Download update on the etiology and treatment of schizophrenia and bipolar

CNS SPECTRUMS
®
T H E I N T E R N AT I O N A L J O U R N A L O F N E U R O P S YC H I AT R I C M E D I C I N E
EXPERT REVIEW SUPPLEMENT
UPDATE ON THE ETIOLOGY AND
TREATMENT OF SCHIZOPHRENIA
AND BIPOLAR DISORDER
AUTHOR
Peter F. Buckley, MD
CME
2
ABSTRACT
Schizophrenia and bipolar disorder are two debilitating mental health disorders, both of which manifest early in adulthood and are associated with severe impairment as well as increased suicide risk. In addition, factors affecting disease
severity, such as substance abuse, are often prevalent in these patient populations. In the United States, the prevalence
of bipolar disorder is believed to be ~3.5%, while the rate for schizophrenia is ~1%. Although each disorder presents with
its own symptom profile, the approaches to treatment are similar and include early diagnosis and use of psychosocial
therapy. Research initiatives, such as genetic studies, are used in both disorders as well. For schizophrenia, treatment
typically includes the combination of an antipsychotic and psychosocial intervention. For bipolar disorder, clinicians commonly prescribe mood-stabilizing drugs (eg, lithium, valproic acid) as first-line treatment. Many of the second-generation
antipsychotics have been approved by the US Food and Drug Administration for bipolar disorder treatment in the manic
phase. Patients who are affected by either disorder also face the challenges of treatment nonadherence, which can be
affected by substance abuse and can hinder symptom remission as well as spur unnecessary medication switches due to
nonresponse. Family members play a key role in the treatment of either disorder.
This expert review supplement focuses on treatment options and research strategies being utilized for the management and
advanced understanding of schizophrenia and bipolar disorder. Research examining the pharmacology of commonly used
medications for the treatment of both disorders is also presented.
CNS S p e c t r 1 3 : 2 ( S u p p l 1 )
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EXPERT REVIEW SUPPLEMENT
An expert review of clinical challenges in psychiatry
Accreditation Statement
Target Audience
This activity has been planned and implemented in accordance with the Essentials and Standards of the Accreditation
Council for Continuing Medical Education (ACCME)
through the joint sponsorship of the Mount Sinai
School of Medicine and MBL Communications,
Inc. The Mount Sinai School of Medicine is accredited by the ACCME to provide continuing medical
education for physicians.
This activity is designed to meet the educational needs
of psychiatrists.
Learning Objectives
• Recognize the etiology and genetic links between bipolar disorder and schizophrenia.
• Discuss existing and future treatments of schizophrenia and the importance of compliance and individualized treatment.
• Evaluate the existing and future treatments of bipolar
disorder relating to mechanism of action and combination treatment.
Credit Designation
The Mount Sinai School of Medicine designates this educational activity for a maximum of 2 AMA PRA Category 1
Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Faculty Affiliation and Disclosures
Peter F. Buckley, MD, is professor and
chairman in the Department of Psychiatry
and Health Behavior at the Medical College
of Georgia in Augusta.
Dr. Buckley is a consultant to AstraZeneca,
Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer,
Solvay, and Wyeth; receives grant/research
support from AstraZeneca, the National Institute of Mental
Health, Pfizer, Solvay, and Wyeth; and receives honorarium/
expenses from Bristol-Myers Squibb, Janssen, and Pfizer.
Faculty Disclosure Policy Statement
It is the policy of the Mount Sinai School of Medicine to
ensure objectivity, balance, independence, transparency,
and scientific rigor in all CME-sponsored educational activities. All faculty participating in the planning or implementation of a sponsored activity are expected to disclose to the
audience any relevant financial relationships and to assist
in resolving any conflict of interest that may arise from the
relationship. Presenters must also make a meaningful disclosure to the audience of their discussions of unlabeled or
unapproved drugs or devices.
This activity has been peer reviewed and approved by Eric
Hollander, MD, Professor of Psychiatry and Chair at Mount
Sinai School of Medicine. Review Date: December 21, 2008.
Acknowledgment of Commercial Support
Funding for this activity has been provided by an educational grant from Eli Lilly and Company.
Peer Reviewer
Statement of Need and Purpose
Eric Hollander, MD, reports no affiliation with or financial interest in any organization that may pose a conflict
of interest.
This activity was also peer reviewed by an anonymous
reviewer who reports no affiliations with or financial interest in any organization that poses a conflict of interest.
The management of bipolar disorder and schizophrenia
share common goals: avoid re-hospitalization, manage
behavioral symptoms, and promote functional recovery.
Bipolar disorder is a common, severe, chronic illness
associated with significant comorbidity. Previous studies estimated the prevalence of bipolar disorder at 1%,
but emerging data show a prevalence of ~5%. Patients
need an integrated approach to treatment, including differentiating mood-stabilizing pharmacotherapy and psychotherapeutic measures. Recognition of the broader
spectrum of bipolar disorders and their adequate treatment is paramount because the mortality rate of the
disease is 2–3 times higher than that of the general
population. Schizophrenia is among the world’s top 10
causes of long-term disability. Approximately 1% of the
US population is affected by schizophrenia, with similar
rates across different countries. Full functional recovery
in schizophrenia patients is quite rare; <20% of patients
have sustained remission of their symptoms. Atypical
antipsychotics have become a first-line option in both
bipolar disorder and schizophrenia. Although these medications are associated with fewer movement disorders
and a lower risk of tardive dyskinesia than typical antipsychotics, they are linked to adverse metabolic side effects.
With the increasingly widespread use of atypical antipsychotics, psychiatrists must be vigilant in monitoring and
treating complex, fragile clinical populations.
CNS Spectr 13:2 (Suppl 1)
© MBLCommunications
To Receive Credit for this Activity
Read this supplement, reflect on the information presented, and complete the CME posttest and evaluation
form. To obtain credit, you should score 70% or better.
Early submission of this posttest is encouraged to measure outcomes for this CME activity. Please submit this
posttest by February 1, 2010 to be eligible for credit.
Release Date: February 1, 2008
Termination Date: February 28, 2010
The estimated time to complete this activity is 2 hour(s).
A related audio CME PsychCastTM will also be available
online in March 2008 at cmepsychcast.mblcommunications.com and via iTunes.
2
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UPDATE ON THE ETIOLOGY AND TREATMENT
OF SCHIZOPHRENIA AND BIPOLAR DISORDER
By Peter F. Buckley, MD
Impact of Schizophrenia and Bipolar Disorder
on the Affected Populations
Suicide risk aside, both bipolar disorder and schizophrenia
are life-shortening conditions, and patients who suffer from
either condition have a high rate of medical comorbidity and
develop health problems at a significantly younger age than
members of the general population (Slide 2).8-10
Schizophrenia and bipolar disorder are two of the most
common psychiatric disorders, both listed by the World
Health Organization as being among the most debilitating illnesses in the developed world.1 Both disorders tend to manifest early in adulthood, which contributes to their profound
impact. Both illnesses also have a particularly high association with mortality. In addition, suicide attempts in patients
with bipolar disorder are more likely to be lethal than for
those in the general population.2 The overall rate of suicide
in patients with bipolar disorder is ~1% annually, which is 60
times higher than in the general population. Among bipolar
patients, 25% to 60% will attempt suicide at least once.
Approximately ≤18.9% of deaths in this patient population
are attributed to suicide,3 which is a rate three times higher
than that in patients with other mood disorders.4
Studies also indicate that substance use appears to play a
role in suicide risk. Of bipolar patients with a substance use
disorder, 39.5% attempt suicide compared to 23.8% of those
without a substance use disorder.5 Other risk factors for suicide for patients with bipolar disorder include previous suicide
attempt and feelings of hopelessness. Risk factors for suicidal behavior are family history of suicide, increasingly severe
affective episodes, and early onset bipolar disorder (Slide 1).6
SLIDE 2
Bipolar Disorder Comorbidity 8-10
Substance use
56%
Alcohol abuse
49%
Anxiety disorder
71%
Social phobia
47%
Posttraumatic stress disorder
39%
There is also a high rate of substance abuse among
patients with schizophrenia as well as among those with
bipolar disorder (56%).11 Researchers theorize that the frequency of substance abuse in these populations may be
an attempt at self-medication for the patient. Additionally,
recent research suggests that there may even be a genetic
vulnerability that could explain in part why some patients
with schizophrenia abuse drugs.12
The need for physical healthcare and prolonged psychiatric care, the impact of crisis management and possibly legal
management, comorbidity, substance abuse, and the burden of care on families and society—including the loss of
human potential and productivity—all contribute to the difficulty and importance of addressing these two disorders.
SLIDE 1
Suicide Risk Factors in Bipolar Disorder 6
A meta-analysis of international literature found the
following risk factors in more than one study.
Risk Factors for Suicide
• Previous suicide attempt
• Hopelessness
Prevalence
Risk Factors for Suicidal Behavior
• Family history of suicide
• Early-onset bipolar disorder
• Increasingly severe affective episodes
• Comorbid drug or alcohol abuse
The prevalence of bipolar disorder was traditionally
believed to be ~1%, but more recent evidence suggests
that subtypes of the disorder have been underrepresented
and the actual prevalence rate may be closer to 3.5%.13,14
Schizophrenia is believed to be less common than bipolar
disorder and has a prevalence of ~1%.15 There is currently
no conclusive evidence that either condition is increasing
or decreasing in prevalence. There are noted regional
variations in prevalence, and both conditions appear to be
overrepresented in immigrants (although there is some
conflicting evidence for that finding).16,17
Suicide prevalence rates for patients with schizophrenia are similarly grim. The conventional wisdom long held
that 10% of patients with schizophrenia would commit
suicide, but this was found to overestimate the likelihood
of suicide in older patients. The actual prevalence rate is
now believed to be ~5%.7
Dr. Buckley is professor and chairman in the Department of Psychiatry and Health Behavior at the Medical College of Georgia in Augusta.
Disclosures: Dr. Buckley is a consultant to AstraZeneca, Bristol-Myers Squibb, Janssen, Pfizer, Solvay, and Wyeth; receives grant/research support
from AstraZeneca, the National Institute of Mental Health, Pfizer, Solvay, and Wyeth; and receives honorarium/expenses from Bristol-Myers Squibb,
Janssen, and Pfizer.
CNS Spectr 13:2 (Suppl 1)
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Exploring Multifactorial Etiology
tion, they may be able to deliver more effective treatment
approaches, particularly in regard to prevention of secondary
disability related to serious mental illness. Addressing this
treatment gap will require public health assistance.
Diagnosis is also impeded by the high rate of alcohol
and drug use in these patient populations. When substance abuse is a part of the clinical picture, it can be very
difficult to piece together the pathway to deterioration.
Availability of good collaborative information from family
or friends is an important element to diagnosis.
Both schizophrenia and bipolar disorder are highly
familial, with heritability estimates ranging from 59% to
87%.18,19 These estimates suggest that genes are overwhelmingly important in both disorders, which indicates
that these disorders may be more similar in etiology than
previously suspected. The genetics of both schizophrenia and bipolar disorder are common and complex. There
is some overlap in chromosome 13 and 15 linkage, which
suggests that dichotomy between these two disorders
may be less significant than suspected (Slide 3).20
SLIDE 4
Age of Schizophrenia Onset with Family History 24
SLIDE 3
Genes of Interest in Both Schizophrenia and Bipolar Disorder
Mean Age of Onset
Males: 27.8 years
Females: 31.5 years
20
Schizophrenia
Both Disorders
DTNBP1
DAOA(G72)
DAO
DISC1
RGS4
NRG1
BDNF
Age of onset was later for females with positive family
history; positive family history did not affect the median
age of onset for males.
DTNBP1=dystrobrevin binding protein 1; DAO=D-amino-acid oxidase;
RGS4=regulator of G-protein signalling 4; DAOA(G72)=D-amino acid oxidase activator; DISC1=disrupted in schizophrenia 1; NRG1=neuregulin 1;
BDNF=brain-derived neurotrophic factor.
SLIDE 5
Prodromal Symptoms in Bipolar Disorder 25
Manic:
• Increased energy or goal-directed activity
Environmental contributions to the disorders may be
quite broad. Obstetric complications had ocurred in 20%
of mothers of schizophrenia patients, with no particular
complication specifically indicated.21 In addition, there is
the curious finding that patients with schizophrenia are
more likely to have been born from February through May,
during the so-called “season of birth effect.”22 There is
also growing interest in the age of parents when they conceive, with several studies suggesting that children born
to older fathers have a higher risk of schizophrenia.23
There is no clear single factor that accounts for either
schizophrenia or bipolar disorders. There are multiple
contributing factors, and some researchers have suggested that neither disease constitute one single condition. Perhaps one set of symptoms is more determined
by genetic factors and another by environmental factors.
These are complex disorders, and much more research is
needed before they are fully understood.
Manic or psychotic:
• Grandiose ideas
Psychotic:
• Strange or unusual (non-grandiose) idea
• Suspiciousness
• Hallucinatory experiences
SLIDE 6
Scale of Prodromal Symptoms for Schizophrenia Version 26
Diagnosis in the Prodromal Stage
The pathways by which patients affected by bipolar disorder and/or schizophrenia are diagnosed and present for care
are highly variable. Both of these disorders are stigmatizing
conditions that often occur in youth or early adulthood (Slide
4)24 and often have a prodrome phase during which the
symptoms are not as florid or obvious as in the full-blown
course of the disorder (Slides 5 and 6).25,26 The symptoms of
these disorders can be mistaken for physical illness, moodiness, and substance abuse. It may not be obvious to the
patient or their family that bipolar disorder or schizophrenia is
the cause of the symptoms and/or behaviors.
There appears to be a period during which patients develop more florid illness before they are able to connect with
treatment services; this period is referred to as the “duration
of untreated illness.”27 If clinicians can shorten that duraCNS Spectr 13:2 (Suppl 1)
© MBLCommunications
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1.
1.1
1.2
1.3
1.4
1.5
Positive
Unusual thought content
Suspiciousness
Grandiosity
Perceptual abnormalities
Conceptual disorganization
2.
2.1
2.2
2.3
2.4
2.5
2.6
Negative
Social isolation or withdrawal
Avolition
Decreased expression of emotion
Decreased experience of emotion
Decreased ideational richness
Deterioration in role functioning
3.
3.1
3.2
3.3
3.4
Disorganization
Odd behavior or appearance
Bizarre thinking
Trouble with focus and attention
Impairment in personal hygiene
4.
4.1
4.2
4.3
4.4
General Symptoms
Sleep disturbance
Dysphoric mood
Motor disturbances
Impaired tolerance to stress
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Treatment of Schizophrenia
In schizophrenia, as in bipolar disorder, medications
are the bedrock of treatment. However, medications are
only partially effective, and their mechanism of action is
still poorly understood.
Antipsychotics function in a variety of methods. Thus
far, researchers have yet to identify an antipsychotic
that does not have appreciable binding to dopamine (D).
Binding to D2 receptors is important, but is not the only
effective mechanism of action. One of the most powerful agents, clozapine, binds very weakly to dopamine
receptors. Aripiprazole causes a fine-tuning effect on
the dopamine system.28 Some agents bind strongly to D
receptors while some bind weakly. Some agents find a
balance between D and serotonin (5-HT) receptors while
other drugs bind to many neurotransmitters with little
discernment. Despite showing some efficacy in many
cases, there is no single defined mechanism by which
these antipsychotics function.
Medications are only one facet of successful schizophrenia treatment. It is extremely important that patients
with serious mental illness receive the highest level of
support, not only from family members but also from
friends, colleagues, and the community in general.29 It
is also important that the patient’s family receive guidance and support from clinicians. This support will not
only enable them to better assist the patient in daily
interactions, but also helps them manage the stress
that accompanies having severe mental illness in the
family.30 Families play a major role in care.31
Establishing this support base is of particular importance in enabling patients to successfully return to
work. While current treatment approaches for schizophrenia are generally effective in terms of treating positive symptoms, many are less successful in establishing
community support and enabling patients to return to
leading generally productive lives.32
A strong relationship between caregiver and patient
has been shown to have a positive influence on
the career and work performance for schizophrenia
patients,33 and vocational rehabilitation programs and
psychosocial therapy specifically targeted toward
improving social and job functioning have shown some
promise.34,35 These programs and therapy options have
helped in removing barriers to job seeking, although
patient readiness and effort to return to the work force
continues to be a major factor.36
For patients with more severe illness who would generally be admitted to a public inpatient facility, Assertive
Community Treatment (ACT) can be an option. In ACT,
patient care is managed by a multidisciplinary team (at
least comprising of a psychiatrist, nurse, psychologist,
and social worker) and is tailored specifically to meet
the patient’s individual needs. Care is available 24 hours
a day, and support is provided to family members as
well (Slide 7).37 The cost of this focused, interdisciplinary
treatment is high, but it has been shown relatively effective at rehabilitating schizophrenia patients and reducing
relapse rates.38
CNS Spectr 13:2 (Suppl 1)
© MBLCommunications
It is generally recognized that while other symptoms
may play a small role, cognitive deficits such as impaired
memory and the inability to concentrate most severely
impact the ability of a patient with schizophrenia to find
and maintain employment.39 Accordingly, there has been
a good deal of interest in treatments geared toward
cognitive enhancement. Several psychosocial and cognitive-behavioral therapies (CBT) have attempted to target
cognitive functioning, generally with limited success.40,41
Recent evidence has suggested that the very high
prevalence of tobacco use among schizophrenia patients
(≤80%) may be partially explained by the positive effect of
nicotine on cognitive functioning.42,43 The 5-HT2 antagonist
properties of nicotine temporarily offset the suppression of
cognitive functioning caused by some medications, which
may be useful knowledge for the development of medications to improve functioning in this patient population.
There has also been particular interest in whether
existing medications may enhance cognitive functioning.
When atypical antipsychotics were introduced, reports
surfaced that detailed encouraging, but modest, cognitive benefits. However, the most recent research provides little support for a pervasive and robust effect.44
SLIDE 7
Principles of the ACT Model 37
Primary provider
of services
ACT teams aim to provide complete,
uninterrupted mental health services
without the need for outside referral
Out-of-office
services
Patients are treated at home and in
various community settings
Individualized
services
Treatment is fine tuned to meet the
specific needs of each patient, and is
frequently updated to maintain
maximum effectiveness
Assertive approach Care providers are proactive in helping patients remain in treatment and
resume a more independent life
Long-term services
Treatment is geared toward providing the continuing support over the
period of recovery, which often lasts
a number of years
Vocational services Patients are assisted in finding
employment
Substance abuse
services
Any required substance abuse treatment is provided by the ACT team
Psychoeducation
and family support
Patients and patients’ families are
educated and empowered to aid in
the treatment process, bolstering the
patients support system and
increasing autonomy
Community
integration
Patients are encouraged to take
part in community activities and join
organizations
Health care
ACT teams educate patients on
health care and coordinate general
health services
ACT=Assertive Community Treatment.
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Future Research
Researchers are evaluating the use of a variety of different medications, such as those prescribed for Alzheimer’s
disease, to treat the cognitive deficits associated with
schizophrenia.45 However, it is important to note that none
of these medications have been approved by the United
States Food and Drug Administration for this indication.
There is also increased interest in drugs with more selective targets, such as the glutamate system and D1 receptors.46,47 The US government has funded investigations in
an important initiative treating cognition in schizophrenia as
a core outcome measure. These investigators are developing and field testing new metrics and novel compounds.48
Some of the compounds being tested now are particularly
novel and require equally novel methods for testing.
Clearly, the clinical decision-making about treatment
of schizophrenia remains complex and perhaps involves
more art than science. Much of the research that may one
day drive new treatment approaches is focused on theories of the etiology and pathophysiology of schizophrenia.
Researchers are now moving into genome research,
searching for associations between particular candidate
genes that may be relevant for neurotransmitter metabolism and examining how these genes are expressed in
relation to particular aspects of the illness.59,60
SLIDE 8
Texas Medication Algorithm for Schizophrenia51
Choice of antipsychotic should be guided by considering the clinical characteristics of the patient and the efficacy and side-effect
profiles of the medication.
Treatment Response
Results of the Clinical Antipsychotic Trials of Intervention
Effectiveness (CATIE) study49 have been debated not only by
academic professionals but also by members of the public
policy field. Perhaps the most unifying conclusion is a reaffirmation that treatment of schizophrenia is highly individualized. Two treatments may match up well, but that does not
indicate that a particular patient on a certain drug would not
have a better outcome on another medication.50 Inevitably,
the clinician must match the symptom profile of each patient
with susceptibility to adverse events and the tolerability profile of the medication, while simultaneously evaluating the
current understanding of the robustness of the treatment
effect for each class of medications. Furthermore, each
medication or combination must be given a reasonable trial
period with attention to dosing (Slide 8).51
Despite efforts to optimize treatment, many patients
do not respond well after intervention. Treatment refractory schizophrenia continues to be a substantial clinical
challenge.52 Before determining that a medication is ineffective for a patient, the clinician must confirm that the
patient is demonstrating compliance with treatment (Slide
9).53-55 Noncompliance with treatment is strongly associated with substance use, which complicates prognosis
and may lead a clinician to erroneously deem the patient’s
condition as treatment refractory.56,57 It is also essential to
make certain the patient is adhering to the recommended
medication dosing. For many newer medications, information is not yet available on proper dosing for patients who
exhibit signs of treatment refractory illness.
Although it is often a necessary element of treatment,
switching medications further complicates the course of
treatment. Many patients may not stay on one medicine for
a long enough duration to obtain full benefit, and it is difficult
to determine whether a patient is truly refractory or not.
For truly refractory patients, the medication that has shown
the most efficacy is clozapine. However, clozapine also has
a substantial side-effect profile. Thus, there may be a tendency for clinicians to avoid this drug,51 although both the
CATIE study and the Cost Utility of the Latest Antipsychotics
in Severe Schizophrenia study58 suggest that it may have a
more robust effect on refractory patients (Slide 10).
CNS Spectr 13:2 (Suppl 1)
© MBLCommunications
Any stage(s) can be skipped depending on clinical picture or history
of antipsychotic failure and returning to an earlier stage may be
justified by history of past response.
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* First-episode patients usually require lower antipsychotic dosing and should
be closely monitored due to greater sensitivity to medication side effects.
Lack of consensus on inclusion of FGAs as option for first episode.
† If patient is inadequately adherent at any stage, the clinician should assess
and consider a long-acting antipsychotic preparation, such as risperidone
microspheres, haloperidol decanoate, or fluphenazine decanoate.
‡ A treatment refractory evaluation should be performed to reexamine diagnosis, substance abuse, medication adherence, and psychosocial stressors. CBT or psychosocial augmentation should be considered.
§ Whenever a second medication is added to an antipsychotic (other than
clozapine) for the purpose of improving psychotic symptoms, the patient is
considered to be in stage 6.
SGA=second-generation antipsychotic; FGA=first-generation antipsychotic; ECT=electroconvulsive therapy; RCT=randomized controlled trial;
CBT=cognitive-behavioral therapy.
6
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Also, researchers can now use imaging procedures to
measure the amount of dopamine in the synaptic cleft
between brain cells and to explore complex interactions
between dopamine and other neurotransmitters.61 Time
will tell just how much these novel approaches will translate into the clinical realm.
SLIDE 11
Elements of Comprehensive Care for Bipolar Disorder
Education for monitoring early-warning signs of relapse
Counseling, support, and psychosocial interventions
Attention to psychiatric and physical comorbidities
Involvement and support of family members and others in
the patient’s life
SLIDE 9
Reasons for Nonadherence53-55
Appropriate pharmacotherapy
Patient-Related Factors
• Symptoms
• Cognitive function
• Healthcare beliefs
• History of substance abuse
• Previous nonadherence
Attention to medication side effects
Support to gain/maintain employment
Patients with bipolar disorder often abuse alcohol and
drugs—most commonly, alcohol and marijuana are abused,
followed by cocaine and other opiates. A relationship may
exist in which reward circuits in the brain may cause a
higher propensity for patients with mental illness to engage
in drug abuse. The effects of drug abuse for bipolar disorder patients include more frequent and prolonged affective
episodes, decreased compliance with treatment, a lower
quality of life, and increased suicidal behavior.
The most commonly used medication for the treatment
of bipolar disorder is lithium, which is one of the oldest and
frequently-used mood-stabilizing drugs available. Lithium
has shown efficacy in the treatment of bipolar disorder
symptoms throughout the course of the illness and may
be particularly effective in preventing suicide.63 A variety
of anticonvulsants and anti-epilepsy medications, such as
valproic acid and carbamazepine, have also shown variable degrees of efficacy in mood stabilization.64
Increasingly, clinicians have begun to use second-generation antipsychotics, such as aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone, for variable degrees of mood
stabilization.65,66 Many of these drugs have been tested and
are FDA-approved for acute stabilization in the manic phases.31
Over time, some of these medications have obtained indications for and are being increasingly used in the maintenance
phase of the illness. However, it is also important to recognize
that many of these drugs do not have approval for use in
mood disorders, either in the acute or maintenance phase of
the illness. It is important that clinicians remain aware of the
approval status of these drugs, particularly as off-label use of
antipsychotics is strongly discouraged.
Some studies are examining medication/therapy combination treatment of bipolar disorder, including a variety of
different treatment techniques. Among the psychosocial
and counseling options are general counseling and support,
focused CBT, and interpersonal therapy (Slide 12).67
Although each of these therapy modalities have been
shown to be helpful in reducing relapse over time in
patients with bipolar disorder, researchers have not determined if one option is better than another.67 What researchers have concluded is that despite the type of medication
or counseling intervention, when medication is used as the
bedrock of treatment in order to achieve mood stability in
a patient and is combined with any psychological therapy,
the effect of the medication is boosted.
Medication-Related Factors
• Lack of efficacy
• Distressing side effects
• High doses
• Medication type
• Regimen complexity
Environmental Factors
• Caregiver support
• Family and social support
• Financial cost
• Practical barriers
Clinician-Related Factors
• Poor therapeutic alliance
• Attitude of staff
SLIDE 10
Drug Efficacy Pathway: Clinical Antipsychotic Trials for
Intervention Effectiveness (CATIE) Phase 2
44% of patients choosing clozapine in the efficacy pathway of the CATIE phase 2 trial were able to remain on
clozapine for the remainder of the study, as opposed to
18% of patients receiving other atypical antipsychotics
Patients remained on clozapine for an average of 10
months, as opposed to an average of 3 months for other
antipsychotics
Symptom reduction was greater for patients taking
clozapine than for patients taking other antipsychotics
Treatment of Bipolar Disorder
For bipolar disorder, a mainstay of treatment includes
use of medications in conjunction with psychosocial interventions, which is similar to treatment approaches for
schizophrenia.62 With a stable mood, psychosocial and other
counseling options can assist patients in mediating stressors that may contribute to relapse, reduce hospitalizations,
and improve general functioning. Without intervention, the
likelihood that medication alone will buffer against relapse
is low, as is the likelihood that patients will continue to take
medication as prescribed for as long as is necessary. A comprehensive approach works best (Slide 11).
CNS Spectr 13:2 (Suppl 1)
© MBLCommunications
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February 2008
EXPERT REVIEW SUPPLEMENT
An expert review of clinical challenges in psychiatry
Medication Limitations
High levels of support are also extremely important for
patients with any mental illness including bipolar disorder. Patient family, friends, and community are all key in
helping patients maintain a medication regimen, which,
in turn, better assures that the patient will improve. In
addition, the Depression Bipolar Support Alliance, which
manages support groups for patients with these disorders and creates information literature on mental health,
is an excellent resource for patients.68 While researchers
have studied the effects of positive family and community intervention for patients with mental illness,
additional studies are warranted to assess the types of
interventions that are most beneficial.69 Clinicians should
also work with patients with bipolar disorder on reentering other areas of their lives also affected by disorder
symptoms, such as the work environment.
Investigators at the National Institute of Mental Health
recently published results of two important and large
pragmatic trials: the Systematic Treatment Enhancement
Program for Bipolar Disorder (STEP-BD) and CATIE.71,72
Researchers in the CATIE study examined the use of antipsychotics in the treatment of schizophrenia, while the
STEP-BD study assessed patients with bipolar disorder.
Both studies showed that there are limitations in current
treatment in terms of effectiveness, the ability of medication to treat target symptoms, and presence of drugs side
effects (Slide 13).71 Because medications are often not
as effective as clinicians would like, many patients are
switched numerous times in order to find the most effective treatment with the lowest side-effect profile.
SLIDE 13
SLIDE 12
Results of the Systematic Treatment Enhancement Program
for Bipolar Disorder Study 71
Psychosocial Treatments Used in Bipolar Disorder 67
Collaborative Care
Patients are provided with educational materials geared
toward training them to take an active role in managing
their own symptoms, periodically meeting with a clinician
58.5% of participants symptomatic at entry had
recovered by 2-year follow-up
48.5% of participants had experienced symptom
recurrence by 2-year follow-up
Cognitive-Behavioral Therapy
Patients are educated about the course of bipolar disorder and then trained in problem solving, mood episode
intervention, and cognitive restructuring
70% of recurrences were to the depressive pole
Future Bipolar Disorder Treatments and
Research: Mood Stabilizers
Interpersonal and Social Rhythm Therapy
Treatment focus is on disruption of social routines and
sleep/wake cycles. Therapists aid patients in conflict
resolution and provide strategies for maintaining a
constant cycle of rising and going to bed
Medications approved for the treatment of epilepsy may
be investigated by researchers for mood stabilization.73
Newer antipsychotics are also investigated for mood stabilization properties alone and in combination with other mood
stabilizers for a more additive effect. Add-on treatments
have also been investigated. One idea that attracted much
attention involved adding omega-3 fatty acids to boost
response to primary medication. This investigation was
controversial and did not pan out as originally promised.74
Although various add-on strategies have been investigated
(usually in small pilot studies), there is a lack of real evidence
regarding these strategies. Accordingly, clinicians need to be
extremely careful in off-label use of medications, which is to
be strongly discouraged and avoided. Moreover, the promotion of medications for uses not formally approved by the
Food and Drug Administration (FDA) is not acceptable. Thus,
clinicians should remain cognizant of what is, and even more
importantly, what is not approved for use in bipolar disorder.
Family-Focused Therapy
Therapists meet with both patients and patients’
relatives, guiding them in understanding the course of
bipolar disorder and collaboratively adopting strategies
to prevent manage mood episodes
Pharmacology of Bipolar Disorder
The structure and function of various medications continues to be an area of great interest and challenge for
researchers. There is no unified method of action for drugs
that treat mental health disorders, including bipolar disorder. There is also not a single condition or mechanism that
the medications are counteracting or even a final common
pathway on which the medications are working.
For example, lithium is a very complex drug in that
it does not act directly on receptors and appears to
have more downstream effects on cells and metabolism.
Anticonvulsants may have selective effects on particular
neurotransmitters, particularly γ-aminobutyric acid (GABA)
or glutamate, but these drugs may also have effects in
terms of reducing excitability in epilepsy and altering second messenger systems. If anticonvulsants, such as carbamazepine, valproate, or lamotrigine, have treatment effects
for patients with mental health conditions similar to effects
found in patients with epilepsy, these drugs may provide
stabilization for patients with mood disorders.70
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Etiology and Pathophysiology Research
Genetics is now moving forward into the area of the
genome, in which researchers seek to find associations
between particular candidate genes. These genes may be
relevant for the metabolism of a neurotransmitter. In addition, expression in patients with serious mental illness or
expression in relation to a particular aspect of illness are
also related to these genes. Beyond classical genetics,
association genetics works to tease out particular abnormalities, and then examine protein expression.
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EXPERT REVIEW SUPPLEMENT
An expert review of clinical challenges in psychiatry
Brain structure is another important area of research in
the understanding of bipolar disorder. Structural imaging of
patients with schizophrenia and bipolar disorder has provided
ample evidence that brain structure is altered in patients with
serious mental illness.75 That is not a finding found through
the study of one patient. However, this brain alteration is
prevalent when disorders are studied at a group level. Such
changes in brain structure may actually get worse over time,
particularly in patients who do not respond to medication.
There is also great interest in the role of neurotrophins
and neuroplasticity in bipolar disorder and in schizophrenia, for example, brain derived neurotrophic factor (BDNF)
promotes cell development and synaptogenesis. Impaired
BDNF expression has been reported in mood disorders
and reduced BDNF has been associated with relapse of
depression.76 There is also evidence for abnormalities of
neurotrophins in schizophrenia.77
Conclusion
Although bipolar disorder and schizophrenia each present with a varied and differing symptom profile, there
are some similarities in approaches to treatment for
both disorders. Treatment of schizophrenia and bipolar
disorder often include use of medications in conjunction
with psychosocial interventions. Mood-stabilizing medications are typically used for bipolar disorder treatment,
while newer-generation antipsychotics are often first-line
treatment for schizophrenia. Psychosocial therapies have
been shown to be effective when paired with appropriate
medications for both disorders. Ongoing research continues into mechanisms of etiology and possible pathophysiology utilizing both genetic and imaging techniques.
References
1. Murray CJL, Lopez AD, eds. The Global Burden of Disease: A Comprehensive
Assessment of Mortality and Disability from Diseases, Injuries, and Risk
Factors in 1990 and Projected to 2020. 1st ed. Cambridge: Harvard School
of Public Health on behalf of the World Health Organization and the World
Bank; 1996.
2. Baldessarini RJ, Pompili M, Tondo L. Suicide in bipolar disorder: risks and
management. CNS Spectr. 2006;11(6):465-471.
3. Goodwin FK, Jamison KR. Manic-Depressive Illness. New York, NY: Oxford
University Press; 1990.
4. Jamison KR. Suicide and bipolar disorder. J Clin Psychiatry. 2000;61(suppl 9):47-51.
5. Dalton EJ, Cate-Carter TD, Mundo E, Parikh SV, Kennedy JL. Suicide risk
in bipolar patients: the role of co-morbid substance use disorders. Bipolar
Disord. 2003;5(1):58-61.
6. Hawton K, Sutton L, Haw C, et al. Suicide and attempted suicide in
bipolar disorder: a systematic review of risk factors. J Clin Psychiatry.
2005;66(6):693-704.
7. Palmer BA, Pankratz VS, Bostwick JM. The lifetime risk of suicide in schizophrenia: a reexamination. Arch Gen Psychiatry. 2005;62(3):247-253.
8. Buckley P. Considerations of Medical Comorbidity in Schizophrenia. Available
at: www.medscape.com/infosite/schizophrenia-management/article-4.
Accessed December 18, 2007.
9. Newcomer JW. Medical risk in patients with bipolar disorder and schizophrenia. J Clin Psychiatry. 2006;67(suppl 9):25-30.
10. Krishnan KR. Psychiatric and medical comorbidities of bipolar disorder.
Psychosom Med. 2005;67(1):1-8.
11. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with
alcohol and other drug abuse. Results from the Epidemiologic Catchment
Area (ECA) Study. JAMA. 1990;264(19):2511-2518.
12. Caspi A, Moffitt TE, Cannon M, et al. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in
the catechol-O-methyltransferase gene: longitudinal evidence of a gene X
environment interaction. Biol Psychiatry. 2005;57(10):1117-1127.
CNS Spectr 13:2 (Suppl 1)
© MBLCommunications
13. Merikangas KR, Akiskal HS, Angst J, et al. Lifetime and 12-month prevalence
of bipolar spectrum disorder in the National Comorbidity Survey Replication.
Arch Gen Psychiatry. 2007;64(5):543-552.
14. Kessler RC, Chiu WT, Demler O, et al. Prevalence, severity, and comorbidity of
12-month DSM-IV disorders in the National Comorbidity Survey Replication
(NCS-R). Arch Gen Psychiatry. 2005;62(6):617-627.
15. Regier DA, Narrow WE, Rae DS, et al. The de facto US mental and addictive disorders service system. Epidemiologic catchment area prospective
1-year prevalence rates of disorders and services. Arch Gen Psychiatry.
1993;50(2):85-94.
16. Selten JP, Sijben N. First admission rates for schizophrenia in immigrants
to the Netherlands: The Dutch National Register. Soc Psychiatry Psychiatr
Epidemiol. 1994;29(2):71-77.
17. Grove W, Clayton PJ, Endicott J, et al. Immigration and major affective disorder. Acta Psychiatr Scand. 1986;74(6):548–552.
18. Kendler KS. Twin studies of psychiatric illness. Current status and future
directions. Arch Gen Psychiatry. 1993;50(11):905-915.
19. Kendler KS. Genetic epidemiology in psychiatry. Taking both genes and environment seriously. Arch Gen Psychiatry. 1995;52(11):895-899.
20. Craddock N, O’Donovan MC, Owen MJ. The genetics of schizophrenia and
bipolar disorder: dissecting psychosis. J Med Genet. 2005;42(3):193-204.
21. Cannon M, Jones PB, Murray RM. Obstetric complications and schizophrenia:
historical and meta-analytic review. Am J Psychiatry. 2002;159(7):1080-1092.
22. O’Callaghan E, Gibson T, Colohan HA, et al. Season of birth in schizophrenia.
Evidence for confinement of an excess of winter births to patients without a
family history of mental disorder. Br J Psychiatry. 1991;158:764-769.
23. Zammit S, Allebeck P, Dalman C. Paternal age and risk for schizophrenia. Br J
Psychiatry. 2003;183:405-408.
24. Gorwood P, Leboyer M, Jay M, et al. Gender and age at onset in schizophrenia: impact of family history. Am J Psychiatry. 1995;152(2):208–212.
25. Correll CU, Penzner JB, Frederickson AM, et al. Differentiation in the preonset
phases of schizophrenia and mood disorders: evidence in support of a bipolar
mania prodrome. Schizophr Bull. 2007;33(3):703-714.
26. Addington J. The diagnosis and assessment of individuals prodromal for
schizophrenia psychosis. CNS Spectr. 2004;9(8):588-594.
27. Peralta V, Cuesta MJ, Martinez-Larrea A, et al. Duration of untreated psychotic illness: the role of premorbid social support networks. Soc Psychiatry
Psychiatr Epidemiol. 2005;40(5):345-349.
28. Kapur S, Mamo D. Half a century of antipsychotics and still a central role
for dopamine D2 receptors. Prog Neuropsychopharmacol Biol Psychiatry.
2003;27:1081-1090.
29. Scott JE, Dixon LB. Psychological interventions for schizophrenia. Schizophr
Bull. 1995;21(4):621-630.
30. Dixon LB, Lehman AF. Family interventions for schizophrenia. Schizophr Bull.
1995;21(4):631-643.
31.National Alliance on Mental Illness. About Mental Illness. Available at:
www.nami.org/Template.cfm?Section=By_Illness&Template=/TaggedPage/
TaggedPageDisplay.cfm&TPLID=54&ContentID=23037. Accessed on
December 18, 2007.
32. McGurk SR. Neurocognition as a determinant of employment status in schizophrenia. J Psychiatr Pract. 2000;6(1):190-196.
33. Davis LW, Lysaker PH. Therapeutic alliance and improvements in work
performance over time in patients with schizophrenia. J Nerv Ment Dis.
2007;195(4):353-357.
34. Lehman AF. Vocational rehabilitation in schizophrenia. Schizophr Bull.
1995;21(4):645-656.
35. Killackey EJ, Jackson HJ, Gleeson J, Hickie IB, McGorry PD. Exciting career
opportunity beckons! Early intervention and vocational rehabilitation in
first-episode psychosis: employing cautious optimism. Aust N Z J Psychiatry.
2006;40(11-12):951-962.
36. Liu KW, Hollis V, Warren S, Williamson DL. Supported-employment program
processes and outcomes: experiences of people with schizophrenia. Am J
Occup Ther. 2007;61(5):543-554.
37. Principles of the ACT Model. Available at: www.actassociation.org/actModel. Accessed on December 18, 2007.
38. Phillips SD, Burns BJ, Edgar ER, et al. Moving assertive community treatment
into standard practice. Psychiatr Serv. 2001;52(6):771-779.
39. Holthausen EA, Wiersma D, Cahn W, et al. Predictive value of cognition for
different domains of outcome in recent-onset schizophrenia. Psychiatry Res.
2007;149(1-3):71-80.
40. Bell M, Fiszdon J, Greig T, Wexler B, Bryson G. Neurocognitive enhancement
therapy with work therapy in schizophrenia: 6-month follow-up of neuropsychological performance. J Rehabil Res Dev. 2007;44(5):761-770.
41. Granholm E, McQuaid JR, McClure FS, et al. Randomized controlled trial of
cognitive behavioral social skills training for older people with schizophrenia:
12-month follow-up. J Clin Psychiatry. 2007;68(5):730-737.
42. Levin ED, Rezvani AH. Nicotinic interactions with antipsychotic drugs, models
of schizophrenia and impacts on cognitive function. Biochem Pharmacol.
2007;74(8):1182-1191.
9
February 2008
EXPERT REVIEW SUPPLEMENT
An expert review of clinical challenges in psychiatry
43. Prochaska JJ, Hall SM, Bero LA. Tobacco Use Among Individuals With
Schizophrenia: What Role Has the Tobacco Industry Played? Schizophr Bull.
2007. In press.
44. Goldberg TE, Goldman RS, Burdick KE, et al. Cognitive improvement after treatment with second-generation antipsychotic medications in first-episode schizophrenia: is it a practice effect? Arch Gen Psychiatry. 2007;64(10):1115-1122.
45. Stys PK, Lipton SA. White matter NMDA receptors: an unexpected new
therapeutic target? Trends Pharmacol Sci. 2007;28(11):561-566.
46. Robbins MJ, Starr KR, Honey A, et al. Evaluation of the mGlu8 receptor as a
putative therapeutic target in schizophrenia. Brain Res. 2007;1152:215-227.
47. Castner SA, Williams GV. Tuning the engine of cognition: a focus on NMDA/
D1 receptor interactions in prefrontal cortex. Brain Cogn. 2007;63(2):94-122.
48. Buchanan RW, Davis M, Goff D, et al. A summary of the FDA-NIMH-MATRICS
workshop on clinical trial design for neurocognitive drugs for schizophrenia.
Schizophr Bull. 2005;31(1):5-19.
49. Manschreck TC, Boshes RA. The CATIE schizophrenia trial: results, impact,
controversy. Harv Rev Psychiatry. 2007;15(5):245-258.
50. Glick ID. Understanding the results of CATIE in the context of the field. CNS
Spectr. 2006;11(suppl 7):40-47.
51. Moore TA, Buchanan RW, Buckley PF, et al. The Texas medication algorithm
project antipsychotic algorithm for schizophrenia: 2006 update. J Clin
Psychiatry. 2007;68:1751-1762.
52. Kucukalić A, Dzubur-Kulenović A, Mehmedika-Suljić E. Relapse prevention in
schizophrenia - new therapeutic challenges. Psychiatr Danub. 2007;19(4):362-366.
53. Perkins DO, Johnson JL, Hamer RM, et al. Predictors of antipsychotic
medication adherence in patients recovering from a first psychotic episode.
Schizophr Res. 2006;83(1):53-63.
54. Lacro JP, Dunn LB, Dolder CR, Leckband SG, Jeste DV. Prevalence of and risk
factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature. J Clin Psychiatry. 2002;63(10):892-909.
55. Buckley PF, Wirshing DA, Pierre J, Bushen P, Resnick S, Wishing SC. Lack of
insight and treatment adherence in schizophrenia. CNS Drugs. 2007;21:129-141.
56.Valenstein M, Ganoczy D, McCarthy JF, Myra Kim H, Lee TA, Blow FC.
Antipsychotic adherence over time among patients receiving treatment for
schizophrenia: a retrospective review. J Clin Psychiatry. 2006;67(10):1542-1550.
57.Tunis SL, Faries DE, Stensland MD, Hay DP, Kinon BJ. An examination of factors affecting persistence with initial antipsychotic treatment in patients with
schizophrenia. Curr Med Res Opin. 2007;23(1):97-104.
58.Tandon R, Carpenter WT, Davis JM. First- and second-generation antipsychotics:
learning from CUtLASS and CATIE. Arch Gen Psychiatry. 2007;64(8):977-978.
59. Egan MF, Straub RE, Goldberg TE, et al. Variation in GRM3 affects cognition,
prefrontal glutamate, and risk for schizophrenia. Proc Natl Acad Sci U S A.
2004;101(34):12604-12609.
60.Harrison PJ, Weinberger DR. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry. 2005;10:40-68.
61. Laruelle M, Frankle WG, Narendran R, Kegeles LS, Abi-Dargham A. Mechanism
of action of antipsychotic drugs: from dopamine D(2) receptor antagonism to
glutamate NMDA facilitation. Clin Ther. 2005;27(suppl A):S16-S24.
62.Huxley NA, Parikh SV, Baldessarini RJ. Effectiveness of psychosocial
treatments in bipolar disorder: state of the evidence. Harv Rev Psychiatry.
2000;8(3):126-140.
63.Fountoulakis KN, Vieta E, Siamouli M, et al. Treatment of bipolar disorder: a
complex treatment for a multi-facet disorder. Ann Gen Psychiatry. 2007;6(1):27.
64.Sachs GS, Thase ME. Bipolar disorder therapeutics: maintenance treatment.
Biol Psychiatry. 2000;48(6):573-581.
65.Perlis R. Review: adding second generation antipsychotics to mood stabilizers
reduces acute mania symptoms. Evid Based Ment Health. 2007;10:111.
66.Surja AA, Tamas RL, El-Mallakh RS. Antipsychotic medications in the treatment of bipolar disorder. Curr Drug Targets. 2006;1217-1224.
67.Miklowitz DJ, Otto MW, Frank E, et al. Psychosocial treatments for bipolar depression: a 1-year randomized trial from the Systematic Treatment
Enhancement Program. Arch Gen Psychiatry. 2007;64(4):419-426.
68. Depression Bipolar Support Alliance. Available at: www.dbsalliance.org.
Accessed on January 18, 2008.
69.Justo L, Soares B, Calil H. Family interventions for bipolar disorder. Cochrane
Database Syst Rev. 2007;(4):CD005167.
70.Amann B, Grunze H, Vieta E, Trimble M. Antiepileptic drugs and mood stability. Clin EEG Neurosci. 2007;38(2):116-123.
71.Perlis RH, Ostacher MJ, Patel JK, et al. Predictors of recurrence in bipolar
disorder: primary outcomes from the systematic treatment enhancement program for bipolar disorder (STEP-BD). Am J Psychiatry. 2006;163(2):217-224.
72.Lieberman JA, Stroup TS, McEvoy JP, et al, and the Clinical Antipsychotic
Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of
antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med.
2005;353(12):1209-1223.
73.Zaremba PD, Białek M, Błaszczyk B, Cioczek P, Czuczwar SJ. Non-epilepsy
uses of antiepilepsy drugs. Pharmacol Rep. 2006;58(1):1-12.
74.Chiu CC, Huang SY, Chen CC, Su KP. Omega-3 fatty acids are more beneficial
in the depressive phase than in the manic phase in patients with bipolar I
disorder. J Clin Psychiatry. 2005;66(12):1613-1614.
75.Yurgelun-Todd DA, Silveri MM, Gruber SA, Rohan ML, Pimentel PJ. White
matter abnormalities observed in bipolar disorder: a diffusion tensor imaging
study. Bipolar Disord. 2007;9(5):504-512.
76. Shaltiel G, Chen G, Manji HK. Neurotrophic signaling cascades in the
pathophysiology and treatment of bipolar disorder. Curr Opin Pharmacol.
2007;7(1):22-26.
77. Buckley PF, Mahadik S, Pillai A, Terry A Jr. Neurotrophins and schizophrenia.
Schizophr Res. 2007;94(1-3):1-11.
Update on the Etiology and Treatment
of Schizophrenia and Bipolar Disorder
PsychCast
TM
CNS Spectr 13:2 (Suppl 1)
By Peter F. Buckley, MD
An audio CME PsychCastTM version will
also be available online in March 2008 at
cmepsychcast.mblcommunications.com
and via iTunes.
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EXPERT REVIEW SUPPLEMENT
An expert review of clinical challenges in psychiatry
UPDATE ON THE ETIOLOGY AND TREATMENT
OF SCHIZOPHRENIA AND BIPOLAR DISORDER
Accreditation Statement
This activity has been planned and implemented in accordance with the Essentials and Standards of the Accreditation Council for Continuing Medical
Education (ACCME) through the joint sponsorship of the Mount Sinai School of Medicine and MBL Communications, Inc. The Mount Sinai School of
Medicine is accredited by the ACCME to provide continuing medical education for physicians.
Credit Designation
The Mount Sinai School of Medicine designates this educational activity for a maximum of 2 AMA PRA Category 1 Credit(s) TM. Physicians should only
claim credit commensurate with the extent of their participation in the activity.
Faculty Disclosure Policy Statement
It is the policy of the Mount Sinai School of Medicine to ensure objectivity, balance, independence, transparency, and scientific rigor in all CME-sponsored educational activities. All faculty participating in the planning or implementation of a sponsored activity are expected to disclose to the audience
any relevant financial relationships and to assist in resolving any conflict of interest that may arise from the relationship. Presenters must also make a
meaningful disclosure to the audience of their discussions of unlabeled or unapproved drugs or devices. This information will be available as part of the
course material.
All psychiatrists may participate in the CME program. To receive credit for this activity, complete the answer form provided on the following
page as directed and return it to CME Director, CNS Spectrums, 333 Hudson Street, 7th Floor, New York, NY 10013; or fax it to 212-328-0600.
This quiz is also available at www.cnsspectrums.com. Termination date: February 28, 2010. Early submission of this posttest is encouraged. Please
submit this posttest by February 1, 2010 to be eligible for credit.
To obtain credit, you should score 70% or better.
CME QUESTIONS
5. The mechanism of action for antipsychotic medications:
1. Which of the following statistic(s) is/are true about
bipolar disorder-related suicide rates?
A. Never entails blocking the dopamine (D)2 system
B. Sometimes entails blocking the D2 system
C. Is quite diverse
D. B and C
A. Suicide rates are ~1% annually, 60 times greater than
the general population
B. Up to 18.9% of deaths in this population are related
to suicide
C. None of the above
D. Both A and B
6. Assertive Community Treatment does not:
A. Describe a collaborative care structure
B. Require patients to meet rehabilitation thresholds
C. Provide 24-hour care
D. Reduce relapse rates
2. Both bipolar disorder and schizophrenia:
A. Have high rates of medical comorbidity
B. Are typically not diagnosed until after 30 years of age
C. Usually improve over time
D. Both B and C
7. Improvement of cognitive function in schizophrenia
patients is:
3. Among the following symptoms, which can be mistaken
for bipolar disorder and schizophrenia?
A. Sometimes associated with nicotine consumption
B. An area that has very little research
C. The main outcome measure of schizophrenia
D. Never seen with atypical antipsychotics
A. Moodiness, physical illness
B. Physical illness, selfishness
C. Substance abuse
D. Both A and C
8. Before deeming a patient’s condition as treatment refractory,
what should clinicians do?
4. Which of the following options does “duration of untreated illness” refer?
A.
B.
C.
D.
A. Determine patient’s treatment compliance
B. Determine whether the patient engages in substance use
C. Determine that correct dosing is being prescribed
D. All of the above
The total span of time during which symptoms arose
Patient’s self-recall of symptom onset
Conjecture of symptom onset using clinical scales
Period where illness develops before treatment
onset
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