so good.
The problem for me was changing from citalopram to mirtazapine. The first task was to come off the citalopram, which was far more difficult than either myself or my GP had anticipated.
When I wrote my earlier entry I was about five days into a two-week regime of reducing my dose of citalopram from 40mg to 20mg per day, before going on to a daily dose of 15mg mirtazapine.
As I had 40mg citalopram tablets I decided to do the first part by taking a 40mg tablet every other day. I was advised not to do this, and for anyone thinking of coming off a drug this way, it’s an absolute no-no. Do not do it, dude. Best get a new prescription for 20mg tablets. Or at least cut the 40mg tabs in half.
Nine days in and I was a wreck. Mrs Crox was away at a conference, and I was alone in the house (inasmuch as one can ever be alone with Crox Minor, Crox Minima, Canis Primus Croxorum, Canis Secundus Croxorum, Naughtypants Not His Real Name, Feliculus Primus Croxorum, Feliculus Secundus Croxorum, Darth Kitteh, Serpens Primus Croxorum, Serpens Secundus Croxorum, Squirty Benson Wilberforce III et alii.) On the morning of the tenth day I was curled up in a ball sobbing. What I was suffering from was SSRI Discontinuation Syndrome, or, as I’m in Norfolk and it’s winter, cold turkey. Nobody told me what this was like. Cold turkey hurts. Physically. All over. It feels like being kicked vigorously in all parts of the body at once, simultaneously, and at the same time. It is not nice.
I went to the GP again. It was a different GP, who counselled me not to wait any longer before starting the course of mirtazapine prescribed earlier. He also prescribed me some diazepam to help me through any rough patches in the ensuing days.

A molecule of diazepam. This looks like a tricyclic that’s turned into a bicyclic with one of the wheels falling off. A new hope for molecular giraffes yet!
The ensuing days were just horrible. First, I had no citalopram at all, and was on 15mg mirtazapine per day – just the starting dose. This is not meant to tackle the depression, but just to get my body used to a new drug. My GP (the first one) told me (later) that this is is normal practice – the side effects of a sudden hit of a full dose of mirtazapine are, he implied, even worse than for a starting dose (I experienced dizziness and some tiredness, which are well-known side effects of mirtazapine).
So there I was without any active antidepressant at all, and I have to tell you, friends, that it was beyond ghastly incarnate with bells on. Not only was I depressed (and everything that goes with it) but tired and prone to mild dizzy spells. To take the edge off the anxiety I flipped some diazepam, which stopped me being a paranoid monster, but made me very drowsy indeed – not a restful, natural form of drowsiness, but a synthetic, fast-food kind of numbness.
Roger Waters, the musician and lyricist of the band which Glaswegians will know as Punk Fluid, put this very well in a song called Comfortably Numb whose lyrics rank as among the most profound in what is admittedly a rather shallow canon:
There is no pain, you are receding.
A distant ship, smoke on the horizon
You are only coming through in waves.
Your lips move, but I can’t hear what you’re saying.
When I was a child, I caught a fleeting glimpse
Out of the corner of my eye.
I turned to look but it was gone -
I cannot put my finger on it now,
The child is grown, the dream is gone.
I have become comfortably numb.
That was me to a tee – Comfortably Numb.
Yesterday I went back to the GP (the first one) on an appointment made for me by Mrs Crox (I wouldn’t have been capable of doing this myself.) I went to the surgery feeling very confused, angry, mistreated and generally hung out to dry. That’s when the Doc advised me to come off the diazepam immediately (hooray!) and prescribed me a therapeutic dose of 30mg mirtazapine, effective immediately (double hooray!)
Then I went home. I took a 30mg tab of mirtazapine and had a nap. When I woke up, witness a curious transformation. I was my old self again. Bloody exhausted and wrung out, to be sure, but I felt … there is no other way to put this … normal. I’ll review my progress with the GP in a week, and maybe another week after that I can be unleashed on the rest of the world.
Now, all of this excitement and general pharmacological brouhaha set me to reflect on my recent experience (note – an activity that’s very hard to do when one is taking diazepam) and in particular the relation between the nitty-gritty of molecules on the one hand, and the more indefinable but nevertheless recognisable traits such as ‘personality’ and ‘self’ on the other. A number of questions occurred to me, a selection of which might include -
What does it mean to say that one feels ‘normal’, as I did above, that I was ‘my old self’ again?
What is the meaning of ‘self’?
How do I work this?
Who put the benzedrine in Mrs Murphy’s Ovaltine?

A molecule of benzedrine. This looks uncannily like a unicycle that might be ridden by a giraffe (giraffe not pictured.)
My experiences suggest that many aspects of matters to which we attribute reason and action are heavily influenced, if not absolutely governed, by the relative quantities and activities of a small number of rather simple chemicals (which is why I have gone into these in such detail.) What we think of as the ‘self’ is not something that exists on a higher plane, but a resultant expression of chemical activity which we recognise (and in others) as the ‘self’.
This is something that I shall be addressing in the final chapter of The Beowulf Effect, on the meaning of ‘sentience’. When we think of the ‘self’, we tend to think of that black box that’s between incoming sensations and outgoing actions, which is also conveniently expressed as a metaphor in which we – the ‘self’ – is the witness to a performance of our life as we live it. Or, to use a more childlike image, the little person inside our heads that watches things happen.
Given that it’s incredibly easy to dent this ‘Cartesian Theatre’ idea (for example – who is watching the watcher? Who is watching the watcher of the watcher? And who is keeping an eye on this bunch of intellectuals, anyway?) it’s something that’s very persuasive, such that it takes a philosopher of the calibre of Daniel Dennett to effect a comprehensive demolition (which he does in his book Consciousness Explained.) Dennett marshals much evidence to show that the Cartesian Theatre does not exist – there is no one ‘place’ in the brain that’s the seat of the ‘soul’; no little people looking out of one’s eyes as windows; and no ‘mind stuff’ that directs action on the basis of information received.
One might argue, of course, that such a crude, phrenological picture of the workings of the brain doesn’t account for the fact that any particular function of the brain that we can recognise results from the interaction of many different systems and subsystems in a distributed way. What one considers the ‘self’ is the final output (depending on what one means by ‘final’, and possibly even ‘output’) of lots of different pieces of the brain firing in certain habitual ways in response to particular or general stimuli.
But even when one accounts for the organisational relationship between neuronal circuitry and one’s subjective experience, you can’t get away from the drugs. It is quite clear to ‘me’ on the basis of my own self-experimentation that the feeling of ‘me’ is determined very largely by the balance of serotonin in ‘my’ brain. And if that is the case – which I can no longer doubt – what price love, hate, friendship, religious fervour, truth and beauty?
Discuss.
As a postscript, I’d like to thank my family and my many colleagues and friends who have sent wishes of support over the past few weeks. Some of these have been very moving and have told their own stories. Some of my friends, whom I thought I knew well to be happy, positive people, have, like me, been plagued by depression and have their own stories to tell. All your wishes are very much appreciated.







Wow. Eloquence and wisdom. And a few jokes room.
Great kudos to you Henry. Very glad your molecules are feeling better.
I see that Brunel University is going to specialise in Self.
Dear Henry
As I said to Pen, I understand totally what you went through. I’m still on 150mg of Venaflaxine but CBT therapy has been very useful as has relaxation classess. Now attending a spiritual healer in Barkingside(know you’re probably pish pash this as a scientist although it’s horses for courses). The ironic thing is I was perscrobed free exercise by my therapist but the exercise coordinators can’t sign it as my meds are giving me heart palpatations and my blood pressure is too high! You can’t win. Glad your better. love to the family xxxxxxxx keep rocking!
Welcome back, indeed.
That whole reflection about the nature of “self” and the chemicals and their remarkable, shifting balance – it’s scary, isn’t it? Everything really is relative. Or: we are only the stories we tell ourselves about who we think we are, a continuous monologue.
If you’re up for more reading, I highly recommend Douglas Hofstadter’s “I Am A Strange Loop” (reviewed at http://www.scientificamerican.com/article.cfm?id=a-new-journey-into-hofsta). Interesting thoughts about death and “souls”, which have an echo in this discussion about the construction of “self”. The souls of loved ones, in this view, “live” on as the stories we tell ourselves about those loved ones. Stories that get close to their experience, or part thereof, but that get less resolved over time, or over distance from the individual. Our own stories about our experiences define our selves to our selves, but also to the people around us. Those buried experiences that haven’t been the object of much of a neurological narrative… isn’t that the physiological root of psychotherapy?
Have a great weekend.
(Forgive me all the quotation marks, please, Mr. Editor.)
oh, so happy you are feeling more like ‘self’ and less like a ball of hurt. ’tis indeed a very bad place to be in. Hope you have a good weekend and continue on.
A very moving and informative blogpost, thanks for all the chemical structures! I’m geekily happy looking at them and trying to remember conversations about “exchanging a c-in a hexaring to a N in a pentaring….” but end up liking the “errr” in your 3rd comment instead ^^
As for the self and the brain, sometimes I get scared realising that this heart and the “feelings” really migt just be synapses blinking in the brain and sometimes the get rerouted and lost in all the white and grey matter… and somewhere in there I’d like it to be ‘me’ and ‘my core’ or soul … and then I realise it is lent so maybe I should take this to heart and contemplate a little more. And maybe we are more ‘self’ due to the actions and things we do (to others and ourself) than ‘only’ our thoughts and feelings? That our self extend with these actions and therefore, we are so much more than thoughts and body….
or it’s too early in the morning and I’m ranting odd stuff. Better stop.
(just wanted to add in on the happy, it’s a warm fuzzy feeling that you are feeling better. best wishes to the inhabitants of the house of the unicycles!)
Very Happy to hear of the improvement!
If it’s any consolation there is an FDA bulletin out recommending that patients not use 40 mg/d and above due to cardiac concerns. So in the long run you may be better off.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm269481.htm
That’s of the citalopram/celexa, I meant…
Glad the new stuff is appearing to work out ok, Henry.
My head still hurts from flipping the mirtazapine over and superimposing it on the mianserin to spot the differences – which is a small thing to be bothered by, admittedly.
*nods*
Clonazepan.
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Wow – there’s a lot of chemistry going on. I hope it’s all settling down and you’re adjusting to the new treatments.
While I’ve never experienced clinical depression, I do recognise that feeling of not being yourself. It’s a phrase that people tend to throw around quite lightly to mean that they feel a bit under the weather, but when you actually experience it yourself in its literal sense it’s just so alien and disconcerting. In my case this happened for a few months during the final year of my PhD, after a very traumatic breakup (we’d been together for a couple of years, he was coming back from a few months working overseas, and had led me to believe that we’d be moving in together and getting engaged – but then called two days before he was due back to inform me that he was bringing his new girlfriend with him instead, and to give me a full and complete list of every little thing he didn’t like about me. In retrospect it was the best thing that ever happened to me, as it allowed me to move to Vancouver and meet my husband, but obviously I didn’t know that at the time). I was a mess for months, and when I say I didn’t feel like myself I mean that I didn’t recognise my own thoughts and feelings as belonging to me. It was as if I opened my mouth and spoke with a completely different accent and intonation, or something, but internally and constantly. And when it reversed, it reversed suddenly, like you said – I had a thought that was like my usual ones, and BOOM! I was back. Very very weird.
Oh, and by the way – thanks for giving me some evidence to back up my long-held assertion that cheese is therapeutic!
Okay so maybe the chemical weather dictates our mood, but you could compare that to using measures of the money supply to try to explain the downfall of coal mining or the property bubble?