Antidepressants, antipsychotics and benzos all increase suicide attempts in a new study

A new study a JAMA network open found that antidepressants do not prevent suicide. The researchers concluded that antidepressants, antipsychotics and benzodiazepines 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 a decrease in suicide attempts.

Overall, our data suggest that treatment with antidepressants, antipsychotics, or mood stabilizers does not appear to reduce suicidal behavior in BPD patients, write the researchers.

In terms of actual deaths from suicide (rather than suicide attempts), stimulant drugs were associated with a decrease, while other drug classes were not associated with any changes, with the exception of benzodiazepines, which were associated with a significant increase in suicide deaths.

The researchers write: Alarmingly, benzodiazepine treatment was related to a 4-fold increased risk of completing suicide in patients with BPD.

Johannes Lieslehto led a team of researchers at the University of Eastern Finland and Hospital in Niuvanniemi, Finland, and at Karolinska Institutet, Stockholm, Sweden. They included 22,601 people with BPD (84.3% women) from a Swedish national database from 2006 to 2021.

The diagnosis of borderline personality disorder is a controversial 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 her response to the abuse or at least medicalizing the result of the trauma. Both doctors and the general public can use the diagnosis to dismiss and invalidate people’s experiences, leading to lower quality medical and psychiatric care.

Although BPD is controversial, it serves as a useful proxy for people who are at increased risk of suicide in this study. In this study, a third of the participants (32.4%) had attempted it in the past. Suicide attempts, self-harm behaviors, and death by suicide are all considered common features of the diagnosis of BPD. Therefore, researchers are concerned with finding a solution to reduce this risk.

Although the researchers note that psychotherapy, like dialectical behavior therapy, is considered effective for preventing suicide, they add that nearly everyone diagnosed with BPD is prescribed psychiatric medications in addition to (or instead of) therapy. In the current study, 81.5% were taking antidepressants, while others were taking antipsychotics (41.1%), mood stabilizers (31.7%), benzodiazepines (56%) and stimulants (24.4%). Many patients have been prescribed multiple classes of drugs.

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 unable to assess whether the patients received psychotherapy.

During the study, there were 8,513 hospitalizations after suicide attempts and 316 deaths by suicide. The stimulants lisdexamphetamine (Vyvanse) and methylphenidate (Ritalin) have been associated with a reduced risk, as has the antidepressant vortioxetine (Trintellix). Mood stabilizers such as lithium, lamotrigine and valproic acid have not been 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). . Similarly, most antipsychotics were associated with an increased risk of suicide attempts, including aripiprazole (Abilify), risperidone (Risperdal), haloperidol (Haldol), flupethixol, and zuclopenthixol.

An alternative explanation for the findings is that people with BPD are prescribed psychiatric drugs at times of increased suicide risk, meaning that the drugs may not cause suicide attempts but simply be increased during the risk of suicide attempts.

However, the researchers performed further analyzes to rule out this explanation, statistically accounting for the first few months after the drug was prescribed, and this did not change their results. Furthermore, even if this were true, it would not explain the surprising finding that benzodiazepines are associated with a huge increase in risk. Also, it should be noted that there is no evidence that drugs reduce suicide, except for stimulant drugs.

Why can ADHD medications help reduce the risk of suicide? The researchers suggest that stimulant drugs may decrease impulsivity, a key characteristic of many people who attempt suicide.

They write, “Meta-analytic 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.”

Similarly, researchers argue that benzodiazepines increase impulsivity and aggression, which may explain the association with an increased risk of suicide.

Antidepressant medications, despite being prescribed to people at risk of suicide, have repeatedly been shown to increase the risk of suicide, 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 stopped 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 efficacy research study of an unselected national sample of BPD patients, ADHD medication use, potentially due to decreased 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 for. Finally, benzodiazepine use has been associated with a markedly increased risk of suicide.

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Lieslehto, J., Tiihonen, J., Lhteenvuo, M., Mittendorfer-Rutz, E., Tanskanen, A., and Taipale, H. (2023). Comparative efficacy of pharmacotherapies for the risk of attempted or completed suicide among people with borderline personality disorder. JAMA network open, 6(6): e2317130. doi:10.1001/jamanetworkopen.2023.17130 (Link)