Serotonin syndrome following introduction of venlafaxine following withdrawal of phenelzine: implications for drug washout periods

Abstract

We report here a case of serotonin syndrome (SS) following initiation of venlafaxine 2 weeks after withdrawal of a monoamine oxidase inhibitor (MAOI), phenelzine, and also following repeated retrials of venlafaxine initiation. The case has clinically important implications regarding the period of time necessary for monoamine oxidase biosynthesis following use of an irreversible MAOI. SS is characterized by the presence of autonomic nervous system symptoms (such as hyperthermia, diaphoresis, mydriasis, nausea, shivering, hypertension, tachycardia, and diarrhoea), mental status changes (such as agitation, hypomania, and confusion), and neuromuscular abnormalities (such as myoclonus, incoordination, hyperreflexia, tremors, clonus, and muscle rigidity [Sternbach, 2003]). SS can be a life-threatening condition and occurs acutely due to markedly increased serotonin levels in brain, often following a coprescription or overdose of serotonergic drugs. These drugs can increase serotonin levels by inhibiting metabolism (such as MAOI), increasing formation (such as l-tryptophan), inhibiting reuptake (such as selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs)), increase release (such as amphetamines) or increasing postsynaptic receptor sensitivity (such as lithium). Overdose with a SSRI alone results in mild SS in about 15% of people but does not usually lead to severe toxicity [Isbister et al. 2007]. The occurrence of the syndrome is highest with a combination of SSRIs and MAOIs, though it is also reported with other serotonergic drug combinations. Sternbach described criteria to diagnose SS (Table 1) and highlighted the importance of identifying it since it is usually reversible following discontinuation of the offending drug(s), supportive treatment and addition of a serotonin antagonist (such as cyproheptadine or chlorpromazine) in more severe cases [Sternbach, 1991]. Table 1. Sternbach’s criteria [Modified after Sternbach 1991]. There have been previous case reports of patients who experienced an SS when a serotonin reuptake inhibitor (SRI) has been introduced after the traditionally recommended 2-week washout from an irreversible MAOI [Sternbach, 2003]. However, we have been unable to identify any instance in the literature where a patient has been rechallenged with a SRI (such as an SSRI, SNRI or a TCA) after a further period of washout following the occurrence of SS.