Journal of Cognitive Psychotherapy: An International Quarterly

Volume 21, Number 1 • 2007

INTRODUCTION

Combined Cognitive-Behavior Therapy

and Pharmacotherapy

Jesse H. Wright, MD, PhD

University of Louisville, Kentucky

B
ecause cognitive-behavior therapy (CBT) is based on a psychological model for under-
standing and treating mental disorders, the preponderance of the research and clinical
development of this approach has been concerned with psychological mechanisms of
action. Relatively little attention has been paid to potential interactions with biologically based
treatments, the possible neurobiological effects of CBT, or the building of integrative methods
for combining CBT with pharmacotherapy. For the most part, CBT and pharmacotherapy have
developed as separate, and to some extent competing, treatment methods.
Despite having different proposed mechanisms of action and treatment delivery methods,
CBT and pharmacotherapy have several shared features. They both are: (1) empirically proven
treatments with a history of extensive research on efficacy; (2) pragmatic and action oriented; (3)
used with a broad range of patients who have a wide variety of diagnoses; and (4) endorsed as
effective interventions by panels and organizations such as the American Psychiatric Association
and the National Institute for Clinical Excellence (NICE).
As two of the most widely used and respected treatments, CBT and pharmacotherapy
would appear to have much to offer one another. For example, methods from CBT such as the
collaborative-empirical therapeutic relationship, practical techniques to reduce hopelessness
and reverse patterns of avoidance, and interventions to improve adherence might be beneficial
for patients being treated with pharmacotherapy. In turn, targeted use of medication to lower
agitation, improve energy, decrease psychotic symptoms, or improve concentration might make
certain patients more accessible to CBT, promote learning in psychotherapy, or enhance the
overall outcome (Wright, 2004).
Research on combined CBT and pharmacotherapy began in the 1980s with classic trials,
which compared CBT alone to tricyclic antidepressants plus clinical management and to the
two treatments offered together (Blackburn, Bishop, Clen, Whalley, & Christie, 1981; Hollon
et al., 1992; Murphy, Simons, Wetzel, Lustman, 1984). Although these trials found no statistically
significant advantage for combined treatment over the treatments provided individually, there
was a trend for superiority for CBT plus an antidepressant. Subsequent analyses of these trials,
including meta-analyses (Friedman, Wright, Jarrett, & Thase, 2006; Hollon et al., 2005), have
suggested that there was inadequate sample size in each individual study to find a significant

© 2007 Springer Publishing Company 3

4 Introduction

difference between treatments offered singly or together. Larger trials or meta-analyses have
substantiated a better outcome for combined treatment for depression (Friedman et al., 2006;
Hollon et al., 2005; Keller et al., 2000). Studies of combined treatment of anxiety disorders have
had mixed results. Several major reviews and meta-analyses have found that benzodiazepines
typically do not add to the efficacy of CBT for various anxiety disorders (Bakker, van Balkom, &
van Dyck, 2000; van Balkom et al, 1997; Westra & Stewart, 1998). In fact, there is some evidence
that high-potency benzodiazepines such as alprazolam may actually impair the efficacy of CBT
for panic disorder (Marks et al., 1993). Westra and Stewart (1998) concluded that longer acting
benzodiazepines such as diazepam did not have this deleterious effect on CBT.
Antidepressants are often used for anxiety disorders, and there is considerable evidence that
they can provide effective treatment (Bakker et al., 2000; De Beurs, van Balkom, Lange, Koele,
& van Dyck, 1995; Sharp, Power, Simpson, Swanson, & Anstee, 1997; Westra & Stewart, 1998).
These drugs offer advantages over benzodiazepines because they are less likely to cause depen-
dence or impair learning and memory, and thus are better choices for combined treatment with
CBT. Reviews of studies with tricyclic antidepressants (TCAs) have found that combined treat-
ment is often more effective in the acute phase of therapy, but these advantages may disappear
over the long term. Naturalistic follow-up studies are hard to interpret because patients often
stop medications or enter other forms of therapy. Research with selective serotonin reuptake
inhibitors (SSRIs) for anxiety disorders has usually documented superior results for combined
treatment with CBT (Bakker et al., 2000; De Beurs et al., 1995; Sharp et al., 1997). Differences
between outcomes with TCAs and SSRIs may possibly be due to the enhancement of learning
and memory with SSRIs as compared to a negative impact on learning and memory from TCAs
(Wright, 2004).
Studies of combined therapy for depression and anxiety disorders have made significant
contributions to the understanding of differential outcome between treatments. However, there
have been many problems with these studies that make it difficult to generalize findings to clinical
practice (Wright, 2004). Perhaps the greatest problem is that most research on combined therapy
has pitted CBT versus pharmacotherapy and has not offered an integrated, comprehensive, or
flexible form of combined therapy that maximizes the potential advantages of this approach.
Patients are treated by clinicians who follow specific protocols for treatments as separate entities
instead of offering an integrated method. Medication choices and doses are usually rigidly pre-
scribed, whereas in typical clinical practice, medication regimens can be modified if side effects
or lack of response are encountered. Also, analyses of mean responses in randomized, controlled
trials may obscure individual variations, in which positive interactions between treatments may
be encountered in some patients while negative interactions may occur in others.
In this edition of the Journal of Cognitive Psychotherapy, investigators and clinicians who
have been working with schizophrenia, bipolar disorder, and eating disorders describe key
research findings and clinical methods for using medication together with CBT. One of the
most exciting recent developments in CBT has been the dramatic increase in research studies
and clinical applications for the treatment of psychosis. David Kingdon, who has played a
leading role in developing CBT for severe mental disorders, and his associates detail methods
of combining CBT with medication for schizophrenia. They conclude that a growing number
of research studies have documented that CBT can have add-on effects to antipsychotic
medication. Although the results of studies have varied, there is substantial evidence that
adding CBT to pharmacotherapy can reduce hallucinations, delusions, and negative symp-
toms of schizophrenia to a greater extent than treatment as usual with medication and clinical
management.
The treatment of bipolar disorder requires pharmacotherapy with mood stabilizers or other
effective medications, such as atypical antipsychotics, as Monica Basco and her coworkers indicate
in their article on combined therapy for this condition. However, Basco has pioneered efforts to
 Introduction 5

develop adjunctive CBT methods for bipolar disorder (Basco & Rush, 2005). These methods are
directed at symptom monitoring, developing effective coping strategies for symptoms not fully
controlled by medication, managing stress, and reducing the risk of relapse. Research on com-
bined treatment for bipolar disorder is still at a very early stage, but some studies have shown
positive effects of adding CBT to mood stabilizers. CBT appears to offer promise as a treatment
for bipolar disorder, but the results of early studies suggest that ongoing therapy may be required
to obtain enduring effects.
Wayne Bowers, an expert on the treatment of eating disorders, and his associate Arnold
Anderson observe that CBT has frequently been found to be superior to medication in the
treatment of bulimia nervosa and binge-eating disorder, but that combinations of CBT and med-
ication typically lead to better outcomes than medication alone. Because there are a significant
number of patients with these conditions who do not respond to CBT, a stepped-care approach
is recommended, in which CBT is first used alone. If satisfactory results are not obtained, then an
antidepressant can be added. With anorexia nervosa, there is little solid evidence for the efficacy
of CBT, but a combination of nutritional counseling, cognitive and behavioral interventions, and
judicious use of medications may offer opportunities for effective treatment in difficult clinical
situations.
The great majority of the research studies completed to date on combined treatment have
focused on comparing the differential outcomes of CBT versus pharmacotherapy or CBT plus
medication versus treatment as usual. The potential interactions between treatments, such as the
actions of medications on cognitive processing, which could enhance participation in CBT, or the
biological effects of CBT, which could work together with medication in additive or synergistic
mechanisms, have not been adequately investigated.
A deeper understanding of the processes of interaction between CBT and pharmacotherapy
could lead to advances in treatment methods. For example, preliminary research with PET scan
and other imaging techniques has found that CBT and pharmacotherapy can have similar actions
on brain pathways for the treatment of obsessive-compulsive disorder (OCD) and anxiety disor-
ders (Baxter et al., 1992; Furmark et al., 2002; Schwartz, Stoessel, Baxter, Martin, & Phelps, 1996)
but quite different actions when the treatments are used for depression (Goldapple et al., 2005).
Research conducted by Goldapple and coworkers (2005) found that antidepressants activated
brain pathways from the "bottom up," whereas CBT appeared to act from the "top down," with
cortical activity preceding limbic system and deeper brain structure activity. One of the intrigu-
ing possibilities of this type of research is that specific neural circuits could be detailed in which
CBT and pharmacotherapy augment one another in reversing the CNS pathology associated with
major mental disorders.
While clinicians await the results of future studies on combined CBT and biologically oriented
interventions, practical issues such as choosing the form of treatment, learning about the posi-
tive and negative features of medications, and gaining skill in combining therapies continue to be
important challenges. This edition of the Journal of Cognitive Psychotherapy contains three articles
that should help readers learn more about combining CBT and medication in clinical practice.

REFERENCES
Bakker, A., van Balkom, A. I., & van Dyck, R. (2000). Selective serotonin reuptake inhibitors in the treatment
of panic disorder and agoraphobia. International Clinical Psychopharmacology, i5(Suppl. 2), 25-30.
Basco M. R., & Rush A. ]. (2005). Cognitive-behavioral therapy for bipolar disorder. New York: Guilford.
Baxter, L. R., Ir., Schwartz, ). M., Bergman, K. S., Szuba, M. P., Guza, B. H., Mazziota, J. C, et al. (1992).
Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive
disoidei:. Archives of General Psychiatry, 49, 681-689.
6 Introduction

Blackburn, I. M., Bishop, S., Glen, A. I. M., Chistie, J. E., et al. (1981).The efficacy of cognitive therapy
in depression: A treatment trial using cognitive therapy and pharmacotherapy, each alone and in
comhination. British Journal of Psychiatry, 139, 181-189.
De Beurs, E., van Balkom, A. J. L. M., Lange, A., Koele, P., & van Dyck, R. (1995). Treatment of panic dis-
order with agoraphobia: Comparison of fluvoxamine, placebo, and psychological panic management
combined with exposure and of exposure in vivo alone. American Journal of Psychiatry, 152, 683-691.
Friedman, E. S., Wright, J. H., Jarrett, R. B., & Thase, M. E. (2006). Combined medication and cognitive
therapy for mood disorders. Psychiatric Annals, 36(5), 320-328.
Furmark, T, Tillfors, M., Marteinsdottir, I., Fischer, H. Pissiota, A., Langstrom, B., et al. (2002). Common
changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive-
behavioral therapy. Arc/lives of General Psychiatry, 59, 425-433.
Goldapple, K., Segal, Z., Garson, C, Lau, M., Bieling, P., Kennedy, S., et al. (2004). Modulation of cortical-
limbic pathways in major depression: Treatment-speciflc effects of cognitive behavior therapy. Archives
of General Psychiatry, 61, 34-41.
Hollon, S. D., DeRubeis, R. J., Evans, M. D., Wiemer, M. J., Garvey, M. J., Grove, W. M., et al. (1992).
Cognitive therapy and pharmacotherapy for depression: Singly and in combination. Archives of General
Psychiatry, 49,774-781.
Hollon, S. D., Jarrett R. B., Nierenberg, A. A., Thase, M. E., Trivedi, M., & Rush, A. J. (2005). Psychotherapy
and medication in the treatment of adult and geriatric depression: Which monotherapy or combined
treatment? Journal of Clinical Psychiatry, 66, 455-468.
Keller, M. B., McCullough, J. P, Klein, D. N., Arnow, B., Dunner, D. L, Gelenberg, A. J., et al. (2000). A
comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their
combination for the treatment of chronic depression. New England Journal of Medicine, 1462-1470.
Marks, 1. M., Swinson, R. P, Basoglu, M., Kuch, K., Noshiruani, H., O'SuUivan, G., et al. (1993). Alprazolam
and exposure alone and combined in panic disorder with agoraphobia: A controlled study in London
and Toronto. British Journal of Psychiatry, 162, 776-787.
Murphy, G. E., Simons, A. D., Wetzel, R. D., & Lustman, P. J. (1984). Cognitive therapy and pharmacothera-
py: Singly and together in the treatment of depression. Arc/iives o/Genera/ftyc/iiatry, 33-41.
Sharp, D. M., Power, K. G., Simpson, R. J., et al. (1997). Global measures of outcome in a controlled com-
parison of pharmacological and psychological treatment of panic disorder and agoraphobia in primary
care. British Journal of General Practice, 47, 150-155.
Schwartz, J. M., Stoessel, P. W., Baxter, L R., Jr., et al. (1996). Systematic changes in cerebral glucose
metabolic rate after successful behavior modiflcation treatment of obsessive-compulsive disorder.
Archives of General Psychiatry, 53, 109-113.
van Balkom, A. J. L. M., Bakker, A., Spinhoven, P., et al. (1997). A meta-analysis of the treatment of panic
disorder with or without agoraphobia: A comparison of psychopharmacological, cognitive-behavioral,
and combination treatments. Journal of Nervous and Mental Disease, 185, 510-516.
Westra, H. A., & Stewart, S. H. (1998). Cognitive behavioural therapy and pharmacotherapy: Complementary
or contradictory approaches to the treatment of anxiety? Clinical Psychology Review, 18, 307-340.
Wright, J. H. (2004). Combined cognitive therapy and pharmacotherapy. In R. Leahy (Ed.), Contemporary
cognitive therapy (pp. 341-366). New York: Guilford.

Correspondence regarding this article should be directed to Jesse H. Wright, MD, PhD, Department of Psychiatry
and Behavioral Sciences, Norton Psychiatric Center, 200 East Chestnut Street, Louisville, KY 40232. E-mail:
jwrigh t@iglou. com