ANTIDEPRESSANTS: WHY SUCH RELIANCE?

June 25th 2009, Michael Jackson suffered cardiac arrest due to acute Propofol and Benzodiazepine intoxication at his home in LA. When his physician Dr. Conrad Murray found him, he wasn’t breathing and had a feeble pulse. He was later pronounced dead at Ronald Reagan UCLA Medical Centre. Coroner’s report stated that he died from a combination of drugs, the anesthetic Propofol and the anxiolytic (inhibits anxiety) Lorazepam. Traces of other less significant drugs such as Midazolam, Diazepam, Lidocaine and Ephedrine were located in his body.

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Propofol is used as an anesthetic and is a fast-acting sedative. Its key functional characteristic is its rapid onset and offset of action. In the US it was also used for death penalty execution in the state of Missouri. Allen Nicklasson, the convicted killer, was administered Propofol and he was declared dead 8 minutes after ingestion. Lorazepam is a muscle relaxant and is used for insomnia, anxiety, seizures and for sedating aggressive patients. Midazolam is similar to Lorazepam and used for severe insomnia and anxiety. Michael was given 4mg. Diazepam, known as Valium is used for insomnia and anxiety. Michael was given 10 mg on the morning he died. Lidocaine is used by dentists to anaesthetise gums. Michael was given Propofol diluted with Lidocaine. Ephedrine is used as a stimulant and appetite suppressant. Hours before his death, Michael’s frail body bore equivalence to a chemical plant. Sure, due to his wealth, many of these drugs were easily accessible to him but it must take willful blindness not to see what he is going through yet drugs were legally ingested into him by responsible physicians.

Joan Rivers the actress also died after complications from Propofol ingestion. Illegal drug related deaths is common: Philip Seymour Hoffman, Whitney Houston, Kurt Cobain, John Belushi, Elvis Presley, Jim Morrison, Jimi Hendrix, the list is endless. Prescription related drug overdose however intrigues us and here are a few famous deaths: Heath Ledger, Bruce Lee, Marilyn Monroe. Sigmund Freud also died from prescription drug overdose (morphine) but it was a physician-assisted suicide due to Freud’s terminal cancer stage. History is replete with many drug related deaths.  The idea of this blog is not to present the facts or sensationalism associated with drug abuse rather what is it that makes people rely on antidepressants (prescription drugs) conveniently and make it their life time accompaniment. To understand this let us journey a bit into what is depression and what antidepressants do?

WHAT IS DEPRESSION?

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Depression as per DSM-III-R and DSM IV include vegetative symptoms as well as depressed mood, a loss of interest or pleasure and a preoccupation with thoughts of worthlessness and guilt (Taylor et al., 1997). As we encounter challenges in life, it is customary to lose state, feel down at times, discouraged and forlorn but persistence of this state for months and perhaps years is construed as chronic and categorized as clinical depression. If one is asked to define depression here are the eliciting terms: Hopeless, sad, despondent, dejected, social withdrawal, loss of energy, scant interest in doing anything, no motive force, feeling tired, low self esteem, insomnia or hypersomnia (excessive sleeping), anhedonia (‘without pleasure’- Greek term), various bodily pains etc.

Depression can invoke anger, frustration, irritability, resentment and deluge of other affects/emotions. Acute form of depression can trigger worthlessness and loss of meaning consequently invoking suicidal thoughts. Some people who experience depression may also feel anxious but not all anxious people are depressed. Normal healthy people could face daily anxiety; be it job, relationship, health, business, finances, old age, children’s future and so on but they may not have lost their drive or motive force and perhaps many even see these as existential challenges and pull through. Such people have anxiety but not depression.

Depression on the contrary has an element of indolence built into it. It takes away the sense of agency, responsibility, motive force and action centricity due to the low debilitating state the mind has confined itself in. Well to the purists, it is not the mind that confines itself in depression rather we do depression due to the specific way in which we interpret both external sensory stimuli as well as organismic stimuli. When I speak about alleviating depression by reorienting stimuli, it considers psychologically induced depression and not genetic, hereditary or any form of congenital brain or chemical disorders which may need stabilization and maintenance with anti-depressant prescription drugs.

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In prosecutions for homicide, motive is very important similarly for depression there exist causal aspects. Early onset of trauma be it bereavement of a loved one, lack of secure attachment between infant and parents, physical and psychological abuse, accident, loss of job, relationship, physical neglect in childhood, hormonal changes, post partum, social reclusion any of these could trigger a diminished state and if left psychologically unattended could result in a kind of preservation of this state over time. There are many cases where a chronically depressed person doesn’t even know he/she is depressed as they construe their state as a natural disposition. We know that protracted depression can attenuate the quality of life leading to fatality and in certain cases, nudge one on to suicide.

To avoid any of these negative affect arousal states and for a quick reprieve from it, antidepressants are prescribed expeditiously by the medical fraternity. Is this justified and how ethical is it? Prior to understanding this, let us first drift a bit into the biochemistry  of the brain.

NEUROTRANSMITTERS AND THEIR ROLE

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We have heard the cliché ‘cells that fire together, wire together’. Neurotransmitters makes the cells fire together and is involved in transmission of nerve impulses i.e. it is the messenger that takes signals in the brain from one nerve cell to another. Neurotransmitters carry the messages such as, when the heart should beat, increase or decrease its beat. It instructs the lung when to increase and decrease breathing, notifies the stomach when to digest food as well as triggers the autonomous nervous system to activate during conditions of threat. Neurotransmitters are of two kinds: inhibitory and excitatory. Serotonin is an inhibitory neurotransmitter hence it does not stimulate the brain rather is a stabilizer of mood when there is excessive excitatory firing in the brain. As people age, there is decrease in serotonin but sustained exercise can increase its production. Serotonin is referred to as the ‘happy chemical’ in the brain. Dopamine, serotonin, oxytocin and endorphins are the happiness producing chemicals in the body. Serotonin falls under the monoamine category, as do the other neurotransmitters, noradrenaline and dopamine but then how is serotonin different from dopamine?

Dopamine is both an excitatory as well as an inhibitory neurotransmitter. It also sends signals between nerves and is responsible for the goal directed behaviour and drive. It is called the motivation molecule. Dopamine plays a key role in motor control, attention, levels of awareness, general pleasure and arousal, cognitive control and other lower-level functions. Parkinson’s disease and ADHD are conditions due to loss or dysfunctionality of dopamine secreting neurons in addition to other causes. Medical drugs can increase dopamine as does risk-taking and thrill-seeking behaviours, mindfulness,  food supplements, diet, vitamin reinforcements, goal accomplishments, exercise etc. Almonds, apples, avocado, bananas, green tea, oat meal, water melon, green leafy vegetables, wheat germ and intake of antioxidants all of these can increase dopamine levels. Strangely sleep deprivation and insomnia also increases dopamine levels in the striatum. One may feel very groggy and fatigued but there is an upsurge in dopamine levels.shutterstock_33100939Cigarettes increase dopamine levels in the brain. The nicotine in cigarettes works like a dopamine imposter meaning it increases the levels of dopamine and because of this artificial surge, the body reduces its normal production of dopamine and serotonin. When an addict attempts to quit, the dopamine levels from artificial sources (cigarettes) have been abruptly truncated but the natural dopamine production levels do not immediately restore hence these people get very cranky and depressed.

THE GUT FEEL

Intriguing as it may appear, though serotonin is associated with the brain, 90 % of the serotonin is produced in the gastrointestinal (GI) tract. There is a remarkable gut-brain connection. Akin to neurons in the brain, there are neurons in the gut that produces the neurotransmitter serotonin. The body has two nervous systems: the central nervous system (brain and spinal cord) and the enteric nervous system (the intrinsic nervous systems of the gastrointestinal tract). The information flow between the brain and the gut is a collaborative process. Anxiety and distress affects the guts and the gut also sends significant information to the brain. Serotonin is the mood balancer of the body and has a weighty linkage to depression and aggression. It performs multiple functions such as its presence in the gastrointestinal tract regulates bowel motion and serotonin also helps in formation of blood clots. It influences digestion, body-temperature regulation, sleep habits, appetite, self-esteem, pain tolerance and other functions. Caffeine (coffee is rich in it) can deplete serotonin over time. Mood altering drugs such as Ecstasy and LSD cause a huge surge in serotonin levels but prolonged use could be catastrophic. Natural sunlight is another augmenter of serotonin in the brain.

WHAT ANTIDEPRESSANTS DO?

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After having understood the role of serotonin’s contribution to our sense of well-being and mood stabilization, let us look at how antidepressants work. As serotonin is fired up in the synapse (space between two neurons), some serotonin is reabsorbed by the nerve cell (it is called reuptake) and in this way the nerve cell recycles the serotonin. When this reuptake or reabsorption happens, the first nerve cell doesn’t release sufficient serotonin to fire up the next nerve cell hence the message from one nerve cell to the next wont pass through thereby preventing transmission. SSRI (Selective Serotonin Reuptake Inhibitor) works by blocking this reabsorption or inhibiting the reuptake of serotonin thereby ensuring its availability for onward messaging in the brain. It is an anti-depressant and it increases the amount of serotonin in the synapse. Examples of SSRI antidepressants are Citalopram (Cipramil), Escitalopram (Cipralex), Fluoxetine (Prozac), Fluvoxamine (Faverin), Paroxetine (Seroxat), and Sertraline (Lustral). There are multiple categories of antidepressants such as TCA’s, MAOI’s etc. but I have stated SSRI’s here as they are more popular, better tolerated and relatively have lesser side-effects. So do SNRI’s ( Selective norepinephrine reuptake inhibitor).

CONCLUSION

Severe psychotic and many neurotic cases may perhaps need antidepressants to calm them down. If one has the luxury of natural sunlight exposure, systematic exercise regime, diet control, meditation, yoga, change in life style and if they can afford non-pharmacologic treatments such as psychotherapy, CBT etc. these are more beneficial and healthier than taking antidepressants and creating dependency. Sustained exercise, even in old people increases production of serotonin and improves well-being hence exercise itself can be construed as an anti-depressant. Contrary to popular belief, low levels of serotonin doesn’t cause depression rather people with depression seem to have low serotonin levels in their brains. Pharmaceutical firms may like us to believe so but it is one of the myths. When there are so many innocuous ways to improve serotonin levels in the brain why are doctors prescribing antidepressants, in fact it is being over prescribed. Compelling advertising and marketing seems to be one stance to support the surge. Zoloft is an advertised antidepressant and patients go to their physicians and request for it. Doctors are more prone to prescribing these upon insistence from their patients. Global antidepressant market was $ 11 Billion in 2008. There are huge stakes for pharmaceutical industries here.

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Talking therapies such as psychotherapy and counselling, in many countries, are unaffordable to the poor hence there is reliance upon charities who provide such services however there are limitations in resources hence some kind of rationing or long gestation periods exist before a patient sees a therapist. Antidepressants can quickly plug this gap and restore the happy feeling hence the reliance upon it. Modern antidepressants have additional mollifying characteristics such as the same drug can cure OCD, insomnia, fibromyalgia etc. hence patients love it. Celebrities do not have time as they remain inundated in multiple projects. Besides the pressure of work they have to preserve their fame and appearance hence they love to extract every bit of vitality from their body when the going is good. Michael Jackson was a case in point. 50 high intensity shows at London’s O2 arena at the age of 50! This is it, antidepressants and prescription drugs could give a boost, alas!

Here are 10 countries in the order of highest to lowest in antidepressant consumption: Iceland, Denmark, Portugal, Sweden, Finland, Belgium, UK, Spain, Norway, France, Germany and Luxembourg. In China antidepressant market has grown by 20 % in the last 3 yrs. World Health Organization forecasts that depression will displace heart disease by 2020. Depression is indeed a clinical condition but before one can be categorized so and drugs administered, there has to be a patient appraisal process where the non-pharmacological aspects can be seriously emphasized to him/her. Perhaps a combination of drugs and talking therapies may do the trick. This dual modality does exist but the equation is still skewed towards prescription drugs. If patients heighten their awareness to these aspects, the therapeutic path to combat depression may significantly alter from the ongoing anti-depressant enslavement.

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