(Hypo)mania is a known consequence of antidepressants in type I, type II and type III bipolar disorder. This conceptualization often induces the generalized belief that only the introduction of the antidepressant induces the mood switch.

Report the occurence of an understudied therapeutic event with unknown mechanism and associations. Promote clinical attention and further investigation.

Case report of a patient who developed a hypomanic switch upon venlafaxine discontinuation; bibliographic search using PubMed/MedLine database with the following keywords: bipolar; mania; hypomania; venlafaxine; antidepressant; discontinuation.

We report and discuss the case of a 48-year-old woman with previous history of a recurrent depression. The patient was successfully treated with Venlafaxine (300mg/day), Pregabalin (300mg/day) and Clonazepam (0.5mg/day) completing the acute and continuation phases of the treatment. She was then discharged with the indication to maintain treatment for her maintenance phase. After a couple of months the patient initiated slow Venlafaxine discontinuation after which she developed a clinical picture characterized by talkativeness, persistently elevated mood, increased goal-directed activity and unreasonable expenses lasting for an unspecified number of weeks and subsequent severe depressive episode without psychotic symptoms. The patient was again referred to our consultation and medicated with Venlafaxine (300mg/day) and Valproic acid (1000mg/day) remaining depressed and treatment resistant to this day.

Studies show that antidepressant-withdrawal (hypo)mania is a known but rarely reported leading to its unawareness an consequent unknown true incidence. Two hypothetical models may explain this clinical entity: Withdrawal-induced cholinergic overdrive; and Noradrenergic hyperactivity.