Line 1. The algorithm for the treatment of impulsive-behavioral
symptoms in the PD patient bears a strong resemblance to that for
affective dysregulation, as they share some elements of a common
pathophysiology. The impulsive-behavioral symptoms of the personality disorder patient
are the endpoint of a process of disinhibition of affect, impulse,
and cognition. Although most dramatically expressed in
self-destructive or assaultive acts, impulsivity can be manifested
in a broad spectrum of symptomatic behaviors (e.g., binges of
eating, spending. sex, drugs) or as cognitive impassivity (e.g.,
rash judgments).
Impulsive-aggressive behavior in patients with personality
disorders, including suicide, homicide, and other violent behaviors,
correlates with diminished levels of cerebrospinal fluid (CSF)
5-HIAA and blunted neuroendocrine responses to serotonergic
pharmacodynamic challenges (e.g., with d,l-fenfluramine,
m-cholorophenylpiperazine, and buspirone) independent of affective
disorder (Coccaro et al., 1989; Mann, Arango, Marzyk, Theccanat,
& Reis, 19899 Siever & Trestman, 1993). Diminished levels of
CSF 5-HIAA may represent a marker for vulnerability to suicidal
behavior, particularly attempts by violent means. Diminished CSF
5-HIAA is also found in personality disorder patients who have
committed impulsive violent crimes, including homicide. It is
reported in patients who have killed their children or persons
emotionally close to them, as opposed to strangers (Lidberg, Tuck,
Asberg, Scalia-Tomba, & Bertisson, 1985; Linnoila et al., 1983).
Diminished levels of CSF 5-HIAA have been found in borderline
patients years after serious suicide attempts, suggesting that
diminished serotonergic neurotransmission is a marker for suicidal
behavior in this population (Gardner, Lucas, & Cowdry, 1990).
Diminished central serotonergic function has also been demonstrated
in Type II alcoholics who are males with early onset drinking and
antisocial personalities (Limson et al., 1991). Current theory holds
that the executive functions of response inhibition are mediated in
prefrontal cortex by serotonergic neurotransmitter function
(Weinberger, 1993). Recent studies of impulsive-aggressive
individuals using positron emission tomography (PET) neuroimaging
techniques demonstrate decreased activation in prefrontal cortex
consistent with clinical symptoms of disinhibition (Rain: et
al.,1992).
Line 2. The SSRI antidepressants are the treatment of first
choice for impulsive, disinherited behavior in the context of PD.
The effect of SSRI antidepressants on impulsive behavior is
independent of the effect on depression and is supported by two
placebo-controlled studies and five open label trials, utilizing
fluoxetine and sertraline, warranting a support level of "A''
(Coccaro et al., 1990; Cornelius et al., 1990; Kavoussi et al.,
1994; Markovitz, 1995; Markovitz et al., 1991; Norden, 1989; Salzman
et al., 199.5).
Line 3. The effects of SSRI antidepressants on impassivity appear
earlier than the effects on depression, with onset of action within
days in some reports. Similarly, discontinuation of drug following
successful treatment results in the reemergence of impulsive
aggression within days. The duration of treatment following
successful management of impulsive aggression is determined by the
clinical state of the patient, including risk of exposure to life
stressors and progress in learning coping skills. When the target
for treatment is a trait vulnerability, one cannot set a predefined
limit on treatment duration. Line 4. In the event of partial
efficacy, or where clinical need is urgent, a low-dose narcoleptic
may be added. Double-blind trials with BPD patients have
demonstrated anti-impulse actions of low-dose neuroleptics. The
effect of neuroleptics in the PD patient may be nonspecific,
diminishing symptom severity across a broad spectrum of symptoms.
Nonetheless, the effect is rapid in onset, often in hours with oral
use (more rapidly intramuscularly, if needed), and may provide
urgent control over escalating impulsive aggression. Low-dose
neuroleptics can be started before the full fair trial of SSRI
antidepressant is complete. In the event of no efficacy to the SSRI
antidepressant, and where time permits, a "salvage'' trial of a
second SSRI or related antidepressant may be considered, although
there are no published clinical trials of second SSRIs with
impassivity as a target symptom.
Lines 5, 6. Partial efficacy to an SSRI antidepressant may be
enhanced through addition of lithium carbonate for its proven
anti-impulse effects. Studies by Tupin et at., (1973) of impulsive,
criminal adults and by Sheard (1975) of delinquent adolescents
demonstrate a strong effect for lithium carbonate against the
impulsive-aggressive symptoms of the PD patient. The double-blind
studies and additional case reports (e.g., Shader, Jackson, &
Dodes, 1974) support an "A'' recommendation for the use of
lithium for this indication.
In the event of no response to the SSRI trials, MAOI
antidepressants are recommended. Cowdry and Gardner (1988)
demonstrated efficacy against behavioral impassivity for
tranylcypromine in a placebo-controlled crossover study of women
with BPD and "hysteroid dysphoria.'' Soloff et al.,(1989) found
phenelzine effective against anger and irritability in BPD patients,
although not against other affective complaints. As both of these
studies were double blind and placebo controlled, the MAOI
recommendation for use in impulsively, anger, and irritability is
supported at the "A'' level. Combining an MAOI antidepressant
with lithium or an anticonvulsant as augmentation would also appear
to be rational treatment at this point, although there are no
studies of these combinations.
Lines 7, 8. The use of carbamazepine or valproate for impulse
control in the PD patient appears to be widespread in clinical
practice (based on their efficacy in bipolar disorders), although
research studies are inconclusive for efficacy against impulsive
aggression. Cowdry and Gardner (1988; Gardner & Cowdry, 1986b)
reported efficacy for carbamazepine against behavioral impulsively
in the context of borderline disorder with comorbid "hysteroid
dysphoria.'' However, a recent report by De La Fuenta et al., (1994)
failed to replicate this finding in a well-controlled study that
excluded patients with affective disorders. Pending further
research, the level of support for carbamazepine for the specific
indication of impulsive aggression in the PD patient remains at the
"C'' level.
Support for the use of valproate as a treatment for impulsively
in the PD patient is derived from case reports and one open label
trial in which impulsively was significantly diminished among
severely impaired borderline patients (Stein et al., 1995; Wilcox,
1995). Valproate has also been shown to be helpful against the
chronic temper outbursts and mood lability of adolescents with
"disruptive'' behavior disorders (e.g., ADHD. oppositional
disorder, conduct disorder) (Donovan et al., 1997). The paucity of
controlled studies requires a "C'' level of support for this
indication for valproate.
Lines 9, 10. Finally, the atypical neuroleptics may have some
efficacy in the treatment of impulsively, especially against severe
self-mutilation or other impulsive behaviors arising from psychotic
thinking in the context of BPD. Support is at the "C'' level,
derived from one open label trial and one case report (Chengappa et
al., 19959 Frankenburg & Zanarini, 1993). The difficulties and
risks involved in using clozapine (e.g., neutropenia) warrant its
place as treatment of last resort. The newer atypical neuroleptics
do not cause neutropenia and warrant further exploration in the
treatment of patients with refractory impulsive aggression.
Novel approaches
Novel approaches merit consideration by clinicians faced with
specific refractory symptom presentations, although the lack of
clinical testing or widespread experience prohibits recommendation
in a general clinical algorithm.
Opiate antagonists
The repetitive self-injurious behavior (SIB) of the patient with
BPD has been treated with the opiate antagonist naltrexone following
the hypothesis that endogenous opiates may be involved in the
initiation or maintenance of self-injury. Evidence suggesting a role
for the opiate system in SIB includes reports of increased plasma
metenkephalin in habitual mutilators, increased pain thresholds in
BPD patients with histories of SIB, and the phenomenon of topical
analgesia in SIB, which can be blocked by opiate antagonists (Russ,
R0th, Kakuma, Harrison, & Hull, 1994). Treatment trials in
mentally retarded subjects suggest modest results against SlB. Case
reports and small patient series support a similar role in patients
with BPD (McGee, 1997; Sonne, Rubey, Brady, Malcolm, & Morris,
1996).
Psycbostimulants
Is there a role for the Psycbostimulants in treating personality
disorders? Impulsivity often presents as a residual adult symptom of
childhood attention-deficit/hyperactivity disorder (ADHD). It is not
always possible to clearly distinguish the impulsive temperament of
the antisocial or borderline patient from the residual impassivity
of the adult with ADHD. The two syndromes may even be comorbid in
some cases. Where a clearly defined childhood syndrome of ADHD
precedes development of adult personality disorder, use of a
psychostimulant as treatment for adult impulsively is more
appropriately viewed as maintenance treatment for the residual
symptoms of an Axis I disorder. Given the abuse potential of the
Psycbostimulants, full exploration of antidepressant efficacy,
including buproprion (which has dopaminergic actions and is useful
in ADHD), should precede any trial of psychostimulants in the PD
patient. Psychostimulants may also be helpful as activating agents
in the treatment of severely anergic, amotivational depressive
states, although they are not truly antidepressant in this usage.
The careful use of these agents in the PD patient for anergic
depressed mood has some clinical utility, although there is no
research support for the practice at the present time.
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Contributed by Valerie Porr, President of TARA
APD
