Bipolar Disorder: How to Recognize and Treat in Primary Care

Patients with psychiatric disordersoften present a diagnostic challenge-even for psychiatrists. Their demeanormay not readily reveal the nature orseverity of the problem. Nevertheless,there are clues that can help you sortthrough the differential and arrive atthe correct diagnosis.

Here, I focus on how to recognizebipolar disorder, and I also offer recommendationsfor treatment.

PREVALENCE AND IMPACT
The Diagnostic and StatisticalManual of Mental Disorders, FourthEdition (DSM-IV-TR), characterizesmood disorders as primarily disturbancesof emotions and feelings. The 2principal mood disorders are major depressivedisorder and bipolar disorder.Patients with bipolar disorder have recurrentepisodes of both depressionand mania (and sometimes the 2 combined--called a "mixed episode").

Bipolar disorder will develop inapproximately 1% of Americans atsome point in their lives.^1,2 The age ofonset is typically young adulthood-with 30 years the mean-and the disorderaffects men and women equally.^1,2 Genetics play a significant role intransmission of this illness. If one parentin a couple has bipolar disorder,there is a 25% risk that their childrenwill have a mood disorder. If both parentshave bipolar disorder, the risk increasesto between 50% and 75%.²

Persons with bipolar disordertend to be bright, driven, and quick-witted.However, the effects of their illnessoften prevent them from fulfilling theirpotential. The disorder also contributesto the disruption of social relations andmarriages; divorces are common. Between10% and 15% of persons withbipolar disorder commit suicide.¹

TYPES OFBIPOLAR DISORDER
There are several types of bipolardisorder, which are distinguished bythe nature of the episodes and by thepattern with which they recur.

Bipolar I disorder. This is "classic"bipolar disorder and is also referredto as manic-depressive illness.Diagnosis requires the occurrence ofone or more manic episodes or mixedepisodes and at least one major depressiveepisode. (A mixed episode isone in which the patient experiencesquick shifts in mood over a week ormore, and the opposite poles of theserapid fluctuations meet the criteria formanic and depressive episodes. Clinicalsigns of a mixed episode includeagitation, insomnia, psychosis, andsuicidal speculation.) Patients whohave bipolar I disorder usually exhibitsignificant social and occupationaldysfunction.

Bipolar II disorder. Affected patientshave had a mood cycle or cyclesthat range from a major depressiveepisode to hypomania, yet neverextend beyond hypomania to mania.(Hypomania is a persistently energized,elevated, or irritable mood thatlasts several days and is not related toingestion of a particular substance orto a medical condition. Hypomanic patientsdo not have psychotic symptoms-which are common in thosewith mania-and they are able tomaintain self-control.)

Bipolar I or II disorder withrapid cycling. Patients have 4 or moreepisodes of mood disturbance within 1year. The chaotic mood instability seenin these patients can mimic borderlinepersonality disorder. Women are morelikely to have rapid-cycling bipolar disorderthan men.

DIAGNOSIS OF MANIA
The diagnosis of mania or hypomaniadepends almost entirely on theclinical history and presentation.There are no pathognomonic laboratorytests to identify bipolar disorder.However, certain laboratory testsshould be ordered if bipolar disorder-manic or hypomanic phase-issuspected. These include a completeblood cell count, comprehensive metabolicpanel, and urine drug screen.The purpose of such tests is primarilyto rule out medical conditions in thedifferential (Table 1).

Behaviors and speech patterns.Many behavioral clues to a manic orhypomanic episode can be observedduring an office visit. Bipolar patientsin a manic phase typically appear energizedand upbeat but may also be irritable.They may exhibit distinctive,inflated mannerisms. As mania progresses,patients may also chooseclothes, jewelry, hairstyles, and bodypiercings or tattoos that call attentionto their presence. Restless behaviors,such as nail-biting or pacing, and signsof inattentiveness and distractibility,such as mismatched socks, misappliedmakeup, or unkempt hair, may be evident,especially in more advancedstages.

A patient's speech provides especiallyimportant clues to the diagnosisof a manic or hypomanic bipolarepisode. Perhaps most apparent is thatsuch patients simply tend to talk toomuch. Word choice may be very expressiveor even flowery; there may beliberal use of puns or risque humor.The pace may be rapid and pressured.The tone is likely to be tense and loud.Occasionally, affected patients maylaugh infectiously and display a deceptivelightheartedness.

The speech of patients in a manicor hypomanic phase also typicallyshows signs of a breakdown of focus,clarity, and direction. Such signs, inroughly ascending order of seriousness,include:

• Overinclusiveness and circumstantiality-the inclusion of many irrelevantand tedious details.
• Tangentiality-a tendency to dropthe principal theme of a conversationin order to follow a new, obliquely relatedtopic suggested by a remark.
• Looseness of associations--shiftingthoughts without logical connections.
• Flight of ideas-loose associationsthat occur in very rapid succession;pressured, fast-paced "fibrillation" ofthought.

In addition, these patients arelikely to exhibit signs of grandiosity intheir speech. In more advanced stagesthere may be delusions, commonthemes of which include far-reachingfinancial successes, corporate conquests,athletic prowess, and sexualallure.

Clues from the history. The presentationof a number of psychiatricand medical conditions is similar tothat of the manic or hypomanic phaseof bipolar disorder. An astute and carefulhistory taking is key to properdiagnosis.

• Identify medical problems that predisposeto psychiatric disorders. Explorethe patient's personal and familyhistory of psychiatric treatment, substanceabuse, and even civil arrests.
• Ask whether the patient can identifypast periods of a week or longer of persistentlyelevated or irritable moodsthat are not secondary to alcohol,drugs, or another medical condition.
• Inquire about prolonged sleeplessness,heightened energy, and weightloss (which often results from reducedsleep and hyperactivity).
• Ask about errant sexuality, spendingsprees, traffic violations, and other evidenceof impulsive, reckless behavior.
• Question the patient about suchsigns of distractibility and inattentivenessas forgetting a purse or wallet,failing to hang up the telephone, andleaving doors open or electrical appliancesrunning. Throughout, keep inmind that patients have difficulty identifyinga manic or hypomanic phase asan illness.
• You may also want to question a patientabout hallucinations, which canbe present in more advanced manicepisodes. Manic hallucinations are typicallyauditory-"voices" that may callthe patient to action or reincriminatehim or her for failures to achieve. Insome patients, mania may progress tofrank psychosis (psychotic mania); infact, 50% of patients with bipolar disorderwill display psychotic symptoms atsome time during the course of their illness.Patients who exhibit symptomsof psychosis should be referred to apsychiatrist.

A mnemonic that can be helpfulin the diagnosis of mania is DIGFAST.It identifies the primary symptoms of amanic state:

D – distractibility
I – insomnia
G – grandiosity
F – flight of ideas
A – activity increased
S – speech (anxiously pressured and talkative)
T – thoughtlessness (poor judgment and pleasure seeking)

Differential diagnosis. In additionto bipolar disorder, the causes ofmanic behavior most likely to be seenin the primary care setting include alcohol,cocaine, amphetamine, and caffeineintoxications; substance withdrawalsyndromes; anxiety disorders;personality disorders (such as histrionic,borderline, narcissistic, or antisocialpersonality disorders); schizophrenia;and delirium that results fromvarious medical conditions (Table 2).

Alcohol/drug intoxication. Substanceabuse can mimic many psychiatricdisorders. Intoxication with amphetamines,cocaine, or ephedrinebasedcompounds is most likely toproduce signs and symptoms that resemblethose of bipolar disorder. Alcoholintoxication can also elevate andexpand mood or cause irritability thatmimics the irritable mood associatedwith bipolar disorder. However, intoxicatedpersons are more likely to slurtheir words and appear uncoordinatedthan are those in a manic or hypomanicstate, and persons who have usedcocaine or amphetamines are morelikely to exhibit mydriasis.

Bipolar disorder may also coexistwith substance abuse. In fact, bipolardisorder is the axis I psychiatric diagnosismost frequently associated withsubstance abuse.

Substance withdrawal syndromes.Withdrawal from a psychoactive substanceis typically characterized bysigns and symptoms opposite thoseseen during an episode of intoxication.For example, amphetamines and cocaineare CNS stimulants. Duringwithdrawal from these substances, individualstend to become sad, fatigued,and somnolent; withdrawalmay last several days and resemble amajor depression. Alcohol and opioids,on the other hand, are CNS depressants;withdrawal from these substancestends to be activating and cancause sleep fragmentation, diaphoresis,and GI distress. A careful historytaking that involves the family andfriends of the patient-together with aurine drug screen and measurementof blood alcohol level-can help confirmthe diagnosis.

Anxiety disorders. These areamong the most common psychiatricdisorders. The anxiety can be linkedto a specific fear, as in a phobia, or torecollections of a past traumatic event,as in post-traumatic stress disorder.The symptoms are typically physical,such as choking, lightheadedness,chest pain, or autonomic arousal (eg,trembling or palpitations). When theanxiety-provoking stimulus is removed,symptoms lessen and disappear.In patients who have bipolar disorder,symptoms of anxiety are moreconstantly present and are likely tobe accompanied by depressive symptoms.Anxiety disorders can be differentiatedfrom mania by the absence ofdelusions and hallucinations and bythe ability of patients to take directionand maintain self-control.

Personality disorders. Patientswith histrionic, borderline, narcissistic, or antisocial personality disordersoften exhibit erratic behaviors andself-dramatization similar to thoseseen in a manic or hypomanic phaseof bipolar disorder. However, patientswith personality disorders tend to displayless energy and exuberance andare directable and capable of maintainingcontrol. Also, the histories ofpatients with personality disorders reveallong-standing maladaptive behaviorsthat were probably first recognizedin early adulthood and that arenot simply transient responses tostress. Bear in mind that patients maysimultaneously meet the criteria forboth bipolar disorder and a personalitydisorder.

Schizophrenia. This illness mayresemble a bipolar manic episode thathas escalated to the point of psychosis.However, the premorbid history of apatient with schizophrenia usually revealsa person who was less animated,more withdrawn, and more behaviorallypeculiar than someone beforethe onset of a manic episode. Also, more bizarre and less grandiose thanthose of patients in a manic phase ofbipolar disorder.

Delirium. This agitated, confusedstate can resemble mania. It is oftencaused by substance withdrawal butcan be a result of other medical conditions,such as encephalitis, syphilis, orhypoglycemia. However, unlike patientsin a manic state, delirious patientsare often disoriented in allspheres and tend to have vivid tactileand visual-rather than auditory-hallucinations.Tests that can determinethe cause of delirium-and rule outmania-include a urine drug screen,measurement of electrolyte and magnesiumlevels, basic metabolic profile,rapid plasma reagin, and completeblood cell count.

DIAGNOSINGBIPOLAR DEPRESSION
The symptoms of bipolar depressionare identical to those of a unipolardepression (also called a major depressiveepisode) and include sadness,anhedonia, anergy, anorexia, weightloss, insomnia or hypersomnia, psychomotoragitation or retardation, asense of worthlessness, decreasedconcentration, and suicidal ideation.Patients with bipolar disorder, depressedphase, are more likely to appearphysically ill, and symptoms areapt to be more entrenched and profound.As with mania, the key to diagnosisof a bipolar depressive episode isa careful history. Explore the patient'sbackground for evidence of polarity,such as mood swings.

TREATMENT

Acute mania

. The principalclasses of drugs used to treat acutemania include mood stabilizers, antipsychotics,and anxiolytics. Antipsychoticmedications such as phenothiazines,haloperidol, or the neweragents olanzapine, risperidone, andziprasidone-along with a benzodiazepinesuch as clonazepam-canrapidly harness such manic symptomsas hyperactivity, agitation, restlessness,flight of ideas, hallucinations,delusions, and sleeplessness. Administera mood stabilizer (for example,lithium carbonate, valproic acid, orcarbamazepine) at the same time.Mood stabilizers have a delayed onsetof action but become increasingly effectiveover time. Once the mood stabilizerreaches a therapeutic bloodlevel, antipsychotic and anxiolyticmedications can usually be taperedand discontinued.

Refer to a psychiatrist any patientwho does not respond to mood stabilizersor anxiolytics. Patients whodisplay severe manic symptoms oftenrequire hospitalization. When patientsare in any way threatening to themselvesor others, hospitalization isnecessary.

Acute depression. As with unipolardepression, the mainstay oftreatment of bipolar depression isantidepressant therapy. However, it isimperative to keep in mind that inbipolar patients, antidepressant medicationscan sometimes rapidly transforma depressed mood into mania.Once a patient's mood is normalized,antidepressants should be tapered ordiscontinued. If a patient does not respondto antidepressant therapy, referhim to a psychiatrist.

Psychiatrists are able to offer alternativesto pharmacologic therapy.One treatment modality that can beeffective in patients with bipolar disorderis electroconvulsive therapy(ECT). ECT is often effective in resolvinga refractory bipolar depressiveor manic episode. In fact, becausesevere bipolar depression-especiallya depressive episode withpsychotic features-seldom respondsto antidepressants alone, ECT is recommendedas first-line therapy in thissetting. Other treatment options forpatients whose depression is unresponsiveto antidepressants includetherapy, sleep deprivation therapy,and such experimental therapies astranscranial magnetic stimulation andvagus nerve stimulation.

Finally, hospitalization may be requiredin severe bipolar depression toensure a patient's safety.

Long-term prophylaxis. Bipolardisorder is a chronic illness and affectedpatients require continued therapeuticmaintenance. Initiate prophylactictreatment when patients recoverfrom an episode of mania or depression.Keep in mind that if prophylaxisis discontinued, patients are likely tosuccumb to further episodes.

Mood stabilizers are the mainstayof prophylactic therapy. For many patientswith bipolar disorder, a maintenancedosage of a single mood stabilizercan largely prevent futureepisodes. Patients whose illness ismore complex may require low-doseantipsychotic medications along with 1or 2 mood stabilizers to achieve longerperiods of maintenance. The therapeuticgoal should be compliant stabilizationwith minimal medication.

All mood stabilizers are efficacious,although patients may tolerateone better than another. Lithium carbonatehas been in use the longest andis the most cost-effective; however,renal and thyroid function studiesshould be routinely ordered. Monitorhepatic function in patients who takevalproic acid. Carbamazepine therapymay result in neutropenia; order whiteblood cell counts regularly. Serumdrug levels can be obtained for each ofthe mood stabilizers.

References:

REFERENCES:1. Diagnostic and Statistical Manual of Mental Disorders(DSM-IV-TR). 4th ed. Washington, DC: AmericanPsychiatric Association; 2000:345-428.
2. Kaplan HI, Sadock BJ. Comprehensive Textbook ofPsychiatry. 6th ed. Baltimore: Williams & Wilkins;1996:543.
3. Stern TA, Herman JB. Psychiatry Update andBoard Preparation Massachusetts General Hospital.New York: McGraw-Hill; 2000.

FOR MORE INFORMATION:

• Cusack JR, Malaney KR. The diagnostic psychiatricinterview. Emerg Med. August 15, 1989.
• Diagnostic and Statistical Manual of Mental Disorders.DSM-IV. 4th ed. Washington, DC: AmericanPsychiatric Association; 1994.
• Goodwin FK. Anticonvulsant therapy and suiciderisk in affective disorders. J Clin Psychiatry. 1999;60:89-93.
• Jamison KR. Touched With Fire: Manic DepressiveIllness and the Artistic Temperament. New York:Macmillan; 1993.
• Muller-Oerlinghausen B, Berghofer A, Bauer M.Bipolar disorder. Lancet. 2002;359:241-247.