Antidepressant discontinuation symptoms occur with all classes of antidepressant. A well-described discontinuation syndrome occurs with the selective serotonin reuptake inhibitors, common symptoms including dizziness, headache, nausea and lethargy. Rare antidepressant discontinuation syndromes include extrapyramidal syndromes and mania/hypomania. All these syndromes, even isolated discontinuation symptoms, share three common features that facilitate diagnosis; abrupt onset within days of stopping the antidepressant, a short duration when untreated and rapid resolution when the antidepressant is reinstated.
Clinicians need to be familiar with strategies for the prevention and management of such symptoms. Preventive strategies include warning patients about the possibility of discontinuation symptoms, encouraging good antidepressant adherence and tapering antidepressants at the end of treatment. Most symptoms are mild and short-lived. Consequently symptoms that follow planned termination of an antidepressant can often be managed by providing an explanation and reassurance. More severe symptoms should be treated symptomatically or the antidepressant restarted, in which case symptoms usually resolve within 24 h. More cautious tapering can then follow.
Antidepressant discontinuation (withdrawal) symptoms were first reported in association with imipramine (Mann & MacPherson, 1959; Andersen & Kristiansen, 1959), the first tricyclic antidepressant (TCA), shortly after it entered clinical use. These symptoms occur with all classes of antidepressant, including the TCAs, monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs) and miscellaneous others such as mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA). A PubMed review conducted when preparing this article identified reports of discontinuation symptoms with 25 antidepressants. In recent years the phenomenon has attracted increasing interest, in both the scientific literature and in the lay media (BBC Panorama, 2002, 2003). This article provides an overview of the clinical features of antidepressant discontinuation symptoms, with the emphasis on their recognition, prevention and management. Discontinuation symptoms can occur whenever antidepressants are used, i.e. they are not dependent on the presence of any underlying psychiatric disorder. The pharmacokinetics and dynamics of antidepressants, in particular their half-life, are important determinants of discontinuation symptoms, as are individual patient characteristics, but their discussion is beyond the scope of this article (Schatzberg et al, 1997; Haddad, 1998; Bogetto et al, 2002).
Box 1 Antidepressants reported to cause discontinuation symptoms
Tricyclic and related compounds
* Amineptine
* Amitriptyline
* Amoxapine
* Clomipramine
* Desipramine
* Doxepin
* Imipramine
* Nortriptyline
* Protriptyline
* Trazodone
Monoamine oxidase inhibitors
* Isocarboxazid
* Moclobemide
* Phenelzine
* Tranylcypromine
Selective serotonin reuptake inhibitors
* Citalopram
* Escitalopram
* Fluoxetine
* Fluvoxamine
* Paroxetine
* Sertraline
Serotonin and noradrenaline reuptake inhibitors
* Duloxetine
* Milnacipran
* Venlafaxine
Miscellaneous antidepressants
* Mirtazapine (noradrenergic and specific serotonergic antidepressant, NaSSA)
* Nefazodone
Peter M. Haddad and Ian M. Anderson
Peter Haddad is a consultant psychiatrist with Bolton, Salford and Trafford Mental Health NHS Trust (Cromwell House, Cromwell Road, Eccles, Salford, Manchester M30 0GT, UK. Email: peter.haddad@bstmht.nhs.uk) and an honorary senior lecturer at the University of Manchester. His clinical and research interests include the pharmacological treatment of affective disorders and schizophrenia and the safety and adverse effects of psychotropic medication. He was a member of the Guideline Development Group for the National Institute for Health and Clinical Excellence’s guidelines on bipolar disorder (2006). Ian Anderson is Senior Lecturer in Psychiatry at the University of Manchester and an honorary consultant psychiatrist with Manchester Mental Health and Social Care Trust, where he is Director of the Specialist Service for Affective Disorders. His clinical and research interests include the neurobiology and pharmacological treatment of bipolar and unipolar affective disorders. He has been involved in the British Association for Psychopharmacology’s evidence-based guidelines for depression, anxiety disorders and bipolar disorder.
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