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Website: September 2002
Prescriber Update 2002;23(3):37-38
Professor Pete Ellis, Psychiatrist, Department of Psychological Medicine, Wellington School of Medicine.
There have been rare reports of fluoxetine and, more recently, paroxetine and
sertraline being associated with aggressive or suicidal thoughts and behaviour.
Due to similar pharmacological profiles, the same reactions may occur with other
selective serotonin re-uptake inhibitors (SSRIs). It is possible that
these reactions can be attributed to akathisia (involuntary severe motor
restlessness). However, the most common reason for self-harm behaviour
during treatment with any antidepressant is worsening depression. The
development of severe agitation or self-harm behaviour is an indication that the
patient and their antidepressant therapy require prompt review. Patients
should be advised to seek medical attention as soon as possible if they develop
agitation or restlessness, or if their depression worsens.
Reports of aggressive and suicidal behaviour with SSRIs
investigated
Behaviour change may be due to SSRI-induced akathisia
Agitation or harmful behaviour signals need to review both
patient and treatment immediately
Informing patients to seek help may help reduce adverse
outcomes
References
Soon after the introduction of fluoxetine internationally, it was claimed to cause suicidal thinking and behaviour.1 This allegation was investigated by a number of regulatory agencies, including the Food and Drug Administration in the United States in 1991, and was not substantiated. More recently, there have been several further case reports, some given media prominence, and some leading to legal proceedings, not only in relation to fluoxetine2,3 but also to paroxetine and sertraline.4-6 Systematic reviews continue to support the view that selective serotonin re-uptake inhibitors (SSRIs) are effective and are not associated with increased suicidality or increased violence.7 However, these reports1-6 raise questions about whether the small group of patients experiencing the rare side effect of akathisia are at increased risk of suicide.
Detailed case reports1,4 describe the emergence of marked restlessness and agitation, followed by suicidal thinking or behaviour, in patients soon after commencing fluoxetine or other serotonergic agents. This restlessness and agitation may reflect akathisia (involuntary severe motor restlessness). Although more commonly associated with antipsychotics, reflecting dopamine receptor blockade, interactions between the serotonergic and dopaminergic systems may account for akathisia also occurring with SSRIs.8-10 A putative link between akathisia and suicidal behaviour is less clear, and not all of the more recent case reports describe preceding restlessness.1,4 Older groups of antidepressants have also been associated with increased suicidal thinking and behaviour, although not related to increased restlessness.11
The key issues in treating depression are the selection of an appropriate treatment in conjunction with the depressed person, and the use of an adequate dose for an adequate length of time, along with attention to current stressors. The most common reason for suicidal ideation or behaviour during treatment with any antidepressant remains worsening depression. The development of agitation or self-harm behaviour (from any cause) indicates the need to increase support to ensure the patient's safety, as well as a review of treatment to check that it is optimised for that person.
As with many medicines, rare serious side effects may emerge during treatment and patients should be aware of these and what action to take. It is recommended that all patients taking SSRIs should be advised that if they become particularly agitated or restless, they should seek medical advice and stop their antidepressant in the interim. In addition, any serious worsening of their symptoms, particularly in relation to suicidal thoughts, should be reported urgently to their treating doctor (or on-call colleague). Severe agitation, severe restlessness/akathisia, and/or increased suicidality with SSRIs have been added as adverse reactions of current concern.
Competing interests (author): the author is supervising a PhD student whose research has been funded by Eli Lilly. He has accepted invitations from pharmaceutical companies to speak at several meetings relating to prescribing in general, as well as other topics. He has a beneficial interest in shares of certain pharmaceutical companies, including some who manufacture antidepressants, including SSRIs.
Correspondence to Professor Pete Ellis, Department of Psychological Medicine, Wellington School of Medicine, PO Box 7343, Wellington South. E-mail: ellis@wnmeds.ac.nz