Soloff, Algorithm 3

Algorithm for treatment of impulsive-behavioral symptoms

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 PD 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

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