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Psychopharmacological treatments for emotion dysregulation In terms of effect on anxiety, mood stabilizers were shown


to have a moderate effect and antidepressants a small effect.19 Among antipsychotics, olanzepine and aripiprazole were shown to improve anxiety in single RCTs, but the pooled effect size was not significant.19,20


In summary, the four meta-analyses highlight general effects of major classes of drugs on emotional dysregulation. They are limited in their conclusions on individual drugs due to the small number of trials for each drug. In meta-analyses of combined trials of lamotrigine, carbamazepine, topira- mate, and valproate semisodium, mood stabilizers had a large effect on anger and moderate effects on depression and anxiety. In a meta-analysis of combined trials of haloperidol, olanzepine, and aripiprazole, antipsychotics showed a moderate effect on anger, also maintained in single RCTs of these drugs. The SSRIs were shown to be minimally effective against depression in BPD. Omega 3 fatty acids helped reduce depression.


These meta-analyses are limited in their conclusions by significant factors. First, the studies are heterogeneous in their assessment instruments, outcome measures, and sam- ple sizes. Second, there was a limited number of studies per drug assessed and RCTs on one drug often came from the same research group, making it challenging to make a strong conclusion as to its effects. There was also a limited number of drugs investigated, especially among the antipsychotics. Third, the exclusion criteria for most studies limit the applicability of the results to the clinical context: most studies excluded participants with substance use disorders, axis I comorbidity, or suicidal ideation. Fourth, the duration of the studies varied between 6 to 10 weeks, and only on occasion were studies extended to 12 or 24 months. This raises the question of the long-term effect of medication and appropriate duration of treatment, which the meta-analyses could not address.


A major limitation to our paper is the poor representation


of measures of affective instability in these studies. The use of affective instability as an outcome measure was limited to few studies, which used traditional semistructured inter- views (Structured Clinical Interview for DSMIV Axis II Personality Disorders for BPD)24 and retrospective self- ratings such as the Affective Lability Scale.25 Research has shown that these traditional cross-sectional measures are not adequate to capture daily changes in mood: trait questionnaires, retrospective reports, and one time scales of affective instability correlate poorly with measures of affective instability derived from real-time daily recordings of mood taken with experience sampling methodology (ESM).10,26 Also referred to as ecological momentary assessment, ESM uses signaling devices such as telephone beepers, pagers, or handheld electronic units to sample peoples’ internal states, external events, and reactivity to external events as it occurs in real time in the individual’s natural environment, thus eliminating recall bias.2730 The ESM seems to also have an advantage over traditional measures when it comes to capturing response to treatment in depression: daily diary measures were shown to detect


www.slm-psychiatry.com 47


changes in mood faster than weekly retrospective measures of mood, and allowed the collection of information related to other variables such as motor activity, experience of side effects, and adherence to treatment.8 This methodology has not yet been implemented in drug RCTs for BPD but should be considered as an outcome to include in future trials. For interested researchers, Trull and Ebner-Priemer31 and Ebner-Priemer et al32 offer a good overview of the ESM’s advantages and strategies to implement it in research programs of affective instability.


While the tendency is to choose drugs that worked in


treating axis I symptoms, it is important to think of the pathophysiology of affective instability in its own right when guiding our choice of drug treatments. Recent reviews of neuroimaging findings in BPD9,33,34 suggest that affective instability is accompanied by underlying structural and functional changes in brain systems responsible for attention and perception of negative or ambiguous social information, as well as for emotion regulation.


On one hand, when compared with healthy study partici- pants, people with BPD show greater activation of amygdala, temporal cortex, and occipital visual cortex when presented with emotional faces35 or pictures depicting social interac- tions.36 The increased activation of visual and temporal cortex is an expression of increased processing of visual stimuli perceived as potentially dangerous. On the other hand, the up-down modulation of this exaggerated emotional response is impaired. People with affective instability have difficulties engaging brain regions (prefrontal cortex, cingulate cortex, and parietal cortex) that help dampen emotional response, distance oneself from an emotional situation, and shift attention away from perceived negative stimuli.


Unsurprisingly, there is also some evidence that major


neurotransmitter systems in the brain play a role in affective instability.9,33 For example, the overactivity of amygdala is linked to cholinergic hyperarousal in a bidirectional feedback loop, and cholinergic hyperarousal was shown to lead to rapid increase in emotional intensity and to dysphoria.9 Amygdala is also linked to the serotoninergic and adrenergic arousal systems generated in the brain stem.9,33 Some studies suggest that dopamine dysfunction may be related to affective instability as well.33


The treatment of affective instability in the clinical context is


challenging, especially that the current clinical guidelines do not reflect the evidence-based psychopharmacology of the latest meta-analyses. There is no doubt that psychotherapy is the standard of care for treating BPD. However, as the treatment utilization data in the United States and Canada show, clinicians often make use of psychotropic medications to help treat symptoms in this patient population. The following conclusions would be helpful in assisting clinicians choose appropriate treatments. As shown by the most recent meta-analyses, psychotropic drugs have a modest effect on depression and anxiety in the context of BPD. There was not enough data on affective instability as an outcome measure to make a conclusion. Contrary to prior guidelines, SSRIs were


M&B 2011; 2:(1). July 2011


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