PsychoTropical Research - Dr Ken Gillman, Serotonin Syndrome, Mirtazapine, Dual Action Drugs. Serotonin Syndrome - Symptoms.

PsychoTropicalResearch, serotonin and serotonin syndrome research.

Serotonin Syndrome - Symptoms

Serotonin Syndrome - Symptoms

Date Created: 07/02/1999   Last Modified: 28/08/2003   Last Checked: 24/09/2003

There is a spectrum of severity of serotonergic drug effects going from serotonergic side effects in a continuum through to what is arbitrarily (and often imprecisely) called serotonin syndrome (SS). This is more clearly conceptualised as serotonin toxicity. The evidence for this 'spectrum' model for understanding serotonin toxicity is elaborated in papers by A/Prof Whyte and also in my reviews.

The whole field of serotonin toxicity (serotonin syndrome) is comprehensively analysed and updated from the latest data in: Serotonin toxicity (serotonin syndrome): A current analysis at www.psychotropical.com/SerotoninToxicity.doc

Frequent serotonergic effects (not always 'side effects') of selective serotonin reuptake inhibitors in therapeutic doses are, in approximate descending order of frequency of occurrence:-

Inhibition of orgasm (M and F), nausea, drowsiness, insomnia, loose stools, tremor, shivering, nervousness, sweating, fatigue, dizziness.

Other serotonergic symptoms that may occur with ‘monotherapy’ include:

nocturnal myoclonus, excess sweating, teeth chattering, bruxism, shivering, chills, agitation / over confidence / aggressiveness and impaired concentration and thinking.

Symptoms that are characteristic of severe serotonin toxicity are usually of rapid onset (ie 1-2 hours) and after the increase, or addition of, a second serotonergic drug, or an over-dose. This is most commonly an MAOI combined with an SRI.

The key symptoms of serotonin toxicity are:--

  1. Neuromuscular:
    tremor, clonus and myoclonus (including ocular oscillations), hyperreflexia, and (only in severe late stage cases) hypertonia
  2. Mental state:
    agitation (excitement, hyperactivity, restlessness, hypomania), and, only in severe late stage cases, delirium / confusion
  3. Autonomic:
    diaphoresis, flushing, tachycardia, tachypnoea, hypertension, mydriasis and hyperthermia (>38.5 c).

NB mydriasis is a side effect of SSRIs at normal doses, it is not specific to serotonin toxicity (eg is seen with muscarinic blockade from anti-muscarinic drugs) but once serotonin toxicity is established mydriasis may be a good guide to severity.

Serotonergic toxicity may be confidently diagnosed if, following ingestion of a known serotonergic drug, any of the following are present:

Hunter Serotonin Toxicity Criteria ***
1. Spontaneous clonus
2. Any type of clonus + agitation or diaphoresis
3. Tremor + hyperreflexia
4. Hypertonia + temperature > 38ºC + ocular clonus or inducible clonus

Associate Professor Ian Whyte and his toxicology group in Newcastle (Australia) www.hypertox.com have now (Aug 2003) published their analysis of over 2000 cases of serotonergic drug over-dose. This data is definitive because it is by far the largest and best quality dataset in the world literature; it eclipses all previous contributions in this field.

*** Dunkley, E., et al., Hunter Serotonin Toxicity Criteria: a simple and accurate diagnostic decision rule for serotonin toxicity. Quarterly Journal of Medicine, 2003. 96: p. 635-642.

Clinical characteristics predictive of severe serotonin toxicity are fever > 38.5 and hypertonia of upper extremities and truncal muscles, which may precipitate raised Pa CO2. Such severe serotonin toxicity is most likely to be associated with ingestion of a combination of MAOIs together with (S)SRIs.