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V. Disease Definition,
Epidemiology,
and Natural History
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A. Definition and Core Clinical Features
The essential feature of borderline personality disorder is
a pervasive pattern of instability of interpersonal relationships,
affects, and self-image, as well as marked impulsivity that begins
by early adulthood and appears in a variety of contexts. These characteristics
are severe and persistent enough to result in clinically significant
impairment in social, occupational, or other important areas of functioning.
Common and important features of borderline personality disorder
are a severely impaired capacity for attachment and predictably
maladaptive behavior in response to separation. Individuals with
this disorder are very sensitive to abandonment and make frantic
efforts to avoid real or perceived abandonment. They often experience
intense abandonment fears and anger in reaction to even realistic
time-limited separation. Efforts to avoid abandonment may include inappropriate
rage, unfair accusations, and impulsive behaviors such as self-mutilation
or suicidal behaviors, which often elicit a guilty or fearful protective
response from others.
The relationships of individuals with borderline personality
disorder tend to be unstable, intense, and stormy. Their views of
others may suddenly and dramatically shift, alternating between
extremes of idealization and devaluation, or seeing others as beneficent
and nurturing and then as cruel, punitive, and rejecting. These
shifts are particularly likely to occur in response to disillusionment with
a significant other or when a sustaining relationship is threatened
or lost.
The disorder is usually characterized by identity disturbance,
which consists of markedly and persistently unstable self-image
or sense of self. Self-image (goals, values, type of friends, vocational goals)
may suddenly and dramatically shift. Individuals with this disorder
usually feel bad or evil, but they may also feel that they do not
exist at all, especially when feeling unsupported and alone.
Many individuals with borderline personality disorder are
impulsive in one or more potentially self-damaging areas, such as
spending money irresponsibly, gambling, engaging in unsafe sexual behavior,
abusing drugs or alcohol, driving recklessly, or binge eating. Self-mutilation
(e.g., cutting or burning) and recurrent suicidal behaviors, gestures,
or threats are common. These self-destructive acts are often precipitated
by potential separation from others, perceived or actual rejection
or abandonment, or the expectation from others that they assume
more responsibility.
Affective instability is another common feature of the disorder.
This consists of marked mood reactivity (e.g., intense episodic
dysphoria, irritability, or anxiety that usually lasts for a few
hours and only rarely for more than a few days). The usual dysphoric
mood of these individuals is often punctuated by anger, panic, or
despair and is only infrequently relieved by periods of well-being. These
episodes may be triggered by the individual's extreme reactivity
to interpersonal stressors. Individuals with this disorder also
typically have chronic feelings of emptiness. Many experience inappropriate,
intense anger or have difficulty controlling their anger. For example,
they may lose their temper, feel constant anger, have verbal outbursts,
or engage in physical fights. This anger may be triggered by their
perception that an important person is neglectful, withholding,
uncaring, or abandoning. Expressions of anger may be followed by
feelings of being evil or by feelings of shame and guilt. During
periods of extreme stress (e.g., perceived or actual abandonment),
these individuals may experience transient paranoid ideation or
severe dissociative symptoms (e.g., depersonalization).
It is not necessary for an individual to have all of the above
features for borderline personality disorder to be diagnosed. As
indicated in Table 1, the diagnosis is given if at least five of
the nine diagnostic criteria are present.
Transient psychotic-like symptoms (e.g., hearing their name
called) may occur at times of stress. These episodes usually last
for minutes or hours and are generally of insufficient duration
or severity to warrant an additional diagnosis. Another common associated
feature is a tendency for these individuals to undermine themselves
when a goal is about to be reached (e.g., severely regressing after
a discussion of how well therapy is going). Individuals with this
disorder may feel more secure with transitional objects (e.g., a
pet or inanimate object) than with interpersonal relationships.
Despite their significant relationship problems, they may deny that
they are responsible for such problems and may instead blame others
for their difficulties.
Physical and sexual abuse, neglect, hostile conflict, and
early parental loss or separation are more common in the childhood
histories of those with borderline personality disorder than in
those without the disorder.
Axis I disorders and other axis II disorders are often comorbid
with borderline personality disorder. Among the most common comorbid
axis I disorders are mood disorders, substance-related disorders, eating
disorders (notably bulimia), PTSD, panic disorder, and ADHD. Such
axis I comorbidity can complicate and worsen the course of borderline
personality disorder. Commonly co-occurring axis II disorders are
antisocial, avoidant, histrionic, narcissistic, and schizotypal
personality disorders.
Borderline personality disorder is characterized by notable
distress and functional impairment. A majority of patients attempt
suicide. Completed suicide occurs in 8%–10% of
individuals with this disorder, a rate that is approximately 50
times higher than in the general population. Risk of suicide appears
to be highest when patients are in their 20s as well as in the presence
of co-occurring mood disorders or substance-related disorders (87).
Physical handicaps may result from self-inflicted injury or failed
suicide attempts. These individuals often have notable difficulty
with occupational, academic, or role functioning. Their functioning
may deteriorate in unstructured work or school situations, and recurrent
job loss and interrupted education are common. Difficulties in relationships, as
well as divorce, are also common.
The social cost for patients with borderline personality disorder
and their families is substantial. Longitudinal studies of patients
with borderline personality disorder indicate that even though these patients
may gradually attain functional roles 10–15 years after
admission to psychiatric facilities, still only about one-half will
have stable, full-time employment or stable marriages (40, 134).
Recent data indicate that patients with borderline personality disorder
show greater lifetime utilization of most major categories of medication
and of most types of psychotherapy than do patients with schizotypal,
avoidant, or obsessive-compulsive personality disorder or patients
with major depressive disorder (135).
A skilled clinical interview is the mainstay of diagnosing
borderline personality disorder. This approach should be complemented
by knowledge of the DSM criteria and a longitudinal view of the clinical
picture. The additional use of assessment instruments can be useful,
especially when the diagnosis is unclear. Use of such instruments
must be accompanied by clinical judgment.
Certain assessment issues relevant to all personality disorders
should be considered when diagnosing borderline personality disorder.
For the diagnosis to be made, the personality traits must cause
subjective distress or significant impairment in functioning. The
traits must also deviate markedly from the culturally expected and
accepted range, or norm, and this deviation must be manifested in
more than one of the following areas: cognition, affectivity, control
over impulses, and ways of relating to others. Therefore, multiple
domains of experience and behavior (i.e., cognition, affect, intrapsychic
experience, and interpersonal interaction) must be assessed to determine
whether borderline traits are distressing or impairing. The clinician
should also ascertain that the personality traits are of early onset,
pervasive, and enduring; they should not be transient or present
in only one situation or in response to only one specific trigger.
It is important that borderline personality disorder be assessed
as carefully in men as in women.
The ego-syntonicity of the personality traits may complicate
the assessment process; the use of multiple sources of information
(e.g., medical records and informants who know the patient well)
can be particularly helpful in establishing the diagnosis if the
patient's self-awareness is limited. Given the high comorbidity
of axis I disorders with borderline personality disorder, it is
important to do a full axis I evaluation. An attempt should be made
to distinguish axis I states (e.g., mood disorder) from borderline
personality disorder, which can be a complex process. Useful approaches
are to obtain a description of the patient's personality
traits and coping styles when prominent axis I symptoms are absent
and to use information provided by people who have known the patient
without an axis I disorder. If axis I disorders are present, both
the axis I disorders and borderline personality disorder should
be diagnosed.
Because the personality of children and adolescents is still
developing, borderline personality disorder should be diagnosed
with care in this age group. Often, the presence of the disorder
does not become clear until late adolescence or adulthood.
When assessing a patient with borderline personality disorder,
the clinician should carefully look for the presence of risk-taking
and impulsive behaviors, mood disturbance and reactivity, risk of
suicide, risk of violence to persons or property, substance abuse,
the patient's ability to care for himself/herself
or others (e.g., children), financial resources, psychosocial stressors,
and psychosocial supports (e.g., family and friends).
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C. Differential Diagnosis
Borderline personality disorder often co-occurs with mood
disorders, and when criteria for both are met, both should be diagnosed.
However, some features of borderline personality disorder may overlap
with those of mood disorders, complicating the differential diagnostic
assessment. For example, the affective instability and impulsivity
of borderline personality disorder may mimic features of bipolar
disorder, especially bipolar II disorder. However, in borderline
personality disorder, the mood swings are often triggered by interpersonal
stressors (e.g., rejection), and a particular mood is usually less
sustained than in bipolar disorder. Depressive features may meet criteria
for major depressive disorder or may be features of the borderline
personality disorder itself. Depressive features that appear particularly
characteristic of borderline personality disorder are emptiness,
self-condemnation, abandonment fears, self-destructiveness, and
hopelessness (91, 92). It can be particularly difficult to differentiate
dysthymic disorder from borderline personality disorder, given that
chronic dysphoria is so common in individuals with borderline personality disorder.
However, the presence of the aforementioned affective features (e.g.,
mood swings triggered by interpersonal stressors) should prompt
consideration of the diagnosis of borderline personality disorder.
In addition, the other features of borderline personality disorder
(e.g., identity disturbance, chronic self-destructive behaviors,
frantic efforts to avoid abandonment) are generally not characteristic
of axis I mood disorders. In other cases, what appear to be features
of borderline personality disorder may constitute symptoms of an
axis I disorder (e.g., bipolar disorder). A more in-depth consideration
of the differential diagnosis or treatment of the presumed axis
I condition may help clarify such questions.
PTSD is a common comorbid condition in patients with borderline
personality disorder and, when present, should be diagnosed. However,
a history of trauma is often characteristic of patients with borderline
personality disorder and does not necessarily warrant an additional
diagnosis of PTSD. PTSD should be diagnosed only when full criteria
for the disorder are met. PTSD is characterized by rapid-onset symptoms
that occur, usually in adulthood, in reaction to exposure to a recognizable
and extreme stressor; in contrast, borderline personality disorder
consists of the early-onset, enduring personality traits described
elsewhere in this guideline.
Although borderline personality disorder may be comorbid with
dissociative identity disorder, the latter (unlike borderline personality
disorder) is characterized by the presence of two or more distinct identities
or personality states that alternate, manifesting different patterns
of behavior.
Borderline personality disorder is the most common personality
disorder in clinical settings. It is present in 10% of
individuals seen in outpatient mental health clinics, 15%–20% of
psychiatric inpatients, and 30%–60% of
clinical populations with a personality disorder. It occurs in an
estimated 2% of the general population (1, 136).
Borderline personality disorder is diagnosed predominantly
in women, with an estimated gender ratio of 3:1. The disorder is
present in cultures around the world. It is approximately five times
more common among first-degree biological relatives of those with
the disorder than in the general population. There is also a greater
familial risk for substance-related disorders, antisocial personality disorder,
and mood disorders.
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E. Natural History and Course
Long-term follow-up studies of treated patients with borderline
personality disorder indicate that the course is variable. Early
adulthood is often characterized by chronic instability, with episodes
of serious affective and impulsive dyscontrol and high levels of
use of health and mental health resources. Later in life, a majority
of individuals attain greater stability in social and occupational functioning.
In the largest follow-up study to date (137), about one-third
of patients with borderline personality disorder had recovered by
the follow-up evaluation, having solidified their identity during
the intervening years and having replaced their tendency toward
self-damaging acts, inordinate anger, and stormy relationships with
more mature and more modulated behavior patterns. Longitudinal studies of
hospitalized patients with borderline personality disorder indicate
that even though they may gradually attain functional roles 10–15
years after admission to psychiatric facilities, only about one-half of
the women and one-quarter of the men will have attained enduring
success in intimacy (as indicated by marriage or long-term sexual
partnership) (137). One-half to three-quarters will have by that time
achieved stable full-time employment. These studies concentrated
on patients with borderline personality disorder from middle-class
or upper-middle-class families. Patients with borderline personality
disorder from backgrounds of poverty have substantially lower success
rates in the spheres of intimacy and work. Despite these somewhat
favorable outcomes, the suicide rate among patients with borderline
personality disorder is highapproximately 9%.
The risk of suicide appears highest in the young-adult years.
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VI. Review and Synthesis of
Available Evidence
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A. Issues in Interpreting the Literature
The following issues should be considered when interpreting
the literature presented in this guideline on the efficacy of treatments
for borderline personality disorder. Virtually all of the studies involved
adults with borderline personality disorder. While the results may
be applicable to adolescents, there is a paucity of research that
has examined the efficiency of these treatments for this
age group. Although some of these treatments have been evaluated
through randomized, placebo-controlled trialsthe
gold standard for determining treatment efficacy information
for other treatments is available only from case reports, case series,
or retrospective studies, which limits the conclusions that can
be drawn about treatment efficacy.
Another consideration is that efficacy studies (e.g., placebo-controlled
trials) have notable strengths but also some limitations. Although
such studies are necessary to establish that a particular treatment
is effective, there may be limits to how generalizable the study
findings are. For example, inclusion and exclusion criteria result
in particular types of patients being involved in a study. When reviewing
the data presented in this guideline, clinicians should consider
how similar their patient is to the population included in a particular
study. This is particularly important because of the heterogeneous
nature of borderline personality disorder symptoms. Some studies,
for example, select patients with marked impulsivity, whereas others
include patients with prominent affective features. In addition,
many studies have been relatively short-term; longer-term treatment
outcome studies are needed.
Another issue to consider is that some studies are done in
specialized research settings with more expertise and training in
the treatment modality than is generally available in the community.
In addition, the amount of treatment provided in a study may be
greater than is actually available in the community.
When evaluating studies of psychosocial treatments that consist
of multiple elements, such as psychodynamic psychotherapy, it may
be difficult to know which elements are responsible for the treatment
outcome. Another factor to consider is that patients in certain
studies of psychosocial treatment were also taking prescription
medication, and no steps were taken to control for these effects.
Conversely, patients in some studies of medication efficacy also
received psychotherapy, and no steps were taken to control for these
effects. Therefore, the literature on the efficacy of any one particular
treatment is often confounded by the presence of other simultaneous
treatments. It can be difficult, then, to isolate the impact of
a single modality in most treatment efficacy studies involving patients
with borderline personality disorder.
In clinical practice, a combination of treatment approaches
is often used and appropriate. Few data are available on the complex
treatment regimens often required by the realities of clinical practice (e.g.,
the use of multiple medications simultaneously). Many clinically
important and complex treatment questions have not been (and are
unlikely to ever be) addressed in research studies. For such questions,
clinical consensus is the best available guide.
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B. Review of Psychotherapy and Other Psychosocial
Treatments
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1. Psychodynamic psychotherapy
Psychodynamic psychotherapy has been defined as a therapy
that involves careful attention to the therapist-patient interaction
with, when indicated, thoughtfully timed interpretation of transference and
resistance embedded in a sophisticated appreciation of the therapist's
contribution to the two-person field. Psychodynamic psychotherapy
draws from three major theoretical perspectives: ego psychology,
object relations, and self psychology. Most therapeutic approaches
to patients with borderline personality disorder do not adhere strictly
to only one of these theoretical frameworks. The approach of Stevenson
and Meares (20, 138), for example, encompasses the self-psychological ideas
of Kohut and the object relations ideas of Winnicott, whereas the
technique of Kernberg et al. (4, 13, 28) is based on an amalgamation
of ego psychology and object relations theory.
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a) Definition and goals
Psychodynamic psychotherapy is usually conceptualized as operating
on an exploratory-supportive (also called expressive-supportive)
continuum of interventions (Figure 2). At the more exploratory end
of the continuum, the goals of psychodynamic psychotherapy with
patients with borderline personality disorder are to make unconscious
patterns more consciously available, to increase affect tolerance,
to build a capacity to delay impulsive action, to provide insight
into relationship problems, and to develop reflective functioning
so that there is greater appreciation of internal motivation in self
and others. From the standpoint of object relations theory, one
major goal is to integrate split-off aspects of self and object
representations so that the patient's perspective is more
balanced (e.g., seeing others as simultaneously having both positive
and negative qualities). From a self-psychological perspective,
a major goal is to strengthen the self so that there is less fragmentation
and a greater sense of cohesion or wholeness in the patient's
self-experience. On the supportive end of the continuum, the goals
involve strengthening of defenses, the shoring up of self-esteem,
the validation of feelings, the internalization of the therapeutic
relationship, and creation of a greater capacity to cope with disturbing
feelings.
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Of these interventions, only interpretation is unique to the
psychodynamic approach. The more exploratory interventions (interpretation,
confrontation, and clarification) may be focused on either transference
or extratransference issues.
Among the most exploratory forms of treatment, interpretation
is regarded as the therapist's ultimate therapeutic tool.
In its simplest form, interpretation involves making something conscious that
was previously unconscious. An interpretation is an explanatory
statement that links a feeling, thought, behavior, or symptom to
its unconscious meaning or origin. For example, a therapist might make
the following observation to a patient with borderline personality
disorder: "I wonder if your tendency to undermine yourself
when things are going better is a way to ensure that your treatment with
me will continue."
This exploratory intervention addresses something the patient
does not want to accept or identifies the patient's avoidance
or minimization. A confrontation may be geared to clarifying how
the patient's behavior affects others or reflects a denied
or suppressed feeling. An example might be, "I think talking
exclusively about your medication problems may be a way of avoiding
any discussion with me about your painful feelings that make you
feel suicidal."
This intervention involves a reformulation or pulling together
of the patient's verbalizations to convey a more coherent
view of what is being communicated. A therapist might say, "It
sounds like what you're saying is that in every relationship
you have, no one seems to be adequately attuned to your needs."
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(iv) Encouragement to elaborate
Closer to the center of the continuum are interventions that
are characteristic of both supportive and exploratory therapies.
Encouragement to elaborate may be broadly defined as a request for information
about a topic brought up by the patient. Simple comments like "Tell
me more about that" and "What do you mean when
you say you feel 'empty'?" are examples
of this intervention.
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(v) Empathic validation
This intervention is a demonstration of the therapist's
empathic attunement with the patient's internal state.
This approach draws from self psychology, which emphasizes the value
of empathy in strengthening the self. A typically validating comment
is, "I can understand why you feel depressed about that," or, "It
hurts when you're treated that way."
This category includes two interventions that are linked by
the fact that they both prescribe and reinforce certain activities.
Advice involves direct suggestions to the patient regarding how
to behave, while praise reinforces certain patient behaviors by
expressing overt approval of them. An example of advice would be, "I
don't think you should see that man again because you get
beaten up every time you're with him." An example
of praise would be, "I think you used excellent judgment
in breaking off your relationship with that man."
This simple intervention involves succinct comments in support
of the patient's comments or behaviors such as "Yes,
I see what you mean" or "What a good idea."
Some patients with borderline personality disorder receive
a highly exploratory or interpretive therapy that is focused on
the transference relationship. This approach is sometimes called
transference-focused psychotherapy (4, 140). Patients who lack good
abstraction capacity and psychological mindedness may require a
therapy that is primarily supportive, even though it is psychodynamically informed
by a careful analysis of the patient's ego capacities,
defenses, and weaknesses. Most psychotherapies involve both exploratory
and supportive elements and include some, although not exclusive,
focus on the transference. Hence, psychodynamic psychotherapy is
often conceptualized as exploratory-supportive or expressive-supportive psychotherapy
(16, 139, 141).
While there is a great deal of clinical literature on psychodynamic
psychotherapy with patients who have borderline personality disorder,
there are relatively few methodologically rigorous efficacy studies.
One randomized controlled trial assessed the efficacy of psychoanalytically
informed partial hospitalization treatment, of which dynamic therapy
was the primary modality (9). In this study, 44 patients were randomly
assigned to either the partial hospitalization program or general
psychiatric care. Treatment in the partial hospitalization program
consisted of weekly individual psychoanalytic psychotherapy, three-times-a-week
group psychoanalytic psychotherapy, weekly expressive therapy informed
by psychodrama, weekly community meetings, monthly meetings with
a case administrator, and monthly medication review by a resident.
The control group received general psychiatric care consisting of
regular psychiatric review with a senior psychiatrist twice a month,
inpatient admission as appropriate, outpatient and community follow-up,
and no formal psychotherapy. The average length of stay in the partial
hospitalization program was 1.5 years. Relative to the control group,
the completers of the partial hospitalization program
showed significant improvement: self-mutilation decreased, the proportion
of patients who attempted suicide decreased from 95% before treatment
to 5% after treatment, and patients improved in terms of
state and trait anxiety, depression, global symptoms, social adjustment,
and interpersonal problems. In the last 6 months of the study, the
number of inpatient episodes and duration of inpatient length of
stay dramatically increased for the control subjects, whereas these
utilization variables remained stable for subjects in the partial hospitalization
group.
One can conclude from this study that patients with borderline
personality disorder treated with this program for 18 months showed
significant improvement in terms of both symptoms and functioning. Reduction
of symptoms and suicidal acts occurred after the first 6 months
of treatment, but the differences in frequency and duration of inpatient
treatment emerged only during the last 6 months of treatment. In
addition, depressive symptoms were significantly reduced. Although
the principal treatment received by subjects in the partial hospitalization
group was psychoanalytic individual and group therapy, one cannot
definitively attribute this group's better outcome to the
type of therapy received, since the overall community support and
social network within which these therapies took place may have exerted
significant effects. Pharmacotherapy received was similar in the
two treatment groups, but subjects in the partial hospitalization
program had a greater amount of psychotherapy than did the control subjects.
In a subsequent report (10), patients who had received partial hospitalization
treatment not only maintained their substantial gains at an 18-month
follow-up evaluation but also showed statistically significant continued
improvement on most measures, whereas the control group showed only
limited change during the same period.
A study from Australia of twice-weekly psychodynamic therapy
(20) prospectively compared the year before 12 months of psychodynamic
therapy was given with the year after the therapy was received for
a group of poorly functioning outpatients with borderline personality
disorder. Among the 30 completers, there were significant reductions
in violent behavior, use of illegal drugs, number of medical visits,
self-harm, time away from work, severity of global symptoms, number
of DSM-III symptoms of borderline personality disorder, number of
hospital admissions, and time spent as an inpatient. Although this
study did not include a control group, there were dramatic improvements in
patients that support the value of the yearlong treatment intervention.
In another study (21), this same group of 30 patients who
received psychodynamic therapy was compared with 30 control subjects
drawn from an outpatient waiting list who then received treatment as
usual, consisting of supportive therapy, cognitive therapy, and
crisis intervention. The control subjects were assessed at baseline
and at varying intervals, with an average follow-up duration of
17.1 months. In this nonrandomized controlled study, the group receiving
psychodynamic therapy had a significantly better outcome than the
control subjects (i.e., fewer subjects in the treatment versus the control
group still met DSM-III criteria for borderline personality disorder),
even though the group that received psychodynamic therapy was more
severely ill at baseline. This study suggests that psychodynamic
therapy is efficacious, but the investigation has a number of limitations,
including the lack of randomization, different follow-up durations
for different subjects, nonblind assessment of outcome, and lack
of detail about the amount of treatment received by the control
subjects. Without more data on the amount of treatment received,
it is unclear whether the better outcome of the subjects who received
dynamic therapy was due to the type of therapy or the greater amount
of treatment received.
The investigators of the Australian study also did a preliminary
cost-benefit analysis (138) in which they compared the direct cost
of treatment for the 12 months preceding psychodynamic therapy with
the direct cost of treatment for the 12 months following this therapy.
In Australian dollars, the cost of the treatment for all patients
decreased from $684,346 to $41,424. Including
psychotherapy in the cost of treatment, there was a total savings
per patient of $8,431 per year. This cost-effectiveness was
accounted for almost entirely by a decrease in the number of hospital
days. Without a control group, however, one cannot definitively
conclude that the cost savings were the result of the psychotherapy.
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d) Length and frequency of treatment
Most clinical reports of psychodynamic psychotherapy involving
patients with borderline personality disorder refer to the treatment
duration as "extended" or "long term." However,
there are only limited data about how much therapy is adequate or
optimal. In the aforementioned randomized controlled trial of psychoanalytically
focused partial hospitalization treatment (9), the effect of psychotherapy
on reducing hospitalization was not significant until after the
patients had been in therapy for more than 12 months. There are
no studies demonstrating that brief therapy or psychotherapy less
than twice a week is helpful for patients with borderline personality
disorder. Howard and colleagues (142), to study the psychotherapeutic
dose-effect relationship, conducted a meta-analysis comprising 2,431
subjects from 15 patient groups spanning 30 years. One study they examined
in detail involved a group of 151 patients evaluated by self-report
and by chart review; 28 of these patients had a borderline personality
disorder diagnosis. Whereas 50% of patients with anxiety
or depression improved in 8–13 sessions, the same degree
of improvement occurred after 13–26 sessions for "borderline
psychotic" patients according to self-ratings (the same
degree of improvement occurred after 26–52 sessions according
to chart ratings by researchers [143]). Seventy-five
percent of patients with borderline personality disorder had improved
by 1 year (52 sessions) and 87%–95% by
2 years (104 sessions). While this study confirms the conventional
wisdom that more therapy is needed for patients with borderline
personality disorder than for patients with an axis I disorder,
it is unclear whether raters were blind to diagnosis. It appears
that a standardized diagnostic assessment and standard threshold
for improvement were not used, there are no data on treatment dropouts,
and little information is provided about the type of therapy or
the therapists except that they were predominantly psychodynamically
oriented. What can be concluded is that in a naturalistic setting
outpatients who are clinically diagnosed as "borderline
psychotic" will likely need more extended therapy than
will depressed or anxious patients.
While no adverse effects were reported in the aforementioned
studies, psychodynamic psychotherapy has the potential to disorganize
some patients if the focus is too exploratory or if there is too
much emphasis on transference without an adequately strong alliance.
Intensive dynamic psychotherapy may also activate strong dependency
wishes in the patient as transference wishes and feelings develop
in the context of the treatment. It is the exploration of such dependency
that is often essential to help the patient to achieve independence.
This dependence may elicit countertransference problems in the therapist,
which can lead to inappropriate or ineffective treatment. The most
serious examples of this include unnecessary increases in the frequency
or duration of treatment or transgression of professional boundaries.
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f) Implementation issues
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(i) Difficulties with adherence
Most studies report a high dropout rate from dynamic psychotherapy
among patients with borderline personality disorder. However, this
is true for almost all approaches to the treatment of these patients,
and it has not been demonstrated to be any higher for dynamic therapy.
It does, however, emphasize the paramount importance of adequate
attention to the therapeutic alliance as well as to transference
and countertransference issues.
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(ii) Need for therapist flexibility
Early in the treatment, and periodically in the later stages,
a therapist who is also functioning as primary clinician may need
to take a major role in management issues, including limit-setting, attending
to suicidality, addressing pharmacotherapy, and helping to arrange
hospitalization. A stance in which the therapist only explores the
patient's internal experience and does not become involved in
management of life issues may lead to adverse outcomes for some
patients.
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(iii) Importance of judicious transference
interpretation
Excessive transference interpretation or confrontation early
in treatment may increase the risk that the patient will drop out
of therapy. One process study of psychoanalytic therapy with patients
with borderline personality disorder (11) found that for some patients,
transference interpretation is a "high-risk, high-gain" phenomenon
in that it may improve the therapeutic alliance but also may cause substantial
deterioration in that alliance. Therapists must use transference
interpretation judiciously on the basis of their sense of the state
of the alliance and the patient's capacity to hear and
reflect on observations about the therapeutic relationship. A series
of empathic and supportive comments often paves the way for an effective
transference interpretation. Other patients may be able to use transference
interpretation effectively without this much preparatory work.
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(iv) Role of therapist training and
competency
Psychodynamic therapy for patients with borderline personality
disorder is uncommonly demanding. Consultation from an experienced
colleague is highly recommended for all therapists during the course
of the therapy. In some situations, personal psychotherapy can help
the clinician develop skills to manage the intense transference/countertransference
interactions that are characteristic of these treatments.
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2. Cognitive behavior therapy
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a) Definition and goals
Although cognitive behavior therapy has been widely used and
described in the clinical literature, it has more often been used
to treat axis I conditions (e.g., anxiety or depressive disorders)
than personality disorders. Cognitive behavior therapy assumes that
maladaptive and distorted beliefs and cognitive processes underlie
symptoms and dysfunctional affect or behavior and that these beliefs are
behaviorally reinforced. It generally involves attention to a set
of dysfunctional automatic thoughts or deeply ingrained belief systems
(often referred to as schemas), along with learning and practicing
new, nonmaladaptive behaviors. Utilization of cognitive behavior
methods in the treatment of the personality disorders has been described
(19), but because persistent dysfunctional belief systems in patients
with personality disorders are usually "structuralized" (i.e.,
built into the patient's usual cognitive organization),
substantial time and effort are required to produce lasting change. Modifications
of standard approaches (e.g., schema-focused cognitive therapy,
complex cognitive therapy, or dialectical behavior therapy) are
often recommended in treating certain features typical of the personality
disorders. However, other than dialectical behavior therapy (17,
144–147), these modifications have not been studied.
Most published reports of cognitive behavior treatment for
patients with borderline personality disorder are uncontrolled clinical
or single case studies. Recently, however, several controlled studies have
been done, particularly of a form of cognitive behavior therapy
called dialectical behavior therapy. Dialectical behavior therapy
consists of approximately 1 year of manual-guided therapy (involving
1 hour of weekly individual therapy for 1 year and 2.5
hours of group skills training per week for either 6 or 12 months)
along with a requirement for all therapists in a study or program
to meet weekly as a group. Linehan and colleagues (8) reported a
randomized controlled trial of dialectical behavior therapy involving
patients with borderline personality disorder whose symptoms included "parasuicidal" behavior
(defined as any intentional acute self-injurious behavior with or without
suicide intent). Control subjects in this study received "treatment
as usual" (defined as "alternative therapy referrals,
usually by the original referral source, from which they could choose"). Of
the 44 study completers, 22 received dialectical behavior therapy,
and 22 received treatment as usual; patients were assessed at 4,
8, and 12 months. At pretreatment, 13 of the control subjects had been
receiving individual psychotherapy, and 9 had not. Patients who
received dialectical behavior therapy had less parasuicidal behavior,
reduced medical risk due to parasuicidal acts, fewer hospital admissions,
fewer psychiatric hospital days, and a greater capacity to stay
with the same therapist than did the control subjects. Both groups
improved with respect to depression, suicidal ideation, hopelessness,
or reasons for living; there were no group differences on these
variables. Because there were substantial dropout rates overall
(30%) and the number of study completers in each group
was small, it is unclear how generalizable these results are. Nonetheless,
this study is a promising first report of a manualized regimen of
cognitive behavior treatment for a specific type of patient with borderline
personality disorder.
A second cohort of patients was subsequently studied; the
same study design was used (148). In this report, there were 26
intent-to-treat patients (13 received dialectical behavior therapy,
and 13 received treatment as usual). One patient who received dialectical
behavior therapy committed suicide late in the study, and 3 patients
receiving dialectical behavior therapy and 1 patient receiving treatment
as usual dropped out. Nine of the 13 control patients were already
receiving individual psychotherapy at the beginning of the study
or entered such treatment during the study. Patients who received
dialectical behavior therapy had greater reduction in trait anger
and greater improvement in Global Assessment Scale scores.
One year after termination of their previously described study
(8), the Linehan group reevaluated their patient group (5). After
1 year, the greater reduction in parasuicide rates and in severity
of suicide attempts seen in the dialectical behavior therapy group
relative to the control subjects did not persist, although there
were significantly fewer psychiatric hospital days for the dialectical
behavior therapy group during the follow-up year. These findings
suggest that although dialectical behavior therapy produces
a greater reduction in parasuicidal behavior than treatment as usual,
the durability of this advantage is unclear.
In a subsequent report, Linehan and colleagues (149) compared
dialectical behavior therapy with treatment as usual in patients
with borderline personality disorder with drug dependence. Only
18 of the 28 intent-to-treat patients completed the study (7 who
received dialectical behavior therapy and 11 given treatment as
usual). Patients receiving dialectical behavior therapy had more
drug- and alcohol-abstinent days after 4, 8, and 16 months. All
patients had reduced parasuicidal behavior as well as state and
trait anger; there was no difference between the groups. This study,
too, involved small numbers of patients and had substantial dropout
rates, but it represents an important attempt to evaluate the impact
of dialectical behavior therapy with severely ill patients with
borderline personality disorder and comorbid substance abuse.
In all of these studies, it is difficult to ascertain whether
the improvement reported for patients receiving dialectical behavior
therapy derived from specific ingredients of dialectical behavior therapy
or whether nonspecific factors such as either the greater time spent
with the patients or therapist bias contributed to the results.
In a small study in which skills training alone was compared with
a no-skills training control condition, no difference was found
between the groups (unpublished 1993 study of M. M. Linehan
and H. L. Heard). The researchers concluded that the specific
features of individual dialectical behavior therapy are necessary
for patients to show greater improvement than control groups. Linehan
and Heard (150) reported that more time with therapists does not
account for improved outcome. Nonetheless, other special features
of dialectical behavior therapy, such as the requirement for all
therapists to meet weekly as a group, could contribute to the results.
Springer et al. (151) used an inpatient group therapy version
of dialectical behavior therapy for patients with personality disorders,
13 of whom had borderline personality disorder. The patients with
borderline personality disorder exhibited improvement in depression,
hopelessness, and suicidal ideation, but the improvement was not
greater than it was for a control group. In this study, compared with
control subjects, patients receiving the dialectical behavior therapy
treatment showed a paradoxical increase in parasuicidal acting out
during the brief hospitalization (average length of stay was 12.6
days).
Barley and colleagues (152) compared dialectical behavior
therapy received by patients with borderline personality disorder
on a specialized personality disorder inpatient unit with treatment
as usual on a similar-sized inpatient unit. They found that the
use of dialectical behavior therapy was associated with reduced
parasuicidal behavior. It is unclear whether improvement was due
to dialectical behavior therapy per se or to other elements of the
specialized unit.
Perris (153) reported preliminary findings from a small uncontrolled,
naturalistic follow-up study of 13 patients with borderline personality
disorder who received cognitive behavior therapy similar to dialectical
behavior therapy. Twelve patients were evaluated at a 2-year follow-up
point, and all patients maintained the normalization of functioning
that had been evident at the end of the study treatment.
Other controlled studies reported in the literature of cognitive
behavior approaches are difficult to interpret because of small
patient group sizes or because the studies focused on mixed types
of personality disorders without specifying borderline cohorts (154–156).
In summary, there are a number of studies in the literature
suggesting that cognitive behavior therapy approaches may be effective
for patients with borderline personality disorder. Most of these
studies involved dialectical behavior therapy and were carried out
by Linehan and her group. Replication studies by other groups in
other centers are needed to confirm the validity and generalizability
of these findings.
Published data are not available on the cost-effectiveness
of cognitive behavior approaches for treatment of borderline personality
disorder, although Linehan and colleagues (8) reported that patients
receiving dialectical behavior therapy had fewer psychiatric inpatient
days and psychiatric hospital admissions than did control subjects.
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d) Length and frequency of treatment
Short-term cognitive therapy involving 16–20 sessions
has been described as a generic treatment approach; however, the
patient characteristics thought to be necessary for a successful
treatment outcome are not typical of patients with personality disorders
(147). Instead, longer forms of treatment, such as "schema-focused
cognitive therapy" (147), "complex cognitive therapy" (144), or
dialectical behavior therapy (17), are usually recommended.
The standard length of dialectical behavior therapy is approximately
1 year for the most commonly administered phase of the treatment.
It involves 1 hour of individual therapy per week, more than 2 hours
of group skills training per week (for either 6 or 12 months),
and 1 hour of group process for the therapists per week. Other versions
of dialectical behavior therapy, such as that administered in a
brief inpatient setting (151), may be useful but are not necessarily
more effective than other forms of inpatient treatment.
Although there are no reports of adverse effects of cognitive
behavior therapy, including dialectical behavior therapy, as administered
on an outpatient basis, one inpatient study (151) reported a paradoxical
increase in parasuicidal acting out in the dialectical behavior
therapy group compared with the control groupa finding
thought perhaps to be due to the contagion effect within a closed, intensive
milieu.
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f) Implementation issues
Many components of cognitive behavior therapy are similar
to elements of psychodynamic psychotherapy, although they may have
different labels. For example, as Linehan (17) pointed out, focusing
on "therapy-interfering behavior" is similar to
the psychodynamic emphasis on transference behaviors. Similarly,
the notion of validation resembles that of empathy. Beck and Freeman
(19) noted that cognitive therapists and psychoanalysts have the
common goal of identifying and modifying "core" personality
disorder problems. However, psychodynamic therapists view these core
problems as having important unconscious roots that are not available
to the patient, whereas cognitive therapists view them as largely
in the realm of awareness. It is not clear how successfully psychiatrists
who have not been trained in cognitive behavior therapy can implement
manual-based cognitive behavior approaches.
Although dialectical behavior therapy has been well described
in the literature for many years, it is not clear how difficult
it is to teach to new therapists in settings other than that where
it was developed. Variable results in other settings could be due
to a number of factors, such as less enthusiasm for the method among
therapists, differences in therapist training in dialectical behavior
therapy, and different patient populations. Although the Linehan
group has developed training programs for therapists, certain characteristics
recommended in dialectical behavior therapy (e.g., "a matter-of-fact, somewhat
irreverent, and at times outrageous attitude about current and previous
parasuicidal and other dysfunctional behaviors"[17])
may be more effective when carried out by therapists who are comfortable
with this particular style.
The goals of group therapy are consistent with those of individual
psychotherapy and include stabilization of the patient, management
of impulsiveness and other symptoms, and examination and management
of transference and countertransference reactions. Groups provide
special opportunities for provision of additional social support,
interpersonal learning, and diffusion of the intensity of transference
issues through interaction with other group members and the therapists.
In addition, the presence of other patients provides opportunities
for patient-based limit-setting and for altruistic interactions
in which patients can consolidate their gains in the process of
helping others.
Some uncontrolled studies suggest that group treatment (157),
including process-focused groups in a therapeutic community
setting (158), may be helpful for patients with borderline personality disorder.
However, these studies had no true control condition, and the efficacy
of the group treatment is unclear, given the complexity of the treatment
received. Another small chart review study of an "incest
group" for patients with borderline personality disorder
(159) suggested shorter subsequent inpatient stays and fewer outpatient
visits for treated patients than for control subjects. A randomized trial
(160) involving patients with borderline personality disorder showed
equivalent results with group versus individual dynamically oriented
psychotherapy, but the small sample size and high dropout rate make
the results inconclusive. Wilberg et al. (161) did a naturalistic
follow-up study of two cohorts of patients with borderline personality
disorder. This quasi-experimental, nonrandomized study showed that
patients with borderline personality disorder discharged from a
day program with continuing outpatient group therapy (N=12)
did better than those who did not have group therapy (N=31).
They had better global health and lower global severity index symptoms,
lower Health-Sickness Rating Scale scores, lower SCL-90 scores,
lower rehospitalization rates, fewer suicide attempts, and less
substance abuse. There were, however, important differences between
the two comparison groups that could account for outcome differences.
Perhaps the most interesting aspect of group therapy is the
use of groups to consolidate and maintain improvement from the inpatient
stay. Linehan and colleagues (8) combined individual and group therapy,
making the specific effect of the group component unclear. They
reported that, contrary to expectations, the addition of group skills
training to individual dialectical behavior therapy did not improve
clinical outcome. For those patients with borderline personality
disorder who have experienced shame or have become isolated as a
result of trauma, including those with comorbid PTSD, group therapy
with others who have experienced trauma can be helpful. Such groups
provide a milieu in which their current emotional reactions and
self-defeating behaviors can be seen and understood. Groups may
also provide a context in which patients may initiate healthy risk-taking
in relationships. Group treatment has also been included in studies
of psychodynamic psychotherapy; although the overall treatment program
was effective, the effectiveness of the group therapy component
is unknown (9, 162). Clinical wisdom indicates for many patients
combined group and individual psychotherapy is more effective than
either treatment alone.
Group psychotherapy is substantially less expensive than individual
therapy because of the favorable therapist-patient ratio. Marziali
and Monroe-Blum (163) calculated that group psychotherapy for borderline
personality disorder costs about one-sixth as much as individual
psychotherapy, assuming that the fee for individual therapy is only
slightly higher than that for group therapy. However, this potential
saving is tempered by the fact that most treatment regimens for
borderline personality disorder combine group interventions with
individual therapy.
+
d) Length and frequency of treatment
Groups generally meet once a week, although in inpatient settings
sessions may occur daily. In some studies, groups are time-limitedfor
example, 12 weekly sessionswhereas in other studies they
continue for a year or more.
Acute distress from exposure to emotionally arousing group
issues has been reported. Other potential risks of treating patients
with borderline personality disorder in group settings include shared
resistance to therapeutic work, hostile or other destructive interactions
among patients, intensification of transference problems, and symptom "contagion."
+
f) Implementation issues
Groups take considerable effort to set up and require a group
of patients with similar problems and willingness to participate
in group treatment. Patients in group therapy must agree to confidentiality
regarding the information shared by other patients and to clear
guidelines regarding contact with other members outside the group
setting. It is critical that there be no "secrets" and
that all interactions among group members be discussed in the group,
especially information regarding threats of harm to self or others.
The usual goal of couples therapy is to stabilize and strengthen
the relationship between the partners or to clarify the nonviability
of the relationship. An alternative or additional goal for some is
to educate and clarify for the spouse or partner of the patient
with borderline personality disorder the process that is taking
place within the relationship. Partners of patients with borderline
personality disorder may struggle to accommodate the patient's
alternating patterns of idealization and depreciation as well as
other interpersonal behaviors. As a result, spouses may become dysphoric
and self-doubting; they may also become overly attentive and exhibit
reaction formation. The goal of treatment is to explore and change
these maladaptive reactions and problematic interactions between partners.
The literature on the effectiveness of couples therapy for
patients with borderline personality disorder is limited to clinical
experience and case reports. In some cases, the psychopathology
and potential mutual interdependence of each partner may serve a
homeostatic function (164–166). Improvement can occur in
the relationship when there is recognition of the psychological
deficits of both parties. The therapeutic task is to provide an
environment in which each spouse can develop self-awareness within
the context of the relationship.
One report (41) described an escalation of symptoms when traditional
marital therapy was used with a couple who both were diagnosed with
borderline personality disorder. Clinical experience would indicate
the need for careful psychiatric evaluation of the spouse. When
severe character pathology is present in both, the clinician will
need to use a multidimensional approach, providing a holding environment
for both partners while working toward individuation and intrapsychic
growth. Because the spouse's own interpersonal needs or
behavioral patterns may, however pathological, serve a homeostatic
function within the marriage, couples therapy has the potential
to further destabilize the relationship.
+
d) Implementation issues
At times, it might be helpful for the primary clinician to
meet with the spouse or partner and evaluate his or her strengths
and weaknesses. It is important to recognize the contingencies of
the extent of the partner's loyalty and his or her understanding
of what can be expected from the patient with borderline personality
disorder before recommending couples therapy. Couples therapy with patients
with borderline personality disorder requires considerable understanding
of borderline personality disorder and the attendant problems and
compensations that such individuals bring to relationships.
Relationships in the families of patients with borderline
personality disorder are often turbulent and chaotic. The goal of
family therapy is to increase family members' understanding
of borderline personality disorder, improve relationships between
the patient and family members, and enhance the overall functioning
of the family.
The published literature on family therapy with patients with
borderline personality disorder consists of case reports (167–170)
and one published study (12) that found a psychoeducational approach
could improve communication, diminish alienation and burden, and
diminish conflicts over separation and independence. The clinical
literature suggests that family therapy may be useful for some patientsin
particular, those who are still dependent on or significantly involved
with their families. Some clinicians report the efficacy of dynamically
based therapy, whereas others support the efficacy of a psychoeducational
approach in which the focus is on educating the family about the diagnosis,
improving communication, diminishing hostility and guilt, and diminishing
the burden of the illness.
Some clinicians report that traditional dynamically based
family therapy has the potential to end prematurely and have a poor
outcome, since patients may alienate their family members or leave
the treatment themselves because they feel misunderstood (171) when
family involvement is indicated. A psychoeducational approach appears
to be less likely to have such adverse effects; however, even psychoeducational
approaches can upset family members who wish to avoid knowledge
about the illness or involvement in the family member's
treatment.
+
d) Implementation issues
Traditional dynamically based family therapy requires considerable
training and sufficient experience with patients with borderline
personality disorder to appreciate their problems and conflicts
and to be judicious in the selection of appropriate families.
+
C. Review of Pharmacotherapy and Other Somatic Treatments
+
1. SSRI antidepressants
In borderline personality disorder, SSRIs are used to treat
symptoms of affective dysregulation and impulsive-behavioral dyscontrol,
particularly depressed mood, anger, and impulsive aggression, including
self-mutilation.
Early case reports and small open-label trials with fluoxetine,
sertraline, and venlafaxine (a mixed norepinephrine/serotonin
reuptake blocker) indicated significant efficacy for symptoms of
affective dysregulation, impulsive-behavioral dyscontrol, and cognitive-perceptual
difficulties in patients with borderline personality disorder (44–49,
67). Aggression, irritability, depressed mood, and self-mutilation
responded to fluoxetine (up to 80 mg/day), venlafaxine
(up to 400 mg/day), or sertraline (up to 200 mg/day)
in trials of 8–12 weeks (45). An unexpected finding in
some of these early reports was that improvement in impulsive behavior
appeared rapidly, often within the first week of treatment, and
disappeared as quickly with discontinuation or nonadherence. Improvement
in impulsive aggression appeared to be independent of effects on
depression and anxiety and occurred whether or not the patient had
comorbid major depressive disorder (67). Nonresponse to one SSRI did
not predict poor response to all SSRIs. For example, some patients
who did not respond to fluoxetine, 80 mg/day, responded
to a subsequent trial of sertraline. Similarly, patients who did
not respond to sertraline, paroxetine, or fluoxetine subsequently
responded to venlafaxine. In one study, higher doses and a longer
trial (24 weeks) with sertraline converted half of sertraline nonresponders
to responders (45).
Three double-blind, placebo-controlled studies have been conducted.
Salzman and colleagues (44) conducted a 12-week trial of fluoxetine
(20–60 mg/day) in 27 relatively high-functioning subjects
(mean Global Assessment Scale score of 74) with borderline personality
disorder or borderline traits. Other axis I or axis II comorbid
diagnoses were absent, as were recent suicidal behavior, self-mutilation,
substance abuse, and current severe aggressive behavior (i.e., behaviors typical
of patients with borderline personality disorder seeking treatment).
This strategy diminishes generalizability to more seriously ill
patients but has the advantage of allowing for a test of efficacy in
the absence of comorbidity. For the 22 subjects who completed the
study (13 given fluoxetine and 9 who received placebo), significant
reduction in symptoms of anger and depression and improvement in
global functioning were reported for subjects given fluoxetine compared
with those given placebo. Improvement in anger was independent of
improvement in depressed mood. Improvement was modest, with no subject
improving more than 20% on any measure. In addition, a
large placebo response was noted.
Markovitz (45) studied 17 patients (9 given fluoxetine, 80
mg/day, and 8 given placebo) for 14 weeks. This patient
group was noteworthy for the high rate of comorbid axis I mood disorders
(10 with major depression and 6 with bipolar disorder), anxiety
disorders, and somatic complaints (e.g., headaches, premenstrual
syndrome, irritable bowel syndrome). While this group is more typical
of an impaired borderline personality disorder patient population,
comorbidity with affective and anxiety disorders confounds interpretation
of results. Patients receiving fluoxetine improved significantly
more than those given placebo in depression, anxiety, and global
symptoms. Measures of impulsive aggression were not included in
this study. Some patients with premenstrual syndrome and headaches
noted improvement in these somatic presentations with fluoxetine,
whereas none improved with placebo.
A double-blind, placebo-controlled study by Coccaro and Kavoussi
(67) focused attention on impulsive aggression as a dimensional
construct (i.e., a symptom domain found across personality disorders
but especially characteristic of borderline personality disorder).
Forty subjects with prominent impulsive aggression in the context
of a personality disorder, one-third of whom had borderline personality
disorder, participated. There was a high rate of comorbidity with
dysthymic disorder or depressive disorder not otherwise specified;
subjects with major depression and bipolar disorder were excluded.
Anxiety disorders, as well as alcohol and drug abuse, were common.
In this 12-week, double-blind, placebo-controlled trial, fluoxetine
(20–60 mg/day) was more effective than placebo
for treatment of verbal aggression and aggression against objects.
Improvement was significant by week 10, with improvement in irritability
appearing by week 6. Global improvement, favoring fluoxetine, was
significant by week 4. As in the open-label trials and the aforementioned Salzman
et al. study (44), these investigators found that the effects on
aggression and irritability did not appear as a result of improvement
in mood or anxiety symptoms.
In summary, these three randomized, double-blind, placebo-controlled
studies show efficacy for fluoxetine for affective symptomsspecifically,
depressed mood (44, 45), anger (44), and anxiety (45, 67)although
effects on anger and depressed mood appear quantitatively modest.
Efficacy has also been demonstrated for impulsive-behavioral symptomsspecifically,
verbal and indirect aggression (67)and global symptom
severity (44, 45, 67). Effects on impulsive aggression (67) and anger
(44) were independent of effects on affective symptoms, including
depressed mood (44, 67) and anxiety (67). Although the three published
double-blind, placebo-controlled trials used fluoxetine,
open-label studies and clinical experience suggest potential usefulness
for other SSRIs.
The side effect profile of the SSRIs is favorable compared
with that of older tricyclic, heterocyclic, or MAOI antidepressants,
including low risk in overdose. Side effects reported in these studies
are consistent with routine clinical usage.
+
d) Implementation issues
The SSRI antidepressants may be used in their customary antidepressant
dose ranges and durations (e.g., fluoxetine, 20–80 mg/day;
sertraline, 100–200 mg/day). One investigator
used very high doses of sertraline (200–600 mg/day)
for nonresponders, with some improved efficacy (45). At these high doses,
peripheral tremor was noted. There are no published studies of continuation
and maintenance strategies with SSRIs, although anecdotal
reports suggest continuation of improvement in impulsive aggression
and self-mutilation for up to several years while the medication
is taken and rapid return of symptoms upon discontinuation (49, 172, 173). The duration of treatment is therefore a clinical judgment
that depends on the patient's clinical status and medication
tolerance at any point in time.
+
2. Tricyclic and heterocyclic antidepressants
In borderline personality disorder, antidepressants are used
for affective dysregulation, manifested most commonly by depressed
mood, irritability, and mood lability. Evaluation of antidepressant
trials in the treatment of borderline personality disorder must
take into account the presence of comorbid axis I mood disorders,
which are common in patients with borderline personality disorder.
Studies in which there is a preponderance of comorbid axis I depression
would be expected to demonstrate a favorable response to antidepressant
treatments but may not reflect the pharmacological responsiveness
of borderline personality disorder.
Double-blind, placebo-controlled trials of tricyclic antidepressants
in borderline personality disorder have used amitriptyline, imipramine,
and desipramine in both inpatient and outpatient settings. Mianserin,
a tetracyclic antidepressant not available in the United States,
has been used in an outpatient setting. Most of these studies were
parallel comparisons with another medication and placebo. A 5-week
inpatient study of patients with borderline personality disorder
that compared amitriptyline (mean dose=149 mg/day)
with haloperidol and placebo found that amitriptyline decreased
depressive symptoms and indirect hostility and enhanced attitudes
about self-control compared with placebo (51). It is interesting
to note that amitriptyline was not effective for the "core" depressive
features of the Hamilton Depression Rating Scale but rather was
effective for the seven "associated" symptoms
of diurnal variation, depersonalization, paranoid symptoms, obsessive-compulsive
symptoms, helplessness, hopelessness, and worthlessness. Patients
who had major depression were not more likely to respond. Schizotypal
symptoms and paranoia predicted a poor response to amitriptyline.
A small crossover study comparing desipramine (mean dose=162.5
mg/day) with lithium carbonate (mean dose=985.7
mg/day) and placebo in outpatients with borderline personality
disorder and minimal axis I mood comorbidity found no significant
differences between desipramine and placebo in improvement of affective
symptoms, anger, or suicidal symptoms or in therapist or patient perceptions
of improvement after 3 and 6 weeks (61).
A small open-label study that assessed the use of amoxapine
(an antidepressant with neuroleptic properties) in patients with
borderline personality disorder with or without schizotypal personality disorder
found that it was not effective for patients with only borderline
personality disorder (174). However, it was effective for patients
with borderline personality disorder and comorbid schizotypal personality
disorder, who had more severe symptoms. This latter group had improvement
in cognitive-perceptual, depressive, and global symptoms (174).
In outpatients with a primary diagnosis of atypical depression
(which required a current diagnosis of major, minor, or intermittent
depression plus associated atypical features) and borderline personality
disorder as a secondary diagnosis, imipramine (200 mg/day)
produced global improvement in 35% of patients with comorbid
borderline personality disorder. In contrast, phenelzine had a 92% response
rate in the same sample (57). The presence of borderline personality
disorder symptoms predicted a negative global response to imipramine
but a positive global response to phenelzine.
One longer-term study was conducted in patients hospitalized
for a suicide attempt who were diagnosed with borderline
personality disorder or histrionic personality disorder but not
axis I depression (175). In this 6-month, double-blind, placebo-controlled
study of a low dose of mianserin (30 mg/day), no antidepressant
or prophylactic efficacy was found for mianserin compared with placebo
for mood symptoms or recurrence of suicidal acts. (The same investigators
did demonstrate efficacy against recurrent suicidal acts in this
high-risk population with a depot neuroleptic, flupentixol [80].)
These data suggest that the utility of tricyclic antidepressants
in patients with borderline personality disorder is highly questionable.
When a clear diagnosis of comorbid major depression can be made,
SSRIs are the treatment of choice. When atypical depression is present,
the MAOIs have demonstrated superior efficacy to tricyclic antidepressants;
however, they must be used with great caution given the high risk
of toxicity. (Although the SSRIs have not been extensively studied
in atypical depression, at least one double-blind study has indicated
comparable efficacy for fluoxetine and phenelzine for the treatment
of atypical depression [176].) The efficacy of
SSRIs in borderline personality disorder and their favorable safety
profile argue for their empirical use in patients with borderline
personality disorder with atypical depression.
At best, the response to tricyclic antidepressants (e.g.,
imipramine) in patients with borderline personality disorder appears
modest. The possibility of behavioral toxicity and the known lethality of
tricyclic antidepressants in overdose support the preferential use
of an SSRI or related antidepressant for patients with borderline
personality disorder.
Common side effects of tricyclic antidepressants include sedation,
constipation, dry mouth, and weight gain. The toxicity of tricyclic
antidepressants in overdose, including death, indicates that they should
be used with caution in patients at risk for suicide. Patients with
cardiac conduction abnormalities may experience a fatal arrhythmia
with tricyclic antidepressant treatment. For some inpatients with
borderline personality disorder, treatment with amitriptyline has
paradoxically been associated with behavioral toxicity, consisting
of increased suicide threats, paranoid ideation, demanding and assaultive
behaviors, and an apparent disinhibition of impulsive behavior (50, 177).
+
d) Implementation issues
Other antidepressants are generally preferred over the tricyclic
antidepressants for patients with borderline personality disorder.
If tricyclic antidepressants are used, the patient should be carefully monitored
for signs of toxicity and paradoxical worsening. Doses used in published
studies were in the range of 150–250 mg/day of
amitriptyline, imipramine, or desipramine. Blood levels may be a useful
guide to whether the dose is adequate or toxicity is present.
+
3. MAOI antidepressants
MAOIs are used to treat affective symptoms, hostility, and
impulsivity related to mood symptoms in patients with borderline
personality disorder.
MAOIs have been studied in patients with borderline personality
disorder in three placebo-controlled acute treatment trials (55–57).
In an outpatient study of phenelzine versus imipramine that selected
patients with atypical depression (with borderline personality disorder
as a secondary comorbid condition), global improvement occurred
in 92% of patients given 60 mg/day of phenelzine compared
with 35% of patients given 200 mg/day of imipramine
(57). In a study of tranylcypromine, trifluoperazine,
alprazolam, and carbamazepine in which borderline personality disorder
was a primary diagnosis but comorbid with hysteroid dysphoria (55),
tranylcypromine (40 mg/day) improved a broad
spectrum of mood symptoms, including depression, anger, rejection
sensitivity, and capacity for pleasure. Cowdry and Gardner (55)
noted that "the MAOI proved to be the most effective psychopharmacological
agent overall, with clear effects on mood and less prominent effects on
behavioral control." Tranylcypromine also significantly
decreased impulsivity and suicidality, with a near significant effect
on behavioral dyscontrol. When borderline personality disorder is
the primary diagnosis, with no selection for atypical depression
or hysteroid dysphoria, results are clearly less favorable. Soloff
and colleagues (56) studied borderline personality disorder inpatients
with comorbid major depression (53%), hysteroid dysphoria
(44%), and atypical depression (46%); the patient
group was not selected for presence of a depressive disorder. Phenelzine
was effective for self-rated anger and hostility but had no specific
efficacy, compared with placebo or haloperidol, for atypical depression
or hysteroid dysphoria. These three acute trials were 5–6
weeks in duration. A 16-week continuation study of the responding
patients in a follow-up study (68) showed some continuing modest
improvement over placebo beyond the acute 5-week trial for depression
and irritability. Phenelzine appeared to be activating, which was
considered favorable in the clinical setting.
On balance, these studies suggest that MAOIs are often helpful
for atypical depressive symptoms, anger, hostility, and impulsivity
in patients with borderline personality disorder. These effects
appear to be independent of a current mood disorder diagnosis (56),
although one study found a nonsignificantly higher rate of MAOI
response for patients with a past history of major depression or
bipolar II disorder (55).
Phenelzine can cause weight gain (56) and can be difficult
to tolerate. Other side effects include orthostatic hypotension
(55). Fatal hypertensive crises are the most serious potential side
effect of MAOIs, although no study reported any hypertensive crises
due to violation of the tyramine dietary restriction. The initial
clinical picture of MAOI poisoning is one of agitation, delirium,
hallucinations, hyperreflexia, tachycardia, tachypnea, dilated pupils,
diaphoresis, and, often, convulsions. Hyperpyrexia is one of the
most serious problems (178).
+
d) Implementation issues
Doses of phenelzine and tranylcypromine used in published
studies ranged from 60 to 90 mg/day and 10 to 60 mg/day,
respectively. Experienced clinicians may vary doses according to
their usual practice in treating depressive or anxiety disorders.
Adherence to a tyramine-free diet is critically important and requires
careful patient instruction, ideally supplemented by a printed guide
to tyramine-rich foods and medication interactions, especially over-the-counter
decongestants found in common cold and allergy remedies. Given the
impulsivity of patients with borderline personality disorder, it
is helpful to review in detail the potential for serious medical
consequences of nonadherence to dietary restrictions, the symptoms
of hypertensive crisis, and an emergency treatment plan in case
of a hypertensive crisis. Patients must be instructed to discontinue
an SSRI long enough in advance of instituting MAOI therapy to avoid
precipitating a serotonin syndrome.
+
4. Lithium carbonate and anticonvulsant mood stabilizers
Lithium carbonate and the anticonvulsant mood stabilizers
carbamazepine and divalproex sodium are used to treat symptoms of
behavioral dyscontrol in borderline personality disorder, with possible efficacy
for symptoms of affective dysregulation.
The efficacy of lithium carbonate for bipolar disorder led
to treatment trials in patients with personality disorders
characterized by mood dysregulation and impulsive aggression.
Rifkin and colleagues (179, 180) demonstrated improvement in mood
swings in 21 patients with emotionally unstable character disorder,
a DSM-I diagnosis characterized by brief but nonreactive mood swings, both
depressive and hypomanic, in the context of a chronically maladaptive
personality resembling "hysterical character." In
this placebo-controlled crossover study (each medication was taken
for 6 weeks), there was decreased variation in mood (i.e., fewer "mood
swings") and global improvement in 14 of 21 patients during
lithium treatment. Subsequent case reports demonstrated that lithium
had mood-stabilizing and antiaggressive effects in patients with
borderline personality disorder (181, 182).
One double-blind, placebo-controlled crossover study compared
lithium with desipramine in 17 patients with borderline personality
disorder (61). All patients took lithium for 6 weeks (mean dose=985.7
mg/day) and received concurrent psychotherapy. Among 10
patients completing both lithium and placebo treatments, therapists' blind
ratings indicated greater improvement during the lithium trial,
although patients' self-ratings did not reflect significant
differences between lithium and placebo. The authors noted that
therapists were favorably impressed by decreases in impulsivity during
the lithium trial, an improvement not fully appreciated by the patients
themselves. There has never been a double-blind, placebo-controlled
trial of the antiaggressive effects of lithium carbonate in patients
with borderline personality disorder selected for histories of impulsive
aggression.
The anticonvulsant mood stabilizer carbamazepine has been
studied in two double-blind, placebo-controlled studies that used
very different patient groups, resulting in inconsistent findings.
Gardner and Cowdry (55, 62), in a crossover trial, studied female
outpatients with borderline personality disorder and comorbid hysteroid
dysphoria along with extensive histories of behavioral dyscontrol. Patients
underwent a 6-week trial of carbamazepine (mean dose=820
mg/day) and continued receiving psychotherapy. Patients
had decreased frequency and severity of behavioral dyscontrol during
the carbamazepine trial. Among all patients, there were significantly
fewer suicide attempts or other major dyscontrol episodes along
with improvement in anxiety, anger, and euphoria (by a physician's
assessment only) with carbamazepine treatment compared with placebo.
De la Fuente and Lotstra (63) failed to replicate these findings,
although this may be due to their small study group size (N=20).
These investigators conducted a double-blind, placebo-controlled trial
of carbamazepine in inpatients with a primary diagnosis of borderline
personality disorder. Patients with any comorbid axis I disorder,
a history of epilepsy, or EEG abnormalities were excluded. Unlike
in the Cowdry and Gardner study (55), patients were not selected
for histories of behavioral dyscontrol. There were no significant
differences between carbamazepine and placebo on measures of
affective or cognitive-perceptual symptoms, impulsive-behavioral "acting
out," or global symptoms.
Divalproex sodium has been used in open-label trials targeting
the agitation and aggression of patients with borderline personality
disorder in a state hospital setting (70) and mood instability and impulsivity
in an outpatient clinic (66). Wilcox (70) reported a 68% decrease
in time spent in seclusion as well as improvement in anxiety, tension,
and global symptoms among 30 patients with borderline personality
disorder receiving divalproex sodium (with dose titrated to a level
of 100 mg/ml) for 6 weeks in a state hospital.
Patients did not have "psychiatric comorbid conditions" (by
clinical assessment), although 5 had an EEG abnormality (but no
seizure disorders); concurrent psychotropic medications were allowed.
An abnormal EEG predicted improvement with divalproex sodium. The author
noted that both the antiaggressive and antianxiety effects of divalproex
sodium appeared instrumental in decreasing agitation and time spent
in seclusion.
An open-label study by Stein and colleagues (66) enrolled
11 cooperative outpatients with borderline personality
disorder, all of whom had been in psychotherapy for a minimum of
8 weeks and were free of other medications before starting divalproex
sodium treatment, which was titrated to levels of 50–100
mg/ml. Among the 8 patients who completed the study, 4
responded in terms of global improvement and observed irritability;
physician ratings of mood, anxiety, anger, impulsivity, and rejection
sensitivity; and patient ratings of global improvement. There were
no significant changes in measures specific for depression and anxiety,
but baseline depression and anxiety scores were low in this population.
Kavoussi and Coccaro (69) also reported significant improvement
in impulsive aggression and irritability after 4 weeks of treatment
with divalproex sodium in 10 patients with impulsive aggression in
the context of a cluster B personality disorder, 5 of whom (4 completers)
had borderline personality disorder. Among the 8 patients who completed
the 8-week trial, 6 had a 50% or greater reduction in aggression
and irritability. All patients had not responded to a previous trial
with fluoxetine (up to 60 mg/day for 8 weeks).
Only one small, randomized controlled trial of divalproex
has been reported that involved patients with borderline personality
disorder (65). Among 12 patients randomly assigned to divalproex,
only 6 completed a 10-week trial, 5 of whom responded in terms of
global measures. There was improvement in depression, albeit not
statistically significant, and aggression was unchanged. None of
the 4 patients randomly assigned to placebo completed the study.
In summary, preliminary evidence suggests that lithium carbonate
and the mood stabilizers carbamazepine and divalproex may be useful
in treating behavioral dyscontrol and affective dysregulation in
some patients with borderline personality disorder, although further
studies are needed. The only report on the newer anticonvulsants
(i.e., gabapentin, lamotrigine, topiramate) in borderline personality
disorder is a case series in which three of eight patients had a
good response to lamotrigine (183). Because of the paucity
of evidence concerning these agents, careful consideration of the
risks and benefits is recommended when using such medications pending
the publication of findings from systematic studies.
Although lithium commonly causes side effects, most are minor
or can be reduced or eliminated by lowering the dose or changing
the dosage schedule. More common side effects include polyuria, polydipsia,
weight gain, cognitive problems (e.g., dulling, poor concentration),
tremor, sedation or lethargy, and gastrointestinal distress (e.g.,
nausea). Lithium may also have renal effects and may cause hypothyroidism.
Lithium is potentially fatal in overdose and should be used with
caution in patients at risk of suicide.
Carbamazepine's most common side effects include
neurological symptoms (e.g., diplopia), blurred vision, fatigue,
nausea, and ataxia. Other side effects include skin rash, mild leukopenia
or thrombocytopenia, and hyponatremia. Rare, idiosyncratic, but
potentially fatal side effects include agranulocytosis, aplastic
anemia, hepatic failure, exfoliative dermatitis, and pancreatitis.
Carbamazepine may be fatal in overdose. In studies of patients with
borderline personality disorder, carbamazepine has been reported
to cause melancholic depression (64).
Common dose-related side effects of valproate include gastrointestinal
distress (e.g., nausea), benign hepatic transaminase elevations,
tremor, sedation, and weight gain. With long-term use, women may
be at risk of developing polycystic ovaries or hyperandrogenism.
Mild, asymptomatic leukopenia and thrombocytopenia occur less frequently.
Rare, idiosyncratic, but potentially fatal adverse events include
hepatic failure, pancreatitis, and agranulocytosis.
+
d) Implementation issues
Full guidelines for the use of these medications can be found
in the APA
Practice Guideline for the Treatment
of Patients With Bipolar Disorder
(85; included
in this volume). Lithium carbonate and the anticonvulsant mood stabilizers
are used in their full therapeutic doses, with plasma levels guiding
dosing. Routine precautions observed for the use of these medications
in other disorders also apply to their use in borderline personality disorder,
e.g., plasma level monitoring of thyroid and kidney function with
prolonged lithium use, periodic measure of WBC count with carbamazepine
therapy, and hematological and liver function tests for divalproex
sodium.
Anxiolytic medications are used to treat the many manifestations
of anxiety in patients with borderline personality disorder, both
as an acute and as a chronic symptom.
Despite widespread use, there is a paucity of studies investigating
the use of anxiolytic medications in borderline personality disorder.
Cowdry and Gardner (55) included alprazolam in their double-blind,
placebo-controlled, crossover study of outpatients with borderline
personality disorder, comorbid hysteroid dysphoria, and extensive
histories of behavioral dyscontrol. Use of alprazolam (mean dose=4.7
mg/day) was associated with greater suicidality and episodes
of serious behavioral dyscontrol (drug overdoses, self-mutilation,
and throwing a chair at a child). This occurred in 7 (58%) of
12 patients taking alprazolam compared with 1 (8%) of 13
patients receiving placebo. However, in a small number of patients
(N=3), alprazolam was noted to be helpful for anxiety in
carefully selected patients with borderline personality disorder
(52). Case reports suggest that clonazepam is helpful as an adjunctive
agent in the treatment of impulsivity, violent outbursts, and anxiety
in a variety of disorders, including borderline personality disorder
(54).
Although clinicians have presented preliminary experiences
with nonbenzodiazepine anxiolytics in patients with borderline personality
disorder (e.g., buspirone) (184), there are currently no published
studies of these anxiolytics in borderline personality disorder.
Behavioral disinhibition, resulting in impulsive and assaultive
behaviors, has been reported with alprazolam in patients with borderline
personality disorder. Benzodiazepines, in general, should be used
with care because of the potential for abuse and the development
of pharmacological tolerance with prolonged use. These are particular
risks in patients with a history of substance use.
+
d) Implementation issues
In the absence of clear evidence-based recommendations, dose
and duration of treatment must be guided by clinical need and judgment,
keeping in mind the potential for abuse and pharmacological tolerance.
It has been suggested that the relative subjective numbing
and physical analgesia that patients with borderline personality
disorder often feel during episodes of self-mutilation, as well
as the reported sense of relative well-being afterward, might be
due to release of endogenous opiates (185–187). Opiate
antagonists have been employed in an attempt to block mutilation-induced
analgesia and euphoria and thereby reduce self-injurious behavior
in patients with borderline personality disorder.
Clinical case reports (188) and several small case series
have assessed the efficacy of opiate antagonists for self-injurious
behavior, and two suggested some improvement in this behavior (189, 190).
One small, double-blind study involving female patients with borderline
personality disorder with a history of self-injurious behavior who
underwent a stress challenge showed no effect of opiate receptor
blockade with naloxone on cold pressor pain perception or mood ratings
(191). While the stress level may not have been high enough to mimic
clinical situations, the study does not support the theory that
opiate antagonism plays a role in reducing self-injurious behavior.
Despite the few promising clinical case reports, these reports
are very preliminary, and there is no clear evidence from well-controlled
trials indicating that opiate antagonists are effective in reducing
self-injurious behavior among patients with borderline personality
disorder.
Nausea and diarrhea are occasionally reported (190).
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d) Implementation issues
In published reports, the typical dose of naltrexone was 50
mg/day. No time limit for treatment emerges from the literature,
but the effect is presumably reversed when the medication stops.
The primary goal of treatment with neuroleptics in borderline
personality disorder is to reduce acute symptom severity in all
symptom domains, particularly schizotypal symptoms, psychosis, anger,
and hostility.
Early clinical experience with neuroleptics targeted the "micropsychotic" or
schizotypal symptoms of borderline personality disorder. However,
affective symptoms (mood, anxiety, anger) and somatic complaints
also improved with low doses of haloperidol, perphenazine,
and thiothixene. An open-label trial of thioridazine (mean dose=92
mg/day) led to marked improvement in impulsive-behavioral
symptoms, global symptom severity, and overall borderline psychopathology
(78). Similar findings were reported for adolescents with borderline
personality disorder treated with flupentixol (mean dose=3
mg/day) (77), with improvement in impulsivity, depression,
and global functioning.
Systematic, parallel studies that compared neuroleptics without
a placebo control condition also reported a broad spectrum of efficacy.
Leone (73) found that loxapine succinate (mean dose=14.5 mg/day)
or chlorpromazine (mean dose=110 mg/day) improved
depressed mood, anxiety, anger/hostility, and suspiciousness.
Serban and Siegel (74) reported that thiothixene (mean dose=9.4
mg/day, SD=7.6) or haloperidol (mean dose=3.0
mg/day, SD=0.8) produced improvement in anxiety, depression,
derealization, paranoia (ideas of reference), general symptoms,
and a global measure of borderline psychopathology.
Subsequent double-blind, placebo-controlled trials also suggested
a broad spectrum of efficacy for low-dose neuroleptics in the treatment
of borderline personality disorder. Acute symptom severity improved
in cognitive-perceptual, affective, and impulsive-behavioral symptom
domains, although efficacy for schizotypal symptoms, psychoticism,
anger, and hostility was most consistently noted.
Many of the double-blind, placebo-controlled studies of neuroleptics
in borderline personality disorder are noteworthy for biases in
sample selection that strongly affected outcomes. In a study of patients
with borderline or schizotypal personality disorder and at least
one psychotic symptom (which biased the sample toward cognitive-perceptual
symptoms), thiothixene (mean dose=8.7 mg/day for
up to 12 weeks) was more effective than placebo for psychotic
cluster symptomsspecifically illusions and ideas
of referenceand self-rated obsessive-compulsive and phobic anxiety
symptoms but not depression or global functioning (75). The more
severely symptomatic patients were at baseline (e.g., in terms of
illusions, ideas of reference, or obsessive-compulsive and phobic
anxiety symptoms), the better they responded to thiothixene (75).
Cowdry and Gardner (55) conducted a complex, placebo-controlled,
four-drug crossover study in borderline personality disorder outpatients
with trifluoperazine (mean dose=7.8 mg/day). Patients were
required to meet criteria for hysteroid dysphoria and have a history
of extensive behavioral dyscontrol, introducing a bias toward affective
and impulsive-behavioral symptoms. All patients were receiving psychotherapy.
Those patients who were able to keep taking trifluoperazine for 3 weeks
or longer (7 of 12 patients) had improved mood, with significant
improvement over placebo on physician ratings of depression, anxiety,
rejection sensitivity, and suicidality.
Soloff and colleagues (50, 51) studied acutely ill inpatients,
comparing haloperidol with amitriptyline and placebo in a 5-week
trial. Patients who received haloperidol (mean dose=4.8
mg/day) improved significantly more than those receiving
placebo across all symptom domains (50), including global measures,
self- and observer-rated depression, anger and hostility, schizotypal
symptoms, psychoticism, and impulsive behaviors (51). Haloperidol
was as effective as amitriptyline for depressive symptoms.
However, a second study by the same group (56) that used the
same design but compared haloperidol with phenelzine and placebo
failed to replicate the broad-spectrum efficacy of haloperidol (mean
dose=3.9 mg/day). Efficacy for haloperidol was
limited to hostile belligerence and impulsive-aggressive behaviors,
and placebo effects were powerful. Patients in this study had milder
symptoms, especially in the cognitive-perceptual and impulsive-behavioral
symptom domains, than patients in the first study.
Cornelius and colleagues (68) followed a subset of the aforementioned
group who had responded to haloperidol, phenelzine, or placebo for
16 weeks following acute treatment. Patients' intolerance of
the medication, a high dropout rate, and nonadherence
were decisive factors in this study. The attrition rates at 22 weeks
were 87.5% for haloperidol, 65.7% for phenelzine,
and 58.1% for placebo. Further significant improvement
with haloperidol treatment (compared with placebo) occurred only for
irritability (with improvement for hostility that was not statistically
significant). Depressive symptoms significantly worsened with haloperidol
treatment over time, which was attributed, in part, to the side
effect of akinesia. Clinical improvement was modest and of limited
clinical importance.
Montgomery and Montgomery (80) controlled for nonadherence
by using depot flupentixol decanoate, 20 mg once a month, in a continuation
study of recurrently parasuicidal patients with borderline personality
disorder and histrionic personality disorder. Over a 6-month period,
patients receiving flupentixol had a significant decrease in suicidal
behaviors compared with the placebo group. Significant differences
emerged by the fourth month and were sustained through 6 months
of treatment. This important study awaits replication.
The introduction of the newer atypical neuroleptics increases
clinicians' options for treating borderline personality
disorder. To date, findings from only two small open-label trials
have been published, both with clozapine. Frankenburg and Zanarini
(81) reported that clozapine (mean dose=253.3 mg/day,
SD=163.7) improved positive and negative psychotic symptoms
and global functioning (but not depression or other symptoms) in
15 patients with borderline personality disorder and comorbid axis
I psychotic disorder not otherwise specified who had not responded
to (or were intolerant of) other neuroleptics. Improvement was modest
but statistically significant. Patients were recruited from a larger
study of patients with treatment-resistant psychotic disorders,
raising the question of whether their psychotic symptoms were truly
part of their borderline personality disorder.
These concerns were addressed by Benedetti and colleagues
(71), who excluded all patients with axis I psychotic disorders
from their cohort of patients with refractory borderline personality
disorder. Target symptoms included "psychotic-like" symptoms
that are more typical of borderline personality disorder. Patients
had not responded to at least 4 months of prior treatment with medication
and psychotherapy. In a 4-month, open-label trial of 12 patients
treated with clozapine (mean dose=43.8 mg/day,
SD=18.8) and concurrent psychotherapy, a low dose of clozapine
improved symptoms in all domainscognitive-perceptual,
affective, and impulsive-behavioral.
Despite a lack of data, clinicians are increasingly using
olanzapine, risperidone, and quetiapine for patients with borderline
personality disorder. These medications have less risk than clozapine
and may be better tolerated than the typical neuroleptics.
Schulz and colleagues (83) presented preliminary data from a double-blind,
placebo-controlled, 8-week trial of risperidone in 27 patients with borderline
personality disorder who received an average dose of 2.5 mg/day
(to a maximum of 4 mg/day). On global measures of functioning,
there was no significant difference between risperidone and placebo,
although the authors noted that risperidone-treated patients were "diverging
from the placebo group" in paranoia, psychoticism, interpersonal
sensitivity, and phobic anxiety (83). The same group conducted an
8-week, open-label study of olanzapine in patients with borderline personality
disorder and comorbid dysthymia (82). Patients received an average
dose of 7.5 mg/day (range=2.5–10 mg/day).
Among the 11 completers, significant improvement was reported across
all domains, with particular improvement noted in depression, interpersonal
sensitivity, psychoticism, anxiety, and anger/hostility.
These medications require further investigation in double-blind
studies.
In summary, neuroleptics are the best-studied psychotropic
medications for borderline personality disorder. The literature
supports the use of low-dose neuroleptics for the acute management
of global symptom severity, with specific efficacy for schizotypal
symptoms and psychoticism, anger, and hostility. Relief of global
symptom severity in the acute setting may be due, in part, to nonspecific "tranquilizer" effects
of neuroleptics, whereas symptom-specific actions against psychoticism,
anger, and hostility may relate more directly to dopaminergic blockade.
Acute treatment effects of neuroleptic drugs in borderline personality
disorder tend to be modest but clinically and statistically significant.
Two studies that addressed continuation and maintenance treatment
of a patient with borderline personality disorder with neuroleptics
had contradictory results. The Montgomery and Montgomery study (80)
reported efficacy for recurrent parasuicidal behaviors, whereas
the Cornelius et al. study (68) suggested very modest utility for
only irritability and hostility. More controlled trials are needed to
investigate low-dose neuroleptics in continuation and maintenance
treatment.
Dropout rates in neuroleptic trials in borderline outpatients
range from 13.7% for a 6-week trial (73) to 48.3% for
a 12-week trial (75) to 87.5% for a 22-week continuation
study (68). In acute studies, patient nonadherence is often due
to typical medication side effects, e.g., extrapyramidal symptoms, akathisia,
sedation, and hypotension. Patients with borderline personality
disorder who have experienced relief of acute symptoms with low-dose
neuroleptics may not tolerate the side effects of the drug with
longer-term treatment. The risk of tardive dyskinesia must be considered
in any decision to continue neuroleptic medication over the long
term. Thioridazine has been associated with cardiac rhythm disturbances
related to widening of the Q-T interval and should be avoided. In
the case of clozapine, the risk of agranulocytosis is especially
problematic. While the newer atypical neuroleptics promise a more
favorable side effect profile, evidence of efficacy in borderline
personality disorder is still awaited. Neuroleptics should be given
in the context of a supportive doctor-patient relationship in which
side effects and nonadherence are addressed frequently.
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d) Implementation issues
All studies have used a low dose and demonstrated beneficial
effects within several weeks. With the exception of one study that
used a depot neuroleptic (flupentixol, which is not available in
the United States), all medications were given orally and daily.
Acute treatment studies are a good model for acute clinical care
and typically range from 5 to 12 weeks in duration. There is insufficient evidence
to make a strong recommendation concerning continuation and maintenance
therapies. At present, this is best left to the clinician's
judgment after carefully weighing the risks and benefits for the
individual patient. CBC monitoring must be done if clozapine is
used.
The goal of ECT in patients with borderline personality disorder
is to decrease depressive symptoms in individuals with a comorbid
axis I mood disorder, which is present in as many as one-half of
hospitalized patients with borderline personality disorder.
Most of the clinical and empirical literature that describes
experience with ECT in patients with major depression comorbid with
personality disorders does not report results specifically for borderline
personality disorder. Although studies that used a naturalistic
design have had inconsistent findings, patients with major depression
and a comorbid personality disorder were generally less responsive
to somatic treatments than patients with major depression alone.
In one naturalistic follow-up study (based on chart review),
there was no significant difference in recovery rates for 10 patients
with major depressive disorder and a personality disorder (40% recovery)
compared with 41 patients with major depressive disorder alone (65.9% recovery)
(192). In another study, involving 1,471 depressed inpatients, depressed
patients with a personality disorder were 50% less likely
to be recovered at hospital discharge than depressed patients without
a personality disorder (193).
Several uncontrolled studies found that outcome was dependent
on the time of assessment. In one small study (194), there were
no significant differences in immediate response to ECT between depressed
subjects with or without a personality disorder; however, at a 6-month
follow-up evaluation, the patients with a personality disorder had
more rehospitalizations and more severe depression symptoms. Conversely,
in another uncontrolled study of inpatients with major depression
(195), compared with depressed patients without a personality disorder,
those with a personality disorder had a poorer outcome in terms
of depression and social functioning immediately following treatment. However,
after 6 and 12 weeks of follow-up, there were no differences
between the two groups in terms of depression and social functioning.
The number of rehospitalizations did not differ between groups at
the 6-month and 12-month follow-up evaluations.
In another small study (N=16) (196–198)
that used the self-rated Millon Clinical Multiaxial InventoryII
and assessed borderline personality disorder, there was significant
improvement in avoidant, histrionic, aggressive/sadistic,
and schizotypal personality traits with ECT. Improvements were noted
in passive-aggressive and borderline personality traits that did
not reach statistical significance. The presence of pretreatment
borderline traits predicted poorer outcome with ECT (198).
Although the results of these studies appear somewhat divergent,
most found that patients with major depression and a personality
disorder have a less favorable outcome with ECT than depressed patients
without a personality disorder.
Because ECT is not recommended for borderline personality
disorder per se, adverse effects are not described here and can
be found in the APA
Practice Guideline for the Treatment
of Patients With Major Depressive Disorder
(84;
included in this volume).
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d) Implementation issues
The affective dysregulation, low self-esteem, pessimism, chronic
suicidality, and self-mutilation of patients with borderline personality
disorder are often misconstrued as axis I depression. Clinical experience
suggests that, not infrequently, these characterological manifestations
of borderline personality disorder are treated with ECT, often resulting
in a poor outcome. Although there is a paucity of ECT studies involving
patients with borderline personality disorder, a recommendation for
ECT in these patients with comorbid major depression should be guided
by the presence and severity of verifiable neurovegetative symptoms,
e.g., sleep disturbance, appetite disturbance, weight change, low
energy, and anhedonia. These symptoms should ideally be confirmed
by outside observers, as they provide an objective way to assess
treatment response. Perhaps the greatest challenge for the clinician
is not when to institute ECT in the depressed patient with borderline personality
disorder but when to stop. As the neurovegetative symptoms of major
depression resolve, many patients continue to have borderline features
that clinical experience suggests are unresponsive to ECT. Knowledge
of the patient's personality functioning before the onset
of major depression is critical to knowing when the "baseline" has
been achieved. Many patients with borderline personality disorder
who are considered nonresponsive to ECT because of persistence of
depressive features are, in fact, already in remission from their
axis I depression but continue to experience chronic characterological
depressive features.
Notable progress has been made in our understanding of borderline
personality disorder and its treatment. However, there are many
remaining questions regarding treatments with demonstrated efficacy,
including how to optimally use them to achieve the best health outcomes
for patients with borderline personality disorder. In addition,
many therapeutic modalities have received little empirical investigation
for borderline personality disorder and require further study. The
efficacy of various treatments also needs to be studied in populations
such as adolescents, the elderly, forensic populations, and patients
in long-term institutional settings. The following is a sample of
the types of research questions that require further study.