Serotonin Syndrome in combination of SSRI and MAOi

Happy Chemical ? 

Yes, Serotonin literally contributes to the well being and happiness in the living organisms. It is a chemical having variety of functions in the human body. Scientifically named for serotonin is 5-hydroxytryptamine or 5-HT. It is found mostly in the brain, blood platelets and even in the bowels. 

Generally, Serotonin acts as a neurotransmitter which passes the signals of messages from nerve cells. A joy, happiness and well being along with constricting of the smooth muscles are actively regulated by this chemical compound. A day to day sleep- wake cycle is regulated which is the internal clock of the living organisms. Apart from this all, it acts as a coordinating substance in the nervous system. Key role is balancing mood. 

Fig: Serotonin 5-HT pathway  (credit)

Component of protein "tryptophan" combines with tryptophan hydroxylase which is a chemical reactor generates Serotonin. Many people consider as a hormone as some consider a neurotransmitter. It does not cross the blood-brain barrier and those serotonin present inside the brain is mode itself inside the brain. Due to altering serotonin level, it might evoke some medical conditions and alters the psychological functions. 

• If any toxic food you are eating irritates, serotonin is produced from the gut in increasing the transit time or expelling the irritants in the diarrhea ; stimulating the Nausea area of the brain 
• High levels of insulin has direct impact on bone to stimulate osteoporosis.
• A wound is formed, platelets release serotonin in making the blood to clot faster to avoid blood loss. Narrows the blood vessels or vasoconstriction.
• Maintaining the bowel function by serotonin present in the Gastrointestinal tracts. 
• Especially in the brain, serotonin regulates the mood, anxiety and happiness

Serotonin and Depression 

From the past years, depression has been linked with the low levels of serotonin. Till now it is unclear if low serotonin level is causing depression or depression is lowering the serotonin levels. Drug probably altering serotonin levels are mostly used in treating the depression, mood disorders , Parkinsonism and the obesity cases. 

Depression is linked with the imbalance of the neurotransmitter and hormone in the body. The Serotonin Selective Re-uptake Inhibitor are used mostly as anti-depressants. SSRI inhibits the re-absorption of the serotonin which leads to the high levels of serotonin in the synaptic cleft.

Fig: Serotonin biochemistry in the Synaptic Cleft  (credit)

Serotonin from the pre-synaptic neuron is exocytosed in the synaptic cleft which is the free space between the pre-synaptic neuron and post synaptic neuron. From the synaptic cleft, it is transferred to the post-synaptic neuron thorough serotonin receptors. Almost all of the serotonin is not transmitted to the Post synaptic neuron. Some is left over in the synaptic cleft and is broken down by the MAO (Mono - amino Oxidase) .Some serotonin is re-absorbed by the pre-synaptic neuron and serotonin is released again in the synaptic cleft.

So, the Serotonin Selective Re-uptake Inhibitor (SSRI) what they do is that the inactivate the mechanism process of the reuptake of the serotonin in the pre-synaptic neuron. By doing so, the serotonin is excess in the synaptic cleft where the post-synaptic neurons can get enough serotonin to cure depression like condition which has low levels of serotonin and can be managed properly. Even some sorts of anxiety, aggression, low mood, poor memory are sorted out by this group of SSRI drugs. 

Citalopram (Celexa), Escitalopram (Lexapro), Sertaline (Zoloft), Fluoxetine (Prozac) are some of the SSRI drugs approved by Food and Drug Administration (FDA)

Lets, see another group of drug. This is a MAOi (Mono-Amino Oxidase Inhibitor) . 

From the above discussion, when MAO inhibitor group of drug is used, there is inactivation of the MAO to brakdown the serotonin present in the synaptic cleft. Due to this, there is enough serotonin left on the synaptic cleft. MAO is a enzyme that breaks down the serotonin to its product and MAOi inactivates the function.

Seleginine (Zelapar), Isocarboxazid (Marplan), Tranylcypromine (Parnate), are some MAOi drugs.

Serotonin syndrome

Coming to the topic, Depression as a medical condition, when two group of drugs as discussed above, SSRI and MAOi drugs are used simultaneously, serotonin becomes excess in the synaptic cleft. Serotonin toxicity or Serotonin syndrome comes as a medical emergency in such cases. Excess stimulation of the Central Nervous system and peripheral nervous system receptors occurs. 

For the people affecting with migraine and dosing with the triptans takes the SSRI drug, he/she can get this serotonin toxicity. Not only this, people using the recreational drugs as ecstasy are high in risk in geting serotonin syndrome if they are medicated with SSRI. If prescribed drugs of SSRI group is taken simultaneously at certain time of life, 7-8 hours after they develop the serotonin syndrome. 

Carcinoid tumors which are the cancerous tumors found in the GI tracts cause much more serotonin to be released. When people suffer from serotonin toxicity or have serotonin syndrome, they have some sort of agination or restlessness, confusions, sweating, shivering, loss of muscle contraction, headaches.  Autonomic hyperactivity occurs. Increased blood pressure, heart rate or tachycardia, increased temperature of the body or hyperthermia are the common symptoms. 

In the cases of Serotonin toxicity or Serotonin syndrome, there are upto 2 to 12 percent of cases which are severe and has become life threatening. 

Conclusively, treatment to the serotonin syndrome can prolong the life and prevent morbidity and mortality. Monitoring and screening of the tumors related to the abdomen and psychological condition like depression and mood disorder medications should be monitored. At particular time, no two doses of SSRI and MAOi drugs is taken, as it can cause the Serotonin syndrome. These serotonergic drugs works in different pathways and combination can erupt Serotonin Syndrome. 

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Reference: 

NCBI ; PMC [US National Library of Medicine, National Institute of Health] - Serotonin Syndrome

MAYO CLINIC - Serotonin Syndrome

Encyclopedia Birtannica - Serotonin Biochemistry 

Serotonin toxicity

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