This is the fourth of a series of blog posts on the context behind my Physics World article: A physicist’s experience of the mental-health system. There is a lot of backstory. So during the editing process, I sent documents to the editor to help explain some of the views I express in the article. I have decided to add them as blog posts.

This blog post discusses why Alex decided not to include information about their use of Venlafaxine between 2016-2019 in their Physics World article about their experiences with the mental-health system. Alex explains that the drug did not give them much benefit and may have even made their condition worse. He also felt that including even a brief mention of Venlafaxine would have confused the reader and distracted from the points they were trying to make. The post goes on to discuss the complexity of antidepressants and the importance of understanding their binding affinities for different receptors. Alex believes that misinformation about antidepressants led to their prescription of Venlafaxine.

I didn’t want the fact that I took Venlafaxine between 2016-2019 to be in the PhysicsWorld article.

I left it out for reasons I hope will be made clear in this blog post. It was difficult, perhaps impossible, to include without a lot of background information and the drug did not give me much, if any benefit. I actually think it made my condition worse. 

It is true that I believed that I could achieve remission solely through psychotherapeutic methods during the PhD and also true that I actually require medication to treat my illness.

I feel including even a short mention of Venlafaxine would have confused the reader and distract from the points I was trying to make later on. I hope this is made clear in the following story:

After my severe reaction and a few months of taking the therapies route (now early 2016), I realised that I was still extremely susceptible to any stress. The smallest amount would result in days of suffering and pain. This was improving, but too slowly. I only had eight months leave and there were already suggestions from my Supervisor of doing a shorter MPhil instead (which actually made me more determined to get back to the PhD). I therefore went to my GP, who referred me to an NHS psychiatrist. All the GP received was a letter, recommending the prescription of Venlafaxine, an SNRI (Serotonin and Norepinephrine Reuptake Inhibitor). I was scared by the ‘S’ in SNRI. But the psychiatrist’s letter made it clear that it was a weaker drug compared to Sertraline and that it also worked on the Noradrenaline transporter. Given the complexity of the brain, I was told I should expect a different result, and that I would go up on the drug very very slowly.

So, I agreed to take the Venlafaxine. It was pretty horrible going up on the drug, with similar but much milder symptoms to the Sertraline for the first week or so. After a few weeks it settled. The result was that it didn’t make much difference. I was still incredibly prone to stress, but the suffering and pain after each episode was not quite as long. I don’t know if this was placebo or the action of the drug itself. In any case, I just about made it back to my PhD 5 months later.

I took Venlafaxine for 3 years. I was on it for so long not because it was improving my mood, but because I was terrified of my mood regressing if I came off of it. I didn’t want to have to take a break from my PhD again. The decision to come off of it came after my condition deteriorated rapidly at the end of my PhD (I then was forced to discontinue the Venlafaxine in order to take other medications).

Surprisingly, I noticed no difference in my condition after I came off the drug. Confused, I decided to look into how Venlafaxine worked. I was pretty shocked to find out that the classifications of antidepressants do not accurately describe their characteristics.

It seems to me that the binding affinity (how well the drug binds to its target receptor) is a much better indicator of the antidepressant characteristics. I still find binding affinity quite confusing as there are several types of measurement to describe it and the measurements are all related to each other. The most common seems to be the dissociation constant  (Ki). Trying to keep things simple, the dissociation constant essentially describes how likely it is for the antidepressant molecule to release itself from its target receptor. The lower the dissociation constant, the stronger the bind to the receptor.

Sertraline, classed as a selective Serotonin reuptake inhibitor (SSRI) binds very strongly with the Serotonin Transporter (SERT). The dissociation constant for this receptor is 0.15 – 3.3 nM. But Sertraline does not just bind to the SERT. It actually also binds quite well to the Dopamine Active Transporter (DAT) and the sigma 1 adrenaline receptor (Ki of 22 -300 nM and 30 – 50 nM respectively), along with a few others (although with very poor binding).

From my understanding, this is the same for most psychotropic drugs. The antidepressants within the SSRI classification all bind best to the SERT with around the same dissociation constants. However, SSRI’s can have wildly varying dissociation constants to other receptors. Some semi-significantly.

From my conversations with them, I am not sure that some of the clinicians that I have seen are aware of the differing binding affinities for other receptors. I certainly wasn’t aware for a very long time. Every short informational article that I found on the internet made it look like SSRI’s only bind to the SERT.

I believe it is this type of misinformation which led to my prescription of Venlafaxine. It is classed as a Serotonin and Norepinephrine Reuptake Inhibitor (SNRI). The dissociation constant for the SERT is around 80 nM. Compared to the Sertraline it binds very weakly. Importantly, the dissociation constant for the Norepinephrine Transporter (NET) is around 2500 nM. The strength of binding to the NET and SERT is not equal. The result being that it is believed Venlafaxine can only really be classified as an SNRI at doses above 150mg per day. At the dosage I was taking, it is probably better classified as a weak SSRI.

Essentially, I had taken a weak version of Sertraline, the drug that caused my severe reaction, for three years. I have a strong belief that this had an impact on the progression of my illness and the exhaustion that caused me to collapse just after the PhD. But I also believe it was very subtle. The progression was so slow (years) I never realised it was happening. It was only when my condition started to improve with the Pregabalin that I put 2 and 2 together.