A new study in JAMA Network Open found that antidepressants don’t prevent suicide. The researchers concluded that antidepressants, antipsychotics, and benzodiazepine drugs were all associated with increased suicide attempts in people with borderline personality disorder (BPD). “Mood stabilizers” had no effect on suicide attempt rates. ADHD stimulant drugs were the only drug class associated with decreased suicide attempts.
“Altogether, our data suggest that treatment with antidepressants, antipsychotics, or mood stabilizers does not appear to reduce suicidal behavior in patients with BPD,” the researchers write.
In terms of actual deaths by suicide (rather than suicide attempts), stimulant drugs were associated with a decrease, while the other classes of drugs were not associated with any change—except for benzodiazepines, which were associated with a significant increase in deaths by suicide.
The researchers write: “Alarmingly, treatment with benzodiazepines was related to a 4-fold risk increment in suicide completion in patients with BPD.”
Johannes Lieslehto led a team of researchers at the University of Eastern Finland and Niuvanniemi Hospital, Finland, and at the Karolinska Institutet, Stockholm, Sweden. They included 22,601 people with BPD (84.3% women) from a nationwide Swedish database from 2006 to 2021.
The diagnosis of borderline personality disorder is a contested construct that many researchers and clinicians believe should be eliminated from the DSM and ICD. The vast majority of people diagnosed with BPD are women who have experienced significant trauma, most commonly sexual assault, and the diagnosis has been accused of “blaming the victim” for their response to abuse or at least medicalizing the result of trauma. Both clinicians and the general public may use the diagnosis to dismiss and invalidate the person’s experiences, leading to poorer quality medical and psychiatric care.
Although BPD is controversial, in this study, it serves as a useful proxy for people who are at increased risk of suicide. In this study, a third of the participants (32.4%) had attempted in the past. Suicide attempts, self-harm behaviors, and death by suicide are all considered common features of the BPD diagnosis. Thus, researchers are concerned with finding a solution to reduce this risk.
Although the researchers note that psychotherapy, such as dialectical behavior therapy, is considered effective for preventing suicide, they add that almost everyone with a BPD diagnosis is prescribed psychiatric drugs in addition to (or instead of) therapy. In the current study, 81.5% were taking antidepressants, while others were on antipsychotics (41.1%), mood stabilizers (31.7%), benzodiazepines (56%), and stimulants (24.4%). Many patients were prescribed multiple drug classes.
“Despite the paucity of evidence, antidepressants, antipsychotics, and mood stabilizers are routinely used in BPD with the intention of treating suicidal behavior along with symptoms such as mood lability, anger, and impulsivity.” the researchers write.
The researchers were not able to assess whether patients received psychotherapy.
Throughout the study, there were 8,513 hospitalizations after suicide attempts and 316 deaths by suicide. The stimulants lisdexamphetamine (Vyvanse) and methylphenidate (Ritalin) were associated with decreased risk, as was the antidepressant vortioxetine (Trintellix). Mood stabilizers like lithium, lamotrigine, and valproic acid were not associated with any effect on suicide risk.
However, most antidepressants were associated with an increased risk of suicide attempts, including sertraline (Zoloft), fluoxetine (Prozac), paroxetine (Paxil), venlafaxine (Effexor), fluvoxamine (Luvox), duloxetine (Cymbalta), and clomipramine (Anafranil). Likewise, most antipsychotics were associated with an increased risk of suicide attempts, including aripiprazole (Abilify), risperidone (Risperdal), haloperidol (Haldol), flupentixol, and zuclopenthixol.
One alternate explanation for the results is that people with BPD are prescribed psychiatric drugs at times of increased risk for suicide—meaning that the drugs may not be causing suicide attempts but simply being increased during risk for suicide attempts.
However, the researchers did extra analyses to rule out this explanation, statistically accounting for the first few months after drug prescription, and it did not change their results. Moreover, even if this were true, it wouldn’t explain the surprising finding that benzodiazepines are associated with a huge increased risk. Also, it’s notable that there is no signal whatsoever for the drugs being able to reduce suicide—except for stimulant drugs.
Why might ADHD drugs help decrease the risk of suicide? The researchers suggest that stimulant drugs might decrease impulsivity—a key feature of many people who attempt suicide.
They write, “Meta-analytical evidence indicates that treatment with ADHD medications is associated with decreased impulsivity, which is critical given that impulsivity is one of the strongest predictors of suicidal behavior in BPD.”
Likewise, the researchers argue that benzodiazepines have been found to increase impulsivity and aggression, which might account for the association with increased suicide risk.
Antidepressant drugs, despite being prescribed for people at risk of suicide, have been repeatedly shown to increase suicide risk, particularly for children and adolescents. Similarly, although some researchers claim that lithium has the potential to prevent suicide, despite its many risks, a large study was terminated early because the drug had no positive effect, and a recent meta-analysis confirmed that the drug does not reduce suicide.
In conclusion, the researchers write:
“In this comparative effectiveness research study of an unselected nationwide sample of patients with BPD, the use of ADHD medications, potentially due to diminished impulsivity, 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 suicidality in BPD, even when potential protopathic bias was controlled. Lastly, benzodiazepine use was associated with a marked increment in suicide risk.”
Lieslehto, J., Tiihonen, J., Lähteenvuo, M., Mittendorfer-Rutz, E., Tanskanen, A., & Taipale, H. (2023). Comparative effectiveness of pharmacotherapies for the risk of attempted or completed suicide among persons with borderline personality disorder. JAMA Network Open, 6(6): e2317130. doi:10.1001/jamanetworkopen.2023.17130 (Link)