PHARMACOTHERAPY AND BPD DIMEFF, L.A., MCDAVID, J., & LINEHAN, M.M.(1999)
Double-Blind Pharmacotherapy Outcome Studies Using BPD Samples
Double-blind randomized six-week acute treatment
Eleven of the total N (13.8%) failed to complete at least three weeks of the trial. Both
trial with BPD outpatients (n=80). Each condition
medications resulted in statistically significant improvements compared to baseline scores
included 24 female and 16 male Ss. No placebo-
thorughout the evaulation. Ss using loxapine were significantly more improved on anxiety and
control condition was used. The assessment battery
depressed mood at Week 1 and Week 2 as measured by the Brief Psychiatric Rating Scale
focused almost exclusively on measurement of
(BPRS) and systematic nursing observations. Differences between medication conditions
affective dysregulation, including anxiety, depressed
disappeared by Week 4. One statistically significant finding -- reduction in depressed mood on
mood, and hostility, with very limited assessment of
the BPRS-- was observe at the post-treatment follow-up assessessment favoring loxapine.
cognitive dysregulation (only confusion was assessed
Double-blind, randomized trial of outpatients (n=52)
Attrition information is scant. Ten Ss withdrew from the study within the first month due to side
meeting criteria for BPD, Schizotypal Personality
effects and/or inefficacy of the treatment. This group was apparently excluded from the intent to
Disorder (SPD) or both (35.6%). Ss were divided
treat sample (n=52). Of the 52, 46 Ss (88%) remained in the study throughout the three-month
evenly between two active treatment conditions, each
trial. Eighty-four percent were markedly to moderately improved at the 3-month follow-up, with
with 18 males and 8 females. No placebo-control
Ss responded more favorably to thiothixene than haloperidol in reducing general symptoms,
anxiety, depression, and paranoia. Outcomes did not vary as a result of diagnoses. Over 80%
of Ss in both conditions reported numerous adverse medication reactions. It is possible that
that thiothixene’s superior performance in this trial resulted from the failure to use a sufficient
Double-blind, placebo-controlled trial involving
Only 45.8% of experimental Ss (11 of 24) completed the trial, compared to 57.8% Ss in placebo
outpatients (n=50) meeting criteria for BPD and/or
condition (15 of 26). Thiothixene significantly reduced illusions, ideals of reference,
Schizotypal PD. About 40% met diagnostic criteria for
psychoticism, phobic anxiety, and obsessive-compulsivity in comparison to placebo. Near
both BPD and SPD. Ss selected on the basis of
significant trends favoring thiothixene were observed on depersonalization-derealization, anger-
having < 1 psychotic symptom. One week medication
hostility, and somatization. No differences were observed on pre/post depression scores. Ss
washout followed by random assignment to 12-week
with BPD-only has a significantly greater pre/post reduction in social phobia compared to Ss
with SPD or both. No other differences as a result of diagnosis were observed.
Double-blind, placebo-controlled randomized trial in
Ss in all groups demonstrated statistically significant improvements over time, however the
Ss diagnosed with BPD and/or SPD (n=64).
greatest gains occurred in the active medication conditions. Haloperidol was significantly
Following one- week washout, 13 Ss no longer
superior to placebo and amitriptyline across a broad range of symptoms, including subjective
demonstrated ongoing symptom severity so were
complaints of hostility, paranoid or psychotic ideation, anxiety, phobic anxiety, obsessive-
excluded from analysis. The intent to treat sample
compulsive behaviors, and depressed mood and interpersonal sensitivity. Modest effects in the
was restricted to Ss who had taken medications for
amitriptyline condition were limited to reductions in depression. Haloperidol had only a modest
effect against schizotypal symptoms. Haloperidol was equivalent to amitriptyline in reducing
depression. Ss with greatest response to haloperidol presented a sustained pattern of both
affective and schizotypal symptoms. Magnitude of change was modest, but considered
clinically and statistically significant.
Reprinted from permission by publishers and authors. Table published in Dimeff, L.A., McDavid, J., & Linehan, M.M. (1999). Pharmacotherapy for borderline personality disorder: A review of the literature and recommendations for treatment. Journal of Clinical Psychology, 6, 113-138. PHARMACOTHERAPY AND BPD DIMEFF, L.A., MCDAVID, J., & LINEHAN, M.M.(1999)
Double-Blind Pharmacotherapy Outcome Studies Using BPD Samples
Double-blind, placebo-controlled crossover trial in an
Differential completion rates were reported by condition, ranging from 38% (trifluoperazine) to
outpatient setting while Ss also received
75% (tranycypromine). The most favorable outcomes were achieved with tranylcyromine which
psychotherapy. All Ss (n=16) were female and had
enhanced mood, reduced anxiety and impulsivity. Carbamazepine produced dramatic
BPD, as well as histories of severe dysphoric mood
improvements, especially in decreasing the severity of behavioral dyscontrol, however severe
and behavioral dyscontrol but no current major
melancholic depression developed in three Ss. Alprazolam significantly increased behavioral
depression. A full medication trial involved a two-
dyscontrol and suicidality ratings, but was regarded by patients as more beneficial than other
week induction, four week maintenance with constant
agents. Patients having a favorable response to one medication were not likely to respond
dosage, a week of medication taper, and at least one
medication-free week before beginning next drug trial.
Double-blind, placebo-controlled trial of Ss with BPD
Phenelzine was consistently superior to imipramine. Using the more stringent cut off for BPD (5
and atypical depression but no other Axis I diagnosis.
or more criteria), 20% of the original sample responded to the placebo, 38% to imipramine, and
Part of a larger pharmacotherapy trial for atypical
89% to phenelzine. In the second trial, 19% responded favorably to the placebo, 42% to
depression, 40 of the original sample (n=171) met 5 or
imipramine, and 100% to phenelzine. Results from this study demonstrated a strong
more diagnostic criteria for BPD; 61 met 4 or more of
relationship between the number of BPD symptoms and the efficacy of phenelzine. In patients
the BPD criteria. Trial divided into two six-week
having four or more BPD symptoms, 92% of phenelzine- and 35% of imipramine-treated patients
phases; non-responders and Ss who responded to the
were deemed “responders.” In patients meeting fewer than four BPD criteria, there appeared
placebo in the initial phase were removed from the
little difference in efficacy between the two medications (65% of phenelzine-treated patients
second phase while responders received another six
were judged as “responders” compared to 63% of the imipramine-treated patients).
weeks of acute treatment. The second phase was
intended to ensure that clinical gains persisted and
Preliminary findings from a double-blind, random-
Meaningful interpretation of this data and generalization is hampered by significant drop out
order placebo-control crossover trial lasting 22 weeks
rates. Two patients (11.8%) dropped out of treatment before taking any medication. Five
comparable in to the Cowdry & Gardner (1988)
dropped out after completing the first arm (29.4%). Only 58.8% of Ss completed two or more
crossover trial. Ss (n=19) met criteria for BPD; 18
arms of the study. With few exceptions, no significant differences were found between lithium vs.
were female and one was male; 42% had comorbid
placebo and desipramine vs. placebo using the Hamilton Depression Scale and Carroll Scale for
atypical depression. Of the 57 outpatient Ss referred
Depression. While not statistically significant, eight of 11 Ss on lithium improved on measures of
to the study, 24 refused to participate in this trial.
anger and suicidal symptoms (vs. four of 11 in the desipramine condition). The only statistically
significant finding that emerged was on therapists’ rating of improvement, favoring lithium.
Reprinted from permission by publishers and authors. Table published in Dimeff, L.A., McDavid, J., & Linehan, M.M. (1999). Pharmacotherapy for borderline personality disorder: A review of the literature and recommendations for treatment. Journal of Clinical Psychology, 6, 113-138. PHARMACOTHERAPY AND BPD DIMEFF, L.A., MCDAVID, J., & LINEHAN, M.M.(1999)
Double-Blind Pharmacotherapy Outcome Studies Using BPD Samples
Double-blind, placebo-controlled trial in Ss diagnosed
This study was published as a non-peer reviewed chapter, but is the first published outcome data
with BPD (n=17). Acute treatment lasted 14 weeks.
from a controlled clinical trial on the efficacy of SSRIs in Ss with BPD. The review of this study is
Primary measures included Hamilton Anxiety Scale
very general and provides a very limited view of the specific findings. Seven of nine Ss in
(HAM-A), Hamilton Depression Scale (HAM-D), Beck
fluoxetine condition completed the entire trial, compared to seven of eight in the placebo
Depression Inventory (BDI), and Global Assessment
condition. Statistically significant improvements favoring fluoxetine were found across all
outcome measures. Ss receiving fluoxetine continued to demonstrate ongoing significant gains
over time, suggesting that the 14-week trial may have been insufficient to capture the full extent
of improvement able to be derived from its use. In open trials using fluoxetine, Markowitz and
colleagues (1991) reported reductions in self-injury. No data is provided from this double-blind
trial regarding self-injury or other impulsive behaviors.
Double-blind, placebo-controlled randomized trial of
Thirty-two Ss (30%) dropped out from the study. Three way comparisons between groups
consecutive admits with BPD to inpatient psychiatric
revealed superior efficacy of phenelzine, followed by placebo and haloperidol on measures of
hospital (n=108); 82 (75.9%) were female and 26
depression, borderline psychopathology, and anxiety. Pairwise comparisons between
(24.1%) were male. One-week drug washout was
medication and placebo revealed significant efficacy of phenelzine to reduce anger and hostility;
followed by a five-week acute treatment phase.
phenelzine was not efficacious in treating atypical depression or hysteroid dysphoria. Unable to
Patients with drug and/or alcohol deficits or
replicate prior reports demonstrating efficacy of antipsychotics. Phenelzine dosage may have
dependence were excluded from this study.
been insufficient, but patients were experiencing numerous side effects and were uncooperative
Replication study of prior Soloff et al. (1986) research.
about using higher dosage. Unable to replicate prior findings that demonstrated the efficacy of
Double-blind, placebo-controlled continuation study in
The purpose of this continuation trial was to aid in determining how long to continue
14 male and 40 female Ss with BPD (n=54). This 16
pharmacotherapy in patients who have stabilized with acute therapy. Attrition rates considerably
week trial followed a five-week acute therapy phase
high among haloperidol Ss (64%) within the first eight weeks, compared to 28% among placebo
(see Soloff, et al., 1993). Eligibility for this trial was
Ss. While haloperidol continued to be effective beyond the acute phase for irritability, Ss in this
based on improvement obtained in the acute
group had higher levels of depression, hypersomnia, and leaden paralysis. Phenelzine produced
treatment phase as measured by a five or more point
only modest effects beyond acute phase for depression and irritability; it was however activating.
increase on the GAS and an absolute improvement
over the criteria for initial inclusion. Of the 54 Ss, 14
were on haloperidol, 22 on phenelzine, and 18 on
Reprinted from permission by publishers and authors. Table published in Dimeff, L.A., McDavid, J., & Linehan, M.M. (1999). Pharmacotherapy for borderline personality disorder: A review of the literature and recommendations for treatment. Journal of Clinical Psychology, 6, 113-138.
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Psychiatric Times. Vol. 29 No. 3 February 28, 2012Psychiatric Times. Vol. 29 No. 3VANGUARD ISSUES IN PSYCHIATRY Are Animal Models Relevant in Modern Psychiatry? By Andre Menache, BSc(Hons), BVSc, MRCVS | February 28, 2012Dr Menache is Director of Antidote Europe and is a Member of the Belgian Deontological Committeeon Animal Research. The use of animals in medical research became firmly