Naltrexone looks good for borderline personality disorder

The opioid antagonist naltrexone helps reduce symptoms in patients with borderline personality disorder (BPD), with the effect dictated by dose and superior to all available psychoactive drugs, as shown in a study.

“Our findings support a pathogenetic role of the endogenous opioid system (EOS) and the reward system in BPD. Furthermore, dysregulation of the EOS may be counteracted by opioid antagonists,” according to the investigators.

The analysis included 161 adult BPD patients (mean age 31.8 years, 84.5 percent women) who received treatment as inpatients (mean duration of hospital stay 29 days). Concomitant substance use disorders were common (27 percent had alcohol abuse; 15 percent had additional multiple substance use disorder), and more than half of the sample (64 percent) reported at least one suicide attempt. About 83 percent also had at least one first-degree relative with diagnosed psychiatric disorder.

Almost 90 percent of the patients received at least one psychotropic medication, while 72 percent had two or more. The medications used included antidepressants (68 percent), low-potency and high-potency antipsychotics (47 percent and 12 percent, respectively), the opioid antagonist naltrexone (34.2 percent), mood stabilizers (14 percent), benzodiazepines (16 percent), buprenorphine (0.024 percent), and L-methadone as opioid maintenance treatment (0.016 percent).

Stepwise logistic regression analysis revealed that none of the said drugs produced significant improvement, except for naltrexone. Patients given this opioid antagonist recovered with significantly greater frequency (odds ratio [OR], 43.2; p≤0.0001). [Hum Psychopharmacol 2021;doi:10.1002/hup.2800]

Of note, naltrexone was more effective at higher (>50–150 mg per day; OR, 791.8; p≤0.0001) than lower (≤50 mg per day; OR, 26.6; p≤0.0001) doses. Even so, low-dose treatment was better than any other pharmacological treatment.

Female gender and an additional substance use disorder correlated with lower odds of improvement during the treatment period, whereas having first-degree relatives with major depression was associated with higher chances of better clinical outcome.

EOS dysregulation blamed for BPD symptoms

“Evidence from [earlier] studies strongly indicate that the EOS mediates social bonding, attachment, coping with interpersonal stress, affective experiences, and responses. Accordingly, a dysregulation of EOS might be responsible for several core symptoms associated with BPD,” they said. [Psychoneuroendocrinology 1995;20:735-742; Biol Psychiatry 1978;13:607-618; Arch Gen Psychiatry 2003;60:1145-1153]

Opioid antagonists, such as naltrexone, work in two phases, the investigators pointed out. They exert an acute effect by blocking the rewarding effects of problematic self‐destructive symptoms, including self‐harm, substance abuse, or eating disorders. Then, with chronic administration, the drugs potentially restore the neurotransmission via µ‐opioid receptors.

Interestingly, another opioid antagonist, nalmefene, has also demonstrated therapeutic potential in BPD patients. The drug yielded a meaningful reduction in both alcohol consumption and symptoms on a BPD self‐rating instrument. [Int Clin Psychopharmacol 2017;32:231-234]

Innovative, preventative medications needed

In the study cohort, according to the investigators, psychotropic drug treatment was highly utilized, with second‐generation antipsychotics being preferred to tricyclic antidepressants and low‐potency antipsychotics. About a third of all BPD inpatients were treated with naltrexone, owing to an “insiders’ tip” in the hospital that the drug may be useful.

The use of psychotropic medications is a common approach in clinical practice, with limited effects in distinct symptoms in BPD and polypharmacy being highly prevalent despite the lack of evidence, the investigators noted. Meanwhile, international guidelines “favour psychotherapy as first‐line treatment over drug therapy, which is rather considered as adjunctive option at best.” [J Clin Psychopharmacol 2015;35:63-67; Curr Psychiatry Rep 2015;17:534; https://www.nice.org.uk/guidance/cg78/resources/2018-surveillance-of.personality-disorders-nice-guidelines-cg77-and-cg78-pdf-6358811143669]

It delivers a straightforward message that “suitable neurobiological models of BPD delivering biological targets which can be utilized for further investigation of innovative and preventative treatments” constitute a pressing need, they said.