GlaxoSmithKline 2002.

Methods	Study design: Randomised controlled trial Study grouping: Parallel group Blinding: Double Duration: 12 weeks Multicentre
Participants	Baseline characteristics Paroxetine Male, N (%): 10 (33) Age, mean (SD): 51.8 (17.6) Placebo Male, N (%): 11 (46) Age, mean (SD): 46.3 (17.9) Inclusion criteria: Participants were males or females aged > 18 years suffering from 1 or more of the following anxiety disorders of non‐severe degree in axis I: panic attack disorder (with or without agoraphobia), GAD, social anxiety/social phobia or mixed anxiety and depression disorder with significant anxiety; people continuously treated with benzodiazepines (any) for at least 6 consecutive months prior to the screening visit at doses between 2 and 8 mg/day of lorazepam or equivalent; a total score ≤ 16 on the HAM‐A and MADRS at screening and baseline. Exclusion criteria: People suffering (or diagnosed within the 6 months prior to screening) from 1 or more of the following conditions: major depressive episode; post‐traumatic stress disorder; obsessive‐compulsive disorder; eating behavioural disorders, people diagnosed with dysthymia or who had suffered from dysthymia in the 6 months prior to screening; people with a concomitant psychotic disorder, or history of psychotic disorder; people having a concomitant bipolar disorder or history of bipolar disorder, or having a cyclothymic disorder, or had suffered from it in the past; people who met DSM‐IV (protocol appendix O) criteria for substance (alcohol or drugs) abuse or dependence, except for benzodiazepine, within 6 months prior to screening; current suicidal or homicidal risk; and people who had electroconvulsive therapy in the 3 months prior to screening. Pretreatment: No significant group differences
Interventions	Intervention characteristics Benzodiazepine taper schedule: 4‐week open‐label run‐in period during which participants were switched from their original benzodiazepine to an equivalent dosage of chlordemethyldiazepam (between 2 and 8 mg/d). The taper schedule during the treatment phase not described. Benzodiazepine taper + paroxetine 10 mg/d for the first week, 10 to 20 mg/d during weeks 2 to 8, 20 mg/d during weeks 9 to 12(N = 30) Benzodiazepine taper + placebo(N = 24)
Outcomes	Serious adverse events Anxiety: HAM‐A Non‐serious adverse events Relapse to benzodiazepine use Benzodiazepine withdrawal symptoms: BWSQ Benzodiazepine cessation
Identification	Sponsorship source: GlaxoSmithKline Country: Italy Setting: Outpatients Declarations of interest: Not mentioned Comments: Unpublished phase III study Author's name: GlaxoSmithKline Institution: Email: Address: Clinical Study Register (www.gskclinicalstudyregister.com) 2002
Notes	Change scores extracted, final scores not available. Standard deviation calculated from CI using the following formula: SE = (upper limit – lower limit of CI)/3.92 Standard deviation σ = standard error x √n
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "12‐week double blind, multicentre, randomised, placebo‐controlled, parallel group" Comment: Not described
Allocation concealment (selection bias)	Unclear risk	Comment: Not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Subjects were randomised to either paroxetine or placebo and entered the 12‐week double‐blind, randomised treatment phase. Dosage of paroxetine or matched placebo started with..." Comment: Double‐blind and using matched placebo
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: Not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: 2 versus 8 participants withdrew, but ITT analysis data extracted for this meta‐analysis.
Selective reporting (reporting bias)	High risk	Comment: No protocol available, benzodiazepine dose at follow‐up not described.
Other bias	High risk	Comment: Study funded by the study drug manufacturer, no information available on involvement in design, data collection, etc.