It may be difficult to distinguish between clinical features of depression, adverse effects of selective serotonin reuptake inhibitor antidepressants, discontinuation effects and the potentially life-threatening serotonin syndrome. The table below outlines some common features and others that may help identify the problem. A serotonin syndrome can be a medical emergency, while patients with other problems which do not rapidly resolve should be referred for a psychiatric opinion.

Distinguishing between clinical features of a medication discontinuation syndrome, adverse events, depression symptoms (or exacerbation) and a serotonin syndrome

Discontinuation Adverse events Depression Serotonin syndrome

Clinical features Dizziness, nausea, anxiety, headache (most commonly reported symptoms) Asthenia, diarrhoea, nausea, anxiety, dizziness, insomnia, nervousness, somnolence, tremor (most common symptoms) Depression and lack of interest predominate, but can have prominent anxiety and sleep disorder Abdominal cramps, diarrhoea, tremulousness, myoclonus, coma, tachycardia, hypo- or hypertension, confusion, disorientation, diaphoresis, hyperpyrexia, etc.
  • Rapid reduction or stopping of SSRIs
  • Check if patient has altered dose, `forgotten' tablets, or `run out'
  • Mostly in the first 1-2 weeks of treatment
  • Mostly settle if medication is continued
  • Check not a drug interaction, especially SSRI with TCA; stop concurrent TCA
  • Continuation or worsening of initial illness
  • About 10-20% of patients relapse with continued treatment; some improve with an increased dose, others need change of medication
  • Over dosage
  • Drug interaction (especially SSRI + MAOI, or SSRI + TCA)
  • Inadequate drug free interval in changing medications
  • Idiosyncratic reaction
Response to increased SSRI dose Usually relieved Usually worsens No acute change, except possible adverse event Worsens - could be dangerous
Response to decreased SSRI dose Usually worsens Usually relieved No acute change, or subsequent worsening with relapse, or discontinuation syndrome Usually relieved if SSRI ceased, and ceasing interacting medicines if possible
Symptoms persist despite intervention Seek a psychiatric second opinion Seek a psychiatric second opinion Seek a psychiatric second opinion Emergency, seek immediate second opinion, possibly hospitalise

Note: There may be overlap between these conditions and the differentiation may be clinically difficult.

SSRI - selective serotonin reuptake inhibitor
TCA - tricyclic antidepressant
MAOI - irreversible non-selective inhibitors of monoamine oxidases A and B