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November 2009

Milnacipran (Savella)
Milnacipran (Savella) is the third compound to be approved in the United States for the treatment of fibromyalgia syndrome.

Preventing Depression in Adolescents
Current depression in parents negates the positive effects of a group cognitive behavioral prevention program in preventing depression in adolescents.

Anticholinergic Medicines and Cognitive Decline in the Elderly
Anticholinergic medications can impair cognition and memory, especially in elderly patients.

In Brief
Predictors of Mortality in Depressed Patients following Cardiac Events; Disruption of Dopamine Neurotransmission in ADHD

Raising the SSRI Dose: Does It Help?
Selective serotonin reuptake inhibitors (SSRIs) do not appear to have an obvious relationship of dose to likelihood of benefit.

Generic Antidepressants: Bioequivalent?
Generic formulations of antidepressants may not have the same pharmacokinetics and clinical effects as the original brand-name versions.

Lamotrigine in Borderline Personality Disorder
Preliminary research found lamotrigine (Lamictal) superior to placebo in improving symptoms of affective instability and impulsivity in patients with borderline personality disorder.

And a One, and a Two… Exercise for Depression
As an adjunct to medication and psychotherapy or by itself, exercise can be an effective treatment for depression.

Lamotrigine in Borderline Personality Disorder

November 2009

Affective instability is a core feature of borderline personality disorder (BPD).1 Patients with BPD often experience marked mood reactivity and intense episodes of dysphoria, irritability, or anxiety that last for a few hours. Affective instability is believed to drive many other BPD symptoms, such as inappropriate anger; suicidal threats, gestures, and acts; identity disturbances; and chronic emptiness and boredom.

There is little systematic research on medications to diminish affective instability in BPD patients. One placebo-controlled trial found that fluvoxamine (Luvox and others) significantly reduced rapid mood shifts involving anxiety, depression, and irritability in female patients.2 Although not specifically examined for affective instability, several anticonvulsant medications—carbamazepine (Tegretol and others), valproic acid (Depakote and others), and topiramate (Topamax)—may reduce some affective symptoms in BPD, such as anger and anxiety. Limited data suggest lamotrigine (Lamictal) also might be useful for this indication, which led Reich and others to conduct a small study.3

The authors compared lamotrigine, flexibly dosed between 25 and 275 mg/day, and placebo in 28 patients with BPD and significant levels of affective instability. The final daily dose of lamotrigine for the 15 patients who received active medication in this 12-week, double-blind trial ranged from 25 to 225 mg, with a mean of 106.7 mg.

Improvement in affective instability and impulsivity was significantly greater (P < .05 and P = .001, respectively) among patients taking lamotrigine than in those receiving placebo. The most common adverse event among lamotrigine patients was rash, which caused three patients to discontinue treatment. Other adverse effects attributed to lamotrigine were pruritis, sedation, confusion, headache, dizziness, and irritability.

Lamotrigine is not a benign drug. Serious among concerns is the risk of Stevens Johnson syndrome, which is why patients developing rash usually have the medication discontinued. To minimize the risk of Stevens Johnson syndrome, doses of lamotrigine are raised very gradually. But among anticonvulsant drugs, lamotrigine is usually well tolerated. This small study by Reich et al is interesting and useful and points the way to future research. We are still far from an ability to declare lamotrigine safe and effective for patients with BPD. There may be some cases, however, in which a doctor and patient will jointly decide to try lamotrigine as an off-label treatment for this condition after considering risks and alternatives.

1American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association, 1994.

2Rinne T, van den Brink W, Wouters L, van Dyck R: SSRI treatment of borderline personality disorder: A randomized, placebo-controlled clinical trial for female patients with borderline personality disorder. Am J Psychiatry 2002;159:2048–2054.

3Reich DB, Zanarini MC, Bieri KA: A preliminary study of lamotrigine in the treatment of affective instability in borderline personality disorder. Int Clin Psychopharmacol 2009;24:270–275.