The idea that suicide is caused by psychological pain may seem self-evident, but recognizing this fact was once a departure for psychiatry. Depression and other psychiatric disorders—which are often associated with suicide—are diagnoses, and diagnoses are the coin of psychiatry’s realm. But psychological pain is an experience, one that may not be connected to any diagnosis.

The late psychologist Edwin Shneidman, who founded the Los Angeles Suicide Prevention Center in the 1950s, rejected the diagnosis-based medical model of suicidal behavior. He coined the phrase “psychological autopsy,” a procedure he used most famously to establish Marilyn Monroe’s death as a probable suicide. The “autopsy” consists of postmortem interviews with the family and friends of the deceased to establish his or her frame of mind and possible motives for suicide. The implication is that those who knew the victim intimately, not psychiatrists, are in the best position to understand the suicidal act.

Although a review of psychological autopsy studies showed that more than 90 percent of the suicides were associated with diagnosable mental disorders, Shneidman pointed out that no one has ever died of depression but rather of suicide. In an influential 1993 paper, “Suicide as Psychache,” Shneidman proposed that “Suicide is caused by psychache ... hurt, anguish, soreness, aching psychological pain in the psyche, the mind.” He objected to what he felt were simplistic categories when it came to understanding suicide: “If ... feeling guilty or depressed or having a bad conscience or an overwhelming unconscious rage makes one suicidal, it does so only because it is painful.”

In the nearly 25 years since “Suicide as Psychache” was published, research into suicide has focused on destigmatization and the treatment of mental disorders, on neurochemistry and the role of serotonin and serotonin reuptake inhibitors, and on risk factors, such as ready access to guns. Now the concept of mental pain is making a comeback in response to recent neurobiological research, which suggests that pain is processed through the same structures and mechanisms in the brain regardless of whether it is physical or emotional.

Could mental pain be treated like physical pain, and would a reduction in suicidal thoughts follow? A surprising new study by Yoram Yovell of the University of Haifa in Israel and his colleagues addressed that question in a randomized, placebo-controlled trial of very low doses of an opioid, buprenorphine, in severely suicidal subjects.

The authors looked to the concept of “separation distress” to justify the trial of buprenorphine. All young animals, including humans, are distressed when separated from the attachment figures on whom their physical and emotional well-being depends. Very low doses of opioids have been known to ameliorate that distress since the 1970s. Yovell and his colleagues drew on attachment literature, which established that endogenous opioids—the ones that occur naturally in our brains—help us feel good when we are with loved ones. When we separate from loved ones, internal opioid levels drop, and we experience mental pain—the human version of separation distress.

Neurobiological studies have suggested that separation distress overlaps with pain circuitry in the brain in a general “neural alarm system” when an animal, or a person, is under threat. A trial of opioid painkillers, which might quiet that neural alarm system, seemed reasonable.

It was also necessary. Currently there are no medications to quickly relieve suicidal thoughts. Antidepressants can take a month or longer to ease depression, and many psychiatrists today believe, like Shneidman, that depression and suicidal ideation are separate conditions. Treating depression might not even address suicidal thinking. A medication that specifically targets suicidal ideation—quickly—could be lifesaving.

Buprenorphine, sold as Subutex in pure form and as Suboxone when combined with naloxone (which decreases its abuse potential), is an unusual opioid in that it stimulates some, but not all, of the brain’s opioid receptors. It causes less euphoria than opioids such as hydrocodone, an active ingredient in Vicodin, and hydromorphone, the active ingredient in Dilaudid, but relieves pain and withdrawal symptoms. In fact, it was developed as a treatment for opioid addiction. Because it is less pleasurable, it is less likely to be abused, and because it is weaker, patients are less likely to overdose. Individuals who do abuse buprenorphine get high by crushing the tablets and injecting a solution made from the powder. Yovell and his colleagues used a gelatin-based lozenge that dissolves under the tongue to make that impossible.

The researchers recruited patients from four hospitals in Israel and assigned them to receive tiny doses of buprenorphine or placebo. At the outset, the subjects were quite ill; most of them had made suicide attempts in the past, and 57 percent met criteria for borderline personality disorder, which is characterized by chronic suicidal ideation and rejection sensitivity—meaning that mild slights can cause one’s mood to plunge. The Beck Scale for Suicide Ideation was used to rate how suicidal patients were before, during and after the intervention.

The authors found a significant drop in suicidal thinking in the buprenorphine group versus the placebo group. Buprenorphine had a positive effect on depression, but the impact on suicidal thinking was even greater. Further, patients who met criteria for borderline personality disorder benefited even more than patients with depression alone. For the investigators, this finding closed a loop: extreme distress over real or perceived abandonment is a hallmark of borderline personality disorder. In borderline patients, suicidal thoughts may emerge when their highly sensitive separation-distress systems are activated, with a drop in endogenous opioids and subsequent mental pain. The robust improvements in suicidal ideation in borderline patients suggested that buprenorphine treats the psychache associated with abandonment and rejection.

The study could not prove that opioids treat mental pain—it was not designed to do so—but it did show that buprenorphine decreases suicidal ideation. Perhaps the study’s most important contribution is its implication that treatments that help us withstand mental pain may prevent suicide.

Shneidman’s original paper noted that suicide occurs when psychache has become unbearable but that individuals vary in how much pain they can bear. It follows that one can intervene with suicidal patients in two ways—decreasing pain or increasing tolerance. Shneidman believed that psychache derives from “frustrated needs” and that the therapist’s task was to identify and at least partially satisfy those needs. The success of buprenorphine in decreasing suicidal ideation suggests an alternative approach. Opioids do not remove painful stimuli—if we have surgery, for example, the wound is still there—but they allow us to tolerate the pain.

Whether or not buprenorphine is ever developed as a treatment for suicidal ideation may depend on our current national attitude toward opioid use and abuse. Opioids, once marketed to physicians as the first and perhaps most humane response to complaints of pain, have been recast as a treatment best reserved for the terminally ill. Last year, in response to an epidemic of prescription opioid abuse, the U.S. Centers for Disease Control and Prevention took the unusual step of developing prescribing guidelines for the management of chronic pain. Physicians may be unwilling to prescribe opioids for nonapproved indications.

But Yovell and his colleagues’ study provides a rationale for thinking about opioids in a new way. More than that, it suggests that interventions that increase our capacity to tolerate mental anguish may have a powerful role in suicide prevention.