Lamotrigine as a promising approach to borderline personality: An open case series without concurrent DSM-IV major mood disorder

International Mood Center, University of California at San Diego, La Jolla 92093-0603, USA.
Journal of Affective Disorders (Impact Factor: 3.38). 01/1999; 51(3):333-43. DOI: 10.1016/S0165-0327(99)00007-5
Source: PubMed


Borderline personality disorder (BPD) has long defined definitive treatment. Such failure is reflected in repeated suicidal crises, often associated with dysphoric symptoms of a chronic fluctuating nature, whose labile intermittent character does suggest a subthreshold bipolar depressive mixed state. For all these reasons, we hypothesized that the anticonvulsant lamotrigine, touted to be a mood stabilizer with antidepressant properties, might be uniquely beneficial for these patients.
From a base rate of about 300 patients in a community mental health center, we identified eight patients meeting seven or more of the DSM-IV criteria for BPD without concurrent major mood disorders. All patients presented with history of severe suicidal behavior, hostile depression and/or labile moods, stimulant and alcohol abuse, as well as multiple unprotected sexual encounters; one patient was actually HIV positive. All had failed previous trials with different antidepressants and mood stabilizers. All current medications were gradually withdrawn--and when necessary--patients kept on a low dose of a conventional neuroleptics for a few weeks, while lamotrigine was being gradually introduced in 25-mg weekly increments until the patient responded (up to 300 mg/day maximum).
Consistent with previous work by us and others, bipolar family history could be documented in three of eight BPD patients, and worsening on antidepressants in four of eight, providing indirect support to our conceptualization of BPD as a bipolar variant. One patient developed a rash on 25 mg and was dropped from the lamotrigine trial, while another patient was noncompliant. Three who failed lamotrigine, subsequently responded, respectively, to sertraline, lithium-thioridazine combination, and valproate. The remaining three patients showed a robust response to lamotrigine, ranging from 75 to 300 mg/day: their functioning jumped from a mean baseline DSM-IV GAF score in the 40's to the 80's during 3-4 months. Among all responders impulsive sexual, drug-taking and suicidal behaviors disappeared and no longer met the criteria for BPD. At an average follow-up of 1 year, they no longer meet criteria for BPD.
Open uncontrolled results on a small number of patients in a tertiary care center may not generalize to BPD patients at large.
Overall, the BPD response to pharmacotherapy in the present case series was 75%. The fact that five of six pharmacotherapy responders required mood stabilizers, argues against the prevalent view that the depressions of borderline patients belong to unipolarity. Of BPD patients who completed the trial, 50% achieved sustained remission from their personality disorder with lamotrigine monotherapy. The dramatic nature of the response in patients refractory to all previous medication trials and maintenance of a robust response over 1 year, argue against a placebo effect. Controlled systematic investigation of lamotrigine in BPD is indicated.

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    • "However, Pearson's correlation coefficient was used to assess agreement, and not the ICC, which is a methodological shortcoming. Reduced psychosocial functioning, related to personality disorders and assessed as GAF, shows only small changes over time [19]; whereas, improvement of mood disorders is associated with substantial increase in GAF scores [15]. In our studied group, increase in GAF scores was highest in those affected by mood disorders and in those without any personality disorders. "
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    ABSTRACT: The study aimed to examine agreement between patients' and professional staff members' ratings on the Global Assessment of Functioning scale (GAF). A total of 191 young adult psychiatric outpatients were included in a naturalistic, longitudinal study. Axis I and axis II disorders were assessed by means of the Structured Clinical Interview for DSM-IV. Before and after treatment, patients and trained staff members did a GAF rating. Agreement between GAF ratings was analyzed using the intra-class correlation coefficient (ICC). The overall intra-class correlation coefficients before and after treatment were 0.65 and 0.86, respectively. Agreement in different axis I diagnostic groups varied, but was generally lower before treatment as compared to after treatment (0.50-0.66 and 0.78-0.90, respectively). Excessive psychiatric co-morbidity was associated with the lowest inter-rater reliability. Agreement, with respect to change in GAF scores during treatment, was good to excellent in all groups. Overall, agreement between patients' and professionals' ratings on the GAF scale was good before and excellent after treatment. The results support the usefulness of the self-report GAF instrument for measuring outcome in psychiatric care. However, more research is needed about the difficulties in rating severely disordered patients.
    European Psychiatry 10/2008; 23(8):575-9. DOI:10.1016/j.eurpsy.2008.05.001 · 3.44 Impact Factor
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    • "In this regard, it has been suggested that many patients with BPD represent bipolar variants at the subthreshold level (Pinto and Akiskal, 1998). Consistent with this hypothesis, in a treatment response study, Pinto and Akiskal (1998) found that five of six subjects with BPD required mood stabilizers. On the basis of such findings, the authors argued that a " unipolar " hypothesis of BPD is misleading, and hypothesized that the depressive symptomatology of patients with BPD is related to bipolarity rather than to unipolarity. "
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    ABSTRACT: Several lines of evidence have raised the question of whether Borderline Personality Disorder (BPD) is an independent disease entity or it might be better conceptualized as belonging to the spectrum of mood disorders. This study explores a wide array of lifetime mood features (mood, cognitions, energy, and rhythmicity and vegetative functions) in patients with BP and mood disorders. The sample consisted of 25 BPD patients who did not meet the criteria for bipolar disorders, 16 bipolar disorders patients who did not meet the criteria for BPD, 19 unipolar patients who did not meet the criteria for BPD, and 30 non-clinical subjects. Clinical diagnoses were determined by administering the structured clinical interviews for DSM-IV disorders. The Mood Spectrum Self-Report (MOODS-SR) was used for measuring lifetime mood phenomenology. Clinical subjects displayed higher mean scores than normal subjects in all domains of the MOODS-SR, and BPD patients displayed higher scores than unipolar patients in the Mood and Cognition depressive subdomains. Differences between patients with BP and bipolar disorders on MOODS psychopathology did not attain statistical significance for any (sub)domain considered. The results of this study are consistent with previous findings suggesting the importance of mood dysregulations in patients with BPD.
    Psychiatry Research 07/2008; 159(3):300-7. DOI:10.1016/j.psychres.2007.10.002 · 2.47 Impact Factor
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    • "Following publication of an open case series ( Pinto & Akiskal , 1998 ) documenting the efficacy of lamotrigine in treating symp - toms of BPD , Tritt , Nickel , Lahmann et al . ( 2005 ) recruited 27 female out - patients and randomized them to treatment with either lamotrigine or placebo . "
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    ABSTRACT: Borderline personality disorder (BPD) is a chronic psychiatric condition characterized by a pervasive pattern of instability in affect regulation and impulse control. These maladaptive coping strategies predispose individuals with BPD to suicidal behavior, and this diagnosis increases the risk for completed suicide. Empirical data indicate that adverse life events; a history of childhood trauma; and the presence of comorbid psychiatric conditions, in particular major depressive disorder and substance use disorders; confer an elevated risk of suicidal behavior in patients with BPD. Psychopharmacological interventions, including the use of antidepressants, anti-psychotics, and mood stabilizers, are considered in this review in terms of the evidence for their utility in reducing the risk of suicidal behavior in BPD.
    Archives of Suicide Research 02/2008; 12(1):1-19. DOI:10.1080/13811110701542010 · 1.64 Impact Factor
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