Despite the lack of guidance available for practitioners, extensive polypharmacy has become the primary method of treating patients with severe and chronic mood, anxiety, psychotic or behavioral disorders. This ground-breaking new book provides an overview of psychopharmacology knowledge and decision-making strategies, integrating findings from evidence-based trials with real-world clinical presentations. It adopts the approach and mind-set of a clinical investigator and reveals how prescribers can practice 'bespoke psychopharmacology', tailoring care to the individualized needs of patients.
Personality Disorders and Traits
People with borderline personality disorder are like people with third degree burns over 90% of their bodies. Lacking emotional skin, they feel agony at the slightest touch or movement.
▢ Describe the overall symptom-targeted role, alongside general strengths and limitations, of pharmacotherapy in the treatment of personality disorders
▢ Discuss efficacy findings from studies of antipsychotic pharmacotherapy for Cluster A personality disorders intended to mitigate their possible evolution to schizophrenia
▢ Describe the symptom domains most effectively treated by psychotropic medication in borderline personality disorder
▢ Describe the emerging database with hormonal therapies, antiglutamatergic drugs and other novel compounds in the treatment of personality disorders
No psychotropic drug has ever been developed specifically to treat any personality disorder, and the extent to which personality in all its developmental and biopsychosocial complexity even lends itself to the “disease” model – for which pharmacotherapy can be “reparative” – remains an open and debated issue. Personality represents the confluence of temperament, genetic predispositions, cohesion of identity, moral compass, interpersonal responsivity, and coping patterns that are shaped and developed over the course of early life experiences. Personality traits often reflect the interpersonally driven behavioral characteristics described in earlier chapters such as introversion/extroversion, internalizing/externalizing, aggression, harm avoidance/novelty-seeking, empathy and social cognition, antisocial behavior and interpersonal exploitativeness, and the use of developmentally primitive versus mature defense mechanisms. To the extent that personality traits may be maladaptive (e.g., impairing interpersonal effectiveness, leading to self-sabotage or self-harm) and are ego-dystonic, they represent targets for modification and change.
MDD patients responsive to paroxetine significantly improve in neuroticism and extraversion. In fact, after statistically controlling for the effects of paroxetine on those personality features, changes in symptoms of major depression no longer differ from those seen with placebo (Tang et al., 2009)
In patients with body dysmorphic disorder (BDD), more than half have been shown to have comorbid personality disorders, most often avoidant > dependent > obsessive-compulsive > paranoid; fluvoxamine-responsive BDD significantly decreases the diagnosability of these comorbid personality disorders (Phillips and McElroy, 2000)
If medication does have a distinct role in the treatment of personality disorders, it is likely not as the antidote to a discrete syndrome but more targeted to facets of aberrant mood, thinking, cognitive processing, behavior, perception, and impulse control. In the world of personality disorders, traditional thinking has long been to search for diagnosable comorbid psychiatric conditions responsive to pharmacotherapy, then attribute residual psychopathology as more likely reflective of personality and potentially more amenable to psychotherapeutic interventions. Some clinicians outright ignore psychopathology features of personality disorders and convince themselves that symptom etiologies arise from other comorbid psychiatric conditions that may not necessarily be present (such as major depression, bipolar disorder, or anxiety disorders). While it is certainly true that an untreated major psychiatric syndrome can color anyone’s personality – and neglecting to treat a major depression or psychotic episode could lead to erroneous diagnoses of a personality (or cognitive, or other) disorder – the opposite extreme of misattributing personality psychopathology to other explanations brings its own hazards. Such an approach runs the risk of being scientifically disingenuous on several counts:
It presumes with all-or-none thinking that medications only treat diseases and have no role for targeted dimensions of psychopathology seen in personality disorders
It invites overdiagnosis of nonpersonality disorders with the hope and expectation that such nosologic reclassifications will somehow magically improve outcomes or make diagnostic formulations more palatable to patients, insurers, or other stakeholders in the patient’s functioning
It presumes that findings from RCTs of conditions such as major depression, bipolar disorder, schizophrenia, or syndromal anxiety disorders should neatly extrapolate to other conditions with superficial overlapping features – and then runs the risk of classifying cases as “treatment-resistant” when the actual ailment may be a personality disorder as an altogether different entity.
Successful treatment of PTSD has been shown to “eliminate” personality disorder diagnoses in about half of PTSD patients initially assessed as having paranoid, obsessive-compulsive, or avoidant personality disorders (Markowitz et al., 2015).
The RCT evidence base for mood, anxiety or psychotic disorders extrapolates better to the symptom-targeted treatment of personality disorders when one first considers overlapping versus divergent characteristics across study populations. This is why in Chapter 3 we emphasized the importance of gleaning carefully from the Method section of a clinical trial the description of the study sample. Only then can one formulate hypotheses about plausible symptom targets. Consider, for example, the use of antipsychotics in borderline personality disorder: as discussed further below, the evidence base most strongly favors targeting anger, hostility, and paranoia, rather than, say, depression (in fact, haloperidol has shown a meaningful benefit for anger but may worsen depressive symptoms in borderline personality disorder (Mercer et al., 2009)).
When considering overlapping versus nonoverlapping features between bipolar and borderline personality disorders as a Venn diagram (Figure 20.1), we cannot assume from RCTs in bipolar disorder that an antimanic mood stabilizer such as lithium or divalproex will necessarily exert the same overall effect on emotional lability or aggression in the absence of nonoverlapping features such as high energy or rapid speech. Does this mean it would be a waste of time to consider mood stabilizers for overlapping symptoms when nonoverlapping symptoms are absent? Certainly not – so long as the prescriber recognizes and appreciates that such an empirical trial may be more experimental than would be the case if the clear syndrome for which the drug was originally studied was also present.
The bulk of this chapter will therefore consider the strength of evidence that does (and does not) exist for pharmacotherapy trials directed at personality disorder symptoms, alongside the database for extrapolating to personality disorders from pharmacotherapy trials of non-personality-disorder conditions. A caveat in this venture is that most clinical pharmacotherapy trials for personality disorders are comprised either of case reports or open-label studies, with relatively few RCTs (much less adequately powered or replicated RCTs).
An unfortunate reality for afficionados of evidence-based medicine is that there appears to be little incentive for the pharmaceutical industry to devote its resources to conducting regulatory trials in pursuit of a labeling indication for a condition such as borderline personality disorder – either because of the lack of historical precedent for such an undertaking or, perhaps, skepticism on the part of pharmaceutical manufacturers that such an effort would be feasible and acceptable to stakeholders. Indeed, because the presence of a significant personality disorder tends to confer a poorer prognosis when it occurs comorbidly with many other psychiatric disorders, one must recognize that large-scale industry-sponsored FDA registration pharmacotherapy trials in mood, psychotic, anxiety, and other disorders often exclude enrollment of subjects with significant personality disorders – making extrapolations to the care of such patients all the more difficult for the practitioner.
Since DSM-III, modern psychiatric nosology has broadly divided personality disorders into three overarching domains or clusters, commonly referred to as “A” (paranoid, schizoid, and schizotypal), “B” (borderline, histrionic, narcissistic, and antisocial), and “C” (avoidant, dependent, and obsessive-compulsive). While imperfect (e.g., avoidant personality disorders bear conceptual overlap with social anxiety disorder; schizoid versus avoidant features can sometimes be hard to differentiate; borderline and narcissistic pathology both can involve lack of empathy and aggression, but probably for different reasons), we find it can be a useful organizing framework for understanding the core psychopathology of personality disorders, particularly with respect to dimensions that represent viable targets for treatment.