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

Schmahl 2012b.

Study characteristics
Methods 6‐week trial with 4 arms:

  1. naltrexone (50 mg)

  2. naltrexone (200 mg)

  3. placebo 1

  4. placebo 2


Duration of trial: 8 weeks. In both Schmahl 2012a and Schmahl 2012b, the first week (‘week 0’) was without pharmaceutical intervention and served to assess a baseline level. Therapeutic interventions were carried out during the following 6 weeks (‘weeks 1–6’), split into two phases: (a) 3 weeks of treatment with naltrexone and (b) 3 weeks of treatment with placebo (cross‐over design). The sequence of the two treatment phases was randomised and concealed from both the patients and the trial personnel. In both trials, the last week (‘week 7’) was without pharmacological intervention.
Country: Germany
Setting: inpatient and outpatient
Participants Methods of recruitment of patients: Patients were recruited from January 2006 to September 2007 at the Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Mannheim; the Department of Psychiatry and Psychotherapy, University of Rostock; and the Center for Psychosomatic Medicine, Bad Wiessee.
Overall sample size: 16
Diagnosis of borderline personality disorder: DSM‐IV
Means of assessment: IPDE
Mean age: 29.2 years (SD 8.9; range = 18–42)
Sex: 100% women
Comorbidity: pre‐existing substance misuse
Inclusion criteria

  1. Score of at least 18 on the Dissociation Experiences Scale (DES)

  2. Female gender

  3. Aged between 18 and 50 years


Exclusion criteria

  1. Lifetime diagnosis of schizophrenia assessed using the SCID‐I

  2. Psychotic or delusional disorder, current major depressive episode, lifetime diagnosis of opioid dependence, current diagnosis of opioid abuse, liver insufficiency or hepatitis, other major medical or neurological medical condition (as assessed by complete medical and neurological examination)

  3. Pregnancy or lactating

  4. Psychotropic medication two weeks before and during the trial (fluoxetine = 4 weeks; lithium = 8 weeks)

  5. Concomitant treatment with opioid analgesics

  6. Hypersensitivity to naltrexone

  7. Any liver‐related disorder
Interventions Experimental groups
Treatment name: naltrexone (50 + 200 mg naltrexone and blood plasma levels)
Number randomised to group: 16 (cross‐over)
Duration: 3 weeks
Control/comparison groups
Comparison name: placebo
Number randomised to group: 16 (cross‐over)
Duration: 3 weeks
Both groups
Concomitant psychotherapy: non‐specific therapeutic intervention
Concomitant pharmacotherapy: Some pharmacotherapies were not allowed: no psychotropic medication permitted two weeks before and during the trial (fluoxetine = 4 weeks; lithium = 8 weeks). Concomitant treatment with opioid analgesics was an exclusion criterion.
Proportions of participants taking standing medication during trial observation period: no information
Outcomes Primary outcomes

  1. BPD severity, measured the Borderline Symptom scale (BSL‐95) Assessed at weeks 1, 2 and 3 (EOT)

  2. Self‐injury, measured by non‐suicidal self‐injurious acts, as well as the number and duration of flashbacks; all were retrospectively assessed at the end of each week at weeks 1, 2 and 3 (EOT).


Secondary outcomes

  1. Dissociation and psychotic‐like symptoms, measured by Dissociative States Scale (DSS) Assessed at weeks 1, 2 and 3 (EOT)

  2. Depression, measured by BDI and Ham‐D. Assessed at weeks 1, 2 and 3 (EOT)

  3. Adverse effects, measured by UKU (udvalg for kliniske undersogelser) side effect scale. Adverse events were recorded by staff during trials such as physical side effects to medication.
Notes See Schmahl 2012a
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Comment: A computer‐generated randomisation list was used to carry out block randomisation (Schmahl 2012b, p. 62).
Allocation concealment (selection bias) Low risk Quote: "The sequence of the two treatment phases was randomized and concealed from both the patients and the study personnel". (Schmahl 2012b, p. 62).
Blinding of participants and personnel (performance bias)
All outcomes Unclear risk Comment: The study was described as being double‐blind, however, there was no information on how the blinding was secured or if it was adequately maintained throughout the study to permit a judgement of low or high risk of bias.
Blinding of outcome assessment (detection bias)
All outcomes Unclear risk Comment: The study was described as being double‐blind, however, there was no information on how the blinding was secured or if it was adequately maintained throughout the study to permit a judgement of low or high risk of bias.
Incomplete outcome data (attrition bias)
All outcomes Unclear risk Quote: "We carried out both intent‐to‐treat (ITT) analyses (using the LOCF method) and analyses according to protocol (ATP). The results were very similar when using either strategy, and we decided to report the results from ATP analyses only if the results from ITT analyses were markedly different. As we found little support for assuming that the dropouts might be related to treatment, effect size estimates from ATP analyses might be less biased than ITT effect size estimates and were used accordingly. The pattern of dropouts was balanced across treatment condition; in both studies one patient dropped out in both treatment conditions". (Schmahl 2012b, p. 63)
Selective reporting (reporting bias) Unclear risk Comment: secondary outcome in protocol did not state mild‐moderate‐intense adverse events as did the full report. Lack of definition of serious adverse events and non‐serious adverse events
Vested Interest (funding and/or author affiliations) Low risk Quote: "There were no conflicts of interest" (Schmahl 2012b, p. 67).
Other bias Low risk Comment: no apparent other source of bias