BORDERLINE PERSONALITY, PHARMACOTHERAPY AND GABA
- Posted by Editor JPR
- Posted in Editorials & Commentary
Vol 2 #12
Alan Eppel MB, FRCPC
Many clinicians find that the outcomes of pharmacological treatment in borderline personality disorder are very disappointing.
Antidepressants, particularly SSRIs, are prescribed by a preponderance if not the majority of psychiatrists. This is partly rationalized on the basis that impulsivity and aggression are related to serotonin function. The clinical evidence has not supported this hypothesis.
In this context three recent publications open up an alternative avenue of research.
The first study comes from researchers in Heidelberg Germany and Leiden in the Netherlands and published in February 2017 in Neuroimage (1).
The authors note that impulsivity develops from dysfunction in the inhibitory control areas of the brain: the anterior cingulate cortex and the fronto-striatal system. Gamma-aminobutyric acid (GABA) is the major neurotransmitter involved. The results of this functional MRI comparison between patients with borderline personality and healthy controls found that patients have less functional connectivity between the anterior cingulate cortex and the caudate. They concluded that this GABA mediated connectivity in the anterior cingulate, is associated with impulsive sensation seeking.
Another study carried out by members of the same group in Germany examined 26 patients with borderline personality disorder, 22 with ADHD and 30 healthy controls. All subjects were female. Using 1H MR spectroscopy they measured GABA levels and glutamate in the anterior cingulate cortex. Both diagnostic groups had higher scores on impulsivity, anger and aggression compared to the healthy controls. GABA levels were significantly lower in ADHD than in controls. Impulsivity was related to higher levels of glutamate and to lower levels of GABA. Aggression also was associated with lower levels of GABA. This study provides further evidence for the role of these two neurotransmitters in mediating impulsive and aggressive behaviours in this population.
A third study published online in November 2017 examined the relationship between emotion regulation and prefrontal glutamate in patients with cluster B and cluster C personality disorders (3). Twenty two of the subjects had cluster B, 21 cluster C and there were 60 healthy controls. Almost half of the clinical groups were taking low-dose antidepressant medication.
Higher levels of glutamate were found bilaterally in the dorsolateral prefrontal cortex in cluster B patients. There were decreased levels in cluster C patients. Higher levels of glutamate may correlate with poor control of impulsiveness in cluster B patients. Conversely decreased levels of glutamate may be related to emotional over-control in cluster C patients.
These findings provide some preliminary support for the movement away from antidepressants to mood stabilizers in the treatment of impulsivity in borderline personality disorder. Valproate has the most evidence for this although several studies have found olanzapine effective (See additional references below).
- Wang GY, van Eijk J, Demirakca T et al. ACC GABA levels are associated with functional activation and connectivity in the fronto-striatal network during interference inhibition in patients with borderline personality disorder. Neuroimage. 2017 Feb 15;147:164-174. doi: 10.1016/j.neuroimage.2016.12.013. Epub 2016 Dec 7.
- Ende G, Cackowski S, Van Eijk et al. Impulsivity and Aggression in Female BPD and ADHD Patients: Association with anterior cingulate cortex Glutamate and GABA Concentrations. Neuropsychopharmacology. 2016 Jan;41(2):410-8. doi: 10.1038/npp.2015.153.
- Smesny S Große J, Gussew A et al. Prefrontal glutamatergic emotion regulation is disturbed in cluster B and C personality disorders – A combined 1H/31P-MR spectroscopic study. J Affect Disord. 2017 Nov 7;227:688-697. doi: 10.1016/j.jad.2017.10.044.
- Abraham PF, Calabrese JR. Evidenced-based pharmacologic treatment of borderline personality disorder: a shift from SSRIs to anticonvulsants and atypical antipsychotics? J Affect Disord. 2008 Nov;111(1):21-30. doi: 10.1016/j.jad.2008.01.024. Epub 2008 Mar
- Hollander E, Swann AC, Coccaro EF, Jiang P, Smith TB. Impact of trait impulsivity and state aggression on divalproex versus placebo response in borderline personality disorder. Am J Psychiatry. 2005 Mar;162(3):621-4
Bellino S, Bozzatello P, Rocca G, Bogetto F. Efficacy of omega-3 fatty acids
in the treatment of borderline personality disorder: a study of the association
with valproic acid. J Psychopharmacol. 2014 Feb;28(2):125-32. doi:
10.1177/0269881113510072. Epub 2013 Nov 5.
Frankenburg FR, Zanarini MC. Divalproex sodium treatment of women with
borderline personality disorder and bipolar II disorder: a double-blind
placebo-controlled pilot study. J Clin Psychiatry. 2002 May;63(5):442-6
Gescher DM, Malevani J. [Mood stabilizer in the psychopharmacotherapy of
borderline personality disorder]. Fortschr Neurol Psychiatr. 2009
Jul;77(7):389-98. doi: 10.1055/s-0028-1109455. Epub 2009 May 19. Review. German.
Hollander E, Allen A, Lopez RP, Bienstock CA, Grossman R, Siever LJ, Merkatz
L, Stein DJ. A preliminary double-blind, placebo-controlled trial of divalproex
sodium in borderline personality disorder. J Clin Psychiatry. 2001Mar;62(3):199-203.
Huband N, Ferriter M, Nathan R, Jones H. Antiepileptics for aggression and
associated impulsivity. Cochrane Database Syst Rev. 2010 Feb 17;(2):CD003499.
doi: 10.1002/14651858.CD003499.pub3. Review.
Lieb K, Völlm B, Rücker G, Timmer A, Stoffers JM. Pharmacotherapy for
borderline personality disorder: Cochrane systematic review of randomised trials.
Br J Psychiatry. 2010 Jan;196(1):4-12. doi: 10.1192/bjp.bp.108.062984. Review.
Mendonça Júnior FJ, Scotti L, Ishiki H et al. Benzo- and thienobenzo- diazepines: multi-target drugs for CNS disorders. Mini Rev Med Chem. 2015;15(8):630-47. Review
Simeon D, Baker B, Chaplin W, Braun A, Hollander E. An open-label trial of
divalproex extended-release in the treatment of borderline personality disorder.
CNS Spectr. 2007 Jun;12(6):439-43.
Stoffers J, Völlm BA, Rücker G, Timmer A, Huband N, Lieb K. Pharmacological
interventions for borderline personality disorder. Cochrane Database Syst Rev.
2010 Jun 16;(6):CD005653. doi: 10.1002/14651858.CD005653.pub2.
Wilcox JA. Divalproex sodium as a treatment for borderline personality
disorder. Ann Clin Psychiatry. 1995 Mar;7(1):33-7.
Wilcox J. Divalproex sodium in the treatment of aggressive behavior. Ann Clin
Psychiatry. 1994 Mar;6(1):17-20.
Zarghami M, Sheikhmoonesi F, Ala S et al. A comparative study
of beneficial effects of Olanzapine and sodium valproate on aggressive behavior
of patients who are on methadone maintenance therapy: a randomized triple blind
clinical trial. Eur Rev Med Pharmacol Sci. 2013 Apr;17(8):1073-81.