Take once daily -- Part 2

When I took my first anti-depressant in 2001, I was merely one in a long line of people who have used substances of one kind or another to try to stabilize their mental health.

How long a line?

Try 3,500 years long. (Yes, depression's been around that long. Actually, it's been around as long as we have. At some point in the future, I'm going to write an entry on the history of depression. Contrary to what the media would have you believe, depression is most certainly not a modern illness.)

Yes, these are my actual Effexor pills. The reds are 150mgs, the whites, 75mgs

In the beginning, people afflicted with a depression of mood would take plant extracts, including from the poppy (opium), nightshade (Atropa belladonna), Indian hemp (hashish), henbane (hyoscyamine), thorn apple (scopolamine) and St. John’s wort (hypericum oil).

In addition, psychotherapeutic measures, like playing music, dancing, playing theatre and also sleeping in temples (!), were used.

In the 19th century, the introduction of bromide (1826), codeine (1832), chloral hydrate (1869), and paraldehyde (1882), as well as the barbiturates (at the turn of the century) introduced significant improvements in pharmacotherapy.

The modern thymoleptic therapy started in 1957 with the introduction of imipramine. Now about 40 active antidepressants are marketed.

 The one I take is called Venlafaxine Hydrochloride (better known by its brand name, Effexor).

Back in 2001 I was started at 37.5 mgs a day. Over the years my dosage was increased incrementally as I became more tolerant of the given dosage. I now take 375 mgs a day, which is the highest dose recommended by the manufacturer. 

The chemical structure of Effexor.

It belongs to the serotonin-norepinephrine reuptake inhibitor (SNRI) class. The most well-known and presecribed class of anti-depressants are selective serotonin reuptake inhibitors (SSRI).

So that's a whole lot of letters. What exactly do they do?

The general consensus in the neuropsychopharmacology field (there are some dissenters) is that the benefits of antidepressants stem from how they affect certain brain circuits and the chemicals (called neurotransmitters) that pass along signals from one nerve cell to another in the brain. These chemicals include serotonin, dopamine and norepinephrine.

In a brain that's functioning normally, adequate amounts of neurotransmitters are produced and jump efficiently from one synapse to another. For reasons that are not yet completely understood, my brain does not produce enough of these neurotransmitters and the few that do get produced don't behave as they should. Instead of jumping from one synapse to another in my brain they make the jump but then many of them jump back and degrade.

When I take Effexor, it boosts the amount of neurotransmitters and forces them to make the synaptic jump and not jump back (hence the name reuptake inhibitor).

Here's a more detailed look at how it works. You can skip the italicized part if you find science too boring:

1. The presynaptic cell (sending cell) makes serotonin (5-hydroxytryptamine, 5HT) from the amino acid tryptophan and packages it in vesicles in its end terminals.
2. An electrochemical nerve signal passes down the presynaptic cell into its end terminals.
3. The nerve signal stimulates the vesicles containing serotonin to fuse with the cell membrane and dump serotonin into the synaptic cleft.
4. Serotonin passes across the synaptic cleft, binds with special proteins called receptors on the membrane of the postsynaptic cell (receiving cell) and sets up a new electrochemical signal in that cell (the signal can stimulate or inhibit the postsynaptic cell). Serotonin fits with its receptor like a lock and key.
5. The remaining serotonin molecules in the cleft and those released by the receptors after use get destroyed by enzymes in the cleft (monoamine oxidase (MAO) and catechol-o-methyl transferase (COMT)). Some get taken up by specific transporters on the presynaptic cell (reuptake). In the presynaptic cell, the absorbed serotonin molecules get destroyed by MAO and COMT. This enables the nerve signal to be turned "off."

I've often explained the science behind depression and anti-depressants by comparing it to diabetes. A diabetic's pancreas doesn't produce enough insulin and the little that is produced isn't processed properly. That's why diabetics need to take daily insulin injections.

So it is with my brain. Simply put, it doesn't produce enough neurotransmitters and the few that it does aren't processed properly. That's why I need to take daily anti-depressants.

The funny thing is that scientists aren't exactly sure why a reduced level of certain neurotransmitters like serotonin, dopamine and norepinephrine causes depression and anxiety.

Before I talk about how I felt after taking my first anti-depressants, let me tell you what they do NOT do for me.

Despite what many people think, anti-depressants are not happy pills.

They do not make me high. They do not make me euphoric.

They don't even make me happy. Not in the least little bit. 

That's not how they work.

It's much more fun to spend time on the right side.

When I first started taking them in 2001 I was in a serious crisis. It wasn't the worst breakdown I'd ever experienced but it was bad enough I spent two weeks in outpatient programs in an attempt to climb out of the pit I was in.

When I took my first pill, I was expecting my black mood to lift and for me to feel, at the very least, "normal."

After a few days, it was obvious nothing was really happening. My doctor told me to be patient since it would take some time for the medication to reach a therapeutic level. He increased the dosage slightly and I waited.

And waited.

What I was waiting for -- a sudden elevation in mood -- never happened. Instead, it was a slow process, so slow I didn't realize it was working until it, well, worked.

I slowly became aware that my mood was not as black, my nerves not as raw from the constant hum of anxiety. My mood had become more stable, which is all anti-depressants do for me. They blunt the anxiety and -- when they are working properly -- keep me from falling too far.

My greatest fear -- as I outlined in my previous entry -- that I would lose myself, turned out to not be the case. I still have a dry sense of humor. I still gravitate to serious -- and yes, depressing literature and music. I am still not a huge belly laugher.

I am who I always was, but mostly without the crushing lows and non-stop anxiety.

For you see, there is no cure for what I have. The diagnosis of major depressive disorder (recurrent) is a life sentence. It will always be there. Medication is one tool that allows me to get out of bed each day, get dressed and, for the most part, participate in this thing we call life.

There are times when even the medication is not enough. My health-care team refers to it as "breakthrough" depression. That's the times that even though you are doing everything you should be -- taking medication, eating well, sleeping well, exercising, practicing cognitive behaviour therapy and so on -- it shatters your defense barriers and drags you down to the depths.

That happened to me in 2010. After a decade of taking Effexor, it was obvious it wasn't enough. Being at the maximum dosage for so long also meant I was not a candidate for switching medications (Effexor withdrawal is hellish. I know within a couple of hours when I've forgotten a dose. My brain starts to go into meltdown, complete with full-blown anxiety, a heavy sense of dread and, as they're called in the depression field, brain zaps. They feel like shocks of electricity flashing inside your cranium. They are, to put it lightly, a fucking nightmare).

Bedlam asylum. Not a place you'd want to find yourself.

So my GP and psychiatrist decided on a fairly new tactic -- augmentation. There had been some success in
treating treatment-resistant depression by adding a second medication to the mix, usually in the form of an anti-psychotic.

I must admit that when they told me they wanted to put me on an anti-psychotic I was more than a little freaked out. One of the greatest fears of those who suffer from a mental illness is that we'll one day lose our minds, finally reach that tipping point, the event horizon, and be dragged to a place far away from reality, never to return. My first instinct when told I'd be dabbling with a medication typically used on schizophrenics was that it was akin to dabbling with the dark arts. 'No thank you,' I said to myself. 'I'd rather be depressed.'

My doctors patiently explained to me that taking an anti-psychotic did not mean I was psychotic and certainly wouldn't cause me to become psychotic. For reasons (again) not well understood, this class of drug, when administered in tandem with SSRIs or SNRIs, seemed to make the anti-depressants more effective, basically throwing up another layer of defense against a breakthrough.

Unfortunately for me, we had to try several augmenters before we hit upon one that worked. I took Abilify and another one whose name escapes me at the moment. The Abilify turned me into a zombie, the second one an anxiety-drenched basket-case. The third one was a charm -- Seroquel. I started out on a low dose but was rapidly brought up to 300mgs a day.

One good thing about the latest classes of anti-depressants and anti-psychotics is that their respective side-effects are not nearly as bad as the ones from a few decades ago. The side-effects used to be so terrible schizophrenics and depressives would rather be sick than take their meds. Think about that for a second.

That's not to say today's aren't without side-effects. Seroquel also acts as a sedative, so I have to take it an hour before I go to sleep and it can make it difficult to wake up in the morning. It's also notorious for causing people to gain weight through increased appetite, something I experienced first-hand. I gained more than 20 pounds after starting taking it. For the first year it also caused me Restless Leg Syndrome, the feeling that something was inside my legs. It could only be temporarily relieved by moving my legs. Awful, nasty thing.

Thankfully, those were the only side-effects (which are mostly gone now) and it eventually helped beat back the blackness and anxiety to help me get to where I am today.

Not quite as broken, not quite healed.

It's a work in progress.