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Mind & Brain, the Journal of Psychiatry

shown to be minimally effective against depression in BPD. Omega 3 fatty acids helped reduce depression. Most of the evidence point to a large reduction of anger with mood stabilizers and a moderate reduction in anger with some antipsychotics (olanzepine, aripiprazole, or haloperidol).

These results suggest that clinicians should raise their

threshold for prescribing medication for affective instability, anxiety, and depression, but not for anger. Mood stabilizers seem to have the best effect for overall emotion dysregula- tion in BPD. As a class, they are particularly effective in reducing anger and impulsive behaviors, and they are also moderately effective against depressed mood and anxiety. However, the recommendations for individual mood stabi- lizers are based on the results of a limited number of small studies. Clinicians should be aware that these recommenda- tions should be considered in conjunction with other clinical information. According to the current and limited evidence, lamotrigine and topiramate seem to be good first-line treatment choices for anger. For example, lamotrigine was shown in a placebo-controlled RCT37 (n18) to reduce anger in doses titrated from 50 mg to 200 mg over an 8- week course of treatment. A placebo-controlled RCT (n27) showed that lamotrigine in daily doses ranging between 25 225 mg (mean 106.7 mg) was also effective in reducing affective instability.38 The side effects of lamotrigine should be closely monitored: rash, sedation, confusion, headache, dizziness, ataxia, tremor, insomnia, and irritability.37,38 Likewise, three small trials of 8 and 10 weeks duration showed that topiramate in doses titrated from 25 to 250 mg (mean daily doses of 200250 mg) led to a large reduction in anger in both men (n42) and in women (n85). The weight loss associated with topiramate may be a factor to consider when selecting this drug over another. While topiramate is associated with side effects at the higher doses used to treat epilepsy (eg, acute myopia, angle closure glaucoma, urinary tract stones, and cognitive difficulties), it seems to be well tolerated in the doses used to treat anger in BPD.39 One must also recognize that these studies were 8-10 weeks duration and they do not inform about the long-term effects of pharmacological treatment.

These meta-analyses summarize the current state of evi-

dence for pharmacological treatment of emotional dysregula- tion and inform the clinical decision making, but they should be regarded critically. The lack of systematic investigation of major drugs in large scale RCTs prevents us from making definite recommendations. Clinicians must also weigh the benefits of medication over their side effects in the neurologic and metabolic domains.

The psychopharmacology of affective instability requires

more investigation both as a clinical and as a basic science. Future RCTs should focus on using appropriate measures of affective instability such as the ones suggested by proponents of ESM methods. Researchers and clinicians should also join forces to understand better the neuropathophysiology and neurochemistry of affective instability and how that guides the choice of psychopharmacological treatment.

M&B 2011; 2:(1). July 2011 48 Disclosure: Paul S. Links has received an unrestricted educational

grant from Eli Lilly Canada Inc. and the views expressed in this publication are the views of the authors and do not necessarily reflect the views of the Ontario Ministry of Health and Long-Term Care.


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