Introduction

Antidepressants have varying potentials to cause discontinuation syndromes. Symptoms begin within a few days of stopping or reducing the dosage of the drug and are usually mild and short-lived. However, in some patients, antidepressant discontinuation symptoms can produce significant morbidity, be incorrectly attributed to other causes, and lead to subsequent lack of compliance with antidepressant therapy. The best approach to the problem is prevention, which involves educating patients and healthcare professionals about discontinuation symptoms and ensuring that antidepressants are tapered before they are stopped. When symptoms do occur, reassurance is usually sufficient; in some patients, however, there may be a need for symptomatic treatment, temporary reinstatement of the antidepressant (followed by careful tapering), or a switch to fluoxetine (which has a low potential for discontinuation symptoms). More research into this common and clinically relevant syndrome is required so that evidence-based recommendations can be developed.

All Types of Antidepressants Are Implicated

So far, at least 21 different antidepressants have been reported to cause discontinuation symptoms (table 1). All major classes of antidepressants have been implicated.^[1]

Many Different Syndromes Exist

Discontinuation syndromes vary considerably with respect to symptom type, grouping and severity. General features associated with discontinuation syndromes involving different classes of antidepressants are as follows:

• in patients stopping selective serotonin reuptake inhibitors (SSRIs), the most common discontinuation syndrome involves 6 main symptom groups (table 2). Both physical and psychological symptoms may be experienced; the most commonly reported symptoms are dizziness, nausea, lethargy and headache^[2]
• as with SSRIs, tricyclic antidepressant (TCA)-associated discontinuation syndromes also include both physical and psychological symptoms but are much less likely to be associated with sensory abnormalities and problems with equilibrium (table 2). Hypomania, akathisia, parkinsonism, cardiac arrhythmias, panic attacks and delirium have been reported on rare occasions in patients discontinuing TCAs^[1]
• stoppage of venlafaxine can result in an SSRI-like discontinuation syndrome^[1]
• monoamine oxidase inhibitor (MAOI) discontinuation syndromes, particularly those involving tranylcypromine, can result in psychotic confusion, worsening of depressive symptoms, hypomania and generalised seizures.^[1]

Key Clinical Features Suggest the Diagnosis

Common clinical features of antidepressant discontinuation syndromes include the following:

• antecedent antidepressant discontinuation or (less commonly) dosage reduction
• appropriate onset, i.e. usually within a few days of discontinuing or reducing the dose of an antidepressant
• adequate duration of treatment. Antidepressant discontinuation symptoms are rare in patients who have been treated for less than 5 weeks
• short duration (between 1 day and 3 weeks) if left untreated
• rapid reversibility (within 24 hours) on recommencement of the withdrawn drug.^[1]

It is important to note, however, that while most antidepressant discontinuation reactions are mild and transient, others may persist for up to 3 months and/or be associated with substantial morbidity.^[1]

Discontinuation Symptoms Common...

Discontinuation symptom rates in patients taking older antidepressants can be high, as evidenced by reports of 100% with imipramine, 80% with amitriptyline, 33% with clomipramine and 32% with phenelzine.^[1] Abrupt discontinuation of treatment with newer agents such as sertraline,^[3] paroxetine,^[3,4] and venlafaxine^[5] also results in spontaneously reported discontinuation symptoms in at least 1 out of 3 patients. Even higher rates have been documented when patients are specifically asked about symptoms, with one study finding evidence of discontinuation syndromes in 2 out of 3 patients treated with paroxetine and sertraline.^[6]

...Except in Patients Taking Fluoxetine

Good History Makes Diagnosis Easier...

Unexpected physical or psychological symptoms in a patient who has recently stopped taking an antidepressant point to an antidepressant discontinuation syndrome. The diagnosis also becomes clearer when direct questioning reveals noncompliance with therapy in patients currently on an antidepressant prescription.^[1]

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Reviewed: 12/2001