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. 2022 Nov 14;2022(11):CD012956. doi: 10.1002/14651858.CD012956.pub2

Schulz 2007.

Study characteristics
Methods 12‐week trial with 2 arms:

  1. olanzapine

  2. placebo


Duration: 12 weeks (after screening period of 2‐14 days)
Country: Belgium, France, Germany, Norway, Portugal, Spain, Sweden, UK and USA
Setting: outpatient
Participants Method of recruitment of participants: no information
Overall sample size: 314
Diagnosis of borderline personality disorder: DSM‐IV
Means of assessment: Diagnostic Interview for DSM‐IV Personality Disorders (DIPD‐IV) and Zan‐BPD total score of 9 or higher
Mean age: 31.81 years (SD = no information; range = no information)
Sex: 71.02% women
Comorbidity: no information; however, many psychiatric disorders were excluded.
Inclusion criteria

  1. Outpatients of any gender

  2. Aged 18–65 years

  3. Meet all of the DSM–IV general diagnostic criteria for a personality disorder and DSM–IV criteria for borderline personality disorder as determined by the DIPD–IV

  4. ZAN–BPD total score of 9 at the time of randomisation


Exclusion criteria

  1. Bipolar disorder, schizophrenia, major depressive disorder or substance dependence within last 3 months

  2. Current PTSD, panic disorder or obsessive‐compulsive disorder
Interventions Experimental group
Treatment name: olanzapine (2.5‐20 mg/d, mean final dose 7.09 mg/d, SD 5.11)
Number randomised to group: 150
Duration: 12 weeks
Control/comparison group
Comparison name: placebo
Number randomised to group: 155
Duration: 12 weeks
Both groups
Concomitant psychotherapy: no information
Concomitant pharmacotherapy: no medications with primarily CNS activity (except for protocol‐specified benzodiazepines and hypnotics)
Proportions of participants taking standing medication during trial observation period: no information
Outcomes Primary outcomes

  1. BPD severity, measured by number of patients in each group with response/no response, i.e. 50% reduction, at least, in Zan‐BPD total score. Assessed at week 1, 2, 4, 6, 8, 10, and 12 (EOT)

  2. Suicidal behaviour, measured by Zan‐BPD‐suicidal or self‐mutilating behaviour. Assessed at week 1, 2, 4, 6, 8, 10, and 12 (EOT)

  3. Suicidal ideation, measured by OAS‐M‐suicidal ideation. Assessed at week 1, 2, 4, 6, 8, 10, and 12 (EOT)

  4. Mental health status (functioning), measured by Sheehan Disability Scale‐total and GAF. Assessed at week 1, 2, 4, 6, 8, 10, and 12 (EOT)


Secondary outcomes

  1. Anger, measured by Zan‐BPD‐intense anger, OAS‐M‐irritability and SCL‐90‐R‐HOS. Assessed at weeks 1, 2, 4, 6, 8, 10, and 12 (EOT)

  2. Affective instability, measured by Zan‐BPD‐affective instability. Assessed at weeks 1, 2, 4, 6, 8, 10, and 12 (EOT)

  3. Feelings of emptiness, measured by Zan‐BPD‐chronic feelings of emptiness. Assessed at weeks 1, 2, 4, 6, 8, 10, and 12 (EOT)

  4. Impulsivity, measured by Zan‐BPD‐impulsivity and OAS‐M‐aggression. Assessed at weeks 1, 2, 4, 6, 8, 10, and 12 (EOT)

  5. Interpersonal problems, measured by Zan‐BPD‐unstable interpersonal relationships. Assessed at weeks 1, 2, 4, 6, 8, 10, and 12 (EOT)

  6. Avoidance of abandonment, measured by Zan‐BPD‐frantic efforts to avoid abandonment. Assessed at weeks 1, 2,4, 6, 8, 10, and 12 (EOT)

  7. Identity disturbance, measured by Zan‐BPD‐identity disturbance. Assessed at weeks 1, 2, 4, 6, 8, 10, and 12 (EOT)

  8. Dissociative symptoms, measured by Zan‐BPD‐paranoid ideation of disassociation. Assessed at weeks 1, 2, 4, 6, 8, 10, and 12 (EOT)

  9. Depression, measured by MADRS. Assessed at weeks 1, 2, 4, 6, 8, 10, and 12 (EOT)

  10. Attrition

  11. Adverse effects: measured by weight, laboratory values, vitals and ECG as well as the Simpson‐Angus Scale, BARS and IMS. Assessed at weeks 2, 4, 8 and 12 (EOT)
Notes Sample calculation: no information
Ethics approval: yes
Funding source: funded or partially funded by pharmaceutical industry
Conflicts of interest: Dr Schulz has consulted for Eli Lilly, AstraZeneca and Vanda. Authors HCD, QT, YT, DL and SC are employed by Lilly Research Laboratories.
Comments from trial authors (limitations): none mentioned
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Quote: "patients [...] were randomly assigned to treatment". (Eli Lilly 2008, p. 15),
Comment: Randomisation conducted centrally
Allocation concealment (selection bias) Unclear risk Quote: "All participants, study site personnel and investigators were masked to randomisation codes." (Schulz 2008, p. e1)
Comment: Insufficient information on how allocation sequence was concealed and maintained until randomised trial phase started to permit a judgement of low or high risk of bias
Blinding of participants and personnel (performance bias)
All outcomes Unclear risk Comment: Participants and personnel were described as being masked to randomisation codes, however, there was insufficient information about how blinding in the randomised phase was carried out and maintained (e.g. identical capsules of trial medication).
Blinding of outcome assessment (detection bias)
All outcomes Unclear risk Comment: Participants and personnel were described as being masked to randomisation codes, however, there was Insufficient information about how blinding in the randomised phase was carried out and maintained (e.g. blind to adverse events etc.).
Incomplete outcome data (attrition bias)
All outcomes Unclear risk Quote: "Analyses were done on an intent‐to‐treat basis [...] In general, LOCF mean change analyses". (Eli Lilly 2008, p. 5)
Quote: "Of the 314 randomized patients, 305 had both a baseline and a non‐missing post‐baseline observation and were thus qualified for the primary efficacy analysis." (Eli Lilly 2008, p. 16)
Comment: Unclear, what "non‐missing post‐baseline observation" exactly means. However, discontinuing participants were included in the 305 participants whose results were analysed using LOCF.
Continuous outcomes based on LOCF/ITT
314 patients were enrolled and randomly allocated. Outcomes referred partly to all of them, partly to 310 or 305 patients. No further details given
Selective reporting (reporting bias) High risk Comment: Several outcome measures (secondary and adverse events) were reported that were not prespecified according to the trial protocol.
Vested Interest (funding and/or author affiliations) High risk Quote: "This study was sponsored by Eli Lilly. S.C.S. has received honorarium from Eli Lilly, AstraZeneca and Bristol‐Meyers Squibb; grant fees from Eli Lilly, AstraZeneca, Abbott, MIND Institute and the NIMH; and consultation fees from Eli Lilly, AstraZeneca and Vanda. H.C.D., Q.T., Y.T., D.L. and S.C. are employed by Lilly Research Laboratories." (Schulz 2008 p. e1)
Other bias Low risk Comment: No indication of other bias