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Practice Guideline for the Treatment of Patients With Borderline Personality Disorder
Tricyclic and heterocyclic antidepressants
MAOI antidepressants
Lithium carbonate and anticonvulsant mood stabilizers
Anxiolytic agents
Opiate antagonists
Neuroleptics
ECT (electroconvulsive therapy)
PART
B:
BACKGROUND
INFORMATION AND REVIEW OF AVAILABLE EVIDENCE
VI. REVIEW AND SYNTHESIS OF AVAILABLE EVIDENCE
C. REVIEW OF PHARMACOTHERAPY AND OTHER SOMATIC TREATMENTS1. SSRI antidepressants
a) Goals. 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.
b) Efficacy. 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.
...
Markovitz
(45) studied 17 patients (nine given fluoxetine, 80 mg/day, and eight given
placebo) for 14 weeks
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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)
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In summary,
these three randomized, double-blind, placebo-controlled studies show efficacy
for fluoxetine for affective symptoms—specifically, 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 symptoms—specifically, 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.
c) Side effects. 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
a)
Goals. 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
...
b)
Efficacy. Double-blind, placebo-controlled
trials of tricyclic antidepressants in borderline personality disorder
have used amitriptyline, imipramine, and desipramine in both inpatient
and outpatient settings
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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.
c)
Side effects. 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
...
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
a) Goals. MAOIs are used to treat affective symptoms, hostility, and impulsivity related to mood symptoms in patients with borderline personality disorder.
b)
Efficacy. MAOIs have been studied in
patients with borderline personality disorder in three placebo-controlled
acute treatment trials (55–57).
...
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."
...
When borderline
personality disorder is the primary diagnosis, with no selection for atypical
depression or hysteroid dysphoria, results are clearly less favorable.
...
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).
c) Side effects. 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 60–90 mg/day and 10–60 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
a) Goals. 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.
b)
Efficacy. The efficacy of lithium carbonate
for bipolar disorder led to treatment trials in patients with personality
disorders characterized by mood dysregulation and impulsive
aggression.
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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.
c)
Side effects. 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
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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
...
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). 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.
5. Anxiolytic agents
a) Goals. 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.
b)
Efficacy. 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 seven (58%) of 12 patients taking alprazolam
compared with one (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).
...
c) Side effects. 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.
6. Opiate antagonists
a) Goals. 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.
b)
Efficacy.
...
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.
c) Side effects. Nausea and diarrhea are occasionally reported (190).
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.
7. Neuroleptics
a) Goals. 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.
b)
Efficacy. 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.
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The introduction
of the newer atypical neuroleptics increases clinicians’ options for treating
borderline personality disorder.
...
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.
...
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
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Acute treatment
effects of neuroleptic drugs in borderline personality disorder tend to
be modest but clinically and statistically significant.
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More controlled
trials are needed to investigate low-dose neuroleptics in continuation
and maintenance treatment.
c)
Side effects.
...
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.
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Neuroleptics
should be given in the context of a supportive doctor-patient relationship
in which side effects and nonadherence are addressed frequently.
d)
Implementation issues. All
studies have used a low dose and demonstrated beneficial effects within
several weeks
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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.
8. ECT (electroconvulsive therapy)
a) Goals. 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.
b)
Efficacy. 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 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.
c) Adverse effects. Because ECT is not recommended for borderline personality disorder per se, adverse effects are not described here.
d)
Implementation issues.
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