Pharmacological interventions for borderline personality disorder.

The Cochrane database of systematic reviews

Jun 2010

DOI: 10.1002/14651858.CD005653.pub2

Citations:255

Influential Citations:14

Systematic Reviews / Meta-Analyses

Enhanced Details

Methods

Adults with formal DSM-based Borderline Personality Disorder diagnoses; mean age ranged from 21.7 to 38.6 years, with 14 of 28 studies having mean age below 30; majority female; mostly outpatients, with some inpatients or mixed settings; 28 randomized, double-blind trials (some multicentre); data often limited to first period in cross-over trials; exclusions commonly included schizophrenia, bipolar disorder, major depressive disorder, substance-related disorders, acute suicidality; several trials allowed concurrent psychotherapy in some arms or excluded it in others.

Intervention

Regimens varied across trials and included: first-generation antipsychotics (haloperidol 4–16 mg/day oral; thiothixene 2–35 mg/day oral; depots such as flupentixol decanoate), second-generation antipsychotics (olanzapine around 2.5–12 mg/day in some arms; aripiprazole; ziprasidone), mood stabilisers (valproate semisodium titrated to achieve serum levels 50–100 mg/L; mean daily ~850 mg; lamotrigine; topiramate; carbamazepine 200–600 mg/day), antidepressants (amitriptyline 100–175 mg/day; fluoxetine; fluvoxamine; mianserin; phenelzine sulfate), and omega‑3 fatty acids. Durations ranged from about 3 weeks to 24 weeks; administration was typically oral daily, with depot injections used for some agents.

Results

Evidence from 28 randomized trials suggests potential benefits for second-generation antipsychotics (notably aripiprazole and olanzapine) and mood stabilisers (topiramate, valproate semisodium, lamotrigine) on specific BPD symptoms such as interpersonal problems, impulsivity, anger, anxiety, and depressive symptoms, with some effects also seen for omega-3 fatty acids on suicidality. However, no drug consistently reduced overall BPD severity; most beneficial findings come from single studies with small samples and require replication. Olanzapine may be associated with weight gain and possible adverse effects on suicidality in some data; adverse effects reporting was often limited. Antidepressants showed limited or inconsistent benefits for core BPD pathology. Polypharmacy is not supported by the evidence. Treatments should be targeted to defined symptoms, monitored for adverse effects, and longer-term data are lacking.

Limitations

Small sample sizes across trials; many findings rely on single studies; heterogeneity of outcomes and assessment instruments; older trials had less rigorous reporting (pre-CONSORT) with potential biases in randomization and concealment; inconsistent reporting of adverse events; variable use of concomitant psychotherapy and other medications; short study durations limit long-term applicability; generalizability limited to selected outpatient populations with substantial heterogeneity in diagnoses and comorbidities.

Abstract

BACKGROUND Drugs are widely used in borderline personality disorder (BPD) treatment, chosen because of properties known from other psychiatric disorders ("off-label use"), mostly targeting affective or impulsive symptom clusters. OBJECTIVES To assess the effects of drug treatment in BPD patients. SEARCH STRATEGY We searched bibliographic databases according to the Cochrane Developmental, Psychosocial and Learning Problems Group strategy up to September 2009, reference lists of articles, and contacted researchers in the field. SELECTION CRITERIA Randomised studies comparing drug versus placebo, or drug versus drug(s) in BPD patients. Outcomes included total BPD severity, distinct BPD symptom facets according to DSM-IV criteria, associated psychopathology not specific to BPD, attrition and adverse effects. DATA COLLECTION AND ANALYSIS Two authors selected trials, assessed quality and extracted data, independently. MAIN RESULTS Twenty-eight trials involving a total of 1742 trial participants were included. First-generation antipsychotics (flupenthixol decanoate, haloperidol, thiothixene); second-generation antipsychotics (aripirazole, olanzapine, ziprasidone), mood stabilisers (carbamazepine, valproate semisodium, lamotrigine, topiramate), antidepressants (amitriptyline, fluoxetine, fluvoxamine, phenelzine sulfate, mianserin), and dietary supplementation (omega-3 fatty acid) were tested. First-generation antipsychotics were subject to older trials, whereas recent studies focussed on second-generation antipsychotics and mood stabilisers. Data were sparse for individual comparisons, indicating marginal effects for first-generation antipsychotics and antidepressants.The findings were suggestive in supporting the use of second-generation antipsychotics, mood stabilisers, and omega-3 fatty acids, but require replication, since most effect estimates were based on single studies. The long-term use of these drugs has not been assessed.Adverse event data were scarce, except for olanzapine. There was a possible increase in self-harming behaviour, significant weight gain, sedation and changes in haemogram parameters with olanzapine. A significant decrease in body weight was observed with topiramate treatment. All drugs were well tolerated in terms of attrition.Direct drug comparisons comprised two first-generation antipsychotics (loxapine versus chlorpromazine), first-generation antipsychotic against antidepressant (haloperidol versus amitriptyline; haloperidol versus phenelzine sulfate), and second-generation antipsychotic against antidepressant (olanzapine versus fluoxetine). Data indicated better outcomes for phenelzine sulfate but no significant differences in the other comparisons, except olanzapine which showed more weight gain and sedation than fluoxetine. The only trial testing single versus combined drug treatment (olanzapine versus olanzapine plus fluoxetine; fluoxetine versus fluoxetine plus olanzapine) yielded no significant differences in outcomes. AUTHORS' CONCLUSIONS The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods). show less