Upload
rita-el-khabbaz
View
219
Download
0
Embed Size (px)
Citation preview
7/30/2019 Improving Diagnosis
1/21
R E V I E W A R T I C L E
Bipolar Disorder: Improving Diagnosis and
Optimizing Integrated Care
J. L. Culver, B. A. Arnow, and T. A. Ketter
Stanford University, Department of Psychiatry and
Behavioral Sciences
Bipolar disorder is a chronic, severe condition commonly causing substan-
tial mortality and psychosocial morbidity. Challenges in recognition candelay the institution of appropriate management, whereas misdiagnosis
may initiate pharmacologic interventions that adversely affect the conditions
course. Pharmacotherapy remains the foundation of treatment. In addition
to ef ficacy, tolerability is an important consideration in medication choice,
particularly for long-term maintenance because of its impact on adher-
ence. Mood stabilizers are the classic treatments for bipolar disorder. Newer
agents such as atypical antipsychotics may of fer ef ficacy and/or tolerabil-
ity advantages compared with other medications. The role of antidepres-
sants in bipolar disorder remains controversial. Growing evidence indicates
that adjunctive psychosocial interventions improve long-term functioning;
consequently, psychologists are becoming increasingly involved in the long-term care of patients with bipolar disorder. This review seeks to update
psychologists and related healthcare professionals on recent advances
and the current limitations in the diagnosis and treatment of bipolar disorder.
2006 Wiley Periodicals, Inc. J Clin Psychol 63: 7392, 2007.
Keywords: bipolar disorder; diagnosis; care; treatment; psychotherapy
Introduction
Bipolar disorder is a chronic, severe condition that imposes substantial mortality andpsychosocial morbidity on all aspects of a patients life (American Psychiatric Associa-
tion [APA], 2002). The debilitating effects of bipolar disorder can adversely affect employ-
ment, education, finances, and relationships to the detriment of the patient and the family
(APA, 2002; Jamison, 2000). A consequence of this high burden of morbidity is an increase
in the likelihood of attempted and completed suicide, which may be higher for patients
with bipolar disorder than with other mental illnesses.
We thank Bill Wolvey, BSc (PAREXEL MMS), who provided medical writing support on behalf of AstraZeneca.Correspondence concerning this article should be addressed to: Jenifer L. Culver, Research Associate, Clinical
Psychologist, Stanford University Bipolar Disorders Clinic, 401 Quarry Road, Stanford, CA 94305; e-mail:[email protected]
7/30/2019 Improving Diagnosis
2/21
The considerable health burden of bipolar disorder translates into substantial societal
costs. By one estimate, the cost of bipolar disorder in 1991 was $45 billion in the United
States alone (Woods, 2000). By other analyses, the lifetime cost of patients with onset of
bipolar disorder in 1998 was $24 billion (Begley et al., 2001). On a global scale, bipolar
disorder has been ranked the fifth leading cause of disability among individuals aged1544 years and the ninth leading cause of years of life lost due to death or disability
(World Health Organization, 2001).
Despite the burden imposed by bipolar disorder on individuals and on society, this
disorder continues to be poorly recognized, even among healthcare professionals (Ghaemi,
Boiman, & Goodwin, 2000; Hirschfeld, Lewis, & Vornik, 2003; Lish, Dime-Meenan,
Whybrow, Price, & Hirschfeld, 1994). Inadequacies in the identification and manage-
ment of bipolar disorder, although documented over a decade ago (Lish et al., 1994),
remain important problems (Hirschfeld, Lewis et al., 2003). The underdiagnosis or mis-
diagnosis of bipolar disorder, and consequent inappropriate management, represent sig-
nificant clinical problems that can have devastating effects on patients (Dunner, 2003;Grunze et al., 2002; Hirschfeld, Lewis et al., 2003). For example, prepubertal children
misdiagnosed with attention-deficit/hyperactivity disorder (ADHD) may receive stimu-
lants, and adults misdiagnosed with (unipolar) major depressive disorder may receive
antidepressants, both of which can exacerbate the course of bipolar disorder.
In this article, we examine how the diagnosis and management of bipolar disorder
may be enhanced to reduce the considerable burden of this disease on patients and their
caregivers. Particular attention is devoted to providing current evidence-based informa-
tion to aid psychologists and other practitioners of psychosocial interventions
psychotherapists, psychiatrists, and social workerswho are increasingly called upon to
provide services that may substantially benefit the long-term outcome of patients with
this severe, lifelong condition.
Bipolar Disorder
Features
Bipolar disorder usually follows a recurrent and chronic course, with episodes of mania
or hypomania and depression interspersed with periods of less-severe mood disturbance
as well as times with normal mood (euthymia). The periodicity and the severity of the
mood episodes are, however, highly individualized (APA, 2002).
A manic episode is defined in the Diagnostic and Statistical Manual of Mental
Disorders, 4 th Edition, Text Revision (DSM-IV-TR; APA, 2000) as a period of abnormally
and persistently elevated, expansive, or irritable mood, lasting at least one week (or
briefer if the patient is hospitalized). Associated symptoms include inflated self-esteem,
decreased need for sleep, overtalkativeness, distractibility, racing thoughts, and impul-
sivity manifested by excessive involvement in pleasurable activities with a high potential
for painful consequences (e.g., sexual indiscretions, unrestrained shopping sprees).Although
mania often begins with pleasurable feelings of bright mood, heightened energy, and
increased goal-directed activity, progression to problematic euphoria, severe irritability,
and even psychosis can rapidly follow. By definition, mania is severe, and entails psy-
chosis, hospitalization, or serious impairment of social or occupational function. Hypo-mania is a less severe form of mood elevation that does not involve marked impairment
74 Journal of Clinical Psychology, January 2007
7/30/2019 Improving Diagnosis
3/21
A major depressive episode is characterized by at least 2 weeks of pervasively
depressed mood or loss of interest or pleasure, accompanied by symptoms such as weight
loss or gain, appetite disturbance, insomnia or hypersomnia, psychomotor agitation
or retardation, fatigue, inability to concentrate, indecisiveness, and recurrent thoughts
of death or suicidal ideation. In severe cases, patients may experience hallucinations ordelusions.
About 40% of patients with bipolar disorder experience mixed episodes, where symp-
toms of both mania and depression occur at the same time (Evans, 2000).
Bipolar disorder may have its onset with a manic, hypomanic, mixed, or depressive
episode. It appears that men are more likely than women to present initially with a manic
episode ( Kahn, Ross, Printz, & Sachs, 2000; Lish et al., 1994), and women and younger
patients are more likely to present initially with a depressive episode (Bowden, 2001).
Patients commonly experience several depressive episodes before their first manic epi-
sode (APA, 2002). Indeed, depressive symptoms appear more pervasive than mood ele-
vation symptoms in patients with bipolar disorder. Prospective longitudinal studies inbipolar I disorder show that depressive symptoms are present for over 30% of the time,
whereas manic symptoms are present for about 10% of the time (Judd et al., 2002; Post
et al., 2003). The predominance of depressive symptoms is even greater in bipolar II
disorder (Judd et al., 2003). Depression also appears to predominate in patients evalua-
tions of the impact of bipolar disorder on their quality of life (Vojta, Kinosian, Glick,
Altshuler, & Bauer, 2001).
On average, patients experience four episodes during the first 10 years of the dis-
order (Kahn et al., 2000), so that several years may elapse between the first few affective
episodes. However, in the absence of treatment, the cycle length typically shortens (Kahn
et al., 2000; Kleinman et al., 2003; Namjoshi & Buesching, 2001). With time, episodes
tend to become spontaneous rather than reactive, more frequent, more severe, and ulti-
mately resistant to treatment. Rapid cycling, defined as the occurrence of at least four
affective episodes in a year, affects approximately 10% to 20% of patients with bipolar
disorder at some stage during their lifetime (Coryell et al., 2003). Rapid cycling is more
common in women than men, more common in bipolar II disorder, and more frequently
associated with reduced responsiveness to medication (Kupka, Luckenbaugh, Post,
Leverich, & Nolen, 2003).
Definitions and Prevalence
The DSM-IV-TR (APA, 2000) categorizes primary bipolar disorder into four main types:
bipolar I, bipolar II, cyclothymia, and bipolar disorder not otherwise specified (NOS). In
addition, patients may experience symptoms of bipolar disorder secondary to medical
disorders or use of prescription medications (including antidepressants and stimulants),
illicit drugs, or alcohol.
A diagnosis of bipolar I disorder requires a history of at least one manic or mixed
episode, though the vast majority of patients with bipolar I disorder experience depres-
sion more pervasively. Perhaps half of such patients will have experienced one or more
depressive episodes before the first manic episode, increasing the risk of misdiagnosis
with (unipolar) major depressive disorder. Patients with bipolar II disorder have a historyof recurrent major depressive episodes and hypomanic episodes. Cyclothymic disorder is
Improving Diagnosis and Care in Bipolar Disorder 75
7/30/2019 Improving Diagnosis
4/21
bipolar disorder NOS is assigned to patients with evidence of mood disruptions (e.g.,
hypomanias but not syndromal major depressive episodes) who fail to meet the criteria
for the above-mentioned specific bipolar disorders.
A dimensional construct, as opposed to the above categorical approach, has been
suggested as an alternative to the DSM-IV-TR classification system (Akiskal, 1996; Akiskal& Pinto, 1999; Dunner, 2003). This classification, referred to as bipolar spectrum dis-
order, allows inclusion of patients with softer symptoms and would encompass those
with antidepressant-induced hypomanic symptoms (Akiskal et al., 2000). The broader
concept of bipolar spectrum disorder may more meaningfully capture the diversity of
presentations of bipolar symptoms in the clinical setting (Akiskal, 1996). Adopting this
classification may also result in more patients receiving appropriate treatment for bipolar
disorder (Hirschfeld, Calabrese et al., 2003).
Estimates of the lifetime prevalence of bipolar disorder reflect the method of classi-
fication and diagnostic approach adopted. Large studies suggest a prevalence ranging
from 1.3% to 3.7% of the general population (Hirschfeld, Calabrese et al., 2003; Regeeret al., 2004; Regier et al., 1984, 1990). Including the more widely defined bipolar spec-
trum disorder, the prevalence may be as high as 7% (Akiskal et al., 2000; Dunner, 2003;
Kessler et al., 2005; Kleinman et al., 2003). A recent screening study identified bipolar
disorder in 9.8% of patients seeking primary medical care (Das et al., 2005).
Diagnosing Bipolar Disorder
Unfortunately, delayed diagnosis is common in patients with bipolar disorder. Often sev-
eral years elapse between the onset of symptoms and accurate diagnosis (Lish et al.,
1994; Suppes et al., 2001). Failure to seek help, in part because of the perceived stigma
of having a mental illness, contributes to this phenomenon. An estimated 35% of the
patients who have bipolar disorder fail to seek treatment after the initial episode for up to
10 years (Evans, 2000). The inability of medical and mental health providers to recognize
and correctly diagnose bipolar disorder adds further to the delay in instituting appropriate
care. An individual with bipolar disorder may see three or four physicians over the course
of a decade before the correct diagnosis is established (Hirschfeld, Lewis et al., 2003;
Kahn et al., 2000; Lish et al., 1994). An incorrect diagnosis is made in a third of patients
with bipolar disorder who present during their first episode, and almost half of all patients
hospitalized with an initial major depressive episode (particularly if this occurs in a child,
adolescent, or young adult) may, in fact, ultimately prove to have bipolar disorder ( Evans,
2000; Goldberg, Harrow, & Whiteside, 2001).
Establishing the correct diagnosis is complicated by the similarity and overlap of
symptoms between bipolar disorder and other psychiatric disorders, including ADHD
and unipolar depression in children, and unipolar depression and substance abuse in
adolescents (APA, 2000; Bowden, 2001; Dunner, 2003; Hirschfeld, Lewis et al., 2003).
Because patients often present initially with depressive symptoms, a misdiagnosis of
unipolar depression is common, although this misdiagnosis can also occur in patients
presenting with a mixed episode, which may be misdiagnosed as agitated depression
(Bowden, 2001; Ghaemi et al., 2000). Compared with unipolar depression, bipolar depres-
sion is associated with more mood lability and psychomotor retardation (Caligiuri &Ellwanger, 2000; Mitchell et al., 2001), as well as appetite increase (or lack of appetite
76 Journal of Clinical Psychology, January 2007
7/30/2019 Improving Diagnosis
5/21
depression, more recurrences, more atypical (hyperphagic, hypersomnic, anergic) and
mixed features, a higher frequency of suicidal thoughts and hypersomnia during the index
episode, and a more frequent family history of bipolar II disorder and major depression
(Benazzi, 2000, 2003; Hantouche et al., 1998).
Recognition of hypomania presents another diagnostic challenge. Patients presentwith hypomania less frequently, in part because hypomanic characteristics may be per-
ceived as normal by patients, family members, or physicians (Bowden, 2001; Dunner,
2003; Hirschfeld, 2001). One study has suggested that increased goal-directed activity
may be a frequent hypomanic symptom, which, in a semi-structured interview, can assist
diagnosis (Benazzi, 2003). Systematic screening for hypomania in patients with DSM-
IV-TR-defined major depressive episodes has increased the rate of diagnosis of bipolar II
disorder from 22% to 40% (Hantouche et al., 1998). Also, as many patients may fail to
recognize hypomanic episodes, collateral history from significant others can substan-
tially increase diagnostic sensitivity (Gershon & Guroff, 1984). An additional diagnostic
complication is that the DSM-IV-TR definition of hypomaniathat is, a distinct changein behavior lasting at least 4 daysexcludes many patients with briefer episodes of mood
elevation who might fulfill a more inclusive definition (Bowden, 2001; Dunner, 2003).
Furthermore, patients with severe episodes of mania or depression in bipolar disorder
accompanied by prominent psychotic symptoms may be incorrectly diagnosed as having
schizophrenia (APA, 2000; Bowden, 2001; Dunner, 2003; Hirschfeld, Lewis et al., 2003).
Making a correct diagnosis of bipolar disorder is hindered further by the high prevalence
of comorbid psychiatric conditions. Indeed, comorbidity is so common that it is consid-
ered the rule rather than the exception in bipolar disorder (Sachs, 2003). Substance abuse,
alcoholism, and anxiety disorders are particularly frequent comorbidities (Brady & Sonne,
1995; Evans, 2000) and may be patients chief complaints, distracting clinicians from
obtaining a history of prior or concurrent symptoms of bipolar disorder.
Consequences of Misdiagnosis
A delayed or incorrect diagnosis can have significant consequences for the patient with
bipolar disorder. Among these, the most serious is the increased risk of suicide. Up to
50% of patients with bipolar disorder attempt suicide at least once and up to 20% die by
suicide, with the risk highest in the early phases of the illness (Jamison, 2000; Kahn et al.,
2000; Woods, 2000). Maintenance therapy with lithium appears associated with a seven-
fold reduction in suicide rates in patients with bipolar disorder (Tondo & Baldessarini,
2000). Delayed or incorrect diagnosis denies patients the benefits of therapy in reducing
suicide risk (Baldessarini, Tondo, & Hennen, 2003).
Delay in diagnosis and implementation of appropriate treatment additionally leaves
patients at risk for poor symptom control, functional impairment, as well as relationship
and employment problems, increasing the personal and societal burden of illness ( Dun-
ner, 2003; Kahn et al., 2000). In addition, delays may impair the response to subsequent
appropriate treatment, worsening the prognosis (Kahn et al., 2000; Post & Weiss, 2004).
Finally, an incorrect diagnosis may lead to interventions that exacerbate the illness
course. For example, treatment with an antidepressant alone (without concomitant mood
stabilizer or antimanic agent) based on a diagnosis of unipolar depression may induce a
switch in mood to manic or mixed episode, or trigger rapid cycling (Altshuler et al., 1995;Dunner, 2003; Ghaemi et al., 2000; Sachs, Koslow, & Ghaemi, 2000). There is also
Improving Diagnosis and Care in Bipolar Disorder 77
7/30/2019 Improving Diagnosis
6/21
Improving the Diagnosis
Several measures may be adopted to improve the recognition and diagnosis of bipolar
disorder. Given that a majority of patients with bipolar disorder who seek treatment do so
when depressed rather than when manic or hypomanic (APA, 2002; Hirschfeld, 2001), it
is recommended that the possibility of a bipolar diagnosis be excluded in all patients who
present with depressive symptoms, even if mild. This is of particular importance in the
diagnosis of bipolar II disorder, where depression is commonly the presenting symptom
and hypomania may be rarely described by the patient.
The patients personal history should be assessed for evidence of behaviors that
indicate a history of manic, hypomanic, or mixed episodes, and the family history should
be reviewed to determine the presence of mood (particularly bipolar) disorder in rela-
tives. Clinicians should also probe carefully about mood dysfunction and lability (APA,
2002; Bowden, 2001; Hirschfeld, Calabrese et al., 2003). When possible, inclusion of the
patients family and close support group in the evaluation is likely to be helpful, as
patients themselves often fail to report such information, whether by choice, through a
lack of understanding of its significance, or because this behavior is perceived as normal.
Discussion with a close family member may also reveal aspects of the patients behavior
that are less likely to be displayed in an office or hospital environment, such as impul-
sivity (Bowden, 2001). A diagnosis of bipolar disorder should be considered routinely in
patients referred for psychological assessment of substance abuse or anxiety disorders, or
following attempted suicide or criminal offenses.
Increased awareness of symptoms or behaviors indicative of bipolar disorder in a
patient previously diagnosed with another mental illness, such as unipolar depression or
schizophrenia, could also reduce the number of patients who continue to receive inap-
propriate treatment (Bowden, 2001). Clinicians should explore the possibility that comor-bid conditions, such as eating disorders, substance abuse, or anxiety disorderscommon
in patients with bipolar disordermay be obscuring the diagnosis.
A four-item screening checklist, devised by Hirschfeld (personal communication),
may help health professionals establish whether a risk of bipolar disorder exists. Patients
with presumptive unipolar depression, anxiety disorder, substance use disorder, schizo-
phrenia, or ADHD may be briefly assessed with this checklist to exclude bipolar disorder.
The checklist comprises the following questions:
1. Has there ever been a period of time when you were not your usual self and . . .
you felt so good or so hyper that other people thought you were not your normal
self or you were so hyper that you got into trouble?
you got much less sleep than usual and found that you didnt really miss it?
thoughts raced through your head or you couldnt slow your mind down?
you had much more energy than usual?
2. How much of a problem did any of these cause youlike being unable to work;
having family, money, or legal troubles; getting into arguments or fights? (no
problem; minor problem; moderate problem; serious problem)
Answering yes to two or more items in question 1 and moderate or serious to ques-tion 2 warrants further screening with a tool such as the Mood Disorders Questionnaire
78 Journal of Clinical Psychology, January 2007
7/30/2019 Improving Diagnosis
7/21
MDQ assessment successfully excluded 9 out of 10 patients without bipolar disorder
(Hirschfeld et al., 2000).
The utilization of tools such as these by clinical psychologists and related health
professionals would help exclude a diagnosis of bipolar disorder in all patients who
present with depression.
Approaches to Management
Objectives in the management of bipolar disorder include effective treatment of acute
episodes of mania and depression, ongoing prevention of relapses, and attainment of
healthy functioning through symptom control (Figure 1). During episodes of bipolar
depression, in particular, reducing the risk of suicide is a key objective.
Once the acute symptoms of mania or depression have been resolved, long-term
management is required to prevent recurrence, which remains a lifelong risk in patients
with bipolar disorder (APA, 2002). As most pharmacotherapies have limited utility in theacute treatment or prevention of depression in bipolar disorder, psychotherapies can be
important adjuncts. Increasing evidence supports a combination of pharmacotherapy and
psychotherapy for achieving optimal long-term outcome (Vieta et al., 2005). Choosing
the most appropriate management plan for an individual patient, potentially with phar-
macotherapeutic and psychotherapeutic components, remains a major clinical challenge.
When choosing the appropriate pharmacotherapy, consideration should be given to
its efficacy and tolerability profile, such that it fulfills patient expectations and encour-
ages adherence to treatment. Rates of medication nonadherence in bipolar disorder are
high. One study of patients with affective disorders (80% with bipolar disorder) observed
that approximately one third took less than 30% of their medication as prescribed (Scott& Pope, 2002). Nonadherence is related, at least in part, to medication-adverse effectsto
which patients with bipolar disorder appear to show an increased susceptibility (Berk &
Berk, 2003; Chue & Kovacs, 2003; Sachs, 2003). Therefore, good tolerability and safety
of treatment in the long term are key considerations during the maintenance phase.
Other reasons for nonadherence in patients with bipolar disorder include a lack of
understanding of the illness and negative beliefs about medication (Morselli et al., 2003;
Peralta & Cuesta, 1998). The utilization of psychosocial intervention, by addressing these
Fi 1 Th ti bj ti i th t f bi l di d Th t ti f bi l di d
Improving Diagnosis and Care in Bipolar Disorder 79
7/30/2019 Improving Diagnosis
8/21
issues, has been shown to enhance long-term medication adherence and outcome in patients
with bipolar disorder (Colom et al., 2003) and is an example of how successful long-term
management may benefit from an integrated approach, combining pharmacologic treat-
ment and psychosocial intervention.
Pharmacologic Treatment
Pharmacotherapy remains the foundation for the acute and long-term management of
manic, mixed, and depressive episodes of bipolar disorder. Figure 2 illustrates an approach
representative of standards of care for the pharmacologic treatment of manic or mixed
episodes, based on guidelines from the APA (2002). The APA recommendations for the
pharmacotherapy of bipolar depression are outlined in Figure 3. However, not all guide-
lines support the APAs approach to bipolar depression; for example, the World Federa-
tion of Societies of Biological Psychiatry differs in recommending a combination of
antidepressant and conventional mood stabilizer as a first-line approach for all depressedpatients, not only those with severe depression (Grunze et al., 2002). Advances in the
pharmacotherapy of bipolar disorders are sufficiently rapid such that guidelines pub-
lished only 4 years ago are already in need of additional revision (Ketter, 2005).
Medications used in acute treatment may be expected to show efficacy within days to
a few weeks. Once acute mood stabilization is achieved, the major focus of long-term
maintenance treatment is to prevent relapse, reduce new-onset comorbidities, lower sui-
cide risk, limit adverse effects, and optimize function. Patients who remain well on long-
term treatment should be encouraged to continue their regimen to prevent relapse, which
is frequent if therapy ceasesa 50% relapse rate has been reported within 5 months of
abruptly stopping lithium (Suppes et al., 1995). If patients cease treatment, they are alsoat elevated risk of suicide (Tondo et al., 2000). Often combination therapies are needed,
with about three quarters of patients taking more than one medication (Kupfer et al.,
2002).
Even with administration of medications according to guidelines, outcomes remain
inadequate for a large proportion of patients with bipolar disorder. Approximately two
80 Journal of Clinical Psychology, January 2007
7/30/2019 Improving Diagnosis
9/21
thirds of patients with bipolar disorder report persistence of substantial depressive or
manic symptoms over one year of follow up, and only about 10% are illness-free (Post
et al., 2003). Up to 60% of patients fail to regain full occupational and social functioning
(MacQueen, Young, & Joffe, 2001). In view of these limitations of pharmacotherapies,
adjunctive psychotherapies are commonly necessary.
Mood stabilizers. The mood stabilizers (lithium, valproate, carbamazepine, and lam-
otrigine) are crucial agents in the management of bipolar disorder (Ketter, 2005). Lith-
ium, valproate, and carbamazepine are indicated for the treatment of acute mania; lithium
and lamotrigine are indicated for maintenance treatment. Lithium, valproate, and carba-
mazepine appear to stabilize mood from above, in that they are more effective for the
mood-elevation aspects of the disorder (Ketter & Calabrese, 2002). In contrast, lamot-
rigine appears to stabilize mood from below, being more effective for the depressive
aspects of bipolar disorder. Unfortunately, efficacy or tolerability with these agents is
commonly inadequate, necessitating frequent usage of other medication options (described
below) as well as combination therapies.
Atypical antipsychotics. Atypical antipsychotics have emerged as important treat-
ment options for patients with bipolar disorder (Ketter, 2005). The current APA (2000)
guideline supports the use of antipsychotic agents as monotherapy for less severe manic
and mixed episodes, in combination with either lithium or valproate for severe manic and
mixed episodes, and as maintenance therapy in patients with persistent psychosis. Atyp-
ical antipsychotics are preferred over typical antipsychotics by the APA because of their
more benign side-effect profile. In addition, a role for atypical antipsychotics in psy-
chotic bipolar depression is advocated (APA, 2002; Dunner, 2005). Ongoing research
into the efficacy of the atypical antipsychotics continues to extend their potential appli-
cations in bipolar disorder.Atypical antipsychotics have shown efficacy in short-term trials in bipolar mania,
Figure 3. Recommendations for pharmacologic treatment of depressed episodes in patients with bipolar dis-
order (APA, 2002). Guidelines issued by the World Federation of Societies of Biological Psychiatry (Grunzeet al., 2002) recommend a combination of an antidepressant and a mood stabilizer as a first-line approach for alldepressed patients, not only for those with severe depression.
Improving Diagnosis and Care in Bipolar Disorder 81
7/30/2019 Improving Diagnosis
10/21
et al., 2003; McIntyre, Brecher, Paulsson, Huizar, & Mullen, 2005; Sachs, Grossman,
Ghaemi, Okamoto, & Bowden, 2002; Tohen et al., 2002; Tohen et al., 2000; Tohen et al.,
1999; Yatham, Paulsson, Mullen, & Vagero, 2004; Yatham et al., 2003). Trials of olan-
zapine (particularly when combined with fluoxetine) and quetiapine have also demon-
strated significant improvements in patients with bipolar depression (Calabrese et al.,2005; Tohen et al., 2003).
Olanzapine and quetiapine additionally demonstrate efficacy as monotherapy or add-on
therapy in the difficult-to-treat rapid-cycling group (Gonzalez-Pinto et al., 2004; Sanger
et al., 2003; Vieta et al., 2002). A study of maintenance therapy over 47 weeks showed
superiority of olanzapine over divalproex for reduction in manic symptoms (Tohen et al.,
2003). Olanzapine and aripiprazole have been approved for maintenance treatment in
bipolar disorder (Keck et al., 2006; Tohen et al., 2006).
The literature suggests that the atypical antipsychotics share approximately equiva-
lent efficacy in bipolar disorder but possess different and distinctive side-effect profiles
(Keck, Marcus et al., 2003; Keck, Versiani et al., 2003; Ketter, 2005; Sachs et al., 2002;Tohen et al., 2000). Olanzapine and clozapine are associated with the greatest risk of
weight gain, diabetes, and dyslipidemia (American Diabetes Association, American Psy-
chiatric Association, American Association of Clinical Endocrinologists, & North Amer-
ican Association for the Study of Obesity, 2004). Risperidone is associated with prolactin
elevation and extrapyramidal symptoms, and ziprasidone and aripiprazole with akathisia
(Bowles & Levin, 2003; Kleinberg, Davis, de Coster, Van Baelen, & Brecher, 1999;
Mandoki, 1995; Sachs et al., 2002; Sharif, 2003). Quetiapine has been associated with
sedationalso an effect of other atypical antipsychoticsand dry mouth (Sachs et al.,
2004). Clinical impressions suggest a rank order for risk of sedation (highest first) of
clozapine, olanzapine, quetiapine, and risperidone (Zarate, 2000). Zarate also suggested
that anticholinergic side effects, such as constipation, urinary retention, bowel obstruc-
tion, and dry mouth, are less likely to be a problem with quetiapine and risperidone
compared with aripiprazole and clozapine (Zarate, 2000). Because, as mentioned above,
good tolerability is likely to be associated with greater adherence to treatment, consider-
ation of likely side effects forms an important element in the choice of atypical
antipsychotics.
Antidepressants. Although antidepressants are foundational agents for the manage-
ment of unipolar depression, their role in the management of bipolar disorder remains
controversial, because these agents are implicated in causing switches into mania, hypo-mania, or cycle acceleration (APA, 2002). Thus, the use of antidepressants in the absence
of antimanic agents in patients with bipolar disorder is avoided. Recently, the labeling of
all antidepressants has been amended to warn of the risk of mood worsening (suicidal
ideation) with these agents. Thus, in patients with bipolar disorder, efforts are commonly
made to limit exposure to antidepressants, either by attempting to discontinue them rel-
atively soon (compared to unipolar depression) after control of acute depressive symp-
toms, or by using other agents such as mood stabilizers and atypical antipsychotics to
address the depressive symptoms. However, a minority (perhaps 15%) of patients with
bipolar disorder who respond to and tolerate adding antidepressants to antimanic agents
may do better with longer-term administration (Altshuler et al., 2003).
82 Journal of Clinical Psychology, January 2007
7/30/2019 Improving Diagnosis
11/21
of four different psychotropic drugs. Approximately one in four of the patients was ill for
more than three quarters of the time.
There is growing evidence that the benefits of pharmacotherapy can be enhanced if
combined with psychosocial interventions, particularly when psychosocial interventions
are continued regularly during the course of long-term management (Vieta et al., 2005).Controlled trials indicate that integrated administration of pharmacological and psycho-
educational interventions can help improve long-term outcomes in bipolar disorders. The
psychoeducational component of such interventions may offer particular benefits because
many medications commonly used to treat mania and depression are associated with
dose-related side effects. Educating patients and their families about what to expect from
treatment, the possible adverse effects, and what action to take, if any, should these
effects develop, may help patients obtain maximal benefit from therapy (Newman, Leahy,
Beck, Reilly-Harrington, & Gyulai, 2002).
The impact of life events and stressors on the onset and relapse of bipolar disorder
(Johnson & Miller, 1997; Johnson & Roberts, 1995; Malkoff-Schwartz et al., 2000) sug-gests a potential role for psychosocial intervention in its management (Jones, 2004; Kahn
et al., 2000). The research base supporting the benefits of psychosocial interventions in
bipolar disorder is not as comprehensive as in unipolar depression (Pampallona, Bollini,
Tibaldi, Kupelnick, & Munizza, 2004; Thase et al., 1997) or schizophrenia (Pilling et al.,
2002); however, there are emerging data from large, randomized, controlled trials (APA,
2002; Gonzalez-Pinto et al., 2004; Grunze et al., 2002; Jones, 2004; Otto, Reilly-
Harrington, & Sachs, 2003). Psychosocial interventions are common (Lembke et al.,
2004) and are clearly important components of integrated care for patients with bipolar
disorder. They are particularly likely to be of benefit in the maintenance phase of treat-
ment (compared to during acute mania) when they may impact on subsyndromal symp-
toms and help to prevent relapse (Jones, 2004).
The primary goals of psychosocial interventions in patients with bipolar disorder are
symptom reduction, prevention of episodes, and optimization of function. Psychosocial
treatments approach these goals via several routes, each emphasized to varying levels by
the different evidence-based treatments. These include psychoeducation about bipolar
disorder and its treatment, enhancing adherence to medications, improving social and
occupational functioning, increasing recognition of prodromal symptoms to facilitate
early intervention, and addressing behavioral and environmental factors (e.g., irregular
sleep/wake cycles, psychosocial stressors, expressed emotion) that may lead to relapse.
Effective management of bipolar disorder requires self-management, and psychosocial
interventions can provide patients with the necessary skills, knowledge, and tools to
better achieve this.
Psychoeducational approaches. Psychoeducational approaches are aimed at provid-
ing patients with information about bipolar disorder and its treatment. Goals of psycho-
education include increasing patients understanding and acceptance of their disorder to
decrease stigma and enhance treatment compliance. Some psychoeducational interven-
tions emphasize prodromal symptom recognition and the development of coping skills to
prevent relapse. The patient plays a key role in psychoeducational interventions and is
encouraged to be actively engaged.
Results from controlled trials have demonstrated that the addition of psychoeduca-tion to medical management can delay relapse and reduce the number of relapses among
Improving Diagnosis and Care in Bipolar Disorder 83
7/30/2019 Improving Diagnosis
12/21
colleagues (2003), for example, provided evidence that adjunctive group psychoeduca-
tion reduced the number of relapsed patients and the number of recurrences per patient,
and increased time to depressive, manic, hypomanic, and mixed recurrences in compar-
ison with a control group given supportive group therapy ( Figure 4).
Cognitivebehavioral therapy. Cognitivebehavioral therapy (CBT) has a history of
demonstrated efficacy in the treatment of unipolar depression, and results from recent
studies indicate that it may also be an efficacious treatment for bipolar disorder. Cognitive
behavioral therapy for bipolar disorder focuses on changing dysfunctional cognitions and
maladaptive behaviors that contribute to mood dysregulation and increase vulnerability
to mood episodes. Cognitivebehavioral therapy, as adapted for bipolar disorder, consists
of the traditional components of this therapy as employed for patients with unipolar
depression, with the addition of psychoeducation about bipolar disorder and adaptation
of cognitive behavioral skills to increase awareness of mood, improve ability to recog-
nize prodromes, and teach intervention to prevent escalation into a syndromal moodepisode.
Early controlled studies comparing adjunctive CBT with medication alone indicated
that adjunctive CBT yielded fewer relapses, hospitalizations, and subsyndromal mood
fluctuations (Lam & Gale, 2000; Scott, Garland, & Moorhead, 2001). In addition, treat-
ment with CBT resulted in improved adherence to medication regimens and psychosocial
functioning (Lam & Gale, 2000; Scott et al., 2001). Recently, Lam and colleagues (2003)
found that adjunctive cognitive therapy (CT) resulted in fewer relapses and fewer epi-
sodes of depression and mania, even after controlling for previous episodes. Further-
more, patients receiving adjunctive CT had less than half the number of hospitalizations
(15% vs. 33%) and spent only approximately one third of the time hospitalized for bipolar
Figure 4. Efficacy of group psychoeducation as an adjunct to pharmacotherapy in prevention of recurrence of
mania, depression, or mixed episodes. Patients in receipt of standard pharmacologic therapy were randomlyassigned to receive either 21 weekly unstructured group meetings (control) or 21 weekly group psychoeduca-tion sessions. Curves show patients remaining free of relapse during the 21 weeks of treatment and follow-up
i d l k 9 3 03 F A R d i d T i l th Effi f G P h d ti i th
84 Journal of Clinical Psychology, January 2007
7/30/2019 Improving Diagnosis
13/21
episodes compared with those receiving medication alone. In addition, patients receiving
adjunctive CT over 12 months showed better coping with emergent manic symptoms,
increased self-reported medication compliance, and better social functioning compared
with those who received medication alone.
Family-focused therapy. Family treatments have received attention based on research
indicating that high levels of expressed emotion (characterized by family overinvolve-
ment and criticism) among family members are associated with increased risk of relapse
and poor outcomes in bipolar disorder patients (Miklowitz, Goldstein, Nuechterlein, Sny-
der, & Doane, 1986). The family-focused therapy (FFT) approach of Miklowitz and
colleagues (Goldstein & Miklowitz, 1994) includes an assessment of the family and
focuses on psychoeducation, communication skills training, and problem solving. Ran-
domized controlled trials have supported the use of FFT in bipolar disorder. A recent
study found that patients receiving adjunctive FFT were less likely to relapse and sur-
vived an average of 20 weeks longer before relapsing compared with treatment by twosessions of crisis management (Miklowitz et al., 2003). A similar study by Rea and
colleagues (Rea et al., 2003) found no benefit of FFT in reducing the risk of relapse;
however, patients receiving FFT had fewer relapses than those receiving individually
focused treatment. Other benefits of FFT included greater reductions in affective symp-
tom scores (Miklowitz et al., 2003), better medication adherence (Miklowitz et al., 2003),
and lower risk of rehospitalization over a 2-year period (Rea et al., 2003). The results of
these studies provide evidence that FFT may be a useful adjunct to pharmacotherapy for
decreasing the risk of relapse and hospitalization frequently associated with bipolar disorder.
Interpersonal and social rhythm therapy. Interpersonal and social rhythm therapy(IPSRT) for bipolar disorder was adapted from interpersonal therapy by Frank and col-
leagues (1997) at the University of Pittsburgh. IPSRT integrates psychoeducation, social
rhythm therapy, and interpersonal psychotherapy components in a treatment specifically
designed for the management of patients with bipolar disorder. IPSRT combines the basic
principles of interpersonal psychotherapy with behavioral techniques to address the link
between mood and life events affecting social rhythms. Goals of IPSRT include helping
patients stabilize their daily routines, reduce interpersonal problems, and adhere to med-
ication regimens ( Frank, Swartz, & Kupfer, 2000).
Early studies have not found evidence that IPSRT is superior to control treatments in
improving symptomatology or risk for relapse, although IPSRT has been found to resultin greater stability of patients social rhythms compared with a control treatment (Frank
et al., 1997; Frank et al., 2005). In addition, evidence suggests that changing therapy
modality (e.g., from IPSRT to a control therapy or vice versa) resulted in poorer out-
comes compared with not changing therapy modality. These findings support the notion
that instability (in this case of treatment regimens) can contribute to increased vulnera-
bility to relapse in patients with bipolar disorder.
A program of pharmacotherapy (primarily with lithium) and adjunctive psychother-
apy comprised of IPSRT or intensive clinical management over 2 years significantly
reduced suicide attempts among patients with bipolar I disorder (Rucci et al., 2002).
Psychotherapy may therefore extend the protection against suicide offered by lithium orother appropriate therapy.
It is becoming increasingly clear that evidence based adjunctive psychotherapy is an
Improving Diagnosis and Care in Bipolar Disorder 85
7/30/2019 Improving Diagnosis
14/21
disorder treatment practice guidelines (APA, 2002). The evidence reviewed here con-
firms that adjunctive psychosocial treatment is important in this population. Selection of
the optimal psychosocial treatment is limited by the lack of head-to-head comparisons
among these interventions. It is likely that treatment choice will be influenced by patient
choice and the availability of therapists trained in the delivery of specific interventions.In the absence of available therapists trained in the more structured psychotherapies
(CBT, FFT, and IPSRT), psychoeducation will play an important role in the effective
treatment of patients with bipolar disorder. It targets aspects central to many of the treat-
ments discussed here (enhancing illness awareness, improving medication adherence,
teaching prodromal symptom detection and relapse prevention, regulating sleep/wake
cycles, and strengthening the patients support system).
Conclusions
Current delays between onset of symptoms and correct diagnosis leave patients with
bipolar disorder with an impaired quality of life and at increased risk of self-harm. Inap-
propriate treatment because of misdiagnosis may exacerbate the disorder and make it
increasingly resistant to treatment in the longer term. An increased recognition of bipolar
disorder among psychiatrists, psychologists, and other healthcare professionals com-
bined with an awareness of new management approaches may reduce the burden of the
condition on patients, their families, and society.
In pharmacologic management, in addition to mood stabilizers, treatment options
include atypical antipsychotics, which increasingly appear to offer benefits not only dur-
ing acute mania but also during acute bipolar depression and in maintenance therapy.
Psychiatrists, psychologists, and other practitioners of psychosocial interventions can
benefit by reviewing recent research demonstrating the importance of evidence-basedadjunctive psychotherapy in the effective integrated management of bipolar disorder.
References
Akiskal, H. S. (1996). The prevalent clinical spectrum of bipolar disorders: Beyond DSM-IV.
Journal of Clinical Psychopharmacology, 16(2, Suppl. 1), 4S14S.
Akiskal, H. S., Bourgeois, M. L.,Angst, J., Post, R., Moller, H., & Hirschfeld, R. (2000). Re-evaluating
the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar
disorders. Journal of Affective Disorders, 59(Suppl. 1), S5S30.
Akiskal, H. S., & Pinto, O. (1999). The evolving bipolar spectrum. Prototypes I, II, III, and IV.Psychiatric Clinics of North America, 22, 517534.
Altshuler, L., Suppes, T., Black, D., Nolen, W. A., Keck, P. E., Jr., Frye, M. A., et al. (2003). Impact
of antidepressant discontinuation after acute bipolar depression remission on rates of depres-
sive relapse at 1-year follow-up. American Journal of Psychiatry, 160, 12521262.
Altshuler, L. L., Post, R. M., Leverich, G. S., Mikalauskas, K., Rosoff, A., & Ackerman, L. (1995).
Antidepressant-induced mania and cycle acceleration: A controversy revisited. American Jour-
nal of Psychiatry, 152, 11301138.
American Diabetes Association, American Psychiatric Association, American Association of Clin-
ical Endocrinologists, & North American Association for the Study of Obesity. (2004). Con-
sensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes
Care, 27, 596601.
American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders
86 Journal of Clinical Psychology, January 2007
7/30/2019 Improving Diagnosis
15/21
Baldessarini, R. J., Tondo, L., & Hennen, J. (2003). Lithium treatment and suicide risk in major
affective disorders: Update and new findings. Journal of Clinical Psychiatry, 64(Suppl. 5),
4452.
Begley, C. E., Annegers, J. F., Swann, A. C., Lewis, C., Coan, S., Schnapp, W. B., et al. (2001). The
lifetime cost of bipolar disorder in the US: An estimate for new cases in 1998. Pharmacoeco-
nomics, 19(5, Pt. 1), 483495.
Benazzi, F. (2000). Depression with DSM-IV atypical features: A marker for bipolar II disorder.
European Archives of Psychiatry and Clinical Neuroscience, 250, 5355.
Benazzi, F. (2003). Clinical differences between bipolar II depression and unipolar major depres-
sive disorder: Lack of an effect of age. Journal of Affective Disorders, 75, 191195.
Berk, M., & Berk, L. (2003). Mood stabilizers and treatment adherence in bipolar disorder: Address-
ing adverse events. Annals of Clinical Psychiatry, 15, 217224.
Bowden, C., Grunze, H., Mullen, J., Brecher, M., Paulsson, B., Jones, M., et al. (2005). A random-
ized, double-blind, placebo-controlled efficacy and safety study of quetiapine or lithium as
monotherapy for mania in bipolar disorder. Journal of Clinical Psychiatry, 66, 111121.
Bowden, C. L. (2001). Strategies to reduce misdiagnosis of bipolar depression. Psychiatric Ser-
vices, 52, 5155.
Bowles, T. M., & Levin, G. M. (2003). Aripiprazole: A new atypical antipsychotic drug. Annals of
Pharmacotherapy, 37, 687694.
Brady, K. T., & Sonne, S. C. (1995). The relationship between substance abuse and bipolar dis-
order. Journal of Clinical Psychiatry, 56(Suppl. 3), 1924.
Calabrese, J. R., Keck, P. E., Jr., Macfadden, W., Minkwitz, M., Ketter, T. A., Weisler, R. H., et al.
(2005). A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of
bipolar I or II depression. American Journal of Psychiatry, 162, 13511360.
Caligiuri, M. P., & Ellwanger, J. (2000). Motor and cognitive aspects of motor retardation in depres-
sion. Journal of Affective Disorders, 57, 8393.Chue, P., & Kovacs, C. S. (2003). Safety and tolerability of atypical antipsychotics in patients with
bipolar disorder: Prevalence, monitoring and management. Bipolar Disorders, 5(Suppl. 2),
6279.
Colom, F., Vieta, E., Martinez-Aran, A., Reinares, M., Goikolea, J. M., Benabarre, A., et al. (2003).
A randomized trial on the efficacy of group psychoeducation in the prophylaxis of recurrences
in bipolar patients whose disease is in remission. Archives of General Psychiatry, 60, 402 407.
Coryell, W., Solomon, D., Turvey, C., Keller, M., Leon, A. C., Endicott, J., et al. (2003). The
long-term course of rapid-cycling bipolar disorder. Archives of General Psychiatry, 60, 914920.
Das, A. K., Olfson, M., Gameroff, M. J., Pilowsky, D. J., Blanco, C., Feder, A., et al. (2005).
Screening for bipolar disorder in a primary care practice. Journal of the American MedicalAssociation, 293, 956963.
Dunner, D. L. (2003). Clinical consequences of under-recognized bipolar spectrum disorder. Bipolar
Disorders, 5, 456 463.
Dunner, D. L. (2005). Atypical antipsychotics: Efficacy across bipolar disorder subpopulations.
Journal of Clinical Psychiatry, 66(Suppl. 3), 2027.
Evans, D. L. (2000). Bipolar disorder: Diagnostic challenges and treatment considerations. Journal
of Clinical Psychiatry, 61(Suppl. 13), 2631.
Frank, E., Hlastala, S., Ritenour, A., Houck, P., Tu, X. M., Monk, T. H., et al. (1997). Inducing
lifestyle regularity in recovering bipolar disorder patients: Results from the maintenance ther-
apies in bipolar disorder protocol. Biological Psychiatry, 41, 11651173.
Frank, E., Kupfer, D. J., Thase, M. E., Mallinger, A. G., Swartz, H. A., Fagiolini, A. M., et al.
(2005). Two-year outcomes for interpersonal and social rhythm therapy in individuals with
Improving Diagnosis and Care in Bipolar Disorder 87
7/30/2019 Improving Diagnosis
16/21
Gershon, E. S., & Guroff, J. J. (1984). Information from relatives. Diagnosis of affective disorders.
Archives of General Psychiatry, 41, 173180.
Ghaemi, S. N., Boiman, E. E., & Goodwin, F. K. (2000). Diagnosing bipolar disorder and the effect
of antidepressants: A naturalistic study. Journal of Clinical Psychiatry, 61, 804808; quiz 809.
Goldberg, J. F., Harrow, M., & Whiteside, J. E. (2001). Risk for bipolar illness in patients initiallyhospitalized for unipolar depression. American Journal of Psychiatry, 158, 12651270.
Goldstein, M. J., & Miklowitz, D. J. (1994). Family intervention for persons with bipolar disorder.
New Directions of Mental Health Services, 62, 2335.
Gonzalez-Pinto, A., Gonzalez, C., Enjuto, S., Fernandez de Corres, B., Lopez, P., Palomo, J., et al.
(2004). Psychoeducation and cognitive-behavioral therapy in bipolar disorder: An update.
Acta Psychiatrica Scandinavia, 109(2), 8390.
Grunze, H., Kasper, S., Goodwin, G., Bowden, C., Baldwin, D., Licht, R., et al. (2002). World
Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment
of bipolar disorders. Part I: Treatment of bipolar depression. World Journal of Biological
Psychiatry, 3(3), 115124.
Hantouche, E. G., Akiskal, H. S., Lancrenon, S., Allilaire, J. F., Sechter, D., Azorin, J. M., et al.
(1998). Systematic clinical methodology for validating bipolar-II disorder: Data in mid-stream
from a French national multi-site study (EPIDEP). Journal of Affective Disorders, 50, 163173.
Hartman, E. (1968). Longitudinal studies of sleep and dream patterns in manic-depressive patients.
Archives of General Psychiatry, 19, 312329.
Hirschfeld, R. M. (2001). Bipolar spectrum disorder: Improving its recognition and diagnosis.
Journal of Clinical Psychiatry, 62(Suppl. 14), 59.
Hirschfeld, R. M., Calabrese, J. R., Weissman, M. M., Reed, M., Davies, M. A., Frye, M. A., et al.
(2003). Screening for bipolar disorder in the community. Journal of Clinical Psychiatry, 64,
5359.
Hirschfeld, R. M., Keck, P. E., Jr., Kramer, M., Karcher, K., Canuso, C., Eerdekens, M., et al.(2004). Rapid antimanic effect of risperidone monotherapy: A 3-week multicenter, double-
blind, placebo-controlled trial. American Journal of Psychiatry, 161, 10571065.
Hirschfeld, R. M., Lewis, L., & Vornik, L. A. (2003). Perceptions and impact of bipolar disorder:
How far have we really come? Results of the national depressive and manic-depressive asso-
ciation 2000 survey of individuals with bipolar disorder. Journal of Clinical Psychiatry, 64,
161174.
Hirschfeld, R. M., Williams, J. B., Spitzer, R. L., Calabrese, J. R., Flynn, L., Keck, P. E., Jr., et al.
(2000). Development and validation of a screening instrument for bipolar spectrum disorder:
The Mood Disorder Questionnaire. American Journal of Psychiatry, 157, 18731875.
Jamison, K. R. (2000). Suicide and bipolar disorder. Journal of Clinical Psychiatry, 61(Suppl. 9),4751.
Johnson, S. L., & Miller, I. (1997). Negative life events and time to recovery from episodes of
bipolar disorder. Journal of Abnormal Psychology, 106, 449457.
Johnson, S. L., & Roberts, J. E. (1995). Life events and bipolar disorder: Implications from bio-
logical theories. Psychological Bulletin, 117, 434 449.
Jones, S. (2004). Psychotherapy of bipolar disorder: A review. Journal of Affective Disorders, 80,
101114.
Judd, L. L., Akiskal, H. S., Schettler, P. J., Coryell, W., Endicott, J., Maser, J. D., et al. (2003). A
prospective investigation of the natural history of the long-term weekly symptomatic status of
bipolar II disorder. Archives of General Psychiatry, 60, 261269.
Judd, L. L., Akiskal, H. S., Schettler, P. J., Endicott, J., Maser, J., Solomon, D. A., et al. (2002). The
long-term natural history of the weekly symptomatic status of bipolar I disorder. Archives of
88 Journal of Clinical Psychology, January 2007
7/30/2019 Improving Diagnosis
17/21
Keck, P. E., Jr., Calabrese, J. R., McQuade, R. D., Carson, W. H., Carlson, B. X., Rollin, L. M.,
et al. (2006). A randomized, double-blind, placebo-controlled 26-week trial of aripiprazole
in recently manic patients with bipolar I disorder. Journal of Clinical Psychiatry, 67,
626637.
Keck, P. E., Jr., Marcus, R., Tourkodimitris, S., Ali, M., Liebeskind, A., Saha, A., et al. (2003). Aplacebo-controlled, double-blind study of the efficacy and safety of aripiprazole in patients
with acute bipolar mania. American Journal of Psychiatry, 160, 16511658.
Keck, P. E., Jr., Versiani, M., Potkin, S., West, S. A., Giller, E., & Ice, K. (2003). Ziprasidone in the
treatment of acute bipolar mania: A three-week, placebo-controlled, double-blind, randomized
trial. American Journal of Psychiatry, 160, 741748.
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005).
Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comor-
bidity Survey Replication. Archives of General Psychiatry, 62, 593602.
Ketter, T. (2005). Advances in the treatment of bipolar disorders. Washington, DC: American Psy-
chiatric Press.
Ketter, T. A., & Calabrese, J. R. (2002). Stabilization of mood from below versus above baseline inbipolar disorder: A new nomenclature. Journal of Clinical Psychiatry, 63, 146151.
Kleinberg, D. L., Davis, J. M., de Coster, R., Van Baelen, B., & Brecher, M. (1999). Prolactin levels
and adverse events in patients treated with risperidone. Journal of Clinical Psychopharmacol-
ogy, 19, 5761.
Kleinman, L., Lowin, A., Flood, E., Gandhi, G., Edgell, E., & Revicki, D. (2003). Costs of bipolar
disorder. Pharmacoeconomics, 21, 601622.
Kupfer, D. J., Frank, E., Grochocinski, V. J., Cluss, P. A., Houck, P. R., & Stapf, D. A. (2002).
Demographic and clinical characteristics of individuals in a bipolar disorder case registry.
Journal of Clinical Psychiatry, 63, 120125.
Kupfer, D. J., Himmelhoch, J. M., Swartzburg, M., Anderson, C., Byck, R., & Detre, T. P. (1972).Hypersomnia in manic-depressive disease (a preliminary report). Diseases of the Nervous
System, 33, 720724.
Kupka, R. W., Luckenbaugh, D. A., Post, R. M., Leverich, G. S., & Nolen, W. A. (2003). Rapid and
non-rapid cycling bipolar disorder: A meta-analysis of clinical studies. Journal of Clinical
Psychiatry, 64, 14831494.
Lam, D., & Gale, J. (2000). Cognitive behaviour therapy: Teaching a client the ABC modelThe
first step towards the process of change. Journal of Advanced Nursing, 31, 444451.
Lam, D. H., Watkins, E. R., Hayward, P., Bright, J., Wright, K., Kerr, N., et al. (2003). A random-
ized controlled study of cognitive therapy for relapse prevention for bipolar affective disorder:
Outcome of the first year. Archives of General Psychiatry, 60, 145152.
Lembke, A., Miklowitz, D. J., Otto, M. W., Zhang, H., Wisniewski, S. R., Sachs, G. S., et al. (2004).
Psychosocial service utilization by patients with bipolar disorders: Data from the first 500
participants in the Systematic Treatment Enhancement Program. Journal of Psychiatric Prac-
tice, 10, 8187.
Lish, J. D., Dime-Meenan, S., Whybrow, P. C., Price, R. A., & Hirschfeld, R. M. (1994). The
National Depressive and Manic-Depressive Association (NMDA) survey of bipolar members.
Journal of Affective Disorders, 31, 281294.
MacQueen, G. M., Young, L. T., & Joffe, R. T. (2001). A review of psychosocial outcome in
patients with bipolar disorder. Acta Psychiatrica Scandinavia, 103, 163170.
Malkoff-Schwartz, S., Frank, E., Anderson, B. P., Hlastala, S. A., Luther, J. F., Sherrill, J. T., et al.
(2000). Social rhythm disruption and stressful life events in the onset of bipolar and unipolarepisodes. Psychological Medicine, 30, 10051016.
M d ki M W (1995) Ri id f hild d d l I d i k f
Improving Diagnosis and Care in Bipolar Disorder 89
7/30/2019 Improving Diagnosis
18/21
7/30/2019 Improving Diagnosis
19/21
Regier, D. A., Myers, J. K., Kramer, M., Robins, L. N., Blazer, D. G., Hough, R. L., et al. (1984).
The NIMH Epidemiologic Catchment Area program. Historical context, major objectives, and
study population characteristics. Archives of General Psychiatry, 41, 934941.
Rucci, P., Frank, E., Kostelnik, B., Fagiolini, A., Mallinger, A. G., Swartz, H. A., et al. (2002).
Suicide attempts in patients with bipolar I disorder during acute and maintenance phases ofintensive treatment with pharmacotherapy and adjunctive psychotherapy. American Journal of
Psychiatry, 159, 11601164.
Sachs, G., Chengappa, K. N. R., Suppes, T., Mullen, J. A., Brecher, M., Devine, N. A., et al. (2004).
Quetiapine with lithium or divalproex for the treatment of bipolar mania: A randomized, double-
blind, placebo-controlled study. Bipolar Disorders, 6, 213223.
Sachs, G. S. (2003). Unmet clinical needs in bipolar disorder. Journal of Clinical Psychopharma-
cology, 23(3, Suppl. 1), S28.
Sachs, G. S., Grossman, F., Ghaemi, S. N., Okamoto, A., & Bowden, C. L. (2002). Combination of
a mood stabilizer with risperidone or haloperidol for treatment of acute mania: A double-blind,
placebo-controlled comparison of efficacy and safety. American Journal of Psychiatry, 159,
11461154.Sachs, G. S., Koslow, C. L., & Ghaemi, S. N. (2000). The treatment of bipolar depression. Bipolar
Disorders, 2(3, Pt. 2), 256260.
Sanger, T. M., Tohen, M., Vieta, E., Dunner, D. L., Bowden, C. L., Calabrese, J. R., et al. (2003).
Olanzapine in the acute treatment of bipolar I disorder with a history of rapid cycling. Journal
of Affective Disorders, 73, 155161.
Scott, J., Garland, A., & Moorhead, S. (2001). A pilot study of cognitive therapy in bipolar dis-
orders. Psychological Medicine, 31, 459467.
Scott, J., & Pope, M. (2002). Self-reported adherence to treatment with mood stabilizers, plasma
levels, and psychiatric hospitalization. American Journal of Psychiatry, 159, 19271929.
Sharif, Z. A. (2003). Overview of safety and tolerability of atypical antipsychotics used in primarycare. Primary Care Companion to the Journal of Clinical Psychiatry, 5(Suppl. 3), 1421.
Suppes, T., Calabrese, J. R., Mitchell, P. B., Pazzaglia, P. J., Potter, W. Z., & Zarin, D. A. (1995).
Algorithms for the treatment of bipolar manic-depressive illness. Psychopharmacology Bul-
letin, 31, 469474.
Suppes, T., Leverich, G. S., Keck, P. E., Nolen, W. A., Denicoff, K. D., Altshuler, L. L., et al.
(2001). The Stanley Foundation Bipolar Treatment Outcome Network. II. Demographics and
illness characteristics of the first 261 patients. Journal of Affective Disorders, 67(13), 4559.
Thase, M. E., Greenhouse, J. B., Frank, E., Reynolds, C. F., 3rd, Pilkonis, P. A., Hurley, K., et al.
(1997). Treatment of major depression with psychotherapy or psychotherapy-pharmacotherapy
combinations. Archives of General Psychiatry, 54, 10091015.
Tohen, M., Calabrese, J. R., Sachs, G. S., Banov, M. D., Detke, H. C., Risser, R., et al. (2006).
Randomized, placebo-controlled trial of olanzapine as maintenance therapy in patients with
bipolar I disorder responding to acute treatment with olanzapine. American Journal of Psychi-
atry, 163, 247256.
Tohen, M., Chengappa, K. N., Suppes, T., Zarate, C. A., Jr., Calabrese, J. R., Bowden, C. L., et al.
(2002). Efficacy of olanzapine in combination with valproate or lithium in the treatment of
mania in patients partially nonresponsive to valproate or lithium monotherapy. Archives of
General Psychiatry, 59, 6269.
Tohen, M., Jacobs, T. G., Grundy, S. L., McElroy, S. L., Banov, M. C., Janicak, P. G., et al. (2000).
Efficacy of olanzapine in acute bipolar mania: A double-blind, placebo-controlled study. The
Olanzapine HGGW Study Group. Archives of General Psychiatry, 57, 841849.Tohen, M., Ketter, T. A., Zarate, C. A., Suppes, T., Frye, M., Altshuler, L., et al. (2003). Olanzapine
versus divalproex sodium for the treatment of acute mania and maintenance of remission: A
Improving Diagnosis and Care in Bipolar Disorder 91
7/30/2019 Improving Diagnosis
20/21
(1999). Olanzapine versus placebo in the treatment of acute mania. Olanzapine HGEH Study
Group. American Journal of Psychiatry, 156, 702709.
Tondo, L., & Baldessarini, R. J. (2000). Reduced suicide risk during lithium maintenance treat-
ment. Journal of Clinical Psychiatry, 61(Suppl. 9), 97104.
Vieta, E., Pacchiarotti, I., Scott, J., Sanchez-Moreno, J., Di Marzo, S., & Colom, F. (2005). Evidence-based research on the efficacy of psychologic interventions in bipolar disorders: A critical
review. Current Psychiatry Reports, 7, 449455.
Vieta, E., Parramon, G., Padrell, E., Nieto, E., Martinez-Arn, A., Corbella, B., et al. (2002).
Quetiapine in the treatment of rapid cycling bipolar disorder. Bipolar Disorders, 4, 335340.
Vojta, C., Kinosian, B., Glick, H., Altshuler, L., & Bauer, M. S. (2001). Self-reported quality of life
across mood states in bipolar disorder. Comprehensive Psychiatry, 42, 190195.
Winsberg, M. E., DeGolia, S. G., Strong, C. M., & Ketter, T. A. (2001). Divalproex therapy in
medication-naive and mood-stabilizer-naive bipolar II depression. Journal of Affective Disor-
ders, 67(13), 207212.
Woods, S. W. (2000). The economic burden of bipolar disease. Journal of Clinical Psychiatry,
61(Suppl. 13), 38 41.
World Health Organization. (2001). The World Health Report 2001. Mental health: New under-
standing, new hope. Geneva, Switzerland.
Yatham, L., Paulsson, B., Mullen, J., & Vagero, M. (2004). Quetiapine versus placebo in combina-
tion with lithium or divalproex for the treatment of bipolar mania. Journal of Clinical Psycho-
pharmacology, 24, 599 606.
Yatham, L. N., Binder, C., Riccardelli, R., Leblanc, J., Connolly, M., & Kusumakar, V. (2003).
Risperidone in acute and continuation treatment of mania. International Journal of Clinical
Psychopharmacology, 18, 227235.
Zarate, C. A., Jr. (2000). Antipsychotic drug side effect issues in bipolar manic patients. Journal of
Clinical Psychiatry, 61(Suppl. 8), 52 61.
92 Journal of Clinical Psychology, January 2007
7/30/2019 Improving Diagnosis
21/21