Transcript athens-2005-s7

COGNITIVE BEHAVIOUR THERAPY
AND MEDICATION: ADDITIVE
EFFECTS?
Gregoris Simos
CMHC/ Central District, Thessaloniki,
Greece
Reference
Wright J. (2004). Integrating CognitiveBehavioral Therapy and Pharmacotherapy.
In Leahy R. (Ed.) Contemporary Cognitive
Therapy: Theory, Research, and Practice.
Guilford Press, NY (pp 341-366)
Introduction
• Pharmacotherapy and cognitive-behavior therapy
(CBT) are the two most heavily researched forms
of treatment for Axis I disorders.
• Both treatments have been well established as
effective therapies for depression, anxiety
disorders, eating disorders, and other nonpsychotic illnesses
(Marangell, et al., 2002, Dobson, 1989; Robinson, Berman,
and Neimeyer, 1990; Wright. Beck, and Thase, 2002).
CBT and psychosis
• Although psychopharmacology is
generally accepted as the standard
treatment for psychoses, CBT has
recently been shown to have significant
effects in reducing symptoms of
schizophrenia1 and bipolar disorder2
1Drury et al., 1996; Kuipers et al., 1997; Tarrier et al., 1998; Pinto et al. 1999;
Sensky et al., 2000; Rector and Beck, 2001
2 Lam et al, 2004; Jones, 2003; Gonzalez-Pinto et al., 2004
CBT and medication
• Because both CBT and
psychopharmacology are effective
interventions for a wide range of disorders,
there could be possible advantages to
combining these empirically proven
approaches in an integrated treatment
package
Psychotherapy and pharmacotherarapy:
Possible interactions (Uhlenhuth et al., 1969)
1) addition – treatments given together produce
results that are greater than the action of either
component alone
2) potentiation (or synergism) – a positive
interaction which is larger than the sum of the
effects of individual treatments
3) inhibition (or subtraction) – results of treatment
are impaired by combining therapies
Psychotherapy and pharmacotherarapy:
Possible interactions
• Most of the research on treatment
interaction in the subsequent three decades
was designed to measure the results of
combining medication and psychotherapy
on symptom measures at the end of
treatment, thus determining whether the two
treatments together were superior, equal, or
inferior to the therapies given alone.
The cognitive-biological model
• The cognitive-biological model1 provides a
useful vantage point to view possible
interactions between therapies.
• This model specifies that there may be
influences from multiple systems (eg.,
biological, cognitive, behavioral,
interpersonal, and social) on the
development and expression of mental
disorders.
1 Wright
and Thase, 1992; Wright, Thase, and Sensky, 1993
The cognitive-biological model
• A broad array of studies have confirmed
significant relationships between elements of this
model
• Application of the cognitive-biological model to
the study of combined therapy suggests that
outcome could be improved by directing treatment
at more than one system simultaneously or by
promoting interactions with possible favorable
influences (Wright and Schrodt, 1989; Gabbard
and Kay, 2001)
Positive Interactions
 Medications improve concentration and thus facilitate
CBT
 Medications reduce painful affect and/or
physiological arousal, thereby increasing accessibility
to CBT
 Medications can decrease distorted or irrational
thinking, thus adding to the effect of CBT
 CBT improves medication compliance
(Group for the Advancement of Psychiatry, 1975; Wright and
Schrodt, 1989)
Positive Interactions
 CBT helps patients better understand and
manage illness
 CBT can facilitate withdrawal from medication
when desired
 CBT has biological effects and can work in
concert with medication to influence
biochemical abnormalities
(Group for the Advancement of Psychiatry, 1975;
Wright and Schrodt, 1989).
Negative Interactions
 Medications interfere with learning and memory
which negatively influences CBT.
 Medications cause dependency which impairs the
effectiveness of CBT.
 Medications lead to premature relief of symptoms
and undermine motivation to continue in therapy.
 CBT places stress on patients with biological
illnesses and thus adds a burden to those who
should be treated with medication.
(Group for the Advancement of Psychiatry, 1975;
Wright and Schrodt, 1989).
Interactions
• Most research studies have focused on
comparing the outcome of treatment with
medication versus psychotherapy or
combined therapy instead of evaluating
possible mechanisms of interaction
• Thus, only a few of the proposed
interactions have been investigated in a
systematic manner
Learning and memory functioning
• The effects of different types of medication on
learning and memory functioning have been evaluated
in a large number of pharmacologic studies
• For example, tricyclic antidepressants (a) with strong
anticholinergic properties and benzodiazepines (b) have
typically been found to impair learning ability.
• In contrast, serotonin reuptake inhibitors© and newer
antipsychotic medications(d) usually improve cognitive
functioning
(a) Curran, Sakulsriprong, and Lader, 1988; Knegtering, Eijck, and Huijsman, 1994; Richardson et
al., 1994
(b) Hommer, 1991; Wagemans, Notebaert, and Boucart, 1998; Verster, Volkerts, and Verbaten,
2002
© Hasbroucq et al., 1997; Levkovitz et al., 2002; Harmon et al., 2002
(d) Harvey et al., 2000; Stevens et al., 2002; Weiss, Bilder, and Fleischhackler, 2002
Learning and memory functioning
• Learning and memory functioning has rarely been
examined as a possible mechanism of interaction
between CBT and pharmacotherapy
• One group of investigators determined that the
benzodiazepine, alprazolam, interfered with
performance on a word recall task, but not implicit
memory or digit span, in patients being treated
with exposure therapy (Curran et al., 1994)
• However, the possible actions of other
medications on cognitive functioning in patients
receiving CBT remain largely unexplored
CBT in medication compliance
• Several investigations have
documented positive effects for
CBT in improving medication
compliance
• (Cochrane, 1984; Perris and Skagerlind 1994; Lecompte,
1995, Basco and Rush, 1995; Kemp et al., 1996).
CBT in medication compliance
• Cochrane (1984) found that patients taking
lithium who received a CBT compliance
intervention were more likely to adhere to
the medication regimen than those who
received standard care
• Patients who received CBT also had
significantly lower rates of stopping lithium
against medical advice, rehospitalization, or
noncompliance-precipitated episodes of
illness
CBT in medication compliance
• Perris and Skagerlind (1994) found that
CBT enhanced medication adherence in
schizophrenics treated in group homes
• Lecompte (1995) also described CBT
methods for improving medication
adherence in patients with schizophrenia
and observed that this intervention led to a
decline in the frequency of rehospitalization
Negative interactions?
Outcome studies have revealed little evidence
to suggest that most types of medication
impair participation in CBT or that CBT has
any adverse effects on biological treatments
Instead, the weight of evidence supports the
concept that CBT and pharmacotherapy
often compliment one another in enhancing
the response to therapy
Outcome Research
•
•
•
•
•
Depression
Anxiety disorders
Bulimia Nervosa
Schizophrenic Disorder
Bipolar Disorder
Depression.
• Blackburn and coworkers (1981) performed the first
controlled trial that compared CBT alone to
pharmacotherapy (tricyclic antidepressants) and
combined treatment for depression
• Results differed depending on the treatment setting
• Combined treatment was superior to medication in
both hospital and general practice patients and to CBT
alone in the hospital outpatients
• The overall results of this study support an additive
effect for CBT and antidepressant therapy
Depression.
• Another trial comparing CBT with a
tricyclic antidepressant (Murphy et al;
1984) did not find a significant advantage
for combined treatment
• At the end of treatment, all therapies were
found to be equally effective
• However, the percentage of patients with
the best outcome (BDI < 9) was higher for
combined therapy (78%) than the other
treatments (CBT plus placebo = 65%, CBT
= 53%, pharmacotherapy = 56%)
Depression.
• Hollon and coworkers (1992) tested the efficacy
of CBT, imipramine, or combined therapy in the
treatment of 107 non-psychotic depressed
outpatients
• The overall treatment response in the Hollon et al
(1992) study was excellent for all conditions
• Although there was no significant advantage
found for combined treatment, there was a trend
for superior outcome in those who received both
CBT and pharmacotherapy
Depression.
• For example, mean post-treatment Hamilton
Rating Scale for Depression (HRSD) scores
were lowest for combined treatment (4.2) as
compared to CBT (8.8) and pharmacotherapy
(8.4, significance = .17)
• Mean MMPI Depression scores were
significantly lower in patients treated with
combined therapy (61.4) than CBT (71.8) or
pharmacotherapy (72.5, significance = .04)
CBT and medication in double depression
• Miller, Norman, and Keitner (1999) randomly
assigned 26 inpatients with double depression to
20 weeks of treatment with pharmacotherapy or
combined antidepressant and cognitive therapy
• At the end of treatment, those who received
combined therapy had significantly greater
improvement in depressive symptoms and higher
social functioning
• Differences between pharmacotherapy and
combined treatment were quite large in this study
• Mean post treatment HRSD scores were 25.8 for
pharmacotherapy and 13.1 for combined treatment
CBT and medication in chronic depression
• Large multicenter group headed by Keller and
McCullough (Keller et al., 2000).
• A particularly large sample size (n = 662).
• Patients with chronic major depression were randomly
assigned to pharmacotherapy with nefazadone (an
antidepressant with serotonin and norepinephrine
agonist properties), treatment with the cognitivebehavioral-analysis system of psychotherapy (CBASP),
or combined therapy. CBASP is a form of CBT with
modifications for chronic depression (McCullough,
2000).
• Treatment response rates for study completers were
55% for nefazadone, 52% for CBASP, and 85% for
combined treatment
Anxiety Disorders.
• Studies of CBT for anxiety disorders compared to
pharmacotherapy alone versus a combination of
CBT and medications of various types have been
the subject of three major reviews (Spiegel and
Bruce, 1997; Westra and Stewart, 1998; Bakker,
van Balkom, and van Dyck, 2000) and a metaanalysis (Van Balkom et al., 1997)
• Most studies reviewed by these authors examined
the efficacy of a benzodiazepine compared to a
CBT intervention such as exposure therapy or a
combined treatment approach
Anxiety, CBT and SSRIs
A review of studies of SSRIs combined with CBT
found that combination therapy led to the greatest
treatment gains (Bakker, van Balkom, and van
Dyck, 2000)
The positive effects of SSRIs in enhancing learning
and memory (Levkovitz et al., 2002), as compared
to negative actions of tricyclic antidepressants on
cognitive functioning (Curran, Sakulsriprong, and
Lader, 1988), suggest that SSRIs might have a
more favorable interaction profile with CBT than
older antidepressant medications
Anxiety, CBT and tricyclic antidepressants
The largest and most recent trial of combined
therapy with a tricyclic antidepressant and CBT
for panic disorder was conducted at multiple
centers by Barlow and coworkers (2000)
Patients with panic disorder with or without mild
agoraphobia were randomly assigned to treatment
with
• CBT alone,
• imipramine,
• placebo,
• CBT plus imipramine, or
• CBT plus placebo
Anxiety, CBT and tricyclic antidepressants
• The acute treatment phase lasted 3 months.
Responders were seen monthly for 6 months in the
maintenance phase of therapy and then were
followed for an additional 6 months after
maintenance therapy was discontinued
• At the end of acute treatment, all active treatments
were effective and were superior to placebo
• After 6 months of maintenance therapy, CBT plus
imipramine was clearly superior to the other active
treatments (57.1% response rate for combined
treatment compared to 39.5% for CBT and 37.8% for
imipramine)
• However, this advantage disappeared by the end of
the 6 month follow-up interval
Panic disorder
• A meta-analysis of studies of pharmacological,
cognitive-behavioral, and combined treatment for
panic disorder, including a total of 5,011 patients,
was conducted by Van Balkom et al (1997). The
results of this meta-analysis are consistent with the
conclusions of Westra and Stewart (1998)
• The combination of antidepressants plus exposure
therapy was found to be the most effective treatment
for panic disorder
• The mean effect size for combined treatment of
agoraphobia was 2.47 as compared to 1.00 for
benzodiazepines, 1.02 for antidepressants, 1.38 for
exposure alone, and .32 for control conditions
Bulimia Nervosa.
• Most research on combined therapy for
bulimia nervosa has found advantages for
using CBT and an antidepressant together
(Bacaltchuk, et al., 2000)
Bulimia: Meta-analysis
• The results of 7 studies of psychological
treatments given in combination with
pharmacotherapy for bulimia nervosa were
examined in a meta-analysis by Bacaltchuk et al
(2000)
• Five of the seven trials in this analysis included a
CBT treatment condition
• Although this meta-analysis is confounded by
including different forms of psychotherapy, the
overall results favored combined treatment over
medication or psychotherapy alone
Bulimia: Meta-analysis
• Bacaltchuk (2000) noted that the remission
rate (100% reduction in binge episodes) was
42% for combined treatment as compared to
23% for medication alone in these studies
• Remission also was more likely for
combined treatment when compared to
psychotherapy alone
Psychosis.
• Several studies: the impact of adding CBT to
medication for psychotic illnesses.
• Most patients in these studies have suffered
from schizophrenia or related disorders.
• Because of the severity of the illness and strong
evidence for effectiveness of antipsychotic
medication, there have been no trials that have
examined the efficacy of combined treatment
compared to CBT alone
Psychosis.
• Instead, investigators have focused on
determining whether CBT adds to the effect of
medication plus treatment as usual
• All studies completed to date have demonstrated
a positive benefit for combined therapy
Family Behaviour Therapy and
Expressed Emotion
• After treatment, mean number of critical
comments was reduced by 60% (16% in control
group (Lieberman et al., 1984)
• During the following 9 months only 21% of
patients exhibited a significant increase in positive
schizophrenic symptoms compared to 56% in the
control group (Wallace and Liberman, 1985)
• Family interventions have repeatedly shown that
they decrease rates of relapse (Tarrier et al al,
1994; Pitschel-Waltz, et al al, 2001);
Barrowclough et al, 1999; Sellwood, et al, 2001).
CBT and medications in schizophrenia
• CBT has been well tested in
relation to the treatment of residual
symptoms of schizophrenia and is
of proven efficacy and costeffectiveness (National Institute for
Clinical Excellence, 2002)
CBT and medications in schizophrenia
To date, several controlled studies
have examined the efficacy of CBT
for schizophrenia.
Some studies have assessed the role
of CBT during the chronic phase of
the illness, while others tested the
impact of CBT during the acute
phase
CBT and medications in schizophrenia
• Hallucinations, delusions, negative symptioms and
depression have all been shown to be responsive
to CBT (Sensky et al., 2000)
• CBT is the only psychological treatment in
chronic schizophrenia with proven durability at
short-term follow-up (Could et al., 2001)
• The benefits of CBT translate into community
settings (Turkington et al., 2002)
• CBT wpould appear to have the posibility of an
enhanced effect when given with cognitively
sparing antipsychotic medication (Pinto et al.,
1999)
Negative symptoms
Cognitive therapy for schizophrenia: a preliminary
randomized controlled trial
Neil A. Rector *, Mary V. Seeman, Zindel V. Segal
Schizophrenia Research 63 (2003) 1– 11
Meta-analysis: CBT and medications
in schizophrenia
• A meta-analysis of controlled research on
combined CBT and medication for psychosis
(Rector and Beck, 2001) found significant
advantages for using CBT and medication together
• The mean effect sizes for positive symptoms were
1.31 for CBT plus medication and routine care,
0.04 for medication and routine care, and .63 for
supportive therapy plus medication and routine
care
• Similar findings were observed for negative
symptoms.
Review: CBT and medications in
schizophrenia
• Taken together the results of studies of CBT
in psychotic patients indicate that CBT and
medication have significant additive effects.
These research findings have led to
treatment guidelines for including CBT in
the clinical management of schizophrenia in
the United Kingdom.
Review: CBT and medications in
schizophrenia
• In 2002 the Department of Health in the
U.K. sent out a notice that all patients in the
first three years of a psychotic disorder must
have access to cognitive therapy by 2004
CBT and medication in Bipolar Disorder
Gonzalez-Pinto et al. (2004). Psychoeducation and
CBT in bipolar disorder: an update. Acta
Psychiatr Scand, 109, 83-90
“ … CBT diminishes depressive symptoms and
improves quality of life in BD.”
Jones S., (2003). Psychotherapy of bipolar disorder:
a review. J Affect Dis, XXX
“… The clearest evidence is for individual CBT
which impacts on symptom, social functioning
and risk of relapse.”
CBT and medication in Bipolar
Disorder
Lam D., Watkins E., Hayward P., Bight J.,
Wright, K., Kerr N., Parr-Davis, G., Sham P.
(2003).
A randomised controlled study of cognitive
therapy of relapse prevention for bipolar
affective disorder – outcome of the first
year
Archives of General Psychiatry.
CT in Bipolar Disorder
• Randomized controlled (medication only) trial
• Emphasis on relapse prevention
• CT had significant effects both at short and long term
(12 months)
• During 12 months: The CT group had fewer bipolar
episodes, fewer days in a bipolar episode, and fewer
hospitalizations
• CT group had significantly higher social functioning
and fewer affective symptoms in the monthly records of
mood
CT and Bipolar Disorder
Dominic H. Lam, Peter Hayward, Edward R.
Watkins, Kim Wright, Pak Sham
Outcome of a two-year follow-up of
cognitive therapy of relapse prevention in
bipolar disorder
In press in American Journal of Psychiatry
CT and Bipolar Disorder
• During the 30 month observation period: CT
group did significantly better in terms of time
till relapse. Relapse prevention was mainly
evident during the first year.
• CT group spent 110 less days in a bipolar
episode during the 30 months and 54 days less
in a bipolar episode during the last 18 months
• CT group did better during the last 18 months
in mood records, in social functioning, in the
management of prodromal symptoms and in
dysfunctional cognitions
Diagram 1: survival analysis of bipolar episodes throughout the
whole 30 months
S urviva l F unc tio n a t m e a n o f c o va ria te s
1 .2
1 .0
.8
.6
Cum Survival
.4
ALLO C
.2
th e r a p y
0 .0
c o n tr o l
-20
0
20
40
60
80
100
120
140
T im e o f f ir s t b ip o la r e p is o d e ( w e e k s )
Controlling for previous admissions and medication compliance, hazard Ratio = 0.50, 95% CI 0.29 - 0.85,
p=0.012; N=85
Conclusions
• CBT when combined with medication,
whenever appropriate, has an additive
therapeutic effect.
• This effect has been evident in a variety of
studies for a variety of mental disorders
Thank you
for your attention