Serotonin syndrome is life-threatening condition that results from use of some therapeutic and recreational drugs, interaction between certain drugs or over dosage of specific drugs. Serotonin syndrome occurs due to excessive serotonergic activity at nervous system. It is also called as serotonin storm, serotonin sickness or hyperserotonemia.
Characteristic triad of serotonin syndrome consists of somatic effects, autonomic effects and cognitive effect
- Somatic effects include agitation, headache, confusion, hallucinations, unconsciousness or coma and hypo manic behavior.
- Autonomic effects include excessive sweating, shivering, increased body temperature or hyperthermia, increased heart rate and blood pressure, nausea and diarrhea.
- Somatic effects include exaggerated deep tendon reflexes or hyper reflexia with clonus, muscle twitching or myoclonus and tremors
Causes of serotonin syndrome
As the name indicates serotonin syndrome is caused by drugs which has serotonin activity. Either one drug or combination of drugs results in this grave condition. The notorious drugs responsible to cause serotonin syndrome are
- Antidepressant: all classes of antidepressants can precipitate serotonin syndrome like tricylic antidepressants, monoamine oxidase inhibitors, SSRIs and SNRIs. Nefazodone trazodone and bupripion
- Opoids: pethidine, tramadol, bupreorphine, fentanyl and others
- 5-HT1 agonists: sumatriptane and other tryptanes.
- Psychedelics: MDA, MDMA, LSD and 5-Methoxy-diisopropyltryptamine
- CNS stimulants: cocaine, sibutramine, methylphenidate, diethlpropion, phenteramine and methamphetamine.
- Miscellaneous drugs: levodopa, sodium valproate, buspirone,tryptophan, hydroxytryptophane, linezolid, dextramethorphan, metoclopromide, resperidone, ondansteron, ritonavir, olanzapine granisteron and lithium
- Herbs: nutmeg, yohimbe, St John’s Wort,
Signs and symptoms of serotonin syndrome
Symptoms of serotonin syndrome come rapidly even within minutes after an inciting drug. Symptoms may be mild, moderate or severe.
Mild symptoms
- Tachycardia
- Excessive sweating
- Shivering
- Intermittent twitching of muscles called myoclonus and tremors
- Dilated pupils
- Exaggerated tendon reflexes
Moderate symptoms
consist of mild symptoms plus
- Hypertension or high blood pressure
- Hyperthermia or increased body temperatures even reaching 40 °C or 104 °F
- Deep tendon reflexes are more exaggerated as compared in mild symptoms particular these reflexes are more brisk in lower limb as compared to upper limbs.
- Mental state changes including agitation and hyper vigilance
Severe symptoms
manifest additional symptoms of
- Severe tachycardia or increased heart rate
- Severe hypertension
- Shock or circulatory failure
- Temperature rises to more than 41.1 °C or 106 °F
- Rhabdomylisis i.e. muscle breakdown
- Renal failure
- Metabolic acidosis
- Coagulation abnormality i.e. disseminated intravascular coagulation
- Fits
- Patient sinks into deep unconsciousness or coma
Diagnosis
Diagnosis of serotonin syndrome is clinical as no laboratory test is available to diagnose this condition. Patient’s history is very essential in diagnosing serotonin syndrome. It must be enquired what drug if he has taken and should also be asked about certain food like cheese and red wine Diagnostic criteria used for this condition depend on signs and symptoms present in the patient along with drug history which patient might have taken.
Criteria used for diagnosing serotonin syndrome are
- Hunter Serotonin Toxicity Criteria which has high sensitivity and specificity in diagnosis serotonin syndrome
- Sternbach’s criteria again having high sensitivity and specificity.
Hunter Serotonin Toxicity Criteria, diagnose a patient with serotonin syndrome if he has taken some serotonergic agent (drug or food) along with following symptoms
- Spontaneous or inducible clonus or ocular clonus with
- agitation or excessive sweating, or
- Tremor and hyperreflexia, or
- Hypertonia and temperature > 38 °C (100 °F) and inducible clonus or ocular clonus
Management of serotonin syndrome
Management of serotonin syndrome depends on the severity of the symptoms whether mild, moderate or sever. Key principles of management include
- Stopping the drug or any other substance which has precipitated this condition. In case patient has ingested the drugs in large quantity and reach hospital in one hour, gastric lavage may help in clearing the drug from body additionally activated charcoal may decontaminate the drug or substance in gastrointestinal system.
- Administration of drugs that antagonize the effects of serotonin for example cyprohepatidine
- Supportive care for the patient to manage agitation, hyperthermia, control of hypertention and tachycardia. Agitation is controlled with bezodiazepines. For management of hyperthermia benzodiazepines are given to reduce muscle activity as temperature is due to over activity of muscles. In severe cases of hyperthermia patient is sedated and intubated to put on mechanical ventilation. Antipyretics are not recommended for the treatment of hyperthermia. Blood pressure and pulse rate is frequently monitored and controlled with medications.
In mild symptoms only stopping the offending substance and providing supportive care corrects the symptoms.
In case of moderate symptoms, hyperthermia, hypertension, heart rhythm or rate defects are corrected in addition serotonin antagonist cyprohepatidine is also administered.
In case of severe symptoms patient is managed in intensive care setting. Some atypical antipsychotic like olanzapine is administered in adition to cyprohepatidine. Patient may need sedation and neuromuscular paralysis in order to decrease muscle activity and patient is put on mechanical ventilation. For control of blood pressure short acting antihypertensive like nitropruside or esmolol are given, long acting antihypertensive are avoided. If patient is in shock epinephrine, norepinephrine infusions are given.
Prognosis
As serotonergic substances or drugs are discontinued, most of the patients recover within 24 hours except for the drugs that have long half life and take several days to eliminate from the body. Some patients keep on complaining muscle pain even for months. Mortality rate is not so high if early management is carried.