Meta-Analyses of Mood Stabilizers, Antidepressants and Antipsychotics in the Treatment of Borderline Personality Disorder: Effectiveness for Depression and Anger Symptoms

Abstract

The objective of our study was to complete separate meta-analyses of randomized controlled trials of mood stabilizers, antidepressants and antipsychotics to determine whether these medications are efficacious for depression and anger symptoms in borderline personality disorder (BPD). Studies were obtained from OVID Medline, Cochrane Central Register of Controlled Trials, and PsychInfo. References of all original papers and reviews were searched for additional studies. Index terms included: BPD, randomized controlled trials, drug therapy, medication, and treatment. Studies were included if they were randomized double-blind placebo-controlled trials, published in a peer reviewed journal, had a majority of patients with BPD or included patients with BPD where anger was a target of treatment. Preference was given to studies using outcome measures that were well known, validated, objective, and based on intent-to-treat data. Where available, measures of anger that incorporated verbal and other indirect forms of aggression were utilized. The StatsDirect meta-analysis program was used to calculate an effect size and 95% confidence interval for each study. Mood stabilizers, with the exception of divalproic acid, were found to have a large pooled effect size (-1.75, 95% CI = -2.77 to -0.74) for anger. Divalproic acid and carbamazepine had a moderate effect on depression. Antidepressants had a moderate effect on anger reduction, but a small effect on depression. Antipsychotics had a moderate effect on anger; however aripiprazole had a much larger effect-size than other antipsychotics. Antipsychotics did not have an effect for depression. Sources of variation between studies included length of treatment (5-24 weeks), drop out rates (5% to 65%), proportion of patients in psychotherapy (0-100%) and with comorbid mood disorders (0-100%). Unfortunately most studies excluded patients with alcohol and substance abuse, suicidality, and self-harm behaviors. This may limit the ability to generalize our findings to usual clinical practice.

Recent approaches to pharmacotherapy of personality disorders

“…As repeatedly suggested in this article and by others [70][71][72][73][74], future perspectives of research should focus on a series of core topics: large scale multicenter RCTs of mood stabilizers and new anti psychotics in order to confirm prelimi nary evidence; drugtodrug comparisons (e.g., atypical vs traditional antipsychotics, different mood stabilizers) to explore differential effects of medications; fixeddosage and longterm studies in order to determine appropriate doses and duration of treatments; identification of biological, clinical and pharmaco logical fac tors that predict response to drug treatments; assessment of results of combined therapy in comparison with single pharmaco and psychotherapy; and selection of a set of out come measures that can be retained reliable and specific to test drug efficacy and safety in BPD populations.…”

“…In a metaana lysis concerning efficacy of medications on anger and depression in BPD patients, Mercer et al suggested that mood sta bilizers should be considered as firstline ther apy for anger and affective symptoms, rather than SSRIs [72]. Antipsychotics were found to have a medium effect on symptoms of anger and no effects on depression.…”

Pharmacotherapy of personality disorders: what we know and what we have to search for

“…The amount of efficacy studies on BPD made it possible to conduct 7 meta-analysis [115,[117][118][119][120][121][122] which generated somewhat discordant results. The evidences indicated therapeutic benefits of mood stabilizers, such as topiramate, valproate, and lamotrigine in treating affective dysregulation, impulse dyscontrol, and anger.…”

“…In a meta-analysis focusing on anger and depression in BPD, Mercer et al [117] found mood stabilizers to be superior to SSRIs in treating affective symptoms, including depressed mood and anger.…”

Efficacy and Tolerability of Asenapine Compared with Olanzapine in Borderline Personality Disorder: An Open-Label Randomized Controlled Trial

“…Therapeutic effects of antipsychotic drugs were demonstrated across a wide range of symptoms. Whilst their action is primarily directed at alleviating cognitiveperceptual symptoms such as transient paranoid ideation or dissociative symptoms, these agents were further reported to induce significant improvements across other psychopathological domains including mood instability, anxiety, impulsiveness, and aggression [7][8][9].…”