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Mind & Brain, the Journal of Psychiatry


of patients with BPD, but allow for the use of short-term drug therapy during an acute crisis. The 2001 APA guidelines11 on the other hand recommend the use of antidepressants (SSRIs being the first-line) to treat affective disturbances. Newer meta-analyses1821 however seem to suggest a switch from antidepressants to mood-stabilizers and antipsychotics as the medication of choice in affective instability. This paper brings to focus the current evidence for the psychopharmacological treatment of the symptoms of emotional dysregulation included in the DSMV for BPD: affective instability, anger, depression, and anxiety.


Data on the effectiveness of drugs in the treatment of emotional dysregulation in BPD were obtained from the four most recent meta-analyses of placebo-controlled double- blind randomized controlled studies (RCTs).1821 They looked at the effectiveness of antidepressants, mood stabilizers, and antipsychotics at treating specific symptoms of BPD. The largest meta-analysis is the Cochrane systematic review of 28 RCTS of drug treatment for BPD published by 2009.18 The second meta-analysis looked at placebo-controlled double- blind RCTs of drug effectiveness for symptom clusters in severe BPD and/or schizotypal personality disorders, includ- ing affective dysregulation (depressed mood, anxiety, anger, affective lability).19 The third meta-analysis looked at 18 placebo-controlled double-blind RCTs of drug effectiveness for depression and anger symptoms in BPD.20 The fourth meta-analysis looked at 22 placebo-controlled, double- blind RCTs of drug effectiveness for specific symptoms in BPD including affective instability, anxiety, depression, and anger.21 The four meta-analyses overlap greatly in terms of the RCTs included in their statistical analyses and, thus, many of their conclusions converge. Based on these RCTs, the effectiveness of psychotropic drugs on affective instability, anger, depression, and anxiety in BPD is described below based on the magnitude of the effect size reported (small, moderate, or large).


AFFECTIVE INSTABILITY


Most studies did not look at affective instability as a separate measure. Due to lack of direct measurement, only a meta- analysis of studies on olanzepine was performed.18 Olanzepine showed a small improvement in affective instability when compared with the placebo, based on a meta-analysis of three RCTs (n631). One study did not find a difference in effect on affective instability between olanzepine and placebo.22 Olanzepine treatment was accompanied by signi- ficant side effects compared to the placebo: weight gain, increased appetite, somnolence, mouth dryness, changes in liver transaminases, altered lipid profile, increase in prolactin, changes in blood cell count, and decrease in blood calcium.18


There was no effect on affective instability with ziprasidone


in one RCT.18 One placebo-controlled RCT (n27) showed that lamotri-


gine was also effective in reducing affective instability.18 M&B 2011; 2:(1). July 2011 46


One placebo controlled RCT (n38)23 showed a significant decrease in rapid mood shifts after 6 weeks of treatment with fluvoxamine (150200 mg/day). The effect was maintained at 24 weeks. Mood shifts were defined as a change from a neutral mood to a negative mood.


ANGER


Mood stabilizers as a class had the largest effect on reducing anger in all four meta- analyses.1821 For example, the pooled data from seven RCTs (n230) showed a very large effect of mood stabilizers (carbamazepine, valproate semisodium, topiramate, and lamotrigine).19 The evidence for selecting one mood stabilizer over another is based on single studies or small studies and is therefore weaker. It seems to suggest that lamotrigine, topiramate, and carbamazepine had the largest reduction in anger for the short-term (610 weeks) compared to a placebo. Side effects and tolerability should also be considered. The large effect of topiramate was shown in a group of 42 male participants and separately in a group of 85 female participants from three RCTs. Topiramate was accompanied by weight loss compared with the placebo.18 Lamotrigine was shown to reduce anger in one RCT (n18) and carbamazepine was shown to reduce anger in one RCT (n25).20 Valproate semisodium was effective after 10 weeks of treatment in a small RCT (n16), but the effect was lost at 12 months and 24 weeks in another two larger studies.18,20 The effect of mood stabilizers on reducing anger is com- plemented by their effect on reducing impulsive behaviors.19


Antipsychotics as a class showed a small to moderate effect


on anger in the short- and medium-term, in the meta-analysis of six RCTs (n274 participants)20 and the meta-analysis of four of the seven RCTs (n201).19 A separate meta-analysis of three RCTs (n631, two RCTs belong to the same research group) for olanzepine showed that it had only a small effect of anger. Olanzepine maintained its effect on anger at 24-months follow-up.20 Aripiprazole was investigated in one RCT (n52) and it showed a moderate effect on anger, which was highest among antipsychotics. Its effect was maintained at 18-months follow-up.20 Haloperidol was shown to have a small to medium effect over 5 weeks of treatment in a meta-analysis of two RCTs (n114) conducted by same research group.18


Antidepressants (SSRIs and MAO inhibitors, but not amitriptyline) have a small to moderate effect on anger during short-term therapy.20


DEPRESSION AND ANXIETY


There is little evidence to support the use of psychotropic medication for depression in the context of affective instability without a major mood disorder.1820 Only mood stabilizers had a moderate effect on depression, as showed by a meta-analysis of five RCTs (n148) on carbamazepine, valproate, and topiramate.19 Antipsychotics and antidepres- sants had no significant effect. Furthermore, haloperidol was found to worsen depression.20 Supplementary omega 3 fatty acids were found to reduce depression.18


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