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A Review of Bipolar Disorder in Adults

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ini merupakan jurnal yang membahas mengenai penyakit gangguan alam perasaan bipolar pada dewasa
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  [SEPTEMBER] Psychiatry 2006 43  ABSTRACT Objective: This article reviews theepidemiology, etiology, assessment, andmanagement of bipolar disorder.Specialattention is paid to factors thatcomplicate treatment, includingnonadherence, comorbid disorders,mixed mania, and depression. Methods:  AMedline search was conducted fromJanuary of 1990 through December of 2005 using key terms of bipolar disorder,diagnosis, and treatment. Papersselected for further review includedthose published in English in peer-reviewed journals, with preference forarticles based on randomized, controlledtrials and consensus guidelines. Citationsde-emphasized srcinal mania trials asthese are generally well known. Results: Bipolar disorder is a major public healthproblem, with diagnosis often occurring years after onset of the disorder.comorbid conditions are common anddifficult to treat. Management includes alifetime course of medication, usuallymore than one, and attention topsychosocial issues for patients and theirfamilies. Management of mania is well-established. Research is increasingregarding management of depressive,mixed and cycling episodes, as well ascombination therapy. Conclusions: Bipolar disorder is a complex psychiatricdisorder to manage, even forpsychiatrists, because of its manyepisodes and comorbid disorders andnonadherence to treatment.  AReview of Bipolar Disorder in Adults [REVIEW] byDONALD M. HILTY,MD; MARTIN H. LEAMON,MD; RUSSELL F. LIM,MD; ROSEMARY H. KELLY,MD,MPH;and ROBERT E. HALES,MD,MBA  Drs. Hilty and Leamon are Associate Professors of Clinical Psychiatry and Behavioral Sciences at University of Califorinia,Davis; Dr. Limis Associate Clinical Professor of Psychiatry at University of Califorinia,Davis; Dr. Kelly is Intructor,Department of Psychiatry,andFaculty,Certificate Program in Infant Mental Health,University of Washington; and Dr. Hales is Joe Tupin Professor and Chair ofPsychiatry and Behavioral Sciences,University of California,Davis.  ADDRESS CORRESPONDENCE TO:Donald M. Hilty,MD,University of California,Davis,2230 Stockton Blvd.,Sacramento,CA 95817; Phone:(916) 734-8110; Fax:(916) 734-3384; Email:dmhilty@ucdavis.eduDISCLOSURES:Dr.Hilty is on the speakers bureau for Abbott Labs and Eli Lilly.Dr. Hales is a consultant for Sepracor and is on the speakers bureau,APAsymposium support,and teleconference programs for Bristol-MyersSquibb. Drs. Leamon and Lim have no relevant conflicts of interest to disclose.Key Words::bipolar,diagnosis,review,treatment,depression  Psychiatry 2006 [SEPTEMBER] 44 INTRODUCTION Bipolar spectrum disorders are amajor public health problem, withestimates of lifetime prevalence inthe general population of the UnitedStates at 3.9 percent, 1 with a rangefrom 1.5 to 6.0 percent. 2 Bipolardisorder is also associated withsignificant mortality risk, withapproximately 25 percent of patientsattempting suicide and 11 percent of patients completing. 3 Furthermore,inadequate treatment and servicestructure causes high rates of jailingfor bipolar patients. 4 Bipolardepression is still undertreated, too,with patients suffering suchsymptoms 31.9 percent of the timeover nearly 13 years. 5 Review articles for adults 6,7 andpediatric patients 8 imply progress,but we have not fully researcheddepressive episodes, combinationtreatment, health servicesinterventions, and specialpopulations. Practice guidelines, 9 decision trees, 10 and elaboratealgorithms 11,12 are well written, butare not user friendly. More pharmacologic options arenow available, and psychoeducation,self-help, and psychotherapy(individual, couple, and family)interventions are frequently utilized. 9 The Depression and Bipolar Support Alliance has taken a leading role ineducating patients, their families,medical professionals, mental healthprofessionals, and the public at largeabout manic-depressive illness. TheNational Alliance of the Mentally Ill(NAMI) has also sought informationby surveying family members aboututilization and value of mental healthservices. 13 EPIDEMIOLOGY  Bipolar I disorder starts onaverage at 18 years and bipolar IIdisorder at 22 years. 9,14  Acommunitystudy using the Mood DisorderQuestionnaire (MDQ) revealed aprevalence of 3.7 percent. 15 TheNational Comorbidity Study showedonset typically between 18 and 44,with higher rates between 18 and 34than 35 and 54. 1 In a survey of members of the DBSA, more thanhalf of the patients did not seek carefor five years and the correctdiagnosis was not made until anaverage of eight years after they firstsought treatment. 16,17 Bipolar disorder has notconsistently been associated withsociodemographic factors. Males andfemales are equally affected bybipolar I, whereas bipolar II is morecommon in women. No clearassociation between race/ethnicity,socioeconomic status, and locale of home (e.g., rural vs. urban). There isahigher rate of bipolar disorder inunmarried people. 1,14 Economic analyses usually includedirect treatment costs, indirect costsarising from mortality, and indirectcosts related to morbidity and lostproductivity. This is the model forbipolar disorder and others that arelong-term or lifetime disorders.Misdiagnosis leads to exorbitantcosts and mistreatment. 8 Latepresentation, inadequate diagnosis,and undertreatment contributeheavily to costs. ETIOLOGY ANDPATHOPHYSIOLOGY  There is not a single hypothesisthat unifies genetic, biochemical,pharmacological, anatomical, andsleep data on bipolar disorder. 20 Biochemical investigations areunderway for transmitters(catecholamines, serotonin, gammaaminobutyric acid (GABA),glutamate and others), hormones(brain-derived neurotrophic factor,thyroid and others), and steroids—alone and in collaboration. Imagingstudies, emerging throughoutmedicine, may shed light.Epidemiological evidence,particularly studies of concordancein identical and fraternal twins,implies that affective disorders areheritable. For family members of bipolar probands, the morbid risk isbetween 2.9 and 14.5 percent forbipolar disorder and 4.2 and 24.3percent for unipolar disorder,depending on the diagnostic criteriaused and the heterogeneity of theprobands. 19 The degree to whichbipolar I, bipolar II, hypomania,cyclothymia, and unipolar depressionare genetically related or distinctentities is unknown. 20 It remainsunclear if mood disturbance(phenotype) is the best indicator of agenetic etiology. Concerns of patients and their relatives can bedealt with through counseling. Biochemical and pharmacologicstudies led to catecholaminehypothesis to explain bipolardisorder, particularly mania,presuming that mania is due to anexcess and depression is due to adepletion of catecholamines.Norepinephrine has been implicatedmainly because of abnormalitieslinked with depression including itsmodulation by tricyclicantidepressants (TCAs). Dopaminehas been implicated because thedopamine precursor L-dopa,amphetamines, and TCAs oftenproduce hypomania in bipolarpatients. Antipsychotic medicationsthat selectively block dopaminereceptors (e.g., pimozide) areeffective against severe mania.  Anumber of serotonin hypotheseshave been proposed, in isolation, orin relationship to other systems. The“permissive hypothesis” of serotoninfunction states that low serotonergicfunction accounts for both manicand depressive states throughdefective dampening of otherneurotransmitters (mainlynorepinephrine and dopamine). 6 Some use this as an explanation asto why some bipolar patients dobetter on such antidepressants,including rare cases of mania thatdissipate.  Awide range of neuroanatomicaland neuroimaging studies are beingconducted to learn more aboutbipolar disorder. 19 Lesions in thefrontal and temporal lobes are mostfrequently associated with bipolardisorder. Left-sided lesions tend tobe associated with depression andright-sided lesions with mania,though differences may be reversedin the posterior regions of the brain(e.g., the association of depressionwith right parietooccipital lesions).Noabnormalities have been foundconsistently via computed  [SEPTEMBER] Psychiatry 2006 45 tomography (CT)studies, though ventricularenlargement has beensuspected. Magneticresonance imaging(MRI) studies revealan increase in whitematter intensitiesassociated with bipolardisorder andcorrelated with age, 21 though the clinicalsignificance isunknown. Overall,most functionalimaging studies(single-photonemission computertomography [SPECT]and positron emissiontomography [PET])have noted prefrontaland anteriorparalimbichypoactivity in bipolardepression, whilepreliminary studies of manic patients have yielded inconsistentfindings.There are two otherimportant biochemicalmodels for bipolardisorder.Post andcollaborators haveproposed a model thatelectrophysiologicalkindling andbehavioral sensitization underliebipolar disorder, particularly theincreasing frequency of episodesover time. 22 Parallels between thismodel and bipolar disorder includethe following: Predisposing effects of both genetic factors and earlyenvironmental stress; thresholdeffects (mild alterations eventuallyproducing full-blown episodes); earlyepisodes requiring precipitants whilelater ones do not; and repeatedepisodes of one phase leading toemergence of the other. 19 Circadian rhythmdesynchronization has also beenimplicated in bipolar disorder. Animal data indicate that periodicphysiological disturbances can occurif two rhythms becomedesychronized (i.e., if one becomesfree-running in and out of phase withthe other). 19 It is unclear if and how genetics contribute to the course(e.g., rapid cycling), circadian andseasonal rhythms, and the capacityfor kindling and sensitization. Cognitive processing is oftenimpaired in bipolar patients, even ineuthymic patients. 23,24 Executivefunction, visulospatial, memory, verbal fluency, and attentionaldeficits have been noted. This maybe a primary feature of bipolardisorder, secondary to otherdysregulation (e.g., insomnia) orsecondary to comorbid conditions(e.g., substance use). Cognitiveassessment is underutilized inassessing medication side effects, thereturn to the outpatient sector frominpatient, and employing vocationalrehabilitation in preparation forwork. 25 DIAGNOSIS The fourth edition of the  Diagnostic and Statistical Manualof Mental Disorders Text Revision (DSM-IV-TR) includes bipolar Idisorder, bipolar II disorder,cyclothymic disorder, and bipolardisorder not otherwise specified. 26 The episodes are characterized bymania, hypomania, depressive, andmixed episodes. By definition,patients with bipolar I disorder have ManiaDepression SUBSTANCES Intoxication  AmphetaminesAnticholinergicBarbituratesBenzodiazepinesCocaineHallucinogensOpiatesPhencyclidine Withdrawal  AlcoholBarbituratesBenzodiazepines MEDICATIONS  BaleenBromideBromocriptineBronchodialatorsCalcium replacementCaptoprilCimetidineCorticosteroidsCyclosporineDecongestantsDisulfiramHydralazineIsoniazidLevodopaMethylphenidateMetoclopramideMetrizamideProcarbazineProcarbazineProcyclidine SUBSTANCES Intoxication  AlcoholeBarbituratesBenzodiazepinesCannabis Withdrawal  AmphetaminesCocaine MEDICATIONS  AcetazolamideAmantadineAnticholinesterasesAzathioprineBaclofenBarbituratesBenzodiazepinesBleomycineBromocriptineButyrophenonesCarbamazepineChloral hydrateCimetidineClonidineClotrimazoleCorticosteroidsCycloserineDanazolDapsoneDigitalisDisulfiramFenfluramineGresofulvineGuanethidineHydralazineIbuprofenIndomethacinLevodopa/MethyldopaLidocaineMeclizineMetaclopramideMethsuzimideMetronidazoleMithramycinNitrofurantoinOpiatesOral contraceptivesPhenacetinPhenothiazinesPhenylbutazonePhenytoinPrazocinProcainamidePropranololReserpineStreptomycinSulfonamidesTetracyclineTriamcinoloneVincristine  TABLE 1. Medical,surgical,and medication differential diagnosis for mania and depression  Psychiatry 2006 [SEPTEMBER] 46 had at least one episode of mania.Those with bipolar II have haddepressive and hypomanic episodes.Rapid cycling is technically four ormore episodes per year, thoughmany clinicians use the term todescribe mood oscillations day today. Mania occurring in the contextof medication, substances, ormedical illness is known assecondary mania and classifiedseparately. The reason for the sharp increasein epidemiological studies on “bipolarspectrum” is more systematicsampling and more sophisticateddetection of patients with 1 to 2symptoms (only) or those with 4 to 5symptoms, which last 2 to 3 days—often placed in the bipolar nototherwise specified. This is animportant determination, since manyalready responded adversely tostandard antidepressants prescribedbecause the patients were previouslydiagnosed with depression. The differential diagnosis of bipolar disorder is quite extensiveand complex. First, the presentationof patients can be similar to othermood and psychotic disorders,including major depression,schizoaffective disorder, andschizophrenia. A positive familyhistory of mood disorder issuggestive of a mood disorder, evenwhen patients present withprominent psychotic symptoms.Second, bipolar disorder symptomsof recklessness, impulsivity, truancy,and other antisocial behavior are notunique versus substance, personality(borderline, antisocial, and others),and attention deficit hyperactivitydisorders. Third, the relationshipbetween affective illness andpersonality must be considered inmaking the diagnosis of bipolardisorder. Bipolar disorder should always beconsidered in the differentialdiagnosis of patients withdepression, as 3.9 perecent of patients converted to bipolar Idisorder and 8.6 percent convertedto bipolar II disorder upon follow-upover 2 to 11 years. 27 Prospectivepredictors of bipolar I disorder wereacute onset of depression, severity of the depressive episode, andpsychosis, while predictors of bipolarII disorder included mood lability,higher rates of substance abuse,disruption of psychosocialfunctioning, and racing thoughts. 19  ASSESSMENT The evaluation of a bipolar patientinvolves a number of importantclinical and psychosocial issues. Theprimary tool is the neuropsychiatricassessment with the history andphysical examination. Brief histories(less than 30 minutes) may be aliability,due to the complexity of themood course in patients not alreadydiagnosed. Collateral information isrequired in most cases from family,friends, or prior places of treatment. Adelineation of episodic versuschronic symptoms is helpful, exceptwith patients with cycling of moodday-to-day, in a mixed episode, orotherwise very unstable course.Screening instruments can be usedfor manic episodes (e.g. MoodDisorder Questionnaire [MDQ]),though they may have more utility inprimary care settings. The MDQ has13 yes/no items, and seven positiveanswers call for a full clinicalevaluation. 15 The clinician must also assess forthe presence of psychotic features,cognitive impairment, risk of suicide,risk of violence to persons orproperty, risk-taking behavior,sexually inappropriate behavior, andsubstance abuse. In addition, it isimportant to assess for the patient’s PrincipleComments1.Establish and maintain atherapeutic alliance2.Monitor the patient’s psychiatricstatus3.Provide education regardingbipolar disorder 4.Enhance treatment adherence5.Promote regular patterns of activity and wakefulness6.Promote understanding of andadapatation to the psychosocialeffects of bipolar disorder 7.Identify new episodes early 8.Reduce all morbidity and sequelaeof bipolar disorder 9.Promote acceptance of thediagnosis10.Promote emotional wellbeing This is crucial for managing severeepisodes and maintaining adherence. This is necessary for early detection ofrecurrence.Discussion on an ongoing process,use ofeducational brochures,and use ofliterature written by peers is useful for patient.Monitor ambivalences about treatmentand use of psychological defense ofdenial. These factors have an effect on mood.Discuss the cascade effect of the illnessin all psychosocial spheres. This enhances masteryand reducesmorbidity.Early treatment,management ofstressors,and adherence are critical.Reduce stigmatization,promote a senseof “control”through medication,promoteavoidance of siubstances.Enhance self esteem,resolveinterpersonal difficulties,and promote vocation. TABLE 2. Principles of psychiatric management
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