Pascual 2008.

Study characteristics
Methods	12‐week trial with 2 arms: ziprasidone placebo Duration of trial: 12 weeks, following a 2‐week baseline period Country: Spain Setting: outpatient
Participants	Method of recruitment of participants: "[...] referred from clinical service (outpatient and psychiatrics emergency services)" (Pascual 2008, p. e2) Overall sample size: 60 Diagnosis of borderline personality disorder: DSM‐IV Means of assessment: SCID‐II and DIB‐R Mean age: 29.2 years (SD = no information; range = no information) Sex: 81.67% women Comorbidity: no information Inclusion criteria Meeting the DSM‐IV diagnostic criteria for borderline personality disorder, assessed by 2 semi‐structured diagnostic interviews: SCID‐II and DIB‐R Aged between 18 and 45 years No comorbidity with schizophrenia, drug‐induced psychosis, organic brain syndrome, alcohol or other substance dependence, bipolar disorder, mental retardation and major depressive episode in course CGI‐S scores ≥ 4 Current use of medically accepted contraception in the case of female patients Exclusion criteria Schizophrenia Alcohol or other substance dependence Current major depressive episode Bipolar disorder Drug‐induced psychosis Organic brain syndrome Mental retardation
Interventions	Experimental group Treatment name: ziprasidone Number randomised to group: 30 Duration: 12 weeks Control/comparison group Comparison name: placebo Number randomised to group: 30 Duration: 12 weeks Both groups Concomitant psychotherapy: Patients participated in weekly, 2‐hour, non‐specific group psychotherapy sessions. Concomitant pharmacotherapy: allowed to continue with benzodiazepine (maximum of 40 mg/day), antidepressants, and mood stabilisers if initiated prior to inclusion; doses could not be modified. Proportions of participants taking standing medication during trial observation period: In the ziprasidone condition, 76.7% of patients were taking benzodiazepines, 70% were taking antidepressants and 40% were taking mood stabilisers. In the placebo condition, the proportions were 83.3% benzodiazepines, 73.3% antidepressants and 40% mood stabilisers.
Outcomes	Primary outcomes BPD severity, measured by CGI‐BPD‐global. Assessed at baseline and at weeks 2, 4, 6, 8, 0, 12 (EOT) and 14 Suicidal ideation, measured by CGI‐BPD‐suicide. Assessed at baseline and at weeks 2, 4, 6, 8, 0, 12 (EOT) and 14 Psychosocial functioning, measured by SCL‐90‐R‐GSI. Assessed at baseline and at weeks 2, 4, 6, 8, 0, 12 (EOT) and 14 Secondary outcomes Anger, measured by CGI‐BPD‐anger. Assessed at baseline and at weeks 2, 4, 6, 8, 0, 12 (EOT) and 14 Affective instability, measured by CGI‐BPD‐affect instability. Assessed at baseline and at weeks 2, 4, 6, 8, 0, 12 (EOT) and 14 Feelings of emptiness, measured by CGI‐BPD‐emptiness. Assessed at baseline and at weeks 2, 4, 6, 8, 0, 12 (EOT) and 14 Impulsivity, measured by CGI‐BPD‐impulsivity and BIS. Assessed at baseline and at weeks 2, 4, 6, 8, 0, 12 (EOT) and 14 Interpersonal problems, measured by CGI‐BPD‐unstable relations. Assessed at baseline and at weeks 2, 4, 6, 8, 0, 12 (EOT) and 14 Avoidance of abandonment, measured by CGI‐BPD‐abandonment. Assessed at baseline and at weeks 2, 4, 6, 8, 0, 12 (EOT) and 14 Identity disturbance, measured by CGI‐BPD‐identity. Assessed at baseline and at weeks 2, 4, 6, 8, 0, 12 (EOT) and 14 Psychotic paranoid symptoms, measured by CGI‐BPD‐paranoid ideation and BPRS. Assessed at baseline and at weeks 2, 4, 6, 8, 0, 12 (EOT) and 14 Depression, measured by Ham‐D‐17 and BDI. Assessed at baseline and at week 2, 4, 6, 8, 0, 12 (EOT) and 14 Attrition Adverse effects, measured by treatment‐emergent adverse events, EKG, laboratory assessment, UKU Side Effect Rating Scale for extrapyramidal side effects. Assessed at baseline and at weeks 2, 4, 6, 8, 0, 12 (EOT) and 14
Notes	Sample calculation: no information Ethics approval: yes Funding source: funded or partially funded by pharmaceutical industry Conflicts of interest: No conflicts of interest were reported besides partial funding from the pharmaceutical industry. Comments from trial authors (limitations) "[...] due the characteristics of the sample size, the results cannot be extrapolated to inpatients, patients with less clinically severe disorders or patients with active comorbid Axis I disorders." (Pascual 2008, p. e5) "[...] the majority of patients included in our sample were receiving concomitant treatment with benzodiazepines and/or antidepressants. Despite the fact that stable doses were maintained we cannot rule out possible drug‐drug interactions". (Pascual 2008, p. e5) "In spite of randomisation, the placebo group showed greater severity." (Pascual 2008, p. e5) "Another limitation [...] is the high dropout rate [...].By including a psychosocial intervention we pretended to improve compliance and lower dropout rates, but [were] unsuccessful." (Pascual 2008, p. e5) "[...] the psychosocial interventions may have masked the differences between ziprasidone and placebo." (Pascual 2008,p. e5)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization was performed by blocks of 4 generated using the SPSS software package". (Pascual 2008, p. 604)
Allocation concealment (selection bias)	Unclear risk	Comment: no information provided on allocation concealment to permit a judgement of low or high risk of bias
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Comment: The trial was referred to as being double‐blind, however, no information was provided on how blinding was carried out or maintained.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: The trial was referred to as being double‐blind, however, no information was provided on how blinding was carried out or maintained.
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "All analyses were conducted on an intent‐to‐treat basis. [...] Patients were included in the analyses only if they had a baseline measure and at least 1 post‐baseline measure. [...] The end point was based on a last‐observation‐carried‐forward (LOCF) strategy." (Pascual 2008, p. 604 et seq.) Comment: intent‐to‐treat data referred to all participants that were randomly assigned and who initiated the experimental phase (Pascual 2008, p. 605). However, it remained unclear why 5 out of the 65 eligible participants "dropped out during the selection phase". (Pascual 2008, p. 605) Reasons for dropout specified and balanced across the two groups, including withdrawal due to "clinician decision/insufficient treatment effect" (Pascual 2008, p. 605 et seq.) Of the 60 patients enrolled, 29 completed the full 12 weeks of the trial (13 in ziprasidone group, 16 in placebo group). Reasons for early termination: Need of psychiatric hospitalisation: 4 in ziprasidone group/3 in placebo group Adverse events/patient decision: 9/4 Clinician decision/insufficient treatment effect: 3/7 Other reasons: 1/0 Continuous data based on LOCF data of the ITT sample; dichotomous data based on ITT sample
Selective reporting (reporting bias)	Low risk	Comment: The trial protocol was available and all of the prespecified primary and secondary outcomes that were of interest in the review were reported in the prespecified way.
Vested Interest (funding and/or author affiliations)	High risk	Quote: "This study was supported by grants from the Fondo de Investigación Sanitaria (Ministry of Health, Spain), the REM‐TAP Network, and Pfizer, Madrid, Spain. The authors report no additional financial or other relationships relevant to the subject of this article." (Pascual 2008, p. 603)
Other bias	Low risk	Comment: no indication of other bias