Different neurotransmitter pathways in different regions of the brain are involved depending on the etiology.

Myoclonus is occasionally physiologic. But it is usually seen in the presence of systemic metabolic disorders or medication toxicity. It can be seen with neurodegenerative dementing illnesses. It can occur as part of seizures. It is an important manifestation of serotonin syndrome .

Most antidepressants and mood stabilizers can cause myoclonus with toxic overdoses. But it can occur as part of serotonin syndrome at therapeutic doses of medications. Serotonin syndrome is essentially a state of serotonin toxicity and major causes are combination of two or more serotonergic drugs and toxic ingestion of one or more serotonergic drugs. However, it can occur even with one serotonergic agent at a therapeutic dose. Adding medications that inhibit metabolism of the serotonergic agent increases the risk of serotonin syndrome due to higher serotonin levels. Almost all categories of antidepressants (selective serotonin reuptake inhibitors (SSRIs) , serotonin norepinephrine reuptake inhibitors (SNRIs) , tricyclic antidepressants (TCAs) , monoamine oxidase inhibitors (MAOs)) carry risk of serotonin syndrome [1].

Serotonin syndrome can be difficult to distinguish from anticholinergic delirium and neuroleptic malignant syndrome (NMS) . No symptom is pathognomonic but spontaneous clonus is highly predictive of this syndrome [2].

See table for an overview of serotonin syndrome .