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September 2008

Valproate for Agitation in Dementia
In two studies, valproate (Depakote and others) did not seem to decrease agitation and aggression in patients with dementia.

Topiramate in the Treatment of Borderline Personality Disorder
Preliminary research suggests topiramate may be useful in the treatment of borderline personality disorder.

In Brief
Generic Risperidone Now Available; Ginkgo biloba Not Effective for Dementia; Autism Linked to Defects in “Learning” Genes

Quetiapine Augmentation in GAD: A Negative Trial
In a recent study, augmenting paroxetine (Paxil and others) treatment of generalized anxiety disorder with quetiapine (Seroquel) was ineffective.

BTP Announces ASCP Partnership
BTP proudly announces our partnership with the American Society of Clinical Psychopharmacology (ASCP) and extends a warm welcome to all ASCP members.

ECGs for Kids with ADHD?
An electrocardiogram may be advisable for some children before they begin pharmacologic treatment for attention-deficit/hyperactivity disorder.

Topiramate in the Treatment of Borderline Personality Disorder

September 2008

Borderline personality disorder (BPD) is a relatively common condition, occurring in about 2% of American adults.1 A highly disruptive illness, BPD is characterized by anger and aggression, adversely affects social and occupational functioning, and is notoriously difficult to treat. Several forms of psychotherapy are beneficial and have become the mainstays of treatment for BPD.2,3 At best, however, treatment merely lessens symptoms. The disabilities and impairments of BPD persist over time. Medications used to target specific symptoms include selective serotonin reuptake inhibitors (SSRIs), low-dose antipsychotic medications, and mood stabilizers—including anticonvulsants.4

Topiramate (Topamax) is an anticonvulsant that affects AMPA and GABA receptors. Clinical trials in patients with Bipolar Disorder failed to establish its efficacy as a mood stabilizer. Preliminary results suggest it may be helpful in BPD.

Nickel and others studied topiramate to treat aggression in 29 women with BPD.5 Subjects were assigned to 8 weeks of double-blind treatment with placebo or topiramate, titrated to a dose of 250 mg/day in the 6th week. Topiramate proved superior to placebo in almost all of the anger-related rating scales. Patients taking topiramate lost an average of 2.3 kg (5.1 lb) more than those who took placebo (P < .01).

Dr Nickel's group conducted a similar 8-week, double-blind, placebo-controlled study of topiramate, using the same dosing strategy, in 42 male patients with BPD.6 The men also showed significantly greater reduction in anger when treated with topiramate than with placebo. As well, topiramate-treated men lost more weight—an average of 5.0 kg (11.1 lb) (P < .01). Topiramate was well tolerated in both men and women.

The same scientists conducted a 10-week trial of topiramate, 25 to 200 mg/day, versus placebo in 56 women with BPD.7 Among those who took the active medication, improvement was significantly greater in a variety of BPD symptoms, as well as in health-related quality of life. Again, topiramate-treated patients lost more weight during the course of the trial: 5.7 kg (12.7 lb) versus 1.4 kg (3.1 lb) (P < .001). Side effects tended to be mild and included memory problems, difficulty concentrating, fatigue, headache, menstrual pain, dizziness, and paresthesia.

In an 18-month, open-label follow-up of women who had participated in their earlier double-blind trial, Loew and Nickel found that physical pain, function, and perception of health were superior in those who had taken topiramate compared with the placebo group.8 There was also greater mood stability. After a similar 18-month follow-up of their male patients, these authors report persistent benefits in anger improvement for topiramate over placebo, as well as additional weight loss.9

A case report from Cassano and colleagues describes a 24-year-old woman with bipolar II depression and BPD, whom they treated with topiramate, 200 mg/day, for self-mutilation.10 Within 2 weeks, her self-injurious acts stopped. When topiramate was later discontinued, she returned to self-mutilation. These behaviors stopped again when topiramate was reintroduced, and she has remained stable for 9 months.

Similarly, Karila and associates write of a 44-year-old woman who began self-mutilation induced by cocaine abuse.11 On treatment with topiramate, up to 200 mg daily, the patient's self-mutilation stopped.

Adverse effects with topiramate include dizziness, fatigue, somnolence, memory and concentration problems, paresthesia, reduced appetite, and weight loss. These symptoms tend to occur early in treatment and upon dosage increases. Clivas et al describe a 72-year-old woman with BPD who seemed to develop de novo panic attacks with topiramate treatment.12 The drug's cessation and reintroduction appeared related to panic attacks, and the authors cite other similar cases in the literature. Colom and collaborators write of a 30-year-old woman with Bipolar Disorder and an eating disorder, who increased the dose of prescribed topiramate to 450 mg daily in what appeared to be abuse related to a desire to lose more weight.13

All of the double-blind research with topiramate for patients with BPD emerges from a single group. At this time, conclusions must be considered preliminary. Nonetheless, topiramate might be considered in selected patients with BPD.

1Swartz M, Blazer D, George L, et al. Estimating the prevalence of borderline personality disorder in the community. J Personal Disord 1990;4:257-272.

2Levy KN: Psychotherapies and lasting change. Am J Psychiatry 2008;165:556-559.

3Bateman A, Fonagy P: 8-year follow-up of patients treated for borderline personality disorder: Mentalization-based treatment versus treatment as usual. Am J Psychiatry 2008;165:631-638.

4American Psychiatric Association: Quick Reference to the American Psychiatric Association Practice Guidelines for the Treatment of Psychiatric Disorders, Compendium 2006. Washington, DC, American Psychiatric Association, 2006.

5Nickel MK, Nickel C, Mitterlehner FO, Tritt K, Lahmann C, Leiberich PK, Rother WK, Loew TH: Topiramate treatment of aggression in female borderline personality disorder patients: A double-blind, placebo-controlled study. J Clin Psychiatry 2004;65:1515-1519.

6Nickel MK, Nickel C, Kaplan P, Lahmann C, Mühlbacher M, Tritt K, Krawczyk J, Leiberich PK, Rother WK, Loew TH: Treatment of aggression with topiramate in male borderline patients: A double-blind, placebo-controlled study. Biol Psychiatry 2005;57:495-499.

7Loew TH, Nickel MK, Muehlbacher M, Kaplan P, Nickel C, Kettler C, Fartacek R, Lahmann C, Buschmann W, Tritt K, Bachler E, Mitterlehner F, Pedrosa Gil F, Leiberich P, Rother WK, Egger C: Topiramate treatment for women with borderline personality disorder. A double-blind, placebo-controlled study. J Clin Psychopharmacol 2006;26:61-66.

8Loew TH, Nickel MK: Topiramate treatment of women with borderline personality disorder, Part II: An open 18-month follow-up. J Clin Psychopharmacol 2008;28:355-357.

9Nickel MK, Loew TH: Treatment of aggression with topiramate in male borderline patients, part II: 18-month follow-up. Eur Psychiatr 2008;23:115-117.

10Cassano P, Lattanzi L, Pini S, Dell'Osso L, Battistini G, Cassano GB: Topiramate for self-mutilation in a patient with borderline personality disorder. Bipolar Disord 2001;3:161.

11Karila L, Ferreri M, Coscas S, Cottencin O, Benyamina A, Reynaud M: Self-mutilation induced by cocaine abuse: The pleasure of bleeding. Presse Med 2007;36:235-237.

12Clivaz E, Chauvet I, Zullino D, Niquille M, Maris S, Cicotti A, Lazignac Coralie C, Damsa C: Topiramate and panic attacks in patients with borderline personality disorder. Pharmacopsychiatry 2008;41:79.

13Colom F, Vieta F, Benabarre A, Martínez-Arán A, Reinares M, Corbella B, Gastó C: Topiramate abuse in a bipolar patient with an eating disorder. J Clin Psychiatry 2001;62:475-476.

We acknowledge and thank Ivan Goldberg, M.D., who shared most of these references on his psychopharmacology listserv.