Marco 2002.

Methods	Allocation: randomised. Blindness: unclear. Duration: 4 weeks. Funded by NARSAD, the National Alliance for the Mentally Ill, the Stanley Foundation. Active ketoconazole and placebo capsules were provided at no cost by Janssen Pharmaceuticals.
Participants	Diagnosis: schizophrenia or schizoaffective disorder, SCID, DSM III‐R. N = 19. Age: average 48 year (SD 8.5), range 33 to 62 years. Sex: 12 M, 3 F. Setting: outpatient. History: unclear. Excluded: no change in medication in the past 6 weeks, medically unhealthy, no use of other steroid‐containing medications. Country: USA.
Interventions	1. Ketoconazole: started at 200 mg/day and advanced to maximum dose 800 mg/day. N = 8. 2. Placebo: N = 7. Other concurrent treatments: All participants were taking stable doses of antipsychotic medication (including risperidone, perphenazine, haloperidol decanoate and thioridazine) and, when applicable, antidepressant and/or mood stabiliser medication (including clonazepam, lithium, trazodone, benztropine mesylate, diphenhydramine, propranolol, carbamazepine, sucralfate, sertraline, lorazepam and trihexyphenidyl). One participant with schizophrenia was taking no concurrent treatment. As a criterion of clinical stability, all participants were well known to the outpatient psychiatry clinic and had not required any change in medication dosage for a minimum of 6 weeks. No changes in pre‐stabilised, open‐label antipsychotic, antidepressant and/or mood‐stabilising medication regimens were allowed during the study period. Other concurrent treatments (placebo group): All participants were taking stable doses of antipsychotic medication (including risperidone, haloperidol, perphenazine and trifluoperazine) plus, when applicable, antidepressant and/or mood stabiliser medication (including paroxetine, lorazepam, benztropine mesylate, diphenhydramine, fluoxetine, buspirone and methylphenidate). Two participants with schizophrenia were taking no concurrent treatment.
Outcomes	Mental state: total psychotic symptoms (PANSS), positive psychotic symptoms (PANSS), negative psychotic symptoms (PANSS), depression (HAMD). Global state: leaving the study early. Adverse events: general adverse events. Unable to use: cognition. California Verbal Learning Test, Trails A & B, FAS Verbal Fluency Test. Alternate versions of the CVLT and Verbal Fluency Test were used for baseline and week 4 assessments. Data were not provided. Study authors reported no significant differences between groups on cognitive measures.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (from correspondence): "by computer sequence."
Allocation concealment (selection bias)	Low risk	Quote (from correspondence): "Envelopes with key based on numeric code. Pharmacist had filled blinded Rx based on numeric code."
Blinding (performance bias and detection bias) All outcomes	Low risk	Participant/providers: Yes. Quote: "Subjects were randomised to receive in a double‐blind manner..." (pg 157). Outcome assessors: Yes. Quote: "Subjects and blinded raters were not able to accurately guess treatment assignment based on side effects." (pg 159).
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "double‐blind" ‐ probably undertaken.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Subjects and blinded raters were not able to accurately guess treatment assignment based on side effects" (pg 159).
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcome data.
Selective reporting (reporting bias)	High risk	Data reported only for HAMD and cortisol measures. For PANSS, BDI, Bunney‐Hamburg Global Rating Scale and neurocognitive function tests, it was stated that no significant differences were noted (data not reported).
Other bias	High risk	Baseline gender imbalance. Participants in the ketoconazole group seem to be taking a greater number of concomitant medications, suggesting that they may have more severe or complex illness. Those in the ketoconazole group had higher baseline cortisol levels.