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Dr. Nelson: Strategies for improving
ONLINE
pharmacotherapy for patients with BPD ONLY

cologic treatment of
borderline personality disorder
Evidence suggests symptom-targeted
pharmacotherapy can be beneficial

A
Katharine Nelson, MD s psychiatrys understanding of borderline personality disor-
Assistant Professor der (BPD) grows, the literature clearly describes the seriousness
S. Charles Schulz, MD of BPD, as well as these patients high utilization of treatment.
Professor and Head
Pharmacotherapy for BPD remains controversial. The most recent
Donald W. Hastings Endowed Chair
American Psychiatric Association practice guidelines focus on using

symptom domains of this heterogeneous illness to guide medication
Department of Psychiatry selection, yet when these guidelines were published, there was a lack
University of Minnesota Medical School
Minneapolis, MN
of data to support this recommendation.1
This article evaluates medications for BPD and emerging data sup-
porting matching medications to BPD symptom domains, with an em-
phasis on making choices that advance clinical practice. We conclude
by reviewing studies of combined pharmacotherapy and dialectical be-
havior therapy (DBT) and describing how a multidisciplinary team ap-
proach can enhance BPD treatment.

Early research
Early studies of pharmacotherapy for BPD began after the development
CLAIRE MORGAN/MONSOON/PHOTOLIBRARY/CORBIS

of the Diagnostic Interview for Borderlines2,3 and DSM-III criteria for


BPD.4 Researchers recruited patients who fulfilled the diagnostic crite-
ria; however, these participants symptom profiles were highly hetero-
geneous. Although such studies can be useful when starting to test new
treatmentsespecially if they are able to show efficacy over placebo or
explore safetythey are less helpful in guiding clinical practice.
During the 1980s, low doses of first-generation antipsychotics were
evaluated based on hypotheses that BPD was related to schizophrenia.
Case series5 and placebo-controlled trials6,7 pointed to symptom reduc-

Current Psychiatry
Vol. 10, No. 8 31
tion over time and greater than placebo for divalproex in BPD patients with bipolar
BPD patients. Interestingly, in a small study II disorder has implications for targeted
of BPD inpatients, Soloff et al8 compared the treatment (discussed below).
first-generation antipsychotic haloperidol to
amitriptyline and found amitriptyline led Newer antipsychotics. The introduction of
to symptom worsening in some patients. second-generation antipsychotics (SGA) led
Cowdry and Gardner9 compared alpra- some researchers to explore whether these
Pharmacotherapy zolam, carbamazepine, trifluoperazine, and agents could decrease BPD symptoms.
for BPD tranylcypromine in a double-blind, placebo- Case series15 and some (but not all) placebo-
controlled crossover trial of 16 female BPD controlled trials have demonstrated benefit
outpatients. They found antipsychotics were from SGAs such as olanzapine,16-18 aripipra-
not useful. Further, the study found behav- zole,19 and quetiapine.20,21 Initial research on
ioral disinhibition when a benzodiazepine risperidone22 and ziprasidone also suggest-
(alprazolam) was used alone in impulsive ed efficacy for BPD. Two placebo-controlled
patients. studies of olanzapine examined which
These studies provided a basis for the idea symptom groups were most helped; each
Clinical Point that medications could help reduce BPD reported a broad effect.16,17 However, not all
Careful identification symptoms. However, some early investiga- studies of SGAs for BPD patients have been
tors noted that antipsychotics side effects positive.18 Further, metabolic side effects
of comorbid
led some patients to discontinue treatment.6 have been noted for several SGAs, includ-
psychiatric disorders ing olanzapine.18
is a rational first step
in treating patients Next-generation studies Omega-3 fatty acids. Some studies exam-
Antidepressants. Interest in exploring ining omega-3 fatty acids have sparked an
with borderline
pharmacologic treatments for BPD dimin- ongoing interest in this compound. In an
personality disorder ished after the early efficacy trials. Several 8-week, double-blind, pilot study of 30 wom-
events led to a reemergence of this interest, en with BPD, Zanarini23 found omega-3 fatty
including the FDAs approval of the selec- acids demonstrated efficacy over placebo.
tive serotonin reuptake inhibitor fluoxetine
for depression in 1987. Some investigators
hypothesized fluoxetines antidepressant Targeted treatment
properties could help treat BPD symptoms Most studies of BPD pharmacotherapy
and perhaps the serotonin reuptake action have used a classic clinical trial design,
could diminish impulsivity.10 Case series which does not easily translate into rec-
and a double-blind, placebo-controlled ommendations regarding medication se-
trial11 demonstrated fluoxetines efficacy lection for individual patients, especially
in BPD. In 1 study, Salzman et al12 found those with BPD and comorbid illnesses.
fluoxetines greatest impact was on an- Also, existing trials have not fully explored
ger, a major affective dimension of BPD. starting doses, and no maintenance stud-
ies have been published. Therefore, many
Mood stabilizers. When valproic acid clinical application questions remain un-
emerged as a successful treatment for bi- resolved. However, some early treatment
polar disorder, researchers turned their recommendations are supported by recent
ONLINE
ONLY attention to mood-stabilizing anticonvul- meta-analyses that demonstrate effects of
sants for BPD. Numerous case series and medication classes for specific symptom
Discuss this article at controlled trials provided evidence of its domains.
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efficacy.13,14 This was the first time sub- Careful identification of comorbid psy-
CurrentPsychiatry
types of BPD patients were tested pro- chiatric disorders is a rational first step.
spectivelywith the hypothesis that the Diagnosing comorbid disorders, such as
mood-stabilizing anticonvulsants would bipolar disorder, will determine medica-
diminish impulsivity and aggression. The tion choice and impact length of treatment.
Current Psychiatry
positive results of Hollander et al13 and In a double-blind study of 30 women with
32 August 2011 Frankenburg and Zanarini14 in assessing BPD and comorbid bipolar II disorder,
continued on page 36
continued from page 32

Table 1 patient who has overwhelming distress,


it is tempting to start with high medica-
Symptom domains of BPD tion doses; however, clinical experience
Cognitive-perceptual symptoms suggests starting cautiously with lower
Suspiciousness
doses will yield better tolerability and ad-
herence. Based on our clinical experience,
Referential thinking
patients with BPD tend to be highly per-
Paranoid ideation
Pharmacotherapy ceptive to physiologic stimuli and medica-
Illusions
for BPD tion side effects.
Derealization
Further research is needed to answer
Depersonalization clinical questions regarding optimal dosing
Hallucination-like symptoms strategy and treatment, but some studies
Impulsive-behavioral dyscontrol suggest when using SGAs, doses equiva-
Impulsive aggression lent to one-third or one-half the dose used
Deliberate self-harm for treating schizophrenia may be appropri-
Impulsive sexual behavior ate.1,2,17,18 However, for fluoxetine, investiga-
Clinical Point Substance abuse tors have espoused using a dosage higher
When treating Impulsive spending than generally used for depression.10 For
Affective dysregulation mood-stabilizing anticonvulsants, almost
BPD, SGA doses
Mood lability all studies employed the same doses used
equal to one-half or for bipolar disorder.25 Some studies of val-
Rejection sensitivity
one-third the dose Intense anger out of proportion to the stimuli
proic acid have verified appropriate blood
used for treating levelsgenerally 50 to 100 g/mL.
Sudden depressive mood episodes
Controlled trials have not determined
schizophrenia may BPD: borderline personality disorder
whether medications for patients with
be appropriate Source: Reference 24
BPD should be used briefly during times
of stress or for longer periods. Many stud-
ies of medication for BPD have been rela-
Frankenburg and Zanarini14 found dival- tively brief trials that explored whether
proex had a statistically significant effect the drug has any potential efficacy. In our
compared with placebo and could be con- opinion, this issue currently is being ad-
sidered for this specific population. dressed in clinical practice in a trial-and-
When treating a BPD patient who has error manner.
a comorbid illness, it is important not to
ignore BPD symptoms. The chronic emo-
tional dysregulation and ongoing safety Clues to targeted treatment
issues require psychiatrists to educate Although pharmacotherapy for BPD sub-
patients about these symptoms and to ad- types remains controversial, recent meta-
dress them in a multidisciplinary manner. analyses by Ingenhoven24 and Nose26 and
Clarifying prominent symptom do- a Cochrane Review27 (with subsequent
mains can help steer pharmacologic man- online update28) have identified evidence
agement. Many trials have attempted to that supports the use of specific medica-
focus on specific symptom domains, in- tions for treating BPD symptoms. These
cluding cognitive-perceptual disturbances, studies authors acknowledge replication
impulsivity, and affective dysregulation. studies are required because of the limited
Table 124 lists BPD symptom domains and nature of the available data. In contrast, a
associated characteristics. meta-analysis conducted by the National
Collaborating Centre for Mental Health29
did not identify sufficient evidence for
Dosing strategy medication use in BPD on which to base
Developing a medication management official guidelines to advise health care
Current Psychiatry
strategy for BPD patients requires a providers in the United Kingdom. The
36 August 2011 thoughtful approach. When faced with a only medication recommendation in this
Table 2

Which medications improve which BPD symptoms?


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

Clinical Point
meta-analysis is to consider prescribing symptoms (Table 3, page 38). The authors
28
In 1 meta-analysis,
short-term sedative antihistamines during recommended data be interpreted cautious-
mood stabilizers had
crises; this recommendation is not sup- ly, however, because many of the clinical tri-
ported by any clinical trial. als included in their meta-analysis have not a greater effect than
In a meta-analysis of 21 placebo-controlled been replicated and generalizability from re- antipsychotics on
trials of patients with BPD and/or schizo- search populations to clinical populations is BPD patients global
typal personality disorder, Inghoven et al24 not well understood.
functioning
used multiple domains and subdomains,
including cognitive-perceptual symptoms,
impulsive-behavioral dyscontrol, affective DBT and pharmacotherapy
dysregulation, anger, and mood lability, to As is the case with many studies of psy-
assess the efficacy of medication use (Table chiatric medications, early efficacy stud-
2).24 They found: ies of pharmacotherapy for BPD did not
Antipsychotics seemed to have a mod- include structured psychosocial treatment.
erate effect on cognitive-perceptual symp- In 2 double-blind, placebo-controlled trials
toms and a moderate-to-large effect on with a total of 84 patients receiving DBT,
anger. those assigned to olanzapine had better
Antidepressants had a small effect on outcomes on objective rating scales than
anxiety, but no other domains. those on placebo.30,31 Similar trials testing
Mood stabilizers had a very large ef- fluoxetine showed no advantage for the
fect on impulsive-behavioral dyscontrol drug over placebo.32 In a pilot study by
and anger, a large effect on anxiety, and a Moen et al,25 17 patients were assigned to
moderate effect on depressed mood. condensed DBT before being random-
Regarding global functioning, mood ized to divalproex extended release or
stabilizers had a greater effect than anti- placebo. Two patients remitted in the first
psychotics. Both led to greater change than 4 weeks and continued to improve without
antidepressants. medication. If replicated, this finding may
A 2010 Cochrane Review meta-analysis point to a targeted approach to the timing
initially conducted by Leib27 with subse- of medication initiation.
quent online update by Stoffers28 included 28
studies with a total of 1,742 patients and also
identified symptom-targeted BPD domains. Clinical recommendations
This study analyzed pooled data and found Randomized, placebo-controlled BPD trials
support for the use of specific medications, have demonstrated striking improvements
including certain antipsychotics, mood stabi- in patients in placebo groups, which may Current Psychiatry
lizers, and antidepressants, for specific BPD be attributed to the powerful therapeutic Vol. 10, No. 8 37
Table 3

Pharmacotherapy for BPD: Results of a Cochrane review


Class Medication(s)
Cognitive-perceptual symptoms
Antipsychotics Olanzapine, aripiprazole
Impulsive-behavioral dyscontrol
Pharmacotherapy Mood stabilizers Topiramate, lamotrigine
for BPD 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)
Clinical Point Suicidal behavior/suicidality
Antipsychotics Flupenthixol decanoate
Patients with BPD Omega-3 fatty acids Fish oil
respond well to Interpersonal problems
validation of their Antipsychotics Aripiprazole
symptoms and their Mood stabilizers Valproate, topiramate
experience No improvement on any outcome: ziprasidone, thiothixene, phenelzine, fluoxetine, fluvoxamine,
carbamazepine
Do not prescribe to suicidal patients
a

BPD: borderline personality disorder


Source: Reference 28

impact of regular, structured, nonjudgmen- over time, such as the Zanarini Rating
tal interactions within a research protocol. Scale for Borderline Personality Disorder33
Prescribers can enhance a medications or Borderline Evaluation of Severity Over
therapeutic effect by keeping in mind the Time.34
same principles that apply to treatment of Educate patients with BPD about the
other common psychiatric disorders. disorder by making the appropriate diag-
Patients with BPD respond well to valida- nosis and providing reputable educational
tion of their symptoms and their experience. materials (see Related Resources).
Tell patients you take their BPD symptoms Do not diagnose a patient with BPD as
seriously and acknowledge their distress. having bipolar disorder unless they clearly
The goal is to partner with patients to im- meet criteria for bipolar disorder.
prove function, decrease reactivity, and re- Communicate your limitations in
duce emotional pain. When working with advance.
BPD patients, it is appropriate to commu- Orient the patient to the possibility of
nicate a sense of optimism and hopeful- needing to try different medications to deter-
ness about their prognosis and treatment. mine the most helpful agent or combination.
Performing this approach in a caring way Do not de-emphasize risks of medi-
will better preserve the therapeutic alliance. cations or side effects. Serious symptoms
Additional suggestions based on our require medications that bear a risk of side
clinical experience include: effects; communicate these risks to patients
Provide regular medication manage- and carefully weigh the risk-benefit profile.
ment visits. Inform patients you will be responsive
Current Psychiatry
Consider using a structured symp- to making appropriate changes if prob-
38 August 2011 tom rating scale to evaluate symptoms lems arise that are associated with phar-
macotherapy and outweigh the benefit of
medication. Related Resources
Friedel RO. Borderline personality disorder demystified: an
essential guide for understanding and living with BPD. New
York, NY: Marlowe & Company; 2004.
Multidisciplinary teamwork Chapman A, Gratz K. Borderline personality disorder sur-
Best outcomes for patients with BPD are vival guide: everything you need to know about living with
BPD. Oakland, CA: New Harbinger Publications, Inc; 2007.
facilitated by a collaborative team effort.
National Education Alliance for Borderline Personality
Such an approach addresses both the psy- Disorder. www.borderlinepersonalitydisorder.com.
chological and biologic underpinnings of Drug Brand Names
the disorder and can significantly decrease Alprazolam Xanax Quetiapine Seroquel
the possibility of splitting among team Amitriptyline Elavil Risperidone Risperdal
Aripiprazole Abilify Thiothixene Navane
members. To determine ways in which a Carbamazepine Tegretol Topiramate Topamax,
therapist and physician may work togeth- Fluoxetine Prozac Topiragen
Fluvoxamine Luvox Tranylcypromine Parnate
er, clinicians should discuss the:
Haloperidol Haldol Trifluoperazine Stelazine
meaning of medication to the thera- Lamotrigine Lamictal Valproic acid Depakote
pist, psychiatrist, and patient Olanzapine Zyprexa Ziprasidone Geodon
Phenelzine Nardil
potential benefits and limitations of Clinical Point
medication Disclosures Explain to patients
the role of medication in the patients Dr. Nelson receives research/grant support from the
that they may need
overall treatment.35 Minnesota Medical Foundation.
Patients with BPD experience emotional Dr. Schulz receives research/grant support from AstraZeneca, to try different
Otsuka, and Rules-Based Medicine and is a consultant to Bioavail,
crisis. At times, prescribing patterns un- Bristol-Myers Squibb, and Eli Lilly and Company. medications to find
fortunately reflect the practice of adding the most helpful agent
medications to address emotional crisis.
or combination
This practice may partially account for pharmacotherapy of borderline disorders. A double-blind
the high rates of polypharmacy in BPD study of amitriptyline, haloperidol, and placebo. Arch Gen
Psychiatry. 1986;43(7):691-697.
patients.36 Patients with BPD will benefit 8. Soloff PH, George A, Nathan RS, et al. Paradoxical effects
from interacting with a clinician whose ap- of amitriptyline on borderline patients. Am J Psychiatry.
1986;143(12):1603-1635.
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reactive to the patients symptoms and personality disorder. Alprazolam, carbamazepine,
trifluoperazine, and tranylcypromine. Arch Gen Psychiatry.
experiences. A comprehensive treatment 1988;45(2):111-119.
approach includes screening and treating 10. Markovitz PJ, Calabrese JR, Schulz SC, et al. Fluoxetine in
the treatment of borderline and schizotypal personality
comorbid conditions, providing education disorders. Am J Psychiatry. 1991;148(8):1064-1067.
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fluoxetine on anger in symptomatic volunteers with
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interventions for borderline personality disorder. Cochrane
and nonreactive to
their symptoms

Bottom Line
Emerging evidence supports using pharmacologic therapy to improve
specific symptoms of borderline personality disorder. Taking a responsive,
validating, nonreactive management approach that includes evidence-based
psychotherapy will allow a multidisciplinary team of clinicians to provide
Current Psychiatry
40 August 2011 better treatment and achieve a stronger therapeutic alliance.