Evidence-Based Reviews

Pharmacologic treatment of borderline personality disorder

Current Psychiatry. 2011 August;10(8):30-40

References

1. American Psychiatric Association Practice Guidelines. Practice guideline for the treatment of patients with borderline personality disorder. American Psychiatric Association. Am J Psychiatry. 2001;158(10 suppl):1-52.

2. Barrash J, Kroll J, Carey K, et al. Discriminating borderline disorder from other personality disorders. Cluster analysis of the diagnostic interview for borderlines. Arch Gen Psychiatry. 1983;40(12):1297-1302.

3. Kety SS, Rosenthal D, Wender PH, et al. Mental illness in the biological and adoptive families of adopted individuals who have become schizophrenic: a preliminary report based on psychiatric interviews. Proc Annu Meet Am Psychopathol Assoc. 1975;(63):147-165.

4. Diagnostic and statistical manual of mental disorders, 3rd ed. Washington DC: American Psychiatric Association; 1980.

5. Serban G, Siegel S. Response of borderline and schizotypal patients to small doses of thiothixene and haloperidol. Am J Psychiatry. 1984;141(11):1455-1458.

6. Goldberg SC, Schulz SC, Schulz PM, et al. Borderline and schizotypal personality disorders treated with low-dose thiothixene vs placebo. Arch Gen Psychiatry. 1986;43(7):680-686.

7. Soloff PH, George A, Nathan RS, et al. Progress in pharmacotherapy of borderline disorders. A double-blind study of amitriptyline, haloperidol, and placebo. Arch Gen Psychiatry. 1986;43(7):691-697.

8. Soloff PH, George A, Nathan RS, et al. Paradoxical effects of amitriptyline on borderline patients. Am J Psychiatry. 1986;143(12):1603-1635.

9. Cowdry RW, Gardner DL. Pharmacotherapy of borderline personality disorder. Alprazolam carbamazepine, trifluoperazine, and tranylcypromine. Arch Gen Psychiatry. 1988;45(2):111-119.

10. Markovitz PJ, Calabrese JR, Schulz SC, et al. Fluoxetine in the treatment of borderline and schizotypal personality disorders. Am J Psychiatry. 1991;148(8):1064-1067.

11. Coccaro EF, Kavoussi RJ. Fluoxetine and impulsive aggressive behavior in personality-disordered subjects. Arch Gen Psychiatry. 1997;54(12):1081-1088.

12. Salzman C, Wolfson AN, Schatzberg A, et al. Effect of fluoxetine on anger in symptomatic volunteers with borderline personality disorder. J Clin Psychopharmacol. 1995;15(1):23-29.

13. Hollander E, Tracy KA, Swann AC, et al. Divalproex in the treatment of impulsive aggression: efficacy in cluster B personality disorders. Neuropsychopharmacology. 2003;28(6):1186-1197.

14. 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;63(5):442-446.

15. Schulz SC, Camlin KL, Berry SA, et al. Olanzapine safety and efficacy in patients with borderline personality disorder and comorbid dysthymia. Biol Psychiatry. 1999;46(10):1429-1435.

16. Bogenschutz MP, George Nurnberg H. Olanzapine versus placebo in the treatment of borderline personality disorder. J Clin Psychiatry. 2004;65(1):104-109.

17. Zanarini MC, Frankenburg FR. Olanzapine treatment of female borderline personality disorder patients: a double-blind placebo-controlled pilot study. J Clin Psychiatry. 2001;62(11):849-854.

18. Schulz SC, Zanarini MC, Bateman A, et al. Olanzapine for the treatment of borderline personality disorder: variable dose 12-week randomised double-blind placebo-controlled study. Br J Psychiatry. 2008;193(6):485-492.

19. Nickel MK, Muehlbacher M, Nickel C, et al. Aripiprazole in the treatment of patients with borderline personality disorder: a double-blind, placebo-controlled study. Am J Psychiatry. 2006;163(5):833-838.

20. Adityanjee, Romine A, Brown E, et al. Quetiapine in patients with borderline personality disorder: an open-label trial. Ann Clin Psychiatry. 2008;20(4):219-226.

21. Villeneuve E, Lemelin S. Open-label study of atypical neuroleptic quetiapine for treatment of borderline personality disorder: impulsivity as main target. J Clin Psychiatry. 2005;66(10):1298-1303.

22. Rocca P, Marchiaro L, Cocuzza E, et al. Treatment of borderline personality disorder with risperidone. J Clin Psychiatry. 2002;63(3):241-244.

23. Zanarini MC, Frankenburg FR. Omega-3 fatty acid treatment of women with borderline personality disorder: a double-blind placebo-controlled pilot study. Am J Psychiatry. 2003;160(1):167-169.

24. Ingenhoven T, Lafay P, Rinne T, et al. Effectiveness of pharmacotherapy for severe personality disorders: meta-analyses of randomized controlled trials. J Clin Psychiatry. 2010;71(1):14-25.

25. Moen Moore R, Miller M, Lee S, et al. Extended release divalproex for borderline personality disorder. Poster presented at: U. S. Psychiatric and Mental Health Congress; October 13-16, 2007; Orlando, FL.

26. Nose M, Cipriani A, Biancosino B, et al. Efficacy of pharmacotherapy against core traits of borderline personality disorder: meta-analysis of randomized controlled trials. Int Clin Psychopharmacol. 2006;21(6):345-353.

27. Lieb K, Völlm B, Rücker G, et al. Pharmacotherapy for borderline personality disorder: Cochrane Systematic Review of Randomised Trials. Br J Psychiatry. 2010;196(1):4-12.

28. Stoffers J, Völlm BA, Rücker G, et al. Pharmacological interventions for borderline personality disorder. Cochrane Database Syst Rev. 2010;(6):CD005653.-

29. National Collaborating Centre for Mental Health. Borderline personality disorder: the NICE guideline on treatment and management. National clinical practice guideline no. 78. London United Kingdom: RCPsych Publications; 2009.

30. Linehan MM, McDavid JD, Brown MZ, et al. Olanzapine plus dialectical behavior therapy for women with high irritability who meet criteria for borderline personality disorder: a double-blind, placebo-controlled pilot study. J Clin Psychiatry. 2008;69(6):999-1005.

31. Soler J, Pascual JC, Campins J, et al. Double-blind, placebo-controlled study of dialectical behavior therapy plus olanzapine for borderline personality disorder. Am J Psychiatry. 2005;162(6):1221-1224.

32. Simpson EB, Yen S, Costello E, et al. Combined dialectical behavior therapy and fluoxetine in the treatment of borderline personality disorder. J Clin Psychiatry. 2004;65(3):379-385.

33. Zanarini MC, Vujanovic AA, Parachini EA, et al. Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD): a continuous measure of DSM-IV borderline psychopathology. J Pers Disord. 2003;17(3):233-242.

34. Pfohl B, Blum N, St John D, et al. Reliability and validity of the Borderline Evaluation of Severity Over Time (BEST): a self-rated scale to measure severity and change in persons with borderline personality disorder. J Pers Disord. 2009;23(3):281-293.

35. Silk KR. Collaborative treatment for patients with personality disorders. In: Riba MB Balon R, eds. Psychopharmacology and psychotherapy: a collaborative approach. Washington, DC: American Psychiatric Press; 1999:221–277.

36. Zanarini MC. Update on pharmacotherapy of borderline personality disorder. Curr Psychiatry Rep. 2004;6(1):66-70.

Table 2

Which medications improve which BPD symptoms?

Medication	Symptom domain	Effect
Antipsychotics	Cognitive-perceptual	Moderate
Antipsychotics	Anger	Moderate/large
Antidepressants	Anxiety	Small
Antidepressants	Anger	Small
Mood stabilizers	Impulsive-behavioral dyscontrol	Very large
	Anger	Very large
	Anxiety	Large
	Depressed mood	Moderate
BPD: borderline personality disorder Source: Reference 24

Table 3

Pharmacotherapy for BPD: Results of a Cochrane review

Class	Medication(s)
Cognitive-perceptual symptoms
Antipsychotics	Olanzapine, aripiprazole
Impulsive-behavioral dyscontrol
Mood stabilizers	Topiramate, lamotrigine
Antipsychotics	Aripiprazole
Affective dysregulation
Antidepressants	Amitriptylinea (depressed mood)
Mood stabilizers	Topiramate, lamotrigine (anger), valproate (depressed mood)
Antipsychotics	Haloperidol (anger), olanzapine, aripiprazole
Omega-3 fatty acids	Fish oil (depression)
Suicidal behavior/suicidality
Antipsychotics	Flupenthixol decanoate
Omega-3 fatty acids	Fish oil
Interpersonal problems
Antipsychotics	Aripiprazole
Mood stabilizers	Valproate, topiramate
No improvement on any outcome: ziprasidone, thiothixene, phenelzine, fluoxetine, fluvoxamine, carbamazepine
^aDo not prescribe to suicidal patients BPD: borderline personality disorder Source: Reference 28

DBT and pharmacotherapy

As is the case with many studies of psychiatric medications, early efficacy studies of pharmacotherapy for BPD did not include structured psychosocial treatment. In 2 double-blind, placebo-controlled trials with a total of 84 patients receiving DBT, those assigned to olanzapine had better outcomes on objective rating scales than those on placebo.^30,31 Similar trials testing fluoxetine showed no advantage for the drug over placebo.³² In a pilot study by Moen et al,²⁵ 17 patients were assigned to “condensed DBT” before being randomized to divalproex extended release or placebo. Two patients remitted in the first 4 weeks and continued to improve without medication. If replicated, this finding may point to a targeted approach to the timing of medication initiation.

Clinical recommendations

Randomized, placebo-controlled BPD trials have demonstrated striking improvements in patients in placebo groups, which may be attributed to the powerful therapeutic impact of regular, structured, nonjudgmental interactions within a research protocol. Prescribers can enhance a medication’s therapeutic effect by keeping in mind the same principles that apply to treatment of other common psychiatric disorders.

Patients with BPD respond well to validation of their symptoms and their experience. Tell patients you take their BPD symptoms seriously and acknowledge their distress. The goal is to partner with patients to improve function, decrease reactivity, and reduce emotional pain. When working with BPD patients, it is appropriate to communicate a sense of optimism and hopefulness about their prognosis and treatment. Performing this approach in a caring way will better preserve the therapeutic alliance.

Additional suggestions based on our clinical experience include:

Provide regular medication management visits.
Consider using a structured symptom rating scale to evaluate symptoms over time, such as the Zanarini Rating Scale for Borderline Personality Disorder³³ or Borderline Evaluation of Severity Over Time.³⁴
Educate patients with BPD about the disorder by making the appropriate diagnosis and providing reputable educational materials (see Related Resources).
Do not diagnose a patient with BPD as having bipolar disorder unless they clearly meet criteria for bipolar disorder.
Communicate your limitations in advance.
Orient the patient to the possibility of needing to try different medications to determine the most helpful agent or combination.
Do not de-emphasize risks of medications or side effects. Serious symptoms require medications that bear a risk of side effects; communicate these risks to patients and carefully weigh the risk-benefit profile.
Inform patients you will be responsive to making appropriate changes if problems arise that are associated with pharmacotherapy and outweigh the benefit of medication.

Multidisciplinary teamwork

Best outcomes for patients with BPD are facilitated by a collaborative team effort. Such an approach addresses both the psychological and biologic underpinnings of the disorder and can significantly decrease the possibility of “splitting” among team members. To determine ways in which a therapist and physician may work together, clinicians should discuss the:

meaning of medication to the therapist, psychiatrist, and patient
potential benefits and limitations of medication
the role of medication in the patient’s overall treatment.³⁵

Patients with BPD experience emotional crisis. At times, prescribing patterns unfortunately reflect the practice of adding medications to address emotional crisis. This practice may partially account for the high rates of polypharmacy in BPD patients.³⁶ Patients with BPD will benefit from interacting with a clinician whose approach is responsive, validating, and non-reactive to the patient’s symptoms and experiences. A comprehensive treatment approach includes screening and treating comorbid conditions, providing education about the diagnosis, and multidisciplinary involvement combined with rational, targeted pharmacotherapy.

Related Resources

Friedel RO. Borderline personality disorder demystified: an essential guide for understanding and living with BPD. New York, NY: Marlowe & Company; 2004.
Chapman A, Gratz K. Borderline personality disorder survival guide: everything you need to know about living with BPD. Oakland, CA: New Harbinger Publications, Inc; 2007.
National Education Alliance for Borderline Personality Disorder. www.borderlinepersonalitydisorder.com.

Drug Brand Names

Alprazolam • Xanax
Amitriptyline • Elavil
Aripiprazole • Abilify
Carbamazepine • Tegretol
Fluoxetine • Prozac
Fluvoxamine • Luvox
Haloperidol • Haldol
Lamotrigine • Lamictal
Olanzapine • Zyprexa
Phenelzine • Nardil
Quetiapine • Seroquel
Risperidone • Risperdal
Thiothixene • Navane
Topiramate • Topamax, Topiragen
Tranylcypromine • Parnate
Trifluoperazine • Stelazine
Valproic acid • Depakote
Ziprasidone • Geodon

Disclosure