The overall review process is summarised in Figure
Figure 1 Methods and overall process. (a) Conditions mentioned by the GPs ref. (b) Conditions collected via Pubmed searches. (c) Guidelines before 1997, paediatrics, nursing practices, patient information or education, medical records, continuous medical education (more ...)
Defining the limits of the searches
To retrieve the level of evidence for the prescription of ADs in non-psychiatric PC settings, an initial search was performed using the MeSH terms for the 24 medical conditions collected in our previous qualitative study and the terms “antidepressants” and “therapeutic use” in PubMed [21
]. During this process, 30 additional conditions possibly leading to AD prescription were found resulting in a list of 54 conditions or medical circumstances for which ADs could possibly be prescribed. Ten conditions - psychiatric disorders, non-primary care and non-adult conditions - were then excluded: five purely psychiatric disorders, narcolepsy and myotonia because of their low prevalence in primary care, nocturnal enuresis as a paediatric condition and amphetamine withdrawal and cocain dependence being conditions to be managed in multidisciplinary and specialised environment. This process resulted in a list of 44 non-psychiatric disorders manageable in PC and potentially leading to AD prescription in PC (Table
). This list was used for the data collection search strategy.
Conditions included and excluded in the searches
Data collection: search strategy
The terms matching with the 44 conditions and medical circumstances for possible AD prescription were listed in French and English. The MeSH validated translation and synonyms were searched for in the terminology section of the catalogue and index of the French-language Health Resources Website (CISMeF). When there was no MeSH term available for the medical condition or circumstance, the researchers used a broader MeSH term, on a higher level of hierarchy, including the description (e.g., cancer AND antidepressants for “cancer related fatigue, musculoskeletal diseases AND antidepressants for musculoskeletal symptoms). Using this list, searches were performed to find the available guidelines (GL) in the databases of the following government agencies: the French “Haute Autorité de Santé” (HAS), the English National Institute for Clinical Excellence (NICE) and the National Guideline Clearinghouse (NGC), the last one including most international guidelines. The searches were performed from March 2011 to August 2011. The search covered all of the documents made available by the three agencies.
Data collection: additional searches for updated data
During the same period, we performed simultaneously, a search in the Cochrane database of systematic reviews (CDSR) and in Medline on the same basis, using the same criteria and process. For the Medline search, the following limits were used: “clinical trial, meta-analysis, clinical guidelines, randomized controlled trial, and adults, published after 2004”. The aim was to find scientific data published after the launch of the guidelines. Those studies might change the evidence and possibly lead to a change in prescription attitudes. All detailed searches are available in the full version of all guidelines. Individual studies (RCTs in Pubmed) included in this review did not constitute the bulk of the results.
All guidelines before 1997 were excluded, as were those regarding paediatrics, nursing practices, patient information or education, medical records, continuing medical education for care providers, medical imaging, biology and surgical techniques. Full text of guidelines have been downloaded from the agencies databases. All non-psychiatric conditions were included and all standalone psychiatric conditions were excluded. Remaining documents on anxiety, depression and side effects of ADs were also excluded after reading. The documents were independently read and assessed by two researchers (AM & IAA) and disagreements were resolved by discussion. Duplicates were removed. The documents in the databases were crosschecked using a search with the generic term “antidepressants” in order to retrieve any documents that may have been missed by previous searches. In the full text documents, the terms “antidepressant”, “Tricyclic agents”, “TCA”, “SNRI”, “serotonin”, “SSRI”, “tricyclic”, “imipramine”, “monoamine”, “duloxetine”, “venlafaxine” and their French translations were searched for. All guidelines containing the keywords were selected. In order to find the latest evidence, the most recent documents available on each topic in each guideline database were retained when available, and the most up-to-date version of the selected guidelines was kept. The overall process ended with a list of 78 documents.
The final stage of the study aimed to retrieve guidelines on recommended therapeutic use of ADs from these documents. Sections of specific interest were extracted and analysed. Information on pharmaceutical classes, drugs, recommended therapeutic use and level of evidence was collected when available. Agreements and discordances were noted, and inconsistencies between the various guidelines were highlighted. Recommendations from the guidelines were graded according to the EFNS scheme [22
] (Additional file 1