Tollefson 1992.

Study characteristics
Methods	DESIGN Description: randomized, double‐blind, parallel‐group flexible‐dose design with a 1‐week placebo run‐in BLINDING Participants: unclear Assessors: yes Administrators: unclear ALLOCATION CONCEALMENT Method: unclear RANDOMIZATION Method: unclear
Participants	SAMPLE Description: 51 DSM‐III GAD with concurrent alcohol dependence/abuse referred from chemical dependence treatment programmes, 27.5% female, mean age: 38.4 years, baseline HAM‐A score: approximately 25 (from figure 2 in article) SCREENING Primary diagnosis: SCID, HAM‐A score > 18, HAM‐D score < 18, abstinence from alcohol consumption for at least 30 and not more than 90 days Comorbidity: SCID
Interventions	Buspirone 15 mg/day (week 1), ≥ 30 mg/day (week 2) to maximum 60 mg/day (3‐4 week, after which held constant) versus placebo x 24 weeks
Outcomes	Primary outcomes: HAM‐A treatment response (≥ 30% reduction on HAM‐A total score and score < 18 = responders; ≥ 30% reduction on HAM‐A total score only = partial responders; otherwise classified as non‐responders), CGI Secondary outcomes: ASI, HAM‐D Data estimation: LOCF from 4 weeks for efficacy analyses
Notes	INDUSTRY SUPPORT Industry funded: yes Medication provided by industry: unclear Any of the authors work for industry: no ADDITIONAL INFORMATION Drop‐out rates: 16/26 (61.5%) participants in buspirone and 21/25 (84%) in placebo groups
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "subjects were randomised to either buspirone or placebo"
Allocation concealment (selection bias)	Unclear risk	No information on allocation is provided in report
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Study described as "double‐blinded", but no information provided on who was blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "anxiolytic efficacy was determined by blinded HAM‐A score reduction"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Although the proportion of participants who dropped at by 4 weeks was similar between groups (4/26 for buspirone and 5/25 for placebo), there were more drop‐outs by study endpoint in the placebo (21/25 participants) than buspirone group (16/26 participants), with significantly more people in the placebo group dropping out due to lack of efficacy or worsening of symptoms accounting for this difference. Unfortunately, while the authors confirm in the study report that there was no difference in demographics or ratings on the Cloninger personality scale between all 51 randomized participants and the participants who completed at least 4 weeks of treatment, they did not report a similar analysis for study endpoint
Selective reporting (reporting bias)	High risk	Only reported examples of items on questionnaires such as the ASI that were significantly different between groups, without indicating how many comparisons were conducted altogether
Other bias	Unclear risk	Prior benzodiazepine exposure was greater in the buspirone than the placebo group, which may predict a less robust response to buspirone. The trial was industry funded Quote: "the authors wish to acknowledge..[ ]..a concept grant from Mead‐Johnson Pharmaceuticals

ADS: Alcoholism Dependency Scale ; ANCOVA: analysis of covariance; ANOVA: analysis of variance; ASI: Addiction Severity Index; BDI: Beck Depression Inventory; CAPS: Clinician Administered PTSD Scale; CBT: cognitive behaviour therapy; CGI: Clinical Global Impressions scale; DSM: Diagnostic and Statistical Manual; GAD: generalized anxiety disorder; HAM‐A: Hamilton Anxiety scale; HAM‐D: Hamilton Depression scale; IES: Impact of Event Scale; LSAS: Liebowitz Social Anxiety Scale (Clinician administered); LSAS‐SR: Liebowitz Social Anxiety (Self Report); MATCH: Matching Alcoholism Treatment to Client Heterogeneity; MDD: major depressive disorder; MINI: Mini International Neuropsychiatric Interview; MISS: Civilian Mississippi Scales for PTSD; OCDS: Obsessive Compulsive Drinking Scale; PTSD: post‐traumatic stress disorder; SAC: The Substance Abuse Calendar; SAD: social anxiety disorder; SCID: Structured Clinical Interview for DSM‐IV; SPIN: Social Phobia Inventory; TLFB: Timeline Followback scale.