Reduced Risk of Completed Suicide and Suicide Attempts in Borderline Personality Disorder Treated with ADHD Medications.

Journal of Psychiatry Reform vol. 11 #3, March 2024


Author

Alan Eppel MB, FRCPC

ID https://orcid.org/0000-0002-4880-4097


Origins of the Borderline Personality Disorder (BPD) Concept

Borderline Personality Disorder (BPD) became an official diagnosis with the release of the Diagnostic and Statistical Manual of Mental Disorders III (DSM III) in 1980 [1]. The origins of the term “ borderline” date back to the 1940s when it was felt to be a disorder intermediate between neurosis and psychosis. Early nomenclature included “pseudoneurotic schizophrenia”  and “rejection-sensitive dysphoria”. Broad diagnostic validity for the borderline concept was subsequently determined [2]. The International Classification of Diseases (ICD) defines a parallel condition termed “emotionally unstable personality disorder” [3].

Psychotherapies

Therapeutic approaches to patients with BPD initially consisted of psychoanalytic therapies. Over the past two decades, more specific psychotherapies have been employed. Dialectical behaviour therapy is regarded as a first-line treatment [4]. Alternatives include mentalization-based psychotherapy [5] and transference focused psychotherapy [6] which have a moderate research base. Because a large percentage of patients with BPD have a history of childhood trauma, cognitive processing therapy may be required in addition to the other therapies [7].

Medication

The evidence for the effectiveness of medications for BPD is limited. Randomized controlled trials are often of short duration and exclude patients at risk of suicide attempts [8].

Antidepressants have been most frequently prescribed because of the prominence of depressive-like symptoms. However the nature of depressive symptoms in BPD may be qualitatively different from that of major depressive disorder and may have more correspondence to mood changes in bipolar disorder. Evidence for this is born out by worsening of irritability, impulsivity and suicide attempts with tricyclic antidepressants. This has also being noticed with other antidepressants such as selective serotonin reuptake inhibitors particularly in adolescents and younger adults.

Because of affective dysregulation, irritability and anger, antipsychotics have been used, frequently perphenazine, and now more recently second-generation and third generation antipsychotics. Mood stabilizers such as lithium, valproate, carbamazepine, and lamotrigine have been targeted at mood dysregulation, irritability and anger. They have shown some benefit but studies are small with low quality evidence. Benzodiazepines are widely prescribed as part of overall treatment targeting anxiety-related symptoms.

A remarkable recent study by Lieslehto et al. [9] based on the Swedish registered databases has challenged conventional wisdom and practice. The main outcomes were the number of attempted suicides and the number of completed suicides. There were 8513 hospitalizations for attempted suicides and 316 completed suicides. In this study, residents of Sweden between the ages of 16 and 65 years having a registered treatment contact for BPD, (ICD-10 code F60.3), between January 1, 2006 and June 30, 2021, were included. This involved 22,000 patients. Those with comorbid nonaffective psychotic disorder, bipolar disorder, psychotic depression, and other personality disorders were excluded [9].

Of the patients included in the study, 33.7% had comorbid substance use disorder; 56.6% had depression; 71.4% had anxiety disorder; and 17.2% had ADHD at baseline. One third of the sample had attempted suicide previously. Interestingly, 81.5% of the patients had received antidepressants at some point during treatment. More than half the patients were receiving benzodiazepines, 41% had received antipsychotics, and 31% received mood stabilizers. Of note, 24.4% were being treated with medications  for attention deficit hyperactivity disorder (ADHD). In this study quetiapine was the most commonly prescribed antipsychotic; lamotrigine was the commonest prescribed mood stabilizer, and methylphenidate was the commonest used ADHD medication.

The most dramatic finding from the study by Lieslehto et al. [9] was that treatment with ADHD medication was associated with a decreased risk of attempted or completed suicide (hazard ratio [HR] 0.82; 95% CI 0.72 – 0.92). Mood stabilizers, as a group, were not beneficial with a HR of 1.00, antidepressants with a HR of 1.33, and antipsychotics with a HR of 1.22 were not effective in reducing suicide attempts or completed suicide. The second most dramatic finding was that benzodiazepines were associated with a much higher risk of completed suicide with a HR of 4.23 (95% CI 3.23 – 5.53).

Regarding methodology for this study by Lieslehto et al. [9], the use of a registered database has some advantages over randomized controlled trials, in particular the length of the follow-up period. In this study, the average follow-up time was 6.9 years. This exceeds by far that which is possible in randomized controlled trials. Also many randomized controlled trials exclude patients at risk for attempted or completed suicide. In general the numbers of suicidal patients in randomized studies are too small to allow for a statistically relevant difference between those with and without suicidal behaviours or death by suicide. However a randomized controlled trial could provide further support to the conclusions of this study. In particular randomization can avoid the risk of confounding indication bias [10].

Take Away Points

  • Treatment with ADHD medication was associated with a decreased risk of attempted or completed suicide (hazard ratio [HR] 0.82; 95% CI 0.72 – 0.92).
  • Benzodiazepines were associated with a much higher risk of completed suicide with a HR of 4.23 (95% CI 3.23 – 5.53).
  • Mood stabilizers, as a group, with the HR of 1.00, antidepressants with a HR of 1.33, and antipsychotics with a HR of 1.22, reduced the risk of suicide or attempted suicide.

Future Research

One hypothesis is that these findings may be based on the symptom of impulsivity. ADHD medications and benzodiazepines may be moderating on the level of impulsivity. ADHD medications may have the effect of reducing impulsivity thereby reducing suicide attempts. Benzodiazepines can have the opposite effect, leading to disinhibition and increased impulsivity in some cases. Another explanation for the findings of this study is the high rate of coexistence of BPD and ADHD in this population.

Alternatively, it may be that impulsivity has a common neurobiological basis in both conditions related to GABA and glutamate neurotransmission with diminished control by the anterior cingulate over impulsive behaviour [11,12,13].

Further neuroscience research is needed to elucidate the role of specific neurotransmitters and neurocircuits in BPD and ADHD.  Randomized controlled trials are needed to compliment this  observational study.

References:

  1. American Psychiatric Association (APA) Diagnostic and statistical manual of mental disorders. Washington, DC: APA Press; 1980.
  2. Links PS, Steiner M, Offord DR, Eppel A. Characteristics of borderline personality disorder: a Canadian study. Can J Psychiatry. 1988 Jun;33(5):336-40. doi: 10.1177/070674378803300504
  3. ICD-11 Clinical Descriptions and Diagnostic Guidelines for Mental and Behavioural Disorders. 2018. https://gcp.network/en/private/icd-11-guidelines/disorders
  4. Linehan MM. Cognitive-Behavioral Treatment of Borderline Personality Disorder. New York, NY: Guilford Press; 1993
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  6. Kernberg O, Yeomans F,  Clarkin J, Levy J. (2008) Transference focused psychotherapy: Overview and update, The International Journal of Psychoanalysis, 89:3, 601-620.  doi:10.1111/j.1745-8315.2008.00046.x
  7. Resick P, Monson C, Chard K. Cognitive Processing Therapy for PTSD: A Comprehensive Manual. Guilford Publications, Dec 26, 2016.
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  9. Lieslehto J, Tiihonen J, Lähteenvuo M, Mittendorfer-Rutz E, Tanskanen A, Taipale H. Comparative effectiveness of pharmacotherapies for the risk of attempted or completed suicide among persons with borderline personality disorder. JAMA Netw Open. 2023 Jun 1;6(6):e2317130. doi: 10.1001/jamanetworkopen.2023.17130.
  10. Pai M, Kaufman J. Confounding by indication: a most stubborn bias? Bias file 7. The B files, McGill University, Montreal, Canada. https://www.teachepi.org/teaching-resources/bias-case-studies/
  11.  Eppel A. Borderline personality, pharmacotherapy and Gaba. Journal of psychiatry reform; 2017;  December 27;2(12):1-4.
  12. Qu S, Zhou X, Wang Z, Wei Y, Zhou H, Zhang X, Zhu Q, Wang Y, Yang Q, Jiang L, Ma Y, Gao Y, Kong L, Zhang L. The effects of methylphenidate and atomoxetine on Drosophila brain at single-cell resolution and potential drug repurposing for ADHD treatment. Mol Psychiatry. 2023 Nov 13. doi: 10.1038/s41380-023-02314-6. Epub ahead of print.
  13. Solleveld MM, Schrantee A, Puts NAJ, Reneman L, Lucassen PJ. Age-dependent, lasting effects of methylphenidate on the GABAergic system of ADHD patients. Neuroimage Clin. 2017 Jun 2;15:812-818. doi: 10.1016/j.nicl.2017.06.003
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