Pharmacotherapy of Personality Disorder

Relevant neuroscience to guide pharmacotherapy of personality disorder is reviewed. Pharmacotherapy is either (a) mechanism based, aimed at correcting heritable neurobiological trait vulnerabilities that increase the risk of personality disorder, or (b) symptom domain based, aimed at correcting clinical symptoms of personality disorder arranged into four domains. The novel concept of harnessing the brain’s homeostatic functions in order to deliver treatment is introduced, drawing analogy from serotonergic antidepressants. The dynamics of homeostatic optimization is the conceptual basis of the mechanism-based pharmacotherapy. Pharmacological modulation of trait vulnerability associated with excessive Harm Avoidance, Novelty Seeking, Persistence, and low Reward Dependence is reviewed. Pharmacotherapy of impulsive-affective aggression, which is the default affect state of personality disorder, is discussed in detail. Symptom-domain pharmacotherapy, the current standard of care, targets four symptom domains: (a) mood dysregulation, (b) behavior dysregulation, (c) emotional detachment; and (d) cognitive dysregulation. Pharmacotherapy of each is discussed in detail.