Abstract

CHAVEZ-LEON, Enrique; NG, Bernardo  and  ONTIVEROS-URIBE, Martha Patricia. Tratamiento farmacológico del transtorno límite de personalidad. Salud Ment [online]. 2006, vol.29, n.5, pp.16-24. ISSN 0185-3325.

Temperament and character are terms utilized to delinéate the participation of biologic and psychosocial factors in the development of normal and disordered personality. At times, biological factors, and in others rearing, education, psychological and social events at an early age are the main determinants.

The American Psychiatric Association describes Borderline Personality Disorder (BPD) as characterized by a pattern of interpersonal, selfimage and affective instability, as well as notable impulsivity. In this disorder, temperament as an inherited factor plays an important role, as demonstrated by familial studies in which the disorder is more frequently present in the families of probands than non-probands. Other disorders where impulsivity is an outstanding feature, such as antisocial personality disorder and substance abuse, are also frequent in first degree relatives of patients with BPD.

Psychological factors, such as sexual abuse during childhood, are particularly high in this disorder. This is believed to generate features such as emotional instability, distrust, and dissociative states. From this point of view, it is possible that BPD is a form of "adaptation" not only psychological and behavioral, but also biological. Changes in the volume of the amygdala and hippocampus have been described in the brain of women abused during childhood, and those with BPD.

BPD is frequently present in clinical practice, either or not associated to other psychiatric disorders; it can be found anywhere from 11 to 40.4% according to the setting studied. This incidence is even higher in patients with multiple suicide attempts.

The term "borderline" was established when this pathological condition was conceptualized to origínate between neurosis and psychosis. However, current understanding of personality is better explained with a psychobiological model based on various dimensions. There is one related to schizophrenia (cognitive-perceptual organization dimension) and others related to mood disorders (mood regulation dimension), impulse control (impulsivity-aggression dimension), and anxiety disorders (anxiety-inhibition dimension). Patients with BPD show persistent disturbance on the four dimensions. The combination of these disturbances, along with specific defense mechanisms and coping strategies, originate the characteristic behaviors of individuals with BPD.

Regarding the first dimension (cognitive-perceptual organization), BPD patients manifest paranoid ideation and dissociative symptoms usually under severe stress. It is possible that frontal lobe functioning is compromised due to a reactive dopamine and norepinephrine surge in the prefrontal lobe.

The disturbance in the second dimension (mood regulation) is manifested in BPD by rapid mood shifts due to excessive sensitivity to separation, frustration and criticism. Although present in all cluster B personality disorders, mood instability in BPD is responsible for stormy relationships, self-image and self-esteem fluctuations, constant rage and bad temper, physical fights, and feelings of emptiness. This mood instability seems to be related to a serotonin effect on the dopaminergic and noradrenergic systems.

Disturbances in the third dimension (impulsivity-aggression) originate a lack of control in the use of alcohol and/or drugs, as well as binge eating, reckless driving, shopping sprees, suicide gesture/attempts, self mutilation, and uncontrollable/inappropriate anger. Most studies note the inverse relationship between serotonin levels, and impulsivity, aggression, and selfharm behavior.

Finally, abnormalities in the fourth dimension (anxiety-inhibition) manifest as themselves frantic attempts to prevent real or imaginary abandonment. No neurobiological substrate has been proposed in this dimension.

The growing evidence of neurobiological basis favors the utilization of pharmacological agents in the treatment of BPD. This paper reviews available publications on controlled clinical trials, hoping to provide a guide in the prescription of psychopharma-cological agents to the patient with BPD. These patients can benefit from pharmacological treatment for impulsivity, psychotic states, affective instability and depression.

After establishing a diagnosis, and ruling out associated conditions -such as major psychiatric disorders, substance use disorders, and/or general medical conditions-, a treatment plan including medications can be implemented.

Studies on selective serotonin reuptake inhibitors (SSRI's) show the efficacy of fluoxetine in diminishing irritability and aggression and, to a lesser degree, depressed mood. A study adding fluoxetine to behavioral dialectic therapy did not seem to improve the outcome. Fluvoxamine, an antidepressant from the same class, improved emotional lability.

Antipsychotics have shown to be useful. Olanzapine is the most studied of the atypical antipsychotics. Case reports using quetiapine and clozapine have also been published. Haloperidol improved depression, anxiety and anger.

Anticonvulsants such as carbamazepine, valprote and, more recently topiramate, were reported to improve depressed mood, aggression and self-mutilation.

TCA's and MAOI's seemed to help in symptoms such as anxiety, anger, suicidal ideation and rejection sensitivity. In turn, benzo-diacepines were associated with decreased impulse control, in-creased aggression and risk for overdose.

Based on this literature review, the following considerations can be made:

Patients with BPD, where aggressive behavior, self-multilation, or chronic disphoria are the outstanding features, should be started on an antipsychotic and as second option an anticonvulsant. In resistant cases, clozapine or lithium should be considered.

In patients where depressed mood, anxiety, or impulsivity predominate, it is recommended to start an SSRI; as a second option, and only in cases where the patient is reliable, consider a tricyclic antidepressant (TCA), and as a last option, a monoaminoxidaseinhibitor (MAOI).

In the more unstable cases, a combination of two or more medications may be needed. Fortunately, there is one study evaluating the combination of fluoxetine and olanzapine. In the pratice, drug combinations are frequent, and they seem to be matter of craft rather than science, as the clinician commonly uses his/ her experience rather than the limited published evidence.

Treatment with medication should be started at a low dose, slowly increased for at least four weeks, as most controlled studies available do not show improvement earlier. Therefore, it is not recommended to change or add medications before waiting for a reasonable period, in spite of a patient's demand expecting a faster relief to his/her suffering.

Keywords : Bordeline personality diorder; aggression; fluoxetine; olanzapine; valproate; topiramate; carbamazapine.

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