Adding Psychotherapy to Pharmacotherapy: Data, Benefits, and Guidelines for

Integration
Ira D Glick. American Journal of Psychotherapy. New York:
2004.Vol.58, Iss. 2; pg. 186, 23 pgs

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Subjects: Psychotherapy, Drug therapy, Mental disorders
Author(s): Ira D Glick
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title: York: 2004. Vol. 58, Iss. 2; pg. 186, 23 pgs
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Abstract (Document Summary)

Thoughts and behaviors controlled by a disordered brain have brought patients to the
attention of mental health-care providers, who have attempted to change the
dysfunctional behavioral by using either medications and/or psychotherapeutic
intervention. What is relatively new in psychiatric practice is that most patients with Axis
I disorders are receiving combined treatment, rather than either medication alone or
psychotherapy alone. Glick discusses how the clinician integrates medication and
psychotherapy when the data suggest that psychotherapy improves outcome for either
patient and/or family above what medication alone provides.

Full Text (9226 words)

Copyright American Journal of Psychotherapy 2004

"A man's body and his mind with the utmost reverence to both . . . are exactly like a
jacket, and a jacket's linings-rumple the one-you rumple the other."

L Sterne, (1759-67).

The quotation above suggests that it has long been appreciated that brain and behavior are
complexly interrelated. Thoughts and behaviors controlled by a disordered brain have
brought patients to the attention of mental health-care providers, who have attempted to
change the dysfunctional behavior by using either medications and/or psychotherapeutic
intervention. What is relatively new in psychiatric practice is that most patients with Axis
I disorders are receiving combined treatment, rather than either medication alone or
psychotherapy alone (1, 2). But as Lenfant has discussed in other areas of medicine than
psychiatry, "enormous amounts of new knowledge are barreling down the information
highway, but they are not arriving at the doorsteps of our patients" (3). The problem has
been that the potential for integration has generally not been fulfilled, in part because
guidelines are lacking and in part because of financial disincentives to provide the
psychotherapy component (4). As a result, the treatment is usually delivered by two
mental health professionals rather than integrated (5). Since the economics of delivery of
mental health services almost always mandate medication as a first choice intervention,
the essential question is, "what does the psychotherapy part of the equation contribute to
outcome?"

Klerman (6), was in the vanguard of attempting to facilitate the integration of

psychotherapy and pharmacotherapy, when he reviewed their theoretical basis and
described possible "outcomes." He observed that drugs and psychotherapy derive from
different theoretical realms and are therefore theoretically neutral, but ideologically
competitive. At around the same time, Beitman and Klerman (7) edited a volume of
papers dealing with specific types of combined interventions for a variety of disorders,
but there was still very little controlled data supporting the efficacy or effectiveness of
combined treatments. Glick et al. (8) reviewed the combining of medication and
(specifically) family therapy in 1993. Today the field seems less competitive than in the
early 1990s, and there is far greater acceptance of using combinations of medication and
psychotherapy (2). In fact, a recent paper made a strong case for combining treatment
using an integrative model rather than a collaborative treatment model (5).* (One bit of
confusion is that the term "combined treatment" sometimes is used to mean two different
providers-a psychopharmacologist and a psychotherapist, while integrated usually means
using both in an integrated fashion. A psychiatrist can do combined treatment by talking
about medication in parts of the session and psychotherapy in the other). Our aim is to
build on that report focusing on providing guidelines of how to integrate these modalities
and summarizing the data supporting the efficacy of adding psychotherapy to medication.

A major problem in clinical practice is that "even in the absence of compelling evidence
for the additive benefits of combined treatments" (9) it is being used. A second issue is
that in the treatment guidelines for each disorder, there is almost no literature on specifics
of how to do the combined treatment. Since science moves more slowly than practice, we
agree there may be wisdom in the practice of using combined treatment even in advance
of supporting data, but there is a strong need for more specific recommendations for the
practicing psychiatrist when and how to combine treatments over the lifetime of these
disorders. The range of tested interventions is now so broad-medication, family therapies,
individual psychotherapies as well as consumer-support-group interventions (10)-that if
psychiatrists are to lead this multimodal and multidisciplinary therapeutic effort, they
must have a reasonable knowledge of when, and how, to integrate treatment approaches,
enlist the family in the therapeutic strategy, and refer the patient and family to an
appropriate support group.

The paper is about how the clinician integrates medication and psychotherapy when the
data suggest that psychotherapy improves outcome for either patient and/or family above
what medication alone provides.

It is important to state my biases up front. First, I believe psychotherapy needs to be

combined with medication for most Axis I disorders (and probably many Axis II as well).
Although there are many reasons for this (see below where we discuss "rationale") at the
very least it may improve medication compliance, which is a large part of the battle to
improve outcome (13). Second, where effective, psychotherapy alone in some form can
be a first line treatment, e.g., for "mild depression" (15). Third, (and I may be in the
minority of psychiatrists who believe this) family interventions can be a useful
intervention for many Axis I disorders. It is uncommonly used in clinical practice at this
juncture (16). The rationale is that most patients with Axis I disorders have (either or
both) cognitive impairment or their families are heavily involved in management. Fourth,
I do believe that individual therapy is an efficacious modality when combined with
medication, but it is not emphasized here for two reasons. First of all, its use in integrated
therapy has been well described (5) and two, it is commonly in use in clinical practice.
Finally, I do believe psychodynamic individual therapy is useful, although empirical
evidence is rare (5).

COMBINED TREATMENT

RATIONALE

Both medication and psychotherapy are needed for the following general and specific
reasons why: one modality alone is not sufficient. Broadly speaking, the specific aims are
to 1. quickly bring the patient into a state of remission from the illness; 2. reduce the
probability of delay in initiating treatment or eliminate relapse/recurrence; 3. treat both
the symptoms of the patient and ameliorate the stress on the family; 4. enhance adherence
with the medication; 5. enhance psychosocial skills that were lost (or never learned) due
to the psychopathology; 6. teach the patient and the family methods to cope with residual
symptoms; and 7. accelerate the psychotherapeutic process and prevent relapse. Many
patients tend to value psychotherapy more than their physicians do, and for various
reasons (e.g., personal preference, pregnancy, side-effect intolerance, etc.), patients may
be temporarily off medications, but still require treatment.
RESULTS

In this era of evidence-based medicine, considering Axis I disorders known to be

medication responsive, the crucial treatment question is-what data support the contention
that psychosocial intervention improves outcome for patients (and their families) over
what medication alone provides? Accordingly, since this is a paper on combined therapy,
we will selectively examine the data that supports this practice-we will not cover data that
were negative or that showed that psychotherapy can be used alone. That has been done
(17). We know that medication works for some disorders. But is it worth the extra time
and cost to add psychotherapy to medication? If the answer to these questions is 1. "yes,"
then 2. what does it add (in what circumstances, i.e., for which disorders for which
patients and/or their families), 3. what are the data supporting its use, i.e., "results" of
combined treatment, and 4. if it does improve outcome, how do you do it, i.e., guidelines.
Until the last decade, controlled data have been lacking. Consensus guidelines for most
Axis I disorders though have cautiously suggested combining modalities even in the
absence of data-but as mentioned, they do not detail specifics of doing so (18).

A full review of each Axis I and II disorder is beyond the scope of this paper. However,
Nathan and Gorman (17) in their book on "treatments that work," have done a great
service to the field. They have reviewed the literature-disorder by disorder-even grading
the quality of the data. Table I, from their book, reveals that there are seven disorders
with controlled data suggesting that a combination of a medication and some form of
psychosocial intervention is better than medication alone. Parenthetically, it should be
noted that both the American Psychological and Psychiatric Associations have accepted
the same standard criteria for treatment to be empirically supported, i.e., two
independently controlled RCTs showing superiority of the treatment to placebo or at least
equivalence to an empirically supported treatment. The evidence summarized above
supports the finding that combining medication with psychotherapy is more effective than
drugs alone in treatment of schizophrenia, bipolar disorder, depression, ADHD, bulimia,
sleep disorders, and possibly PTSD. In no other disorders has combined treatment met
the standard criteria that establish empirical support.

Why is there so little evidence? In part it is because controlled studies take considerable
time and money, and in part, because some of the studies that have been done have not
found the synergistic or additive benefits we discuss. It also may be that negative findings
result from low power to detect additive benefits of combined treatment over the benefits
of either modality alone. And finally it may be because the methodology is so complex,
i.e. a medication-placebo control may be needed. (Arthur Rifkin, M.D., 2004) (5.1).

By way of illustration of the complexities of such research designs, their results and
application to clinical situations, we will summarize the supporting data on one disorder,
depression.

DEPRESSION
Studies of combined therapy have been done on major depressive disorders, chronic
depression and on dysthymia. Thase et al. (18a) performed a meta-analysis of 595
patients with major depressive disorder that were enrolled in six different protocols. Mild
depressions responded well to both psychotherapy alone and combined treatment, but the
combination treatment for severe depressions was much superior to monotherapy in
terms of overall recovery rates and shorter time to recovery. This result appears similar to
the NIMH-TDCRP (Treatment of Depression Collaborative Research Program) findings,
the largest study of its type (15). Combined treatment in the TDCRP was imipramine plus
clinical management (which included support, encouragement, and general advice).
Significantly more of the combined-treatment group completers reached the recovery
criterion of 6 or less on the Hamilton Rating Scale for Depression in the acute phase,
compared with the control completers (15). However, these effects were not maintained
at the 18-month follow up.

Recently, Burnand et al. (19) have reported data from a randomized controlled trial
(RCT) that psychodynamic therapy combined with medication was more cost-effective
than medication alone for patients with acute major depression. Lenze et al. (20)
examined maintenance treatment on social adjustment in late-life depression. The
maintenance treatment that best maintained improved social functioning was a
combination of IPT and nortriptyline.

Chronic depression, defined as a depression of 24 months or longer, accounts for about

33% of all depressions and is often treated differently than an acute depressive episode.
An algorithm for treating chronic major depression suggests that the combination of
antidepressant and psychotherapy be tried after first attempting a monotherapy approach
(21). Indeed, for chronic depressions these authors feel that a combination of
pharmacotherapy and psychotherapy may be the best treatment. At least in part, this
conclusion comes from a large-scale study of 662 chronically depressed patients who
attended at least one treatment session using nefazodone alone, the cognitive behavioral-
analysis system of psychotherapy alone, or their combination. The study was conducted
by Keller and his colleagues at multiple sites (22). Each monotherapy was responsible for
about 48% remission and satisfactory response, but the combination resulted in a 73 %
overall rate of response. Of the 519 subjects who actually completed the study, the
response rate was equally dramatic: response rate for the nefazodone group was 55%, for
the psychotherapy group 52%, and for the combination, 85%. The Keller et al. (22) data
were further analyzed for the effects of these treatments on psychosocial functioning. All
three treatments resulted in improved functioning in these chronically depressed
outpatients, but the combination treatment (nefazodone plus cognitive behavioral-
analysis system of psychotherapy) produced significantly more improvement than either
treatment alone.
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Table I. SUMMARY OF DISORDERS IN WHICH PSYCHOTHERAPY IMPROVES

OUTCOME OVER MEDICATION ALONE

Among dysthymics, Group CBT augmented the effects of sertraline on some functional
measures (26). Group CBT alone did not have an overall effect on reducing symptoms of
dysthymia or on the quality of life, but for those patients who did respond well to CBT
symptomatically, the improvement in quality of life was equal to that seen in drug alone
responders. It would of course be helpful to identify predictors of response to CBF so
those patients could be selected out for this approach. In a pilot study of dysthymic
patients, Hellerstein et al. (25) prospectively randomized patients to a 36-week
comparison of fluoxetine alone or fluoxetine plus group therapy. There was a small
additional benefit in interpersonal and psychosocial functioning among those dysthymic
patients who responded to the combination. Outcome included not just the alleviation of
symptoms, but better interpersonal and psychosocial functioning. Thus, there are
numerous reasons for combining therapies.

Relapse is a problem for all therapeutic modalities, but there are treatment
discontinuation differences among the modalities. In the NIMH-TDCRP (Treatment of
Depression Collaborative Research Program) (26), investigators reported that 50% of
"recovered" patients who had received pharmacotherapy relapsed following treatment
termination (27). Fewer patients relapsed after CBT (36%), and fewer still with
interpersonal therapy (IPT) (33%), but none of these percentages is worthy of bragging
rights. By way of comparison, in the 4-site collaborative study of combined treatment for
panic disorder, Barlow et al. (28) found CBT alone maintained improvement better (4%
relapse) than imipramine alone (25 % relapse). CBT plus imipramine conferred no
advantage beyond CBT alone in the no-treatment follow-up period, and interestingly, the
addition of imipramine appeared to reduce the long-term benefits of CBT. The drop-out
rate is particularly troubling for clinicians, since patients out of treatment are potentially
detrimental to themselves, their family, and society at large. Clinicians must do their best
to follow their patients, encourage continued treatment, and switch to a different modality
to avert dropping out.

These data-here using depressive disorders as an example-still leave many unanswered

questions, but do provide support for the common practice of combining modalities-at
least for some disorders. Further studies to evaluate the additive effects of evidence-based
drug and psychotherapy treatments are mandatory.

GUIDELINES: GENERAL AND SPECIFIC

There are many models that posit an interaction among biological, psychological, and
environmental factors. One of the most developed and data driven is that of Reiss et al.
(13). Their paper highlights the evocative interaction among genotype, family-
intimates/environment and behavior/ psychopathology as a basis for planning treatment.
We present it here primarily because it serves as a scaffolding for our suggestions for
combined, integrative treatment. Examination of Figure 1 makes clear our key
assumption, i.e., etiology is complex, involving multiple interactive domains which may
require multiple interventions-which of course is why combined therapy may be
necessary.

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Figure 1.
REISS'S EVOCATIVE MODEL

Using this model and, in part, borrowing from our earlier work evaluating the efficacy of
psychiatric care (29-31), we have developed a Quality Treatment Equation (Figure 2). As
a generalization, we suggest that multimodal therapy (i.e., medication, a family
intervention, and an individual therapy like CBT) may be necessary. Obviously, treatment
must be individualized based on the needs of patient (and significant others).

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Figure 2.
A QUALITY TREATMENT MODEL
Two of the three factors on the right side of this conceptual equation are environmental,
one focuses on the psychology of the individual, and medication is assumed to restabilize
the brain, secondarily affecting cognitive and psychosocial functioning. The major issue
involved (in this now well-accepted model) is that for most Axis I disorders, treatment is
usually not fully implemented. That is, there is usually undertreatment (32) or total lack
of a component being prescribed, whether it be medication for depression (33), (34),
psychotherapy (32), or very commonly consumer group help (10). A discussion of the
latter is outside the scope of this report, but please see our earlier paper (ref. 11). There
are many reasons for this-commonly financial limitations, but often due to lack of
awareness of the need.

GENERAL GUIDELINES

In this section, we first provide "general guidelines" that by and large cut across
diagnostic categories. Following this, we discuss each of the modalities we included in
the quality treatment equation, i.e. 1. medication, 2. family intervention, and 3. individual
intervention. Then we include a brief description of "psychoeducation" as it applies to the
three modalities. It is important to reiterate that the literature does not offer the data to
provide very clear guidelines for combined treatment. (B. Beitman, 2003, personal
communications)

Diagnosis

The most effective integration of combined treatments comes not only from making a
DSM-IV-TR diagnosis, but also from an understanding of how the individual and the
family functions (35). Without a diagnostic map, the appropriate treatment may not be
prescribed. So too, without a map of the individual and family-system dynamics, the
clinician will be oblivious to the quagmire of family and individual pathology and how it
affects outcome.

Goals

After identifying and quantifying target symptoms (by severity, prominence, and impact
on functioning), one must set goals for improvement compared to baseline focusing on
these target symptoms. This information will allow the clinician to determine which
symptoms (or cluster of symptoms) may be responsive to which modalities. By setting
goals, the clinician has a more quantifiable method of evaluating what interventions are
effective.

Untoward Effects

By untoward effects we mean not just awareness of medication side-effects, but adverse
changes in individual and family dynamics as well as potentially adverse interactions of
administering combined therapies. For example, medication-induced sedation or
dysphoria may decrease the patient's ability to socialize with family and/or friends.
Within the family dynamics, there may be issues around the patient needing less care, or
becoming more assertive, or family members no longer perceiving the patient as ill or
stigmatized, and, of course, the ensuing loss of secondary gain of being ill. Conversely,
increasing medication dosage may enable a patient (or family) to discuss issues that were
previously too emotionally charged for careful, insightful discussion.

Sequencing Effects

The clinician who accepts the role of a "combination therapist" must be aware of when,
and in what sequence, to use each of the modalities. Since good evidence is not available,
the sequence will vary according to clinical considerations of the type of illness, its
severity, and the clinicianpatient concept of the nature of the illness.

For instance, for psychosis, the clinician may want to medicate first, then add family
and/or individual psychotherapy. In part, this is because of the lack of insight as well as
the denial inherent in the illness (30). A depressed, paranoid, psychotic patient might not
be able to tolerate family therapy until he or she has been reconstituted through the use of
antipsychotic drugs. In nonpsychotic patients, one option is to aim first for a medication
response, i.e., euthymia, then add psychotherapy to deal with residual intrapsychic and
interpersonal issues (34). In some conditions, e.g., a personality disorder for some
patients, one may want to start with psychotherapy then add medication for symptoms
like depression, hallucinations, and delusions while for others the reverse may be true. At
times, especially with adolescents, psychotherapy might wait until a patienttherapist
alliance has been established. In the presence of substance abuse/dependence, a first
priority is to start peer-supportive intervention (as done in Alcoholics Anonymous) before
adding psychotherapy and/or medication.

Where treatments are essentially equal in reducing symptoms, the question arises as to
which treatment should be administered first? O'Conner et al. (37) found that for
obsessive-compulsive disorder it was more beneficial clinically to give medication first
and then move to a combination of medication and CBT. Thase et al. (18a) found
combined treatment to be superior among those with more severe depression, and Keller
et al. (22) found combined treatment to be substantially superior to medication or
psychotherapy alone, at least in the acute phase of treatment for chronic depression (no
long-term findings have yet been published from that trial). Fava et al. (38) have found
that CBT is helpful for the treatment of residual symptoms following pharmacotherapy
for depression.

For Whom Is Combined Family/Individual Treatment and Medication Not Indicated?

The authors believe in the principle of therapeutic parsimony when combining

modalities: if one modality is effective, do not add the second. For some clinical
situations, start with family therapy (for example, when the family problem is paramount,
and/or may interfere with individual psychotherapy or medication adherence), for others,
medication (for example, in the acute psychosis associated with schizophrenia, bipolar
disorder, organic mental disorders, etc). In still others, start both simultaneously and
consider withdrawing one (or both) modalities over time (for example, as a marital
family-systems problem is resolved, the intervention can be tapered or discontinued).
Much of the data on combined treatments appears to show that CBT reduces symptoms
as well as the risk of relapse (39). It may be that this conservative step should be taken
first in less severe cases. The need for medication then may be reduced or eliminated.

One treatment may resolve one illness, but a second treatment may be needed for a
comorbid disorder (for example, if a patient has mood disorder comorbid with alcohol
abuse requiring A.A. intervention), or for residual symptoms, or for long-term
management. There are frequently residual symptoms after the patient no longer meets
full DSM-IV criteria (39), (40), and here a psychosocial therapy like individual therapy
might be needed to eliminate these symptoms or family therapy to help the family cope.
For example, at the very least, putting aside the potential power of a family intervention
by itself, the family-systems approach is an efficacious way to increase medication
compliance (14), (41).

SPECIFIC MODALITIES

This section will describe the components of the quality treatment equation in greater
detail, starting with medication.

Medication

The newer medications, like the second and third generation antidepressants for anxiety
and depression, and the atypical antipsychotics for psychosis, have provided new options
for patients, as well as the need for effective strategies that include (for some) adjunctive
treatments. Effective medication strategies include adequate doses, continuous (rather
than targeted) administration (42), standard, i.e., moderate (rather than low) dose, and the
use of intramuscular injections for noncompliant patients. As mentioned above,
compliance is the central issue and therefore combined therapy is needed. Behavior
therapists have worked out methods to enhance compliance even in elderly patients with
schizophrenia, so that alternatives to intramuscular injections may be available. Roter et
al. (43) summarized 153 studies that evaluated the effectiveness of behavioral
interventions to improve adherence to medical regimens. The techniques used in the
individual studies included direct education, group processes, familial support, behavioral
modalities, and provider interventions. All indicators proved to be effective, but the
magnitude of effect sizes were generally small to medium.

The first task is to establish an alliance with the patient. For example, in the NIMH
Collaborative study, 21% of the variance was related to the power of the therapeutic
alliance in improving compliance with medication. A positive therapeutic alliance was
correlated with positive outcomes in the other three cells (44). As a guideline, we
recommend Gutheil's pharmacotherapeutic alliance that can be defined as "the manner in
which "active efforts are made by the physician to enlist, recruit, and involve the patient
in a collaboration around prescribing medication" (45). Its characteristics are a flexible,
prescriptive stance, and the acknowledgment of uncertainty of cause and effect. Its
objective is the establishment and maintenance of this alliance. The process includes
shared inquiry, shared goals, mutual participation in both the experience and mutual
observation of the process of using medication." Gutheil's pharmacotherapeutic alliance
is clearly less formalized and objective than many of those reviewed by Roter et al. (43),
but it may be equally effective.

Psychiatric Management

The term "psychiatric management" is a rubric that refers to the whole range of
psychotherapeutic services. Psychotherapy has been the treatment of choice for Axis I
disorders historically when medications were not available or effective, or if they were
contraindicated or refused. Most commonly it was employed with the rationale that social
and psychological problems accompany the disorder either as the source or consequence
of the disorder. Winston (46) has thoughtfully reviewed "factors to consider when
choosing and combining appropriate treatment approaches emphasizing issues related to
comorbid conditions, the health-sickness continuum and the therapeutic alliance."

Which type of psychotherapy should be used in which phase of drug treatment? For most
Axis I disorders, when cognitive impairment is suspected (for example, acute bipolar
disorder), we suggest starting with family intervention (rather than individual) in the
acute phase, and family therapy combined with supportive individual therapy in the
maintenance phase. As to which model should be applied when the patient is cognitively
impaired as in acute schizophrenia, we suggest initially a psychoeducational, then a
cognitivebehavioral (rather than psychodynamic) approach in the acute phase (47). In the
continuation and maintenance phases, CBT has been suggested (48). The
psychotherapeutic alliance is characterized by a more receptive, open stance than the
pharmacotherapeutic alliance (45). A very practical question is how long to continue the
psychotherapy and how much to administer? While psychotherapists have expended
considerable effort in devising "brief" interventions, long-term and/or periodic, "booster"
treatment is usually required. Psychotherapy-which can be hard work on the patient's
part-should be given only to the extent that the patient can tolerate and utilize it. Most
importantly, for most Axis I disorders, the patient as well as the family are viewed as
partners on the treatment team rather that adversaries. This takes much work on the part
of the therapist pointing out that their lives (both patient's and family's) are intertwined
and interdependent. It should be pointed out that the psychiatrist usually can't be helpful,
unless both patient and family are "on the team."

Family Intervention

Now, let us look at the family intervention part of the equation using schizophrenia as an
example. Controlled data from our inpatient study (48) and from five outpatient studies
(49) have shown strong support for the concept that this modality adds something above
what medication can do in improving outcome for schizophrenia and bipolar disorder
(14). It is particularly useful for preventing relapse and for improving adherence (49). In
addition, there is increasing evidence of the importance of expressed emotion,
particularly criticism, in the exacerbation and recurrence of Axis I problems. Lam (50)
has described seven components of effective family approaches to schizophrenia, each of
which can be adapted to most Axis I and II disorders. They include: 1. a positive
approach and genuine working relationship between the therapist and family, 2. the
provision of family therapy in a stable, structured format with the availability of
additional contacts with therapists if necessary, 3. a focus on improving stress and coping
in the "here and now," rather than dwelling on the past, 4. encouragement of respect for
interpersonal boundaries within the family, 5. the provision of information about the
biological nature of schizophrenia [and other mental illnesses] in order to reduce blaming
the patient, stigma, and family guilt, 6. use of behavioral techniques, such as breaking
down goals into manageable steps, and 7. improving communication among family
members.

Stated another way, family therapy and pharmacotherapy tend to "normalize" the illness.
The former attempts to educate, improve communication and problem-solving skills, and
resolve dynamic and systems issues; the latter acts to suppress or decrease symptoms.
Each modality has the secondary effect of improving adherence to the other. The family
intervention increases the chance that the patient will adhere to complicated medication
regimens, while medication improves the cognitive disorder so that the patient can
engage in psychotherapy.

Some of the problems we have noted with integrating family therapy include the fact that
many family therapists are perceived as "blaming" the family of the identified patient for
the development of an Axis I or II disorder (10). Second, they are often uncomfortable
with a biological model and/or prescribing medication as well as utilizing DSM-IV
nomenclature. Finally, they may have a bias against working one-on-one with a patient
and therefore do not include individual therapy.

Individual Intervention

Some form of individual supportive interventions are almost always prescribed with
medication-and we strongly support this practice. Choice of individual interventions
include various forms of cognitivebehavioral (CBT), interpersonal (IPT) and personal
therapy for schizophrenia (45). Supportive psychodynamic therapy is still widely used,
although empirical justification is rare (19). The initial aims are to form an alliance,
maintain or build self-esteem, maximize compliance, and diagnose and manage objective
psychopathology. Hogarty et al. (51) have demonstrated that "personal therapy" added to
medication improves long-term outcome by helping patients with schizophrenia cope
with stress and allows them to use social-skills training.

Just as with family intervention, in the context of Axis I and II disorders, there are a
number of problems. They appear to be rooted in misuse of the individual
psychodynamic model as applied to integrated treatment. These include 1. emphasizing
the patient's personality conflicts and character pathology over the patient's overt
symptom manifestations; 2. misdiagnosing objective dependency as psychodynamic
dependency; 3. misdiagnosis of lifelong disability as psychodynamic psychopathology; 4.
labeling cognitive and other changes resulting from Axis-I disorders as a personality
disorder, usually "narcissistic, borderline or hysterical;" 5. treating with psychoanalytic
psychotherapy alone with the expectation that Axis-I symptoms will subside after
personality conflicts are resolved; and 6. overvaluing the effectiveness of the therapist
role, i.e., transference, over the natural history of disease or medication noncompliance.

ADVANTAGES AND DISADVANTAGES OF COMBINING THERAPIES

For biologically oriented patients, psychotherapy promotes a sense of increased

collaboration and targets interpersonal and intrapsychic problems that are usually
neglected. For those patients who are psychologically oriented medication response can
relieve the hopelessness associated with lack of improvement in psychotherapy as well as
target the primary symptoms of the illness. When patients express a preference for one
particular modality, the clinician may have to make the case for combination treatment,
i.e., psychoeducation. Treatment response is faster overall when combining treatments
than when giving each modality alone. Medication (when it improves cognition) can
improve the ability to engage in psychotherapy, although an unpublished study (Manbar
et al., personal communication, 2002) failed to find that medication increased effective
participation in CBT for depressed patients. Similarly each of the psychotherapies can
promote medication compliance. These assertions have been made for many years, but
more evidence is needed to support their validity.

The side-effects associated with medication may lead to early termination of all therapies
(if, for example, a patient feels overmedicated), while the psychotherapy may decrease
the perceived need for medication) e.g., "I can solve this on my own." And, at least in the
short run, there may be increased cost of combining therapies, although in the long run,
costs usually are less if relapse and rehospitalization are prevented.

DISCUSSION

Although this paper focuses on "practical" guidelines for combined treatments, several
further questions require answers. First, is it true that drugs are always effective
therapeutic agents? Second, is it true that psychosocial methods are always effective
therapeutic agents? Third, is it true that adding one modality (here psychotherapy) to the
other is more effective than the use of medication alone?

MEDICATION AND OUTCOME

The literature related to these questions is large, occasionally contentious, and findings
are subject to numerous methodological qualifications and limitations. Drugs are often,
but not always, efficacious although there is usually more than one choice of drug to treat
one problem, symptom or disorder. Lacking success with one, a clinician can turn to a
second in the search for a better outcome. Nevertheless, some patients are refractory to all
drug treatments, and are commonly found to relapse on maintenance doses or upon
treatment termination (52). Thus, there are obvious implications for the addition of
psychotherapy.

For example, as mentioned above, in an 18-month follow-up in the NIMH-Treatment of

Depression Collaborative Research Program (TDCRP), recovery from a Major
Depressive Episode was not good for any treatment and the relapse rates were high: 81%
for subjects treated with imipramine plus clinical management; 74% for those treated
with IPT; and 70% treated with CBT (27). The Barlow et al. 2000 study on panic disorder
(30) showed that following drug alone about 85% of patients relapsed, but only 15%
relapsed when they had psychotherapy plus drug. In a meta-analysis of eight studies on
combined treatment, in addition to high drop-out rates, many instances of unpleasant side
effects and withdrawal symptoms were recorded (53). All eight studies reported that
psychopharmacology alone was associated with a higher drop-out rate than either
combined treatment or psychotherapy alone. Nevertheless, their overall conclusions were
that routine use of combined treatment may expose the patient to unnecessary costs and
side-effects, and that psychotherapy alone should usually be the initial treatment.

For many patients these negative concomitants to medication are readily balanced by a
decrease in symptomatology, a return to full productivity and enjoyment at work, and a
reduction of tension and stress within the family. For many individuals, side-effects are
few, mild and, if present, tolerable, and relapse rate is lowered. If the medication is
discontinued in a graded and supervised manner, withdrawal is minimized.

PSYCHOSOCIAL THERAPIES AND OUTCOME

Psychosocial therapies appeal to some people who find taking drugs aversive. Somatic
side effects of these therapies are rare or unknown, symptoms may be reduced as is
relapse, and there is no withdrawal. Whereas drugs do not educate the patient or his
family about his or her illness or how to cope with it behaviorally, these therapies may
focus directly on education and coping. Many studies have shown that dropout from
psychotherapeutic treatment is usually lower than for medication, but when patients did
dropout it was most often because of dissatisfaction with the treatment (54, 59, 56, 57). It
is also more likely for patients in combined treatment to remain in therapy than for those
in medication alone. For example, de Jonghe et al. (58) found that at 24 weeks of
treatment, 40% of ambulatory patients with major depressive disorder (MDD) assigned to
pharmacotherapy alone stopped their medication, while only 22% of those receiving
combined treatment ended their therapy prematurely.

Proponents of psychosocial and pharmacotherapeutics have a long-standing argument in

the literature regarding bias of the proponents that results in positive findings. Indeed,
there is a known, high correlation between the allegiance of the research team to a
particular theoretical orientation and the outcome of their treatment study (59). Jacobson
and Hollon (57), whom we identify with a nonpharmacologic orientation, agree; Quitkin
et al. (60) (whom we identify with a pharmacologic orientation) reanalyzed a number of
pharmacotherapy and psychotherapy studies to demonstrate the reality of an allegiance
bias in research. Not included in these analyses is the allegiance to combined therapy.
The practitioner awaits the outcome of this debate, but in the meanwhile allegiance bias
might work in the clinician's favor. If the clinician can convince the patient that he
enthusiastically endorses a given treatment, then there would appear to be a higher
chance of treatment success. This is true both for psychotherapy and pharmacotherapy.
As a clinical pearl, we suggest: use allegiance bias when you can.

COMBINED-THERAPIES OUTCOME

Most clinicians believe that combining medications of known effectiveness, with

psychotherapies of known effectiveness, is necessary for the most complete therapeutic
"aftereffect." Telch and Lucas (61) point out that one's rationale for using a combined
drug-psychological treatment is linked to how one conceptualizes the disorder and the
presumed efficacy of the individual treatments being combined. These authors include
treatment specificity as a rationale for combining treatments, but they wrote before the
popularity of SSRIs that are effectively nonspecific for most anxiety and depressive
disorders. Still, specificity of drug and class of disorder remains important. The two other
rationales are mirror images: facilitation of psychological treatment by the addition of
pharmacotherapy, and facilitation of pharmacotherapy by the addition of psychotherapy.

We argue that the treatment plan for any patient evolves not only out of the clinician's
concept of the disorder, but the patient's. Many patients enter a clinical setting with clear
ideas about the nature of their illness, even if those ideas are wrong or incomplete. Before
or after entering treatment many patients learn what they can about their symptoms by
searching through the DSM-IV (62) and scanning the internet for relevant sites. The
patient may say "My family is driving me crazy," and the possibility of family therapy
arises. The patient may say "My brain has a chemical imbalance, and I need a drug to
correct the imbalance," and the clinician may prescribe a medication. The patient may say
"I worry constantly and can't seem to relate to others," and IPT might be the treatment of
first choice. Still another may say that he knows that there is a chemical imbalance in his
brain, but he fears that drugs will change his personality for the worse. Here the clinician
might try an educational program first, followed by a combination of drugs and CBT.
There is little or no empirical evidence to guide these choices, and decisions rest on the
patient-clinician concept of the illness and their belief that one modality will prove
additive or facilitative of the other.

Most of the disorders found in DSM-IV are presumed to have an underlying

pathophysiology, perhaps genetic in origin. In ways not fully understood, stress interacts
with this biological vulnerability to precipitate an episode of psychopathology (63).
Medication affects the underlying biology, thereby allowing the physician (or other
members of the therapeutic team) to effectively work with the family and teach the
patient psychosocial skills, ways of further reducing stress, early recognition of symptom
exacerbation or relapse, and adherence with treatment (64).

In our view, clinicians who can deliver family interventions, are essential to this team
effort. Family support can be decisive in treatment. When the family is not itself
dysfunctional, families can provide the most immediate support group for the patient;
they can be educated to recognize symptoms prodromal to relapse, support compliance of
medications and of psychosocial treatments, and provide reinforcement for behavior
change. Ironically, even where acute pharmacotherapy is successful, bipolar patients may
not have found all aspects of their mania distressing. They may look back on increased
productivity, creativity, and sexual intensity as positive experiences. Psychosocial
intervention may be useful in placing these positive features in context and teaching the
patient how to hold on to these features outside the manic state (65).

In contrast to 20 years ago, the value of psychotherapy in the total treatment package has
changed vastly. Psychotherapeutic treatment modalities are useful to some patients, the
patient's family, and the clinician, but questions remain. For what disorders are they
useful? What is the added value of each? When should they be added to pharmacotherapy
and when should pharmacotherapy be added to them? With what level of
symptomatology is each additional modality most useful? We have already summarized
in Table I the limited evidence for the efficacy of psychotherapy above what medication
can offer. Outcome of combining treatments for other disorders partly can be found in
recent consensus guidelines (66), (67) and in a review paper (5).

CONCLUSION

We emphasized three points: 1. biologic and psychological factors are interactive; 2.

psychotherapy added to medication may improve outcome above what medication alone
will produce; and 3. psychotherapy may insulate better than medication alone against
relapse in many disorders. What we have provided are working guidelines for the
clinician to implement the quality care equation discussed earlier (29). Gabbard (68) has
summarized well some of the issues:

The complexity of the mind-body problem may become obscured by the vicissitudes of
the marketplace in day-to-day practice, but we must never lose track of the need to
address both the person and the illness. We continue to walk a tightrope between the twin
pitfalls of biological and psychological reductionism. The balancing act requires
unswerving attention and concentration, but the satisfactions derived from practicing on
the cutting edge of the mind-brain interface more than make up for the occasional loss of
one's footing and the struggle to regain a safe and sensible position on the high wire.

The integration of therapies for Axis I and II disorders presents major practical and, of
course, economic challenges. The task for the clinician is how to integrate, sequence and
deliver these therapies in the "real world" of front-line psychiatry. We have discussed
both general and specific guidelines focusing on medication, family intervention, and
individual intervention. We provided the available data suggesting that psychotherapy
may add something over what medication can offer. We discussed the theoretical issues
and problems underlying combined integrative treatment-treatment which may be the
treatment of choice to help patients and their families improve the quality of their lives
over the decades that they are afflicted with chronic illness. Further process and outcome
research to evaluate the additive effects of evidence-based drug and psychotherapy
treatments-disorder-by-disorder-is badly needed in order to sharpen combined treatment
guidelines.

Even without the supporting data, for now, for the clinician, the message is-
psychotherapy will improve outcome compared to medication alone for many psychiatric
disorders.

Acknowledgments: Supported in part by a scholar in residence program of The

Rockefeller Foundation at the Bellagio Study & Conference Center, Bellagio, Italy, 2002.
I am indebted to Drs. Jack Maser, Jerald Kay, Glen Gabbard, Bruce Arnow, James Reich,
and Anna Lembke for reviewing earlier drafts of this manuscript.

[Footnote]
* When thinking about combined and integrated therapy, there are many possible issues
that could be discussed. This paper will focus on providing the clinician with practical
guidelines (and the supporting data where it exists and in our experience where it doesn't)
for combining medication and psychotherapeutic interventions for Axis I and II disorders.
We will use the following outline: 1. An introduction to delineate the issues and their
background; 2. A summary of results of controlled, combination therapy studies, i.e., the
data that supports combined treatment; 3. Guidelines including not only general and
specific points, but specific parts (modalities) of a treatment equation, i.e., medication,
psychotherapeutic intervention including discussion of both family intervention and
individual psychotherapy plus psychoeducation; 4. A discussion of the issues around the
guidelines and the data supporting them, and 5. A summary and conclusions.
Because much has been written in texts and journals about the theory and practice of
psychotherapy used alone, or medication used alone or even combining two or more
medications, we do not discuss how or when to use these important strategies here. Nor
do we discuss the nuances of combined therapy delivered by a psychiatrist and a
nonpsychiatrist provider, as this has been well-described (11).
Nor is this paper mostly about combining medication with some form of individual
intervention, since this almost always occurs in practice although with mostly unstudied
outcome (9). Likewise, it is not about combining medication with rehabilitative efforts-
this topic too deserves a separate paper (12). And finally, it is also not about "the differing
models" of combining the two different modalities although we do briefly mention the
Reiss et al. (13) model (see below) by way of providing at least one explanatory model
for our guidelines.

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[Author Affiliation]
IRA D. GLICK, M.D.*

[Author Affiliation]
* Professor of Psychiatry and Behavioral Sciences. Mailing address: Stanford University
School of Medicine, Department of Psychiatry and Behavioral Sciences, 401 Quarry Rd.,
#2122, Stanford, California 94305-5546, e-mail: iraglick@stanford.edu

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