Discussion

To our knowledge, this is the first study to report polypharmacy in a national cohort of people with borderline personality disorder. Psychotropic polypharmacy in people with borderline personality disorder was high, and increased between 2014 and 2019. Our findings were broadly consistent with cohorts of psychiatric out-patient clinics and hospitals in Europe and the USA.^{Reference Soler, Casellas-Pujol, Fernández-Felipe, Martín-Blanco, Almenta and Pascual3,Reference Pascual, Martín-Blanco and Soler4} In a USA cohort of people with borderline personality disorder who required psychiatric hospital admission, 40% were on three or more medications.^{Reference Zanarini10} Two Spanish cohorts of out-patients reported that 47 and 50% were on three or more medications, respectively.^{Reference Soler, Casellas-Pujol, Fernández-Felipe, Martín-Blanco, Almenta and Pascual3,Reference Pascual, Martín-Blanco and Soler4} In a British cohort of out-patients with an ICD-10 diagnosis of emotionally unstable personality disorder, two-thirds were on at least two psychotropic medications.^{Reference Paton, Crawford, Bhatti, Patel and Barnes5}

Psychotropic polypharmacy could be partially explained by the high rates of psychiatric comorbidity, with 84.5% of people with borderline personality disorder meeting criteria for another psychiatric disorder in a community sample.^{Reference Lenzenweger, Lane, Loranger and Kessler11} The most common comorbidities were mood disorders, anxiety disorders and substance use disorders,^{Reference Leichsenring, Leibing, Kruse, New and Leweke12} which may explain the high rates of antidepressant dispensing in this group.

People with personality disorders may be less responsive to pharmacological treatment for comorbid depression, anxiety and post-traumatic stress disorder.^{Reference Bach13,Reference Harned and Valenstein14} Their reported symptom burden remains higher after treatment than those without personality disorders.^{Reference Harned and Valenstein14} When faced with continued patient distress and modest responses to treatment, it can be tempting for clinicians to add new medications despite limited evidence of efficacy. This may lead to psychotropic polypharmacy.^{Reference Rogers and Acton15}

The high burden of sedative medications, in particular quetiapine and lorazepam, were notable. This may be because these medications are utilised during periods of crisis as a means of managing acute distress or challenging behaviours.^{Reference Pascual, Martin-Blanco, Soler, Ferrer, Tiana and Alvarez16} NICE guidelines acknowledge that this approach may be helpful in a crisis, but recommend prescribing a single sedative medication for no longer than a week.¹

An increase in the dispensing of lorazepam from 15.5% in 2014 to 26.7% in 2019 is concerning. Rather than improving emotional regulation, benzodiazepines may worsen affective instability and impulsivity in this group.^{Reference Cowdry and Gardner17} People with borderline personality disorder are more vulnerable to developing benzodiazepine misuse and dependence,^{Reference Tyrer18} and find it more difficult to reduce hazardous use.^{Reference Vorma, Naukkarinen, Sarna and Kuoppasalmi19}

There was persistently high opioid dispensing, which increased between 2014 and 2019 from 44.6 to 46.1%. People with borderline personality disorder are more likely to develop chronic pain.^{Reference Doering20} However, opioids are no longer recommended for the treatment of non-malignant chronic pain,²¹ and people with borderline personality disorder have greater odds of developing a prescription opioid use disorder.^{Reference Tragesser, Jones, Robinson, Stutler and Stewart22}

Dispensing of antipsychotics and mood stabilisers remained high. Antipsychotic medications are associated with neurological side-effects such as extrapyramidal side-effects, acute dystonia and tardive dyskinesia.^{Reference Taylor, Barnes and Young23} In addition, the metabolic effect of antipsychotic medication can lead to increased weight gain and increased risk of developing diabetes.^{Reference Taylor, Barnes and Young23} Rarely, antipsychotics have potential fatal adverse effects such as myocarditis and agranulocytosis.^{Reference Taylor, Barnes and Young23} Mood stabilisers commonly cause drowsiness and weight gain. Sodium valproate and carbamazepine are contraindicated in woman of childbearing age because of their teratogenicity.^{Reference Taylor, Barnes and Young23}

Psychedelics are not currently prescribed in New Zealand. There has been increased excitement about their potential in borderline personality disorder; however, at this time there is insufficient evidence to recommend their use in clinical practice.^{Reference Zeifman and Wagner24}

Polypharmacy may have negative psychological effects too. Widespread use and overreliance on psychotropic medications have been interpreted by some patients as reflecting clinicians’ lack of understanding regarding borderline personality disorder and a generally negative attitude toward patients with borderline personality disorder.^{Reference Rogers and Acton15}

A shift in treatment focus toward psychological interventions may be part of the solution.^{Reference Bohus, Stoffers-Winterling, Sharp, Krause-Utz, Schmahl and Lieb25} To achieve this, improved access to evidence-based psychological treatment for borderline personality disorder is required.^{Reference Zanarini26} In addition to the potential adverse effects of polypharmacy on the body, there is a significant financial burden associated with excessive prescribing for people with borderline personality disorder.^{Reference Baker-Glenn, Steels and Evans27} Ideally, some of this resource would be redirected to evidence-based psychological treatment in the future.

The strength of this study was its use of national databases to achieve a broad overview of current clinical practice. This ensured that all patients with a diagnosis of borderline personality disorder by specialty mental health and addiction services were included. The Pharmaceutical Collection database captured all dispensing of prescription medications.

The study was limited by the quality of diagnostic reporting. The point prevalence of borderline personality disorder in community samples using structured interviews is approximately 1%.^{Reference Ellison, Rosenstein, Morgan and Zimmerman28} The diagnosis was captured at a much lower rate within New Zealand's national databases. A large portion of people with borderline personality disorder may be undiagnosed. Diagnoses made in primary care or by private psychiatrists would not have been captured unless those individuals had contact with publicly funded specialist services. This suggests that our study has captured the most severe disorders. The number of people diagnosed with borderline personality disorder increased from 1932 (2009–2014) to 2368 (2015–2019), but this does not necessarily represent an increase in the prevalence of the disorder. It may be attributable to increased recognition of the disorder among clinicians. We did not receive data on other primary or secondary diagnosis and are therefore unable to report the extent of comorbidity in this group. It is unknown what proportion of the polypharmacy reported in this study was indicated to treat other conditions.

In conclusion, this is the first study to use national data to look at polypharmacy in people with borderline personality disorder. More than half of individuals diagnosed with borderline personality disorder who were dispensed medication were on psychotropic polypharmacy (three or more psychotropic medications), and one in ten were on extensive polypharmacy (seven or more psychotropic medications) in 2019. Psychotropic polypharmacy increased between 2014 and 2019. This is concerning given the lack of evidence for pharmacological treatments in this group. Excessive prescribing has a negative psychological effect on patients^{Reference Rogers and Acton15} in addition to the side-effect burden associated with polypharmacy.^{Reference Zeifman and Wagner24,Reference Stroup and Gray29} Our findings suggest that psychotropic polypharmacy is a significant burden for those with borderline personality disorder.