Medicate Me

History: Fire, Sin and Drills

Swallowing a pill has never been so easy. We have pills for everything now. When my penis goes flaccid, I take a Viagra. When I’m too fat, Xenical. When I can’t concentrate, I hit the streets for Ritalin. Never before have there been so many amazing pills that promise so so much.

Historically, antidepressants relied more on superstition than pharmacology. Mental illness was generally seen as possession by an evil force. Brains infected by devils, souls seized by spirits were the general theories of diagnosis. Remedies included boring into the skull—trepanning—water immersion, sitting on a spinning stool, enemas and basic torture.

Empedocles, a Greek philosopher, was one of the first thinkers to try to track down a physical cause for depression. His theory, which in retrospect is aptly named, was based on the four elements. An imbalance between the elements leads to a physical/mental disturbance in the person. If you were having unpleasant dreams it meant that you had bile in the brain. Treatment: Drain the bile.

This was eventually rejected by Cicero, who posited: “What we call furor, they call melancholia, as if the reason were affected by only a black bile, and not disturbed often by a violent rage, or fear, or grief.” In essence that mental disturbance could manifest in physical symptoms.

With the decline of the Roman Empire and rise of Christianity, trust in logic and scientific advances abated. Explanations of many previously rational explanations for depression fell away for superstitions about devils and supernatural phenomena. The Dark Ages descended with the mentally ill falling into the hands of clerics, rather than doctors in the east and the west. Eventually by the 15th century, mental illness had been equated with sin. Treatment: burning at stake, isolation.

The first real text that addressed depression as a medical topic was published in 1621. The Anatomy of Melancholy by Robert Burton, who offered this advice: “Only take this for a corollary and conclusion, as thou tenderest thine own welfare in this, and all other melancholy, thy good health of body and mind, observe this short precept, give not way to solitariness and idleness. ‘Be not solitary, be not idle.’” Treatment: The evolution of the protestant work ethic allowed people to devote themselves to work. Work. Exercise. Keep the company of others. Perhaps chew on some St John’s wort.

Fast-forward two-hundred years. Freud, psychoanalysis. Brain chemistry—altering chemicals. The realisation that the mind and body were both causes of depression. Treatment: Psychotherapy, valium, lithium.

Up until the 20th century, treatment for mental illness was worse than hit and miss. It was generally just hit, and generally with either a drill or something flammable. That all changed when some crazy guys started experimenting with substances that could mess with the chemicals present in the human brain.

These green and purple pills

Apart from delicious delicious amphetamines and opiates, it wasn’t until the 1950s that targeted antidepressants started being used and even then the discovery was accidental. Two tuberculosis medicines—isoniazid and iproniazid—showed signs of improving mood. Serendipity is amazing.

From here flowed the discovery of tricyclic antidepressants (TCAs) [see sidebar].

The basic assumption behind TCAs and selective serotonin reuptake inhibitors (SSRI) antidepressants is that they stop the reuptake of certain chemicals back into your system so that you can reuse it over and over again. The most commonly prescribed SSRI is fluoxetine, better known by its brand name, Prozac.

Imagine your brain is a ship at a dock. No. Not full of seamen. The only way that a person can come off the boat is if they use a gangway. Nah, fuck it. Refer to diagram 1.

The top thing—as any first yeat psych student will tell you—is an axon terminal, the bottom part is the dendritic spine and the gap between is the synaptic cleft. The axon neurons are connected and use electrochemical signals and neurotransmitter chemicals—serotonin—to transmit impulses from one neuron to the next. Cool?

The dendritic spine receives the electrochemical signals and neurotransmitter chemical. Kinda like wireless internet. Brain chemistry is fun. Serotonin is one of the chemicals used in the transport of the impulses from the axon to the dendritic spine. It plays a role in modulating anger, aggression and other emotions.

When the brain wants to send a ‘happy signal’, it releases serotonin molecules from the axon. When one is received by the dendritic spine, the remaining serotonin molecules are reabsorbed by the axon. Fluoxetine and other SSRIs work by inhibiting the reabsorption of the serotonin, meaning that the signal continues to be received by the dendritic spine for longer. For other forms of antidepressants, the same holds true for norepinephrine and dopamine. Going back to that horrible ship metaphor: all the sailors are blind trying to get off, but every time one escapes the gangway is removed, and no more can cross until the gangway is replaced. When on antidepressants the gangway stays a bit longer.

SideFX

The minor side effects of fluoxetine include, but are not limited to:

- anhedonia (inability to experience pleasure)
- apathy
- nausea
- drowsiness or somnolence
- headache
- clenching of teeth
- extremely vivid and strange dreams
- dizziness
- changes in appetite
- weight loss/gain (measured by a change in bodyweight of 3.5 kg)
- may result in a double risk of bone fractures and injuries
- changes in sexual behaviour
- increased feelings of depression and anxiety
- tremors
- autonomic dysfunction including orthostatic hypotension, increased or reduced
- sweating
- akathisia (inability to sit still)
- liver or renal impairment
- thoughts of suicide
- increased risk of sunburn

It is also probable that if you’re on fluoxetine or another antidepressant you – will become addicted to it. Not the Trainspotting mold, but if you forget to take your pill for one day you’ll start feeling withdrawals. As Renton said: “Too ill to sleep. Too tired to stay awake, but the sickness is on its way. Sweat, chills, nausea. Pain and craving. A need like nothing else I’ve ever known will soon take hold of me. It’s on its way.”

Humans messing around with brain chemistry is like slamming a sledgehammer into a rugby field and then asking another person to find the dent by slotting in a sledgehammer-dent-sized jigsaw piece, blindfolded. Zapping electricity across the hole is optional.

As said before: hit and miss. Although the miss rate has decreased… or has it?

A New Zealand Herald story last year highlighted a literature review that indicated antidepressants don’t work. The study reviewed 47 clinical trials that focused on the six most popular antidepressants. Many professionals were quick to disregard them in all but the most extreme of cases. Pharmac’s director Dr Peter Moodie said the findings were interesting and an evaluation would take place, but “When we’re looking at questions about the efficacy of drugs, we should use a measured approach.”

The study sent many ripples out into the mental health community. Blogs vented against them. Doctors told patients to keep the faith. The Victoria Univerity Counselling Service put on a seminar talking about the issue.

One of the authors of the study, Professor Irving Kirsch, from the University of Hull, said “Given these results, there seems to be little reason to prescribe antidepressant medication to any but the most severely clinically depressed patients.” One Dr John Breeding—with his lovely grey beard—presents an amazing video on YouTube which explains the position adequately.

With the trenches drawn the only logical position seems in deadman’s land. As it always seems with polar arguments, neither side is adequate to fully explain all cases. And just like one size fits all Starter caps, they don’t actually always fit everyone.

Ethical issues

The inherent conflict between the Hip-pocratic Oath (which doesn’t apply to those who aren’t doctors, but the guidelines are respected goals and ethics for those in the health profession to abide by) and the profit motive is a sticking point in whether antidepressants actually work.

The first article of the oath (see sidebox) is perverted by the patent process. Pharm-aceuticals are patented, meaning that com-pany has exclusive rights, and no one can make or manufacture the same product till the patent expires. The patent on fluoxetine expired in 2001, 15 years after the drug was first approved for widespread human use. Until then, Eli Lilly had a monopoly on the production of this drug. The Fortune 500 company, which posted almost US$2 billion profit in 2006, is purposefully making profit off the misfortune of others, with dubious results.

This leads into the sixth article, which points out that we treat humans, not just the affliction, and therefore there is a need to take family and economic stability into account. New Zealand sufferers of depression are lucky: Pharmac subsidises $20.8 million a year, down from over $30 million in 2007, mainly due to new companies cashing in on the whole no-patent thing. So how can pharmaceutical companies reconcile making huge profits when their product has minimal positive effects and there are so many suffering people? Well that is a good question. The New York Magazine reported that 60 percent of Pfizer’s income in 2007 was a straight-out profit of US$12.9 billion, and the Centre for Public Integrity reports that pharmaceutical companies have spent an unprecedented amount of cash money on lobbying—well over US$800 million from 2000 to 2007.

Omelette

It should come as no surprise that there are still gaps in our health system. As McCoy said in Star Trek: The Voyage Home “My God, man. Drilling holes in his head isn’t the answer.”

The findings are mixed. Some people report they’re helped by antidepressants, some people don’t. Some doctors don’t prescribe, some do. Research points that one treatment alone shouldn’t be relied upon and that antidepressants should be used in combination with counselling, exercise and healthy eating. Removing the profit motive from health care and pharmaceuticals would also be a good stepping stone. Repeat business comes when there are no alternatives and there is little repeat business if you cure your target market.

The Hippocratic Oath says “prevention is preferable to cure”, and so the underlying causes should be rooted out and alleviated, rather than the safety net mentality that tells us a pill can fix everything.

Brain Soup

Serotonin

A neurotransmitter when used in your brain (80–90% of serotonin resides in your gut). It sits in the gaps between synapses and just hangs out.

Selective serotonin reuptake inhibitors

These work on the basis that low levels of serotonin in your brain can lead to depression. They stop your brain form reabsorbing it so that it can be used time and time again. Currently the most widely prescribed antidepressants in the world.

Tricyclic antidepressants

These also block serotonin uptake as well as other neurotransmitters. First sold in the 1950s, TCAs have largely been superseeded by SSRIs. The main TCS still used in New Zealand is Amitriptyline.

Fluoxetine

New Zealand’s favourite antidepressant, these little green and purple pills are in the SSRI catagory. Originally developed in the late 70s, it hit the American market in 1986 with the trading name Prozac. It specifically blocks the re-uptake of serotonin and is the first point of call for most first-time depressed persons.

Citalopram

Created in 1989 it is gaining popularity as an alternative to Fluox. For many users the SSRI minor side effects don’t seem to
be an issue. It should not be used with St John’s wort.

Amitriptyline

A lesser used drug in New Zealand it still is prescribed regularly. Residing in the TCA family of antidepressants it is now primarily used for migraine relief. Unfortunately there can be serious side effects and there can be a potentially lethal overdose reaction to them.

Alcohol

It is a depressant. It will not help you get over depression. Although it lowers inhibitions and acts as a relaxant, it is addictive and has many more adverse effects than antidepressants. Can also have bad effects if you are taking proper antidepressants.

Kava

Not a prescribed medication for depression but has a relaxant effect which has been described similar to alcohol or valium. Kava is totally legal, non-addictive when used properly but, like all brain altering
substances, can have side effects. Give it a try!

Exercise

The easiest and cheapest way to treat depression, exercise can boost mood and produce endorphins and is a basic exercise in goal setting and motivation.