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On December 17, 2010, in MEDICAL FACTS, by Dr. Tuchinsky

It’s all about neurotransmitters!

The modern theory about neurotransmitter origin of depression is relatively new and is likely destined for significant revision in the next 10-20 years.

The idea that there is a chemical imbalance behind depressive mood began to emerge in the middle of the twentieth century. Immediately drug companies began a desperate search for the “happy pill”.

First generation of antidepressants.

The first generation of anti-depressants, mainly tricyclics and drugs such as trazodone and nefazodone, had limited success marketing success due to the fact that such high doses were required to achieve even marginal benefit that the side effects were intolerable to most people.

The second generation of antidepressants.

Then in the mid seventies- hallelujah- came the famous SSRIs (Selective Serotonin Reuptake Inhibitors). The chemical mystery of depression appeared to be solved, and it all came down to low levels of the brain neurotransmitter called serotonin, or at least that was the belief imposed on the population by the robust marketing campaign that enabled Prozac to become one of the most successful prescription drugs in history. Unfortunately, soon it became clear that while some people clearly did benefit from SSRIs, at least just as many who still remained depressed. (The interesting ploy in the SSRI story is that patients are told to give it six weeks before the medication will take its effect – and many may experience natural improvement in their depression by that time anyway. Also, it is unclear how many people simply benefit from the placebo effect that medication gives them, rather than due to the pharmacological effect.)

The latest players on the market.

The pharmaceutical scientists began to scratch their heads and wonder if perhaps they have overlooked something. Maybe serotonin was not the only substance that affected our mood. Soon, we were presented with new and more advanced preparations – Effexor (venlafaxine) which affected not only serotonin but norepinephrine as well, and Wellbutrin (burpopion) which also helped to raise dopamine levels. Other brand name antidepressantas began to flood the market-Lexapro, Cymbalta, Savella, Pristiq- just to name a few in the most recent years… And once again,there were some people who found miraculous cure in those drugs, while others noticed nothing but the side effects.

The Quackery.

There are some savvy medical offices out there that advertise themselves as “providing the most advanced treatment in the history of depression.” Supposedly, they test the patient blood for different levels of neurotransmitters and choose the one that is most appropriate for them based on the results of the tests. The patients need to foot a hefty bill that is not covered up by their insurance. The only problem with this seemingly logical approach is that there is no correlation between levels of neurotransmitters in the blood with those that are found in the brain. And it is only those molecules that are present in the brain that really matter. It may be actually possible to measure the level of brain neurotransmitters but it could only be achieved by testing cerebrospinal fluid, not blood, and I am not aware of this being done anywhere outside of research labs.


The science of depression is just beginning to emerge. I am optimistic that somwhere down the road the diagnosis will be much more straightforward, with either a genetic screen or an advanced brain imaging scan, the work of guessing where the problem lies will be virtually eliminated. And even if the serotonin theory eventually becomes disproved, it will never be discounted. The main achievement of Prozac’s ad campaign was that it lifted the veil of stigma and changed public opinion from viewing depression as a weakness or a personal choice to the one of the legitimate disease. And to each depressed person who took it, even if merely as a placebo, it gave something far beyond a high serotonin dose. It gave them Hope.  READ MORE ABOUT DEPRESSION

Image: Boaz Yiftach /


  1. […] 2. Endocannabinoids. Another system that definitely plays role in our mood is endocannabinoid system. A few years ago, Sanofi-Aventis released an anti-obesity drug called Rimonabant on the European market. The drug worked by blocking the cannabinoid receptors of the brain, -the effect exactly opposite to the one exerted by marijuana which stimulates them. The idea was based on the logical conclusion that since cannabis are known to stimulate appetite in most people, the drug with the opposite action on the same receptors will lead to reduced appetite and weight loss. The theory proved it be correct: Rimonabant worked but its time under the sun was cut short as it was withdrawn from the market just a few years later. The reason it was pulled off was due to the reports of the serious side effects, namely severe depression and suicide in people who took it. This confirms that endocannabinoid receptors play a crucial role in our mood.     READ MORE ABOUT DEPRESSION […]

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