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Incidence of early anxiety aggravation in trials of selective serotonin reuptake inhibitors in depression

Journal article
Authors Jakob Näslund
Fredrik Hieronymus
Johan Fredrik Emilsson
Alexander Lisinski
Staffan Nilsson
Elias Eriksson
Published in Acta Psychiatrica Scandinavica
Volume 136
Issue 4
Pages 343-351
ISSN 0001-690X
Publication year 2017
Published at Department of Mathematical Sciences
Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 343-351
Language en
Keywords adverse events, antidepressants, anxiety, depression, mega-analysis, selective serotonin reuptake inhibitors
Subject categories Psychiatry, Pharmacology


© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Objective: Selective serotonin reuptake inhibitors (SSRIs) may aggravate anxiety and agitation during the first days of treatment but the frequency of such reactions remains unknown. Method: We analysed patient-level data from placebo-controlled trials of sertraline, paroxetine or citalopram in depressed adults. Somatic anxiety, psychic anxiety and psychomotor agitation as assessed using the Hamilton Depression Rating Scale (HDRS) were analysed in all trials (n = 8262); anxiety-related adverse events were analysed in trials investigating paroxetine and citalopram (n = 5712). Results: After one but not two weeks, patients on an SSRI were more likely than those on placebo to report enhanced somatic anxiety (adjusted risk 9.3% vs. 6.7%); likewise, mean rating of somatic anxiety was higher in the SSRI group. In contrast, patients receiving an SSRI were less likely to report aggravation of psychic anxiety (adjusted risk: 7.0% vs. 8.5%) with mean rating of psychic anxiety and agitation being lower in the SSRI group. The adverse event ‘nervousness’ was more common in patients given an SSRI (5.5% vs. 2.5%). Neither aggravation of HDRS-rated anxiety nor anxiety-related adverse events predicted poor antidepressant response. Conclusion: Whereas an anxiety-reducing effect of SSRIs is notable already during the first week of treatment, these drugs may also elicit an early increase in anxiety in susceptible subjects that however does not predict a poor subsequent response to treatment.

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