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        Gregoris Simos
CMHC/ Central District, Thessaloniki,
Wright J. (2004). Integrating Cognitive-
 Behavioral Therapy and Pharmacotherapy.
 In Leahy R. (Ed.) Contemporary Cognitive
 Therapy: Theory, Research, and Practice.
 Guilford Press, NY (pp 341-366)
• 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 non-
  psychotic 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
  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
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
• 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
 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).
• 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
(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,
© 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

• (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
 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
• 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
• 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%)
• Hollon and coworkers (1992) tested the efficacy
  of CBT, imipramine, or combined therapy in the
  treatment of 107 non-psychotic depressed
• 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
• 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 cognitive-
  behavioral-analysis system of psychotherapy (CBASP),
  or combined therapy. CBASP is a form of CBT with
  modifications for chronic depression (McCullough,
• 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 meta-
  analysis (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
 • 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
• 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
• 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
• 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
• 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 cost-
  effectiveness (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
  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.,
           Negative symptoms
Cognitive therapy for schizophrenia: a preliminary
            randomized controlled trial

  Neil A. Rector *, Mary V. Seeman, Zindel V.
    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
• Similar findings were observed for negative
    Review: CBT and medications in
• 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
• 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
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
       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
• CT group had significantly higher social functioning
  and fewer affective symptoms in the monthly records of
     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
• 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

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