Nerve cell talk – sertraline (Zoloft)

Dear friend,


I’m sure you had an awesome Thanksgiving. I’m sure there was plenty of food intake. Felt really sleepy after that dinner? The turkey ….. all that tryptophan …… really? That part about the tryptophan …. a little exaggeration ….. did you know that chicken has about the same amount of tryptophan as turkey?


So how about the popular idea that turkey has high amounts of the amino acid tryptophan and that’s what has the soporific effect? Actually, you feel sleepy because of all the carbohydrate you ingest. What’s the mechanism? When the carbohydrates are absorbed into the blood, insulin is released. One of the effects of insulin is absorption of amino acids circulating in the blood. The amino acids that are favored in this absorption by cells are not tryptophan – which means there is a higher percentage of tryptophan left in the blood.


Part of the tryptophan remaining in the blood is absorbed into the brain. In the brain stem, the tryptophan is converted into a neurotransmitter called serotonin. This is a natural calming, even sedating nerve chemical. In another part of the brain, in a pea-sized organ called the pineal gland, some of the serotonin is converted into a hormone called melatonin. Melatonin is the hormone that is released by the pineal gland in response to darkness and induces sleep – it plays a role in the body’s daily circadian rhythm or biological cycle. That’s the reason for the zzzzzs.


Speaking of the neurotransmitter serotonin (chemical name 5-hydroxy tryptamine), it is a neurotransmitter that plays a major role in our feelings and emotions. Serotonin modulates sleep, mood, appetite, sexuality, anger, anxiety and depression. Which means that its biological formation, metabolic and transportation pathways in the body offer ways to manipulate the levels of serotonin in the brain and body, and produce beneficial therapeutic effects.


Research has produced several families of drugs to increase serotonin levels and thereby provide a remedy for depression. One of the most effective classes of drugs is called SSRIs (selective serotonin re-uptake inhibitors). What do they do? They prevent the reuptake of already biosynthesized serotonin into the pre-synaptic cells of the nerves. Wait a minute. What’s pre-synaptic?


Backing up …… Let’s define “synapse”. Synapses are junctions between nerve cells, or between nerve cells and other body cells. There are hundreds of trillions of nerve cells in the human brain. One nerve cell “talks” to other cells across these junctions. How? The “initiating” nerve cell is called the pre-synaptic cell. In the pre-synapse, docked to the membrane, there are microscopic “bags” called synaptic vesicles that store neurotransmitters. So, how exactly is the message sent across. Associated with every thought, every emotion, there is an electrical current that moves across the pre-synaptic nerve cell. The current reaches the synapse, electrically stimulates the synaptic vesicles and opens up channels in the vesicles to let calcium ions come in. These calcium ions activate certain calcium-sensitive proteins to cause the vesicles release neurotransmitters contained within them. The neurotransmitters travel across the synaptic cleft, the narrow space between the pre-synaptic and post-synaptic cells, and bind to receptor cells on the post-synaptic cells. This results in the activation of the receptor cells, following which there is an appropriate action from the post-synaptic cell. What action is that? It could be a transmission of the same message onward to other nerve cells through the similar processes. Or, let’s say the post-synaptic cell is a muscle cell – the appropriate action could be muscle movement, in combination with a whole bunch of other muscle cells.


Now, all the neurotransmitter molecules released by the pre-synaptic cell does not bind to the post-synaptic cell. Some of the molecules just diffuse in the synaptic cleft. Some of these diffused molecules are metabolized by enzymes to metabolites. And some of the diffused molecules are re-absorbed by the pre-synaptic cell.


This last process, the re-absorption …… re-uptake …… is the process that is of interest to us. A selective serotonin re-uptake inhibitor (SSRI) selectively prevents the re-uptake of serotonin by the pre-synaptic cells.


Sertraline (trade name Zoloft in the U.S., Lustral in the U.K., Zosert in India) is the most prescribed anti-depressant in the U.S. It is an SSRI used for treatment of major depression, obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD) and social anxiety disorder (SAD). Unlabeled and investigational indications are eating disorders, generalized anxiety disorder (GAD), impulse control disorders, and treatment of mild dementia-associated agitation in non-psychotic patients.


Black-box warnings are required to given with anti-depressants. They can increase the risk of suicidal thinking in patients upto 24 years of age. Sertraline is not approved for use in major depressive disorder (MDD) in children, but is approved for treatment of OCD in children 6 years of age and above. It is not approved for treatment of bipolar depression.


This medicine should not be taken with other medicines called monoamine oxidase inhibitors (MAOI) – in fact, not even within 14 days of taking an MAOI. Why not? It leads to something called serotonin syndrome. What is that? MAOIs as well as several other drugs decrease the breakdown of serotonin, resulting in high concentrations of serotonin in the brain. Serotonin syndrome creates symptoms such as confusion, hallucinations, fever, high blood pressure, tremors and muscle twitching.


Possible side-effects include headache, nausea, dry mouth, upset stomach, decreased interest in sex or decreased sexual ability.


If sertraline administration is suddenly stopped, withdrawal symptoms include emotional instability, dizziness, headache and bad dreams. In pregnant women, the drug does cross the placenta and reach the child. Sertraline is also secreted in breast-milk.


A theory suggests that depression and other psychiatric complaints are a result of an imbalance of brain chemistry, popularly called chemical imbalance. Critics of this theory state that it is largely promoted by pharmaceutical companies so that they can sell more medication. Whatever be the case, there are situations where depression is effectively treated by using anti-depressants like sertraline, resulting in improvement in the quality of life. It is upto the medical professionals treating the patient to determine whether the depression can be treated by psychological counseling and change of lifestyle including setting and working toward goals in various aspects of life, or whether the condition requires drug therapy.


Until next week, my friend, take care of your health, take care of yourself.


Dr. Ajit Damodaran




2 Responses to “Nerve cell talk – sertraline (Zoloft)”

  1. Doc Says:

    I would only offer a couple of points:
    1. The increased irritability in young adults is often due to undiagnosed bipolar disorder; and SSRI’s (and most other antidepressants) can trigger a manic or mixed state episode.
    2. Zoloft has a bit of secondary activity on Dopamine, which may be somewhat pro-cognitive and pro-motivation.
    3. Most studies have shown that the most effective treatment of depression is a combination of therapy (Cognitive-Behavioral has been most studied) and medications.

    Thanks for the nice article, I’ll be linking to it.

  2. Paul Says:

    Thanks for your clear presentation of this complex material, nice job!

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