Practice
`Guideline
`for the
`Treatment of Patients
`With Bipolar Disorder
`(Revision)
`
`American Psychiatric Association
`
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`Originally published in April 2002.
`
`A guideline watch, summarizing significant developments in
`the scientific literature since publication of this guideline,
`may be available in the Psychiatric Practice section
`of the APA web site at www.psych.org.
`
`Copyright © 2002 American Psychiatric Association
`
`ALL RIGHTS RESERVED
`
`American Psychiatric Association
`
`1000 Wilson Boulevard
`
`Arlington, VA 22209-3901
`
`www.psych.org
`
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`American Psychiatric Association Practice Guidelines
`
`Practice Guideline for the Treatment of Patients
`With Bipolar Disorder (Revision)
`
`Work Group on Bipolar Disorder
`
`Robert M.A. Hirschfeld, M.D., Chair
`Charles L. Bowden, M.D.
`Trisha Suppes, M.D., Ph.D.
`Michael J. Gitlin, M.D.
`Michael E. Thase, M.D.
`Paul E. Keck, M.D.
`Karen D. Wagner, M.D., Ph.D.
`Roy H. Perlis, M.D., Consultant
`
`Steering Committee on Practice Guidelines
`
`John S. McIntyre, M.D., Chair
`Sara C. Charles, M.D., Vice-Chair
`Kenneth Altshuler, M.D.
`Louis Alan Moench, M.D.
`Ian Cook, M.D.
`Stuart W. Twemlow, M.D.
`C. Deborah Cross, M.D.
`Sherwyn Woods, M.D., Ph.D.
`Barry J. Landau, M.D.
`Joel Yager, M.D.
`
`Consultants and Liaisons
`
`Paula Clayton, M.D. (Consultant)
`Marcia Goin, M.D., Ph.D. (Liaison)
`Marion Goldstein, M.D. (Liaison)
`Sheila Hafter Gray, M.D. (Consultant)
`Andrew J. Kolodny, M.D. (Liaison)
`Margaret T. Lin, M.D. (Liaison)
`Grayson Norquist, M.D. (Consultant)
`Susan Stabinsky, M.D. (Consultant)
`
`Robert Johnston, M.D. (Area I)
`James Nininger, M.D. (Area II)
`Roger Peele, M.D. (Area III)
`Daniel Anzia, M.D. (Area IV)
`R. Scott Benson, M.D. (Area V)
`Lawrence Lurie, M.D. (Area VI)
`R. Dale Walker, M.D. (Area VII)
`
`Staff
`
`Rebecca M. Thaler, M.P.H., C.H.E.S., Senior Project Manager
`Robert Kunkle, M.A., Project Manager
`Althea Simpson, Project Coordinator
`Laura J. Fochtmann, M.D., Medical Editor
`Claudia Hart, Director, Department of Quality Improvement and Psychiatric Services
`Lloyd I. Sederer, M.D., Director, Division of Clinical Services
`
`Developed under the auspices of the Steering Committee on Practice Guidelines. Successive drafts reviewed by APA components and members,
`as well as other interested individuals and organizations (see p. 38) and two members of the editorial board of The American Journal of Psychiatry.
`Approved by the APA Board of Trustees in December 2001 and published in April 2002.
`Received by The American Journal of Psychiatry Dec. 10, 2001; accepted Jan. 16, 2002.
`Copyright © 2002 American Psychiatric Association.
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`For Continuing Medical Education credit for APA Practice Guidelines,
`visit www.psych.org/cme
`
`To order the 2004 Compendium of Quick Reference Guides to the
`APA Practice Guidelines,
`visit www.appi.org or call 800-368-5777.
`
`The American Board of Psychiatry and Neurology (ABPN)
`has reviewed the APA Practice Guidelines CME Program
`and has approved this product as part of a comprehensive
`lifelong learning program, which is mandated by the
`American Board of Medical Specialties as a necessary
`component of maintenance of certification.
`
`ABPN approval is time limited to 3 years for each
`individual Practice Guideline CME course.
`Refer to APA’s CME web site for ABPN approval status of each course.
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`Table of Contents
`
`Statement of Intent....................................................................................................................................iv
`Guide to Using This Practice Guideline .................................................................................................... 1
`Introduction................................................................................................................................................ 2
`Overview of the Guideline Development Process................................................................................... 3
`
`PART A: Treatment Recommendations for Patients With Bipolar Disorder ................ 4
`I. Executive Summary of Recommendations .................................................................................... 4
`A. Psychiatric Management ........................................................................................................ 4
`B. Acute Treatment...................................................................................................................... 4
`C. Maintenance Treatment ......................................................................................................... 5
`II. Formulation and Implementation of a Treatment Plan ........................................................... 5
`A. Psychiatric Management ........................................................................................................ 6
`B. Acute Treatment...................................................................................................................... 9
`C. Maintenance Treatment ....................................................................................................... 10
`III. Special Clinical Features Influencing the Treatment Plan ..................................................... 11
`A. Psychiatric Features............................................................................................................... 11
`B. Demographic and Psychosocial Factors.............................................................................. 12
`C. Concurrent General Medical Conditions.............................................................................. 15
`
`PART B: Background Information and Review of Available Evidence ......................... 16
`IV. Disease Definition, Natural History and Course, and Epidemiology ................................... 16
`A. Definition of Bipolar Disorder.............................................................................................. 16
`B. Natural History and Course .................................................................................................. 16
`C. Epidemiology ......................................................................................................................... 17
`V. Review and Synthesis of Available Evidence.............................................................................. 18
`A. Somatic Treatments of Acute Manic and Mixed Episodes................................................. 18
`B. Somatic Treatments of Acute Depressive Episodes ........................................................... 26
`C. Rapid Cycling.......................................................................................................................... 29
`D. Maintenance Treatment....................................................................................................... 30
`E. Psychosocial Interventions.................................................................................................... 32
`F. Somatic Therapies for Children and Adolescents............................................................... 35
`
`PART C: Future Research Needs ................................................................................................... 36
`VI. General Principles............................................................................................................................ 36
`VII. Acute Treatment............................................................................................................................. 36
`A. Manic and Mixed Episodes ................................................................................................... 36
`B. Depressive Episodes .............................................................................................................. 37
`C. Rapid Cycling.......................................................................................................................... 37
`VIII. Maintenance Treatment .............................................................................................................. 37
`IX. Psychosocial Interventions ............................................................................................................ 37
`Appendix I: Educational Sources for Depression and Bipolar Disorder ............................................. 37
`Individuals and Organizations That Submitted Comments ................................................................. 38
`References................................................................................................................................................. 39
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`Statement of Intent
`
`The APA Practice Guidelines are not intended to be construed or to serve as a standard of
`medical care. Standards of medical care are determined on the basis of all clinical data avail-
`able for an individual case and are subject to change as scientific knowledge and technology
`advance and practice patterns evolve. These parameters of practice should be considered
`guidelines only. Adherence to them will not ensure a successful outcome in every case, nor
`should they be construed as including all proper methods of care or excluding other accept-
`able methods of care aimed at the same results. The ultimate judgment regarding a partic-
`ular clinical procedure or treatment plan must be made by the psychiatrist in light of the
`clinical data presented by the patient and the diagnostic and treatment options available.
`These practice guidelines have been developed by psychiatrists who are in active clini-
`cal practice. In addition, some contributors are primarily involved in research or other aca-
`demic endeavors. It is possible that through such activities some contributors have received
`income related to treatments discussed in this guideline. A number of mechanisms are in
`place to minimize the potential for producing biased recommendations due to conflicts of
`interest. The guideline has been extensively reviewed by members of APA as well as by rep-
`resentatives from related fields. Contributors and reviewers have all been asked to base their
`recommendations on an objective evaluation of the available evidence. Any contributor or
`reviewer who has a potential conflict of interest that may bias (or appear to bias) his or her
`work has been asked to notify the APA Department of Quality Improvement and Psychiatric
`Services. This potential bias is then discussed with the work group chair and the chair of the
`Steering Committee on Practice Guidelines. Further action depends on the assessment of
`the potential bias. The development of the APA practice guidelines has not been financially
`supported by any commercial organization.
`This practice guideline was approved in December 2001 and published in April 2002.
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`Guide to Using This Practice Guideline
`
`This practice guideline is based on available evidence and clinical consensus and offers
`treatment recommendations to help psychiatrists develop plans for the care of adult pa-
`tients with bipolar disorder. This guideline contains many sections, not all of which will be
`equally useful for all readers. The following guide is designed to help readers find the sec-
`tions that will be most useful to them. Part A contains the treatment recommendations for
`patients with bipolar disorder. Section I is the summary of the treatment recommendations,
`which includes the main treatment recommendations along with codes that indicate the
`degree of clinical confidence in each recommendation. Section II is a guide to the formula-
`tion and implementation of a treatment plan for the individual patient. This section in-
`cludes all of the treatment recommendations. Section III, “Special Clinical Features
`Influencing the Treatment Plan,” discusses a range of clinical considerations that could alter
`the general recommendations discussed in Section II.
`Part B, “Background Information and Review of Available Evidence,” will be useful to
`understand, in detail, the evidence underlying the treatment recommendations of Part A.
`Section IV provides an overview of DSM-IV bipolar disorder criteria, features of the disorder,
`and general information on its natural history, course, and epidemiology. Section V is a
`structured review and synthesis of published literature regarding available treatments for
`bipolar disorder. Because of the paucity of published data on some important clinical ques-
`tions, unpublished studies as well as those in press were also reviewed and included, al-
`though they were given considerably less weight than published trials.
`Part C, “Future Research Needs,” draws from the previous sections to summarize those
`areas in which better research data are needed to guide clinical decisions.
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`American Psychiatric Association
`
`Introduction
`
`This practice guideline summarizes data on the specific so-
`matic and psychosocial interventions that have been stud-
`ied in the treatment of bipolar disorder. It begins at the
`point at which a diagnostic evaluation performed by a psy-
`chiatrist has raised the concern that an adult patient may
`be suffering from bipolar disorder. According to the criteria
`defined in DSM-IV-TR (1), patients with bipolar I disorder
`have experienced at least one episode of mania; they may
`have experienced mixed, hypomanic, and depressive epi-
`sodes as well. Patients with bipolar II disorder have experi-
`enced hypomanic and depressive episodes. Cyclothymic
`disorder may be diagnosed in those patients who have nev-
`er experienced a manic, mixed, or major depressive epi-
`sode but who have experienced numerous periods of
`depressive symptoms and numerous periods of hypoman-
`ic symptoms for at least 2 years (or 1 year for children [1]),
`with no symptom-free period greater than 2 months. Final-
`ly, patients with depressive symptoms and periods of mood
`elevation who do not meet criteria for any specific bipolar
`disorder may be diagnosed with bipolar disorder not other-
`wise specified. For patients with depressive symptoms and
`no history of mania or hypomania, the psychiatrist should
`refer to the APA Practice Guideline for the Treatment of Pa-
`tients With Major Depressive Disorder (2).
`
`In addition to looking for evidence of the existence of
`a mood disorder, the initial psychiatric evaluation in-
`cludes an assessment for the presence of an alcohol or
`substance use disorder or other somatic factors that may
`contribute to the disease process or complicate its treat-
`ment. The evaluation also requires a judgment about the
`safety of the patient and those around him or her and a de-
`cision about the appropriate setting for treatment (e.g.,
`outpatient, day program, inpatient).
`The purpose of this guideline is to assist the clinician
`faced with the task of implementing a specific regimen for
`the treatment of a patient with bipolar disorder. It should
`be noted that many patients with bipolar disorder also suf-
`fer from comorbid psychiatric illnesses. Although this
`guideline provides considerations for managing comor-
`bidity in the context of bipolar disorder, it is likely that the
`psychiatrist will also need to refer to treatment guidelines
`appropriate to other diagnoses.
`This guideline concerns patients 18 years of age and
`older. Some comments regarding the treatment of bipolar
`disorder in children and adolescents can be found in sec-
`tions III.B.4. (p. 14) and V.F. (p. 35) as well as in more defin-
`itive references (3).
`
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`BIPOLAR DISORDER
`
`Overview of Guideline Development Process
`
`This document is a practical guide to the management of
`patients—primarily adults 18 years of age and older—with
`bipolar disorder and represents a synthesis of current sci-
`entific knowledge and rational clinical practice. This
`guideline strives to be as free as possible of bias toward any
`theoretical approach to treatment.
`This practice guideline was developed under the aus-
`pices of the Steering Committee on Practice Guidelines.
`The development process is detailed in a document avail-
`able from the APA Department of Quality Improvement
`and Psychiatric Services: the “APA Guideline Development
`Process.” Key features of this process include the follow-
`ing:
`
`•
`
`• A comprehensive literature review and development of
`evidence tables.
`Initial drafting by a work group that included psychia-
`trists with clinical and research expertise in bipolar dis-
`order.
`• The production of multiple drafts with widespread re-
`view; seven organizations and more than 40 individuals
`submitted significant comments.
`• Approval by the APA Assembly and Board of Trustees.
`• Planned revisions at regular intervals.
`
`A computerized search of the relevant literature from
`MEDLINE and PsycINFO was conducted. Sources of fund-
`ing were not considered when reviewing the literature.
`The first literature search was conducted by searching
`MEDLINE and PsycINFO for the period from 1992 to 2000.
`Key words used were “bipolar disorder,” “bipolar depres-
`sion,” “mania,” “mixed states,” “mixed episodes,” “mixed
`mania,” “antimanic,” “hypomanic,” “hypomania,” “manic
`depression,” “prophylactic,” “pharmacotherapy,” “mood
`stabilizers,” “mood-stabilizing,” “rapid cycling,” “mainte-
`
`nance,” “continuation,” “child and adolescent,” “antide-
`pressants,” “valproate,” “lithium,” “carbamazepine,”
`“olanzapine,” “risperidone,” “gabapentin,” “topiramate,”
`“lamotrigine,” “clonazepam,” “divalproex,” “psychothera-
`py,” “family therapy,” “psychoeducation,” “course,” “epide-
`miology,” “comorbidity,” “anxiety,” “anxiety disorders,”
`“attention deficit,” “catatonia,” “elderly,” “family history,”
`“gender,” “general medical conditions,” “life events,” “per-
`sonality disorders,” “pregnancy,” “psychosis,” “stress,”
`“substance-related disorders,” “suicide,” “homicide,” and
`“violence.” A total of 3,382 citations were found.
`An additional MEDLINE search for the period from
`1992 to 2001 used the key words “genetic counseling,”
`“family functioning,” “cross-cultural issues,” and “phar-
`macokinetics.” A total of 122 citations were found. A
`search on PubMed was also conducted through 2001 that
`used the search terms “electroconvulsive,” “intravenous
`drug abuse,” “treatment response,” “pharmacogenetic,”
`“attention deficit disorder,” “violence,” “aggression,” “ag-
`gressive,” “suicidal,” “cognitive impairment,” “sleep,”
`“postpartum,” “ethnic,” “racial,” “metabolism,” “hyper-
`parathyroidism,” “overdose,” “toxicity,” “intoxication,”
`“pregnancy,” “breast-feeding,” and “lactation.”
`Additional, less formal, literature searches were con-
`ducted by APA staff and individual members of the work
`group on bipolar disorder.
`The recommendations are based on the best available
`data and clinical consensus with regard to a particular
`clinical decision. The summary of treatment recommen-
`dations is keyed according to the level of confidence with
`which each recommendation is made. In addition, each
`reference is followed by a letter code in brackets that indi-
`cates the nature of the supporting evidence.
`
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`BIPOLAR DISORDER
`
`PART A: Treatment Recommendations for Patients
`With Bipolar Disorder
`
`I. Executive Summary of Recommendations
`
`Each recommendation is identified as falling into one
`of three categories of endorsement, indicated by a brack-
`eted Roman numeral following the statement. The three
`categories represent varying levels of clinical confidence
`regarding the recommendation:
`
`[I] Recommended with substantial clinical confidence.
`[II] Recommended with moderate clinical confidence.
`[III] May be recommended on the basis of individual
`circumstances.
`
`A. Psychiatric Management
`At this time, there is no cure for bipolar disorder; how-
`ever, treatment can decrease the associated morbidity and
`mortality [I]. Initially, the psychiatrist should perform a di-
`agnostic evaluation and assess the patient’s safety and lev-
`el of functioning to arrive at a decision about the optimum
`treatment setting [I]. Subsequently, specific goals of psy-
`chiatric management include establishing and maintain-
`ing a therapeutic alliance, monitoring the patient’s psy-
`chiatric status, providing education regarding bipolar
`disorder, enhancing treatment compliance, promoting
`regular patterns of activity and of sleep, anticipating stres-
`sors, identifying new episodes early, and minimizing func-
`tional impairments [I].
`
`B. Acute Treatment
`1. Manic or mixed episodes
`The first-line pharmacological treatment for more se-
`vere manic or mixed episodes is the initiation of either
`lithium plus an antipsychotic or valproate plus an antipsy-
`chotic [I]. For less ill patients, monotherapy with lithium,
`valproate, or an antipsychotic such as olanzapine may be
`sufficient [I]. Short-term adjunctive treatment with a ben-
`zodiazepine may also be helpful [II]. For mixed episodes,
`valproate may be preferred over lithium [II]. Atypical an-
`tipsychotics are preferred over typical antipsychotics be-
`cause of their more benign side effect profile [I], with most
`of the evidence supporting the use of olanzapine or ris-
`peridone [II]. Alternatives include carbamazepine or ox-
`carbazepine in lieu of lithium or valproate [II]. Antidepres-
`sants should be tapered and discontinued if possible [I]. If
`psychosocial therapy approaches are used, they should be
`combined with pharmacotherapy [I].
`For patients who, despite receiving maintenance
`medication treatment, experience a manic or mixed epi-
`sode (i.e., a “breakthrough” episode), the first-line in-
`tervention should be to optimize the medication dose [I].
`Introduction or resumption of an antipsychotic is some-
`times necessary [II]. Severely ill or agitated patients may
`
`4
`
`also require short-term adjunctive treatment with a ben-
`zodiazepine [I].
`When first-line medication treatment at optimal dos-
`es fails to control symptoms, recommended treatment op-
`tions include addition of another first-line medication [I].
`Alternative treatment options include adding carba-
`mazepine or oxcarbazepine in lieu of an additional first-
`line medication [II], adding an antipsychotic if not already
`prescribed [I], or changing from one antipsychotic to an-
`other [III]. Clozapine may be particularly effective in the
`treatment of refractory illness [II]. ECT may also be consid-
`ered for patients with severe or treatment-resistant mania
`or if preferred by the patient in consultation with the psy-
`chiatrist [I]. In addition, ECT is a potential treatment for
`patients experiencing mixed episodes or for patients expe-
`riencing severe mania during pregnancy [II].
`Manic or mixed episodes with psychotic features usual-
`ly require treatment with an antipsychotic medication [II].
`
`2. Depressive episodes
`The first-line pharmacological treatment for bipolar
`depression is the initiation of either lithium [I] or lamotri-
`gine [II]. Antidepressant monotherapy is not recom-
`mended [I]. As an alternative, especially for more severely
`ill patients, some clinicians will initiate simultaneous
`treatment with lithium and an antidepressant [III]. In pa-
`tients with life-threatening inanition, suicidality, or psy-
`chosis, ECT also represents a reasonable alternative [I].
`ECT is also a potential treatment for severe depression
`during pregnancy [II].
`A large body of evidence supports the efficacy of psy-
`chotherapy in the treatment of unipolar depression [I]. In
`bipolar depression, interpersonal therapy and cognitive
`behavior therapy may be useful when added to pharmaco-
`therapy [II]. While psychodynamic psychotherapy has not
`been empirically studied in patients with bipolar depres-
`sion, it is widely used in addition to medication [III].
`For patients who, despite receiving maintenance
`medication treatment, suffer a breakthrough depressive
`episode, the first-line intervention should be to optimize
`the dose of maintenance medication [II].
`When an acute depressive episode of bipolar disorder
`does not respond to first-line medication treatment at op-
`timal doses, next steps include adding lamotrigine [I], bu-
`propion [II], or paroxetine [II]. Alternative next steps in-
`clude adding other newer antidepressants (e.g., a selective
`serotonin reuptake inhibitor [SSRI] or venlafaxine) [II] or a
`monoamine oxidase inhibitor (MAOI) [II]. For patients
`with severe or treatment-resistant depression or depres-
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`sion with psychotic or catatonic features, ECT should be
`considered [I].
`The likelihood of antidepressant treatment precipitat-
`ing a switch into a hypomanic episode is probably lower in
`patients with bipolar II depression than in patients with
`bipolar I depression. Therefore, clinicians may elect to rec-
`ommend antidepressant treatment earlier in patients with
`bipolar II disorder [II].
`Depressive episodes with psychotic features usually
`require adjunctive treatment with an antipsychotic medi-
`cation [I]. ECT represents a reasonable alternative [I].
`
`3. Rapid cycling
`As defined in DSM-IV-TR (1) and applied in this guide-
`line, rapid cycling refers to the occurrence of four or more
`mood disturbances within a single year that meet criteria
`for a major depressive, mixed, manic, or hypomanic epi-
`sode. These episodes are demarcated either by partial or
`full remission for at least 2 months or a switch to an episode
`of opposite polarity (e.g., from a major depressive to a man-
`ic episode). The initial intervention in patients who experi-
`ence rapid cycling is to identify and treat medical condi-
`tions, such as hypothyroidism or drug or alcohol use, that
`may contribute to cycling [I]. Certain medications, particu-
`larly antidepressants, may also contribute to cycling and
`should be tapered if possible [II]. The initial treatment for
`patients who experience rapid cycling should include lithi-
`um or valproate [I]; an alternative treatment is lamotrigine
`[I]. For many patients, combinations of medications are
`required [II].
`
`C. Maintenance Treatment
`Following remission of an acute episode, patients
`may remain at particularly high risk of relapse for a period
`of up to 6 months; this phase of treatment, sometimes re-
`ferred to as continuation treatment, is considered in this
`guideline to be part of the maintenance phase. Mainte-
`nance regimens of medication are recommended follow-
`ing a manic episode [I]. Although few studies involving
`patients with bipolar II disorder have been conducted,
`consideration of maintenance treatment for this form of
`
`BIPOLAR DISORDER
`
`the illness is also strongly warranted [II]. The medications
`with the best empirical evidence to support their use in
`maintenance treatment include lithium [I] and valproate
`[I]; possible alternatives include lamotrigine [II] or carba-
`mazepine or oxcarbazepine [II]. If one of these medica-
`tions was used to achieve remission from the most recent
`depressive or manic episode, it generally should be con-
`tinued [I]. Maintenance sessions of ECT may also be con-
`sidered for patients whose acute episode responded to
`ECT [II].
`For patients treated with an antipsychotic medication
`during the preceding acute episode, the need for ongoing
`antipsychotic treatment should be reassessed upon enter-
`ing maintenance treatment [I]; antipsychotics should be
`discontinued unless they are required for control of persis-
`tent psychosis [I] or prophylaxis against recurrence [III].
`While maintenance therapy with atypical antipsychotics
`may be considered [III], there is as yet no definitive evi-
`dence that their efficacy in maintenance treatment is com-
`parable to that of agents such as lithium or valproate.
`During maintenance treatment, patients with bipolar
`disorder are likely to benefit from a concomitant psycho-
`social intervention—including psychotherapy—that ad-
`dresses illness management (i.e., adherence, lifestyle
`changes, and early detection of prodromal symptoms) and
`interpersonal difficulties [II].
`Group psychotherapy may also help patients address
`such issues as adherence to a treatment plan, adaptation
`to a chronic illness, regulation of self-esteem, and man-
`agement of marital and other psychosocial issues [II]. Sup-
`port groups provide useful information about bipolar dis-
`order and its treatment [I].
`Patients who continue to experience subthreshold
`symptoms or breakthrough mood episodes may require
`the addition of another maintenance medication [II], an
`atypical antipsychotic [III], or an antidepressant [III].
`There are currently insufficient data to support one com-
`bination over another. Maintenance sessions of ECT may
`also be considered for patients whose acute episode re-
`sponded to ECT [II].
`
`II. Formulation and Implementation of a Treatment Plan
`
`The following discussion regarding the formulation
`and implementation of a treatment plan refers specifically
`to patients with bipolar disorder. Every effort has been
`made to identify and highlight distinctions between bipo-
`lar I and bipolar II disorder in terms of patient response to
`treatment. However, with few exceptions, data from large
`trials have been presented in such a way that making such
`distinctions is difficult. For the treatment of patients with
`major depressive disorder, readers should refer to the APA
`Practice Guideline for the Treatment of Patients With Major
`Depressive Disorder (2).
`
`Initial treatment of bipolar disorder requires a thor-
`ough assessment of the patient, with particular attention
`to the safety of the patient and those around him or her as
`well as attention to possible comorbid psychiatric or med-
`ical illnesses. In addition to the current mood state, the cli-
`nician needs to consider the longitudinal history of the pa-
`tient’s illness. Patients frequently seek treatment during an
`acute episode, which may be characterized by depression,
`mania, hypomania, or a mixture of depressive and manic
`features. Treatment is aimed at stabilization of the episode
`with the goal of achieving remission, defined as a com-
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`BIPOLAR DISORDER
`
`plete return to baseline level of functioning and a virtual
`lack of symptoms. (Following remission of a depressive ep-
`isode, patients may remain at particularly high risk of re-
`lapse for a period up to 6 months; this phase of treatment,
`sometimes referred to as continuation treatment [4], is
`considered in this guideline to be part of maintenance
`treatment.) After successfully completing the acute phase
`of treatment, patients enter the maintenance phase. At
`this point, the primary goal of treatment is to optimize
`protection against recurrence of depressive, mixed, manic,
`or hypomanic episodes. Concurrently, attention needs to
`be devoted to maximizing patient functioning and mini-
`mizing subthreshold symptoms and adverse effects of
`treatment.
`Of note, in the treatment recommendations outlined
`in this guideline, several references are made to adding
`medications or offering combinations of medications. Pa-
`tients with bipolar disorder often require such combina-
`tions in order to achieve adequate symptom control and
`prophylaxis against future episodes. However, each addi-
`tional medication generally increases the side effect bur-
`den and the likelihood of drug-drug interactions or other
`toxicity and therefore must be assessed in terms of the
`risk-benefit ratio to the individual patient. This guideline
`has attempted to highlight medication interactions used
`in common clinical practice that are of particular concern
`(e.g., interactions between lamotrigine and valproate or
`between carbamazepine and oral contraceptives). In addi-
`tion, for several of the medications addressed in this
`guideline, different preparations or forms are available
`(e.g., valproic acid and divalproex). Although the guideline
`refers to these medications in general terms, the form of
`medication with the best tolerability and fewest drug in-
`teractions should be preferred.
`At other times in treatment, it may be necessary to dis-
`continue a medication (e.g., because of intolerable side ef-
`fects) or substitute one medication for another. It is prefer-
`able to slowly taper the medication to be discontinued
`rather than discontinuing it abruptly.
`In this revision of the previously published Practice
`Guideline for the Treatment of Patients With Bipolar Disor-
`der (5), the term “mood stabilizer” has been omitted. Sev-
`eral definitions of what constitutes a mood stabilizer have
`been proposed and generally include such criteria as prov-
`en efficacy for the treatment of mania or depression, ab-
`sence of exacerbation of manic or mixed symptoms, or
`prop