Algorithms
for pharmacological treatment of personality dimensions:
Symptom-specific
treatments for cognitive-perceptual, affective, and impulsive-behavioral
dysregulation
by
Paul H. Soloff, MD
This
article is based on a presentation at the 19th annual Menninger Winter
Psychiatry Conference, held March 9-14, 1997, at Park City, Utah. This
article is supported by NIMH Grant # MH 48463. Dr. Soloff is professor
of psychiatry, Department of Psychiatry, University of Pittsburgh School
of Medicine. Correspondence may be sent to Dr. Soloff at Western Psychiatric
Institute and Clinic, 3811 O'Hara Street, Pittsburgh, PA 15213.
A
pharmacological approach to treating patients with personality disorders
(PD) is based on evidence that some dimensions of personality are
mediated by variations in neurotransmitter physiology and are responsive
to medication effects. Target symptoms for pharmacotherapy in the
PD patient are derived from expressions of cognitive-perceptual, affective,
and impulsive-behavioral dysregulation of central neurotransmitter
functions. Pharmacotherapy is directed at state symptoms during periods
of acute decompensation and at trait vulnerabilities, which represent
the diathesis to future episodes. A basic assumption of this approach
is that neurotransmitter biology transcends Axis I and Axis II definitions
and that closely related symptoms may share a common pathophysiology,
independent of categorical definition. A common pathophysiology implies
the possibility of shared responsiveness to medication. Using a dimensional
definition of symptom domains, the author has developed treatment
algorithms for cognitive-perceptual symptoms, affective dysregulation,
and impulsive-behavioral dyscontrol in personality disorder patients.
(Bulletin of the Menninger Clinic, 62[2], 195-214)
Personality
diagnoses are syndromes of related and interacting dimensions, each
of which may have unique origins in psychosocial develop-merit or
biological temperament. Popular empirical models define three (Eysenck
& Eysenck, 1976), five (Costa & McCrae, 1992), or seven (Cloninger,
Svrakic, &; Przybeck, 1993) basic dimensions of personality that
can be used to define recognizable clinical types. Personality dimensions
may be genetically mediated or acquired in the course of development.
While it is customary to discuss the biologically mediated dimensions
of personality (e.g., temperament) apart from the learned characteristics
(e.g., character), this distinction is artificial and obscures the
extensive interaction and overlap between neurobiology and the psychosocial
origins of personality. The neurobiology of perception, cognition,
information processing, and regulation of affect and impulse strongly
conditions the expression of one's needs and the range of one's behavioral
responses, providing a matrix in which interpersonal relatedness develops.
A healthy mother-infant bond depends on the conditioning of each to
the other's temperament. Life experiences, especially early life trauma,
may profoundly alter both biology and psychology of personality development.
A personality disorder (PD) is said to be present when dimensions
of personality lead to patterns of experience and behavior that are
pervasive and inflexible and that cause distress or impairment (American
Psychiatric Association, 1994).
A
pharmacological approach to the treatment of personality disorders
is based on evidence that some dimensions of personality appear to
be mediated by variations in neurotransmitter physiology and are responsive
to medication effects. Specifically, the regulation of cognition,
perception, affect, and impulse appears to be dependent on the actions
of specific neurotransmitter systems. Symptoms arising from dysregulation
of these systems are the true targets of pharmacotherapy in the personality
disorder patient. Pharmacotherapy is used to treat both state symptoms
during periods of acute decompensation and trait vulnerabilities,
which represent the biologic diathesis to future episodes. This duality
of effect raises serious methodological and ethical issues concerning
the appropriate definition and assessment of target symptoms, measurement
of change, and duration of treatment (e.g., how long does one treat
temperament)? By targeting the neurotransmitter physiology that regulates
cognition, perception, affect, and impulse, pharmacotherapy may modify
temperament, allowing for significant relearning in interpersonal
behavior. Pharmacotherapy is not an appropriate treatment for chronic,
dysfunctional attitudes about the self or others and is best viewed
as an adjunctive treatment, not a substitute for psychotherapy. Medication
cannot cure character.
Target
symptoms for pharmacotherapy in the PD patient may be derived from
the symptomatic expressions of cognitive-perceptual, affective, and
impulsive-behavioral dysregulation. This theoretical model follows
studies of symptom response patterns in pharmacotherapy trials of
severely impaired inpatients with borderline personality disorder
(BPD), a strategy known as pharmacological behavioral dissection.
In one such study, Soloff and associates (1989) defined three broad
symptom response patterns following treatment with amitriptyline,
haloperidol, or placebo among severely impaired BPD inpatients. The
three broad response patterns defined by factor analysis of symptom
changes were termed "global depression," "hostile depression,"
and "schizotypal" symptom-change factors, after the dominant
assessment measures in each factor. The change patterns defined recognizable
clinical presentations of patients with BPD. Patients with the global
depression response pattern had a preponderance of "atypical"
depressive symptoms, anxiety, and somatic complaints. They presented
as withdrawn, pervasively depressed individuals, clearly distinguishable
from the angry, demanding, entitled patients who made up the hostile
depressed group. The schizotypal pattern defined the transient cognitive-perceptual,
psychotic-like experiences of the borderline patient under stress.
Symptoms of impulsive-behavioral dyscontrol were not initially identified
as a separate symptom change pattern in this factor analytic study
but were associated with both affective and cognitive dysregulation.
Subsequent pharmacological research (detailed later in this article)
has demonstrated the independence of impulsive-behavioral dysregulation
as a separable symptom domain with discrete responsiveness to pharmacotherapy
independent of affective or cognitive symptoms.
The
neurobiology of personality dimensions transcends our definitions
of Axis I and II disorders. The categorical definitions that separate
Axis I and II are statistical constructs and are not based on etiology
or neurobiology. By targeting personality dimensions for pharmacotherapy,
we are making the basic assumption that closely related symptoms in
Axis I and Axis II disorders may share a common etiology in neurotransmitter
physiology. For example, we assume that the pathophysiology of mild
thought disorders in Axis II patients may be related to the same dysfunction
found in more severe thought disorders of Axis I patients. Similarly,
disinhibition of affect and impulse may be mediated by a common neurotransmitter
in BPD and some bipolar disorders. Severity and other disease factors
clearly separate the clinical disorders; however, the common elements
of pathophysiology suggest the possibility of shared responsiveness
to medication. This principle remains the most rational guide for
pharmacotherapy trials in the PD patient.
Using
a dimensional perspective and a psychobiological model of personality
dimensions, pharmacotherapy of the PD patient may be reframed as symptom-specific
treatments. Treatment algorithms can be defined from research and
case experience to provide assistance to the clinician in selecting
medications for the principal target dimensions in the PD patient:
cognitive-perceptual symptoms, affective dysregulation, and symptoms
of impulsive-behavioral dyscontrol.
Development
of a treatment algorithm for personality dimensions
Algorithms
are defined as "rule-based deductive systems that operate with
inputs, sequences, timeframes and outputs" (Jobson &: Potter,
1995, p. 457). In the setting of clinical medicine, algorithms provide
decision trees assisting clinical judgments involving diagnoses and
treatments. They reveal our decision-making processes, requiring that
we justify each step in a treatment course. Rush and Prien (1995)
divide this process into strategic decisions--determining what is
wrong, whether to treat, and what treatment to use--and tactical decisions,
concerned with how to conduct the treatment and what to do following
success (or failure). Algorithms must incorporate an empirical database
of research studies, but must also be guided by actual clinical experience,
reflecting the judgments required in "real-life" applications
to specific patients and situations. Patients seen in clinical practice
rarely fit the artificial standards imposed for selection into controlled
research trials. The practicing clinician is often faced with comorbid
medical and psychiatric illnesses, wide heterogeneity in syndrome
presentations, intolerance of side effects, patient preferences in
choice of treatment, and social and economic factors affecting compliance,
which are "controlled out" of the research trial (see Rush
6c Prien, 1995, for review).
Jobson
and Potter (1995) have described a model for development of treatment
algorithms primarily intended for Axis I affective disorders, which
relies on reviews of treatment literature and consensus opinions of
experts well versed in both research literature and clinical experience.
These methods may be applied to address the treatment of Axis II personality
dimensions. This article represents an initial offering of treatment
algorithms for personality dimensions, based on literature review
and the author's clinical experience. These algorithms are intended
to promote interest, discussion, and research, which, it is hoped,
will lead to formation of expert panels to further refine the algorithms.
Algorithms
are rule-based systems. Three rules were applied to clinical decisions
at each level: (1) Preference is given to medications for which efficacy
has been most strongly supported by empirical research; (2) safer
medications are given preference over those that incur more risk in
overdose, abuse, or noncompliance; and (3) preference is given to
rapidly acting drugs where clinical need is acute, although a slower
acting agent might have more specificity (e.g., rapid treatment of
psychotic symptoms with neuroleptics might take priority over treatment
of an underlying depressed mood with antidepressants, although the
psychotic symptom might be a direct product of the depressed mood).
To be most broadly applicable and most conservative, the algorithms
assume treatment in an outpatient setting.
We
followed Jobson and Potter's (1995) convention of assigning a rating
for each recommendation on the strength of available research evidence
(e.g., A = supported by "multiple randomized, controlled trials,"
B = supported by "at least one randomized, controlled clinical
trial," and C = "supported by opinion, case reports, and
studies that do not meet randomized, control-trial criteria").
Well-controlled clinical trials with negative outcomes reduce the
overall level of a recommendation based on several positive outcome
studies. There are several important limitations to this method. Recommendations
of efficacy based on single-trial studies (especially treatment of
"first episodes" in previously medication-naive subjects)
are not truly comparable to trials in patients who have failed multiple
medication treatments (e.g., patients on the second or third step
of a treatment algorithm). Given the diversity in methods, patient
characteristics, and assessment measures found in the treatment literature,
one can generalize claims for efficacy only after multiple replications.
Statistically significant differences in research measures do not
always translate into clinically important differences between patients
on drug and placebo. In this regard, it is important to keep in mind
the large effect sizes achieved by placebo treatments in pharmacotherapy
trials in PD, although the placebo condition may be reported as less
improved than the active drug.
