Serotonin Syndrome – How can genetic screening help?
Rates of serotonin syndrome have risen in line with the increasing use of pro serotonergic pharmacological agents. In the coming years, Pharmacogenetics and Rxight™ are set to change this. Pregenetic testing will allow those at risk to be moved onto alternate treatments, or if this is not possible, for their cases to be monitored carefully.
Serotonin acts up 7 different receptors, 5HT 1 – 7, some of which have multiple forms (eg 5HT 2A, 5HT2B). It seems that no single receptor is responsible for development of serotonin syndrome symptoms, although 5HT 2A has been suggested to have a substantial role.
Serotonergic neurons are found in the CNS, predominantly in the midline raphe nuclei. This system controls a number of activities including food intake, affective behaviour, wakefulness, migraine, emesis, nociception and motor tone. Evidently the mis activation of these systems results in a complex clinical picture
A raised concentration of serotonin is the principle mechanism of action in a number of drugs, and is a side result in a number of others. Many drugs cause serotonin toxicity including:
- Tricyclic antidepressants
- Selective serotonin reuptake inhibitors (SSRIs)
- Over the counter cough remedies
- Anti emetics
- MDMA or “ecstasy”
Symptoms of Serotonin Syndrome
Serotonin syndrome symptoms can range from mild to severe, resulting in death in the most extreme cases. These symptoms (increasing in severity) include:
- Altered Mental status
- Clonus (inducible and then sustained)
- Muscular hypertonicity
At this point, the syndrome becomes life threatening.
One of the challenges with symptoms of serotonin syndrome is that at the mild end of the spectrum, it is easy to miss and so doses of already toxic drugs may be increased. Pharmacogenetics could provide a useful marker for the use of these drugs. Individuals at risk would be more closely monitored, and these early symptoms would be better identified.
Pharmacogenetics and Rxight™
The Rxight™ program provides pre genetic screening for a huge number of known drug interactions. With regards to serotonin syndrome, the P450 cytochrome enzyme 2D6 has been implicated in serotonin syndrome. Around 8% of whites are genetically deficient in P450 2D6 and therefore are more susceptible to drugs broken down by this enzyme. These drugs include venlafaxine, paroxetine, tricyclics, dextromethorphan and methadone. Testing for this enzyme, and others with a role in serotonin breakdown, will prove crucial in limiting pro serotonergic drugs to these patients and thus reducing the case burden of serotonin syndrome.