Long-Term Pharmacological Treatments of Anxiety Disorders: An Updated Systematic Review

  • Giampaolo Perna
  • Alessandra Alciati
  • Alice Riva
  • Wilma Micieli
  • Daniela Caldirola
Anxiety Disorders (A Pelissolo, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Anxiety Disorders


Many aspects of long-term pharmacological treatments for anxiety disorders (AnxDs) are still debated. We undertook an updated systematic review of long-term pharmacological studies on panic disorder (PD), generalized anxiety disorder (GAD), and social anxiety disorder (SAD). Relevant studies dating from January 1, 2012 to August 31, 2015 were identified using the PubMed database and a review of bibliographies. Of 372 records identified in the search, five studies on PD and 15 on GAD were included in the review. No studies on SAD were found. Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy. Paroxetine, escitalopram, and clonazepam can be effective for long-term treatment of PD. However, further studies are needed to draw conclusions about the long-term benzodiazepine use in PD, particularly for the possible cognitive side-effects over time. Pregabalin and quetiapine can be effective for long-term treatment of GAD, while preliminary suggestions emerged for agomelatine and vortioxetine. We did not find any evidence for determining the optimal length and/or dosage of medications to minimize the relapse risk. Few investigations have attempted to identify potential predictors of long-term treatment response. Personalized treatments for AnxDs can be implemented using predictive tools to explore those factors affecting treatment response/tolerability heterogeneity, including neurobiological functions/clinical profiles, comorbidity, biomarkers, and genetic features, and to tailor medications according to each patient’s unique features.


Anxiety Long term Pharmacological treatment Panic disorder Generalized anxiety disorder Social anxiety disorder 



The authors thank Massimiliano Grassi, MSc, and Raffaele Balletta, MD, Department of Clinical Neurosciences, Villa San Benedetto Menni, Hermanas Hospitalarias, FoRiPsi, Albese con Cassano, Como, Italy, for their contribution to literature search. Mr. Grassi and Mr. Balletta have no conflicts of interest to declare.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Giampaolo Perna
    • 1
    • 2
    • 3
  • Alessandra Alciati
    • 1
  • Alice Riva
    • 1
  • Wilma Micieli
    • 1
  • Daniela Caldirola
    • 1
  1. 1.Department of Clinical NeurosciencesHermanas Hospitalarias, Villa San Benedetto Menni Hospital, FoRiPsiComoItaly
  2. 2.Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life SciencesUniversity of MaastrichtMaastrichtNetherlands
  3. 3.Department of Psychiatry and Behavioral SciencesLeonard Miller School of Medicine, University of MiamiMiamiUSA

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