The study offers a novel and neuropsychologically informed theoretical framework, as well as a cogent step forward to test transdiagnostic concepts in addiction research, with direct implications for assessment, diagnosis, staging of disorder, and treatment.

Journal Pre-proof J o u r n a l P r e -p r o o f 30.

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It is anticipated that creation of an OCRD grouping will contribute to accurate identification and appropriate treatment of affected patients as well as research efforts aimed at improving our understanding of the prevalence, assessment, and management of its constituent disorders.

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•Rua Tiradentes, 171 bloco 2 apartamento 903• Niterói, RJ 24210-510. Brazil.• e-mail: mmendlowicz@yahoo.com Carla Marques-Portella Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. CONFLICT OF INTEREST AbstractThe selective serotonin reuptake inhibitors (SSRIs) are considered the first-line pharmacological treatment for PTSD. However, even when treated with this class of drugs, response rates rarely exceed 60% and less than 20-30% of the patients achieve full remission. The aim of this study was to address this limitation by systematically reviewing the options left for the treatment of PTSD when patients do not respond satisfactorily to or tolerate SSRIs. A systematic review covering all original articles, letters and brief reports published in any language until October 2008 was conducted through searches in the ISI/Web of Science, PubMed and PILOTS databases. The search terms included the pharmacological class of each agent or its generic name plus "PTSD" or "stress disorder" in the title, in the abstract or as a keyword. Sixty-three articles were selected, covering the following categories: antipsychotics, anticonvulsants, adrenergic-inhibiting agents, opioid antagonists, benzodiazepines and other agents. None of the identified agents reached the level A of scientific evidence, 5 reached level B, 7 level C and 13 level D. The non-antidepressant agent with the strongest scientific evidence supporting its use in PTSD is risperidone, which can be envisaged as an effective add-on therapy when patients did not fully benefit from previous treatment with SSRIs. Prazosin, an adrenergicinhibiting agent, is a promising alternative for cases of PTSD where nightmares and insomnia are prominent symptoms. So far, there is no consistent empirical support for using benzodiazepines in the prevention or in the treatment of PTSD, although these drugs could alleviate some associated non-specific symptoms, such as insomnia or anxiety. Further controlled clinical trials and metaanalysis are needed to guide clinicians in their search of effective pharmacological alternatives to antidepressants in PTSD.