Researchers from Finland and Sweden used nationwide Swedish register databases to investigate the comparative effectiveness of several commonly used pharmacological treatments (i.e., antipsychotics, antidepressants, mood stabilizers, benzodiazepines, and ADHD medications) on the risk of attempted or completed suicides in patients with borderline personality disorder (BPD). The results have shown that the use of attention-deficit/hyperactive disorder (ADHD) medications was consistently associated with a reduced risk of suicide. However, the use of antidepressants, antipsychotics, or mood stabilizers was not associated with a reduced risk of suicide in patients with borderline personality disorder, even when potential protopathic bias was controlled. Furthermore, the use of benzodiazepines was associated with a marked increase in suicide risk.
Approximately 5% to 10% of individuals with BPD eventually die by suicide, and the lifetime prevalence of suicidal ideation and attempts in patients with BPD is 84% to 94%. The authors noted that psychotherapy, especially dialectical behavior therapy, has been shown to be effective in reducing suicidal behavior. However, due to limited access to psychotherapeutic treatments, most patients with BPD are treated with pharmacotherapy.
Previous large observational studies examined the effectiveness of antipsychotics on suicidal behavior in patients with personality disorders, including BPD. A nationwide Danish registry study of 79 253 individuals (42 987 patients with BPD) found 32% lower rates of suicidal behavior during antipsychotic treatment compared to the time without antipsychotic treatment. Because treatment with antipsychotics is associated with a lower risk of suicide in patients with schizophrenia, it is possible that these results were influenced by the fact that patients with a comorbid psychotic disorder were not excluded from this study, the authors said.
Also, patients with BPD are often treated with benzodiazepines, despite augmented impulsivity and aggression-related issues that may facilitate suicidal behavior. In addition, over one-third of individuals with BPD have comorbid ADHD symptoms, and the existing evidence suggests that ADHD medications are associated with a decreased risk of suicide for patients with ADHD.
About the study
The authors used Swedish electronic nationwide patient registries, which contain comprehensive data for individuals receiving public health care. The study included residents of Sweden, who had registered treatment for BPD according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10, code F60.3) between January 1, 2006, and June 30, 2021. The study comprised an unselected nationwide sample of 22 601 patients with BPD aged 16 to 65 years (mean age, 29.2 years) with up to 16 years of follow-up (mean follow-up, 6.9 years). The study excluded individuals with comorbid nonaffective psychotic disorders (codes F20-F29), bipolar disorder (code F31), psychotic depression (code F32.3), and personality disorders other than BPD (codes F60-61 except F60.3).
The majority of patients were women (84.3%) and single without children (57.7%). There were comorbidities, including substance use disorder in 33.7%, depression in 56.6%, anxiety disorder in 71.4% and ADHD in 17.2% of patients.
During the 16-years of follow-up (mean follow-up, 6.9 years), one-third of the sample, 8513 patients (32.4%) had attempted suicide, and 316 patients completed suicide. The median time from diagnosis of BPD to the first hospitalization for attempted suicide was 271 (55-895) days, whereas the median time from diagnosis of BPD to completion of suicide was 1300 (412-2605) days.
Most patients were treated with antidepressants (81.5%) at some point during the follow-up, of which sertraline was the most commonly used (28.7%). Also, more than half of the patients were taking benzodiazepines (56.0%) at some point during follow-up.
41.1% of patients were treated with antipsychotics, 31.7% with mood stabilizers, and 24.4% with ADHD medications. The most common antipsychotic was quetiapine (24.2%), the most common mood stabilizer was lamotrigine (24.0%), and the most common ADHD medication was methylphenidate (18.8%). To control protopathic bias, sensitivity analyses were conducted, omitting the initial 1 or 2 months of medication exposure from the analysis.
The findings revealed that treatment with ADHD medications, especially stimulant compounds, was associated with a decreased risk of attempted or completed suicide. Up to a 48% decrease in the probability of suicide completion in patients with BPD was attributable to treatment with ADHD medications. The lowest risk of attempted or completed suicide was found for lisdexamphetamine.
However, no other pharmacotherapy (i.e., antidepressants, antipsychotics, mood stabilizers, or benzodiazepines) was associated with a reduced risk of suicide. Mood stabilizer treatment was not associated with the main outcome. Treatment with antidepressant or antipsychotics was associated with an increased risk of attempting or completing suicide. Out of all the antidepressant medications that have been investigated, paroxetine was associated with the highest risk of attempting or completing suicide. Out of all the explored antipsychotic medications, zuclopenthixol was associated with the highest risk of attempting or completing suicide. Among the investigated pharmacotherapies, treatment with benzodiazepines was associated with the highest risk of attempting or completing suicide. These findings remained essentially unchanged even when the first 30 or 60 days of each medication exposure period were omitted.
The limitations of this study were the lack of specific clinical parameters, such as the severity of BPD symptoms and indications for pharmacotherapy, and the lack of information regarding concomitant psychotherapy, such as dialectical behavioral therapy.
The authors concluded that their main findings indicate that, compared with individuals’ nonuse periods, ADHD medication was associated with a reduced risk of attempted or completed suicide, possibly due to diminished impulsivity. Treatment with antidepressants, antipsychotics, or mood stabilizers does not seem to reduce suicidal behavior in patients with BPD. Treatment with benzodiazepines was consistently associated with an increased risk of attempting and completing suicide. The authors proposed that treatment with ADHD medications should be the preferred option for individuals with BPD with ADHD symptoms and suicidal behavior. Benzodiazepines should be used with caution among patients with BPD due to their association with increased risk of suicide.
The article was published in JAMA.
Lieslehto J et al. Comparative Effectiveness of Pharmacotherapies for the Risk of Attempted or Completed Suicide Among Persons With Borderline Personality Disorder. JAMA Netw Open. 2023;6(6): e2317130. (Open Access) https://jamanetwork.com/article.aspx?doi=10.1001/jamanetworkopen.2023.17130