Management of Bipolar Disorder
`
`KIM S. GRISWOLD. M.D.. M.l-".H., and LINDA F. PESSAR. M.D.
`State University of New York at Buffalo. Buffalo. New York
`
`Bipolar disorder most commonly is diagnosed in persons between 18 and 24
`years of age. The clinical presentations of this disorder are broad and include
`mania. hypomania and psychosis. Frequently associated comorbid conditions
`include substance abuse and anxiety disorders. Patients with acute mania must
`be evaluated urgently. Effective mood stabilizers include lithium, valproic acid
`and carbarnazepine. A comprehensive management program. including collab-
`oration between the patienfs family physician and psychiatrist. should be
`implemented to optimize medical care. (Am Fam Physician 2l]OU:62:1343-53,
`1357-8.)
`
`O A patient informa-
`tion handout on bipo~
`lar disorder; written by
`the authors of this
`article, is provided
`on page 1357.
`
`Eli] This article
`exemplifies the AAFP
`2000 Annual Clinical
`Focus on mental health.
`
`ipolar disorder is characterized by
`variations in mood, from elation
`
`andlor irritability to depression.
`This disorder can cause major dis-
`ruptions in family, social and
`occupational life. Bipolar I disorder is defined as
`episodes of full mania alternating with episodes
`
`TABLE 1
`
`Causes of Secondary Mania
`
`Substance abuse
`
`Amphetamines
`Caffeine
`Cocaine
`
`Over~the—counter diet pills (e.g.,
`phenylpropanoiaminel
`Methylphenidate (Ritalin)
`
`Drug withdrawal states
`Ethanol
`Monoamine oxidase inhibitors
`
`Sympathomimetic agents
`Tricyclic antidepressants
`
`Therapeutic agents
`lsoniazid
`Levodopa
`Monoamine oxidase inhibitors
`Steroids
`
`Tricyclic antidepressants
`
`Toxic metabolic states
`
`Hyperthyroidism
`Electrolyte abnormalities
`
`Central nervous system disorders
`Multiple sclerosis
`Brain tumor
`
`Sleep deprivation
`Structural damage to right
`(non-dominant} hemisphere
`Temporal lobe (complex partial)
`seizures
`
`Infections
`
`Encephalitis
`Syphilis of the centrai nervous system
`Sepsis
`
`Adapted with permission from Krautharnrner C. Klen-nan GL. Secondary mania.
`Arch Gen Psych l9?8;35:l333-9, and Cassem NH. Depression.
`in: Hackett Tl‘?
`Cassem NH, eds. Massachusetts General Hospital handbook of general hospital
`psychiatry: 2d ed. Litrleton, Mass.‘ PSG, 1987.227-60.
`
`of major depression. Patients with mania often
`exhibit disregard for danger and engage in high-
`risk behaviors such as promiscuous sexual
`activity, increased spending, violence, substance
`abuse and driving while intoxicated.
`Bipolar
`Il disorder is characterized by
`recurrent episodes of major depression and
`hypomania. Hypomania is manifested by an
`elevated and expansive mood. The behaviors
`characteristic of hypomania are similar to
`those of mania but without gross lapses of
`impulse and judgment. I-lypomania does not
`cause impairment of function and may actu-
`ally enhance function in the short term.
`Bipolar l disorder is typically diagnosed
`when patients are in their early 20s. Manic
`symptoms can rapidly escalate over a period
`of days and frequently follow psychosocial
`stressors. Some patients initially seek treat-
`ment
`for depression. Other patients may
`appear irritable, disorganized or psychotic.
`Difierentiating true mania from mania result-
`ing from secondary causes can be challenging
`(Table l)."
`
`Bipolar II disorder typically is brought to
`medical attention when the patient
`is
`depressed. A careful history will usually illu-
`minate the diagnosis. Some depressed patients
`exhibit hypomania when given antidepres-
`sants.’ This variation is sometimes referred to
`
`as bipolar III disorder. The criteria for major
`depressive episode and manic episode, as
`described in the Diagnostic and Statistical
`Manual of Mental Disorders. 4th ed. (DSM-
`IV), are summarized in Table 2.‘
`
`Si-‘.P'TE.l\«'lBl-ZR 15. 2000 i VOLUME 62, NUMBER 6
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`TABLE 2
`
`Criteria for Major Depressive Episode and Manic Episode
`
`Major depressive episode
`Five or more of the following symptoms have been present during the same 2-week period and represent a change from previous
`functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.
`. Depressed mood most of the day, nearly every day, as indicated by either subjective report {e.g., feeis sad or empty) or
`observation made by others {eg., appears tearful). Note: In children and adolescents, can be irritable mood.
`. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either
`subjective account or observation made by others)
`. Significant weight loss when not dieting or weight gain (e.g.. a change of more than 5% of body weight in a month).
`or decrease or increase in appetite nearly every day. Note: In children, consider failure to make expected weight gains.
`. insomnia or hypersomnia nearly every day
`. Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness
`or being slowed down)
`. Fatigue or loss of energy nearly every day
`_ Feelings of worthlessness or excessive or inappropriate guilt {which may be delusional) nearly every day {not merely self-reproach
`or guilt about being sick)
`. Diminished ability to think or concentrate, or indeciseveness, nearly every day (either by subjective account or as observed
`by others)
`. Recurrent thoughts of death {not just fear of dying). recurrent suicidal ideation without a specific plan, or a suicide attempt or a
`specific plan for committing suicide
`Manic episode
`A. A distinct period of abnormally and persistently elevated. expansive , or irritable mood, lasting at least 1 week {or any duration
`if hospitalization is necessary)
`B. During the period of mood disturbance. three (or more) of the following symptoms have persisted (four if the mood is only irritable)
`and have been present to a significant degree:
`1.
`Inflated self-esteem or grandlosity
`2.
`Decreased need for sleep le.g., feels rested after only 3 hours of sleep)
`3.
`More talkative than usual or pressure to keep talking
`4. Flight of ideas or subjective experience that thoughts are racing
`5.
`Distractibility li.e., attention too easiiy drawn to unimportant or irrelevant external stimuli)
`6.
`Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation
`7.
`Excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g.. engaging in unrestrained
`buying sprees, sexual indiscretions, or foolish business investments)
`
`Reprinted with permission from American Psychiatric Association. Diagnostic and statistical rnanuai of mentai disorders. 4th ed. Wash-
`ington, .D.C.: American Ps,vchiatric Association, 19945322332. Copyright I994.
`
`The Authors
`
`is assistant professor of family medicine and psychiatry
`KIM S. GRISWOLD, M.D., M.P.H..
`in the Department of Family Medicine at the State University of New York (SUNY) at Buf-
`falo School of Medicine and Biomedical Sciences. She received a masters degree in pub-
`lic health from Yale University, New Haven, Conn., and completed a faculty development
`fellowship in primary care at Michigan State University College of Human Medicine, East
`Lansing. After graduating from the SUNY—Buffa|o School of Medicine and Biomedical Sci-
`ences. she completed a family practice residency at Buffalo {N.Y.l Genera! Hospital.
`
`UNDA F. PESSAR, MD, is a psychiatrist and associate professor of clinicai psychiatry
`and family medicine at SUNY—Buffalo School of Medicine and Biomedical Sciences,
`where she is also director of medical student education in psychiatry. She received a
`medical degree from Columbia University College of Physicians and Surgeons, New
`York City, and completed a psychiatry residency at New York State Psychiatric Insti-
`tuteicolumbia Presbyterian Medical Center, New York City.
`
`Address correspondence to Kim S. Griswioid, M.D., M.F.'H., Department ofFamily Med-
`icine, State University of New York at Buffalo, Center for Urban Research in Primary
`Care, 135 Grant St, Buffalo. NY 14213. Reprints are not avaiiabie from the authors.
`
`Epidemiology
`
`The lifetirrte prevalence of bipolar disorder
`1 percent, which compares to a lifetime
`is
`prevalence of 6 percent for unipolar depres-
`sion.’ The prevalence of bipolar disorder does
`not differ in males and females,‘ The disorder
`
`affects persons of all ages. The epidemiologic
`catchment area study revealed the highest
`prevalence in the 18-to~24-year age group.’ In
`some patients, however, bipolar disorder does
`not become manifest until patients are older.
`One study reported ne'w—onset bipolar disor-
`der in patients older than 60 years.‘
`is
`The incidence of bipolar disorder
`increased in first-degree relatives of persons
`with the disorder, as is the incidence of other
`
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`Bipolar Disorder
`
`
`
`family physician and her psychiatrist. A
`patient with bipolar disorder should be
`encouraged to plan pregnancy so that the
`dosage of her psychiatric medication can be
`slowly tapered. The risk of relapse is increased
`with abrupt discontinuation.”
`Relapse during pregnancy must be treated
`aggressively with mood stabilizers. The patient
`should be admitted to the hospital. If lithium
`therapy is required,
`the patient should be
`counseled regarding the increased risk of car-
`diovascular malformations in fetuses exposed
`to lithium. Breast-feeding during lithium
`therapy is discouraged because lithium is
`excreted in breast milk.“
`
`During the postpartum period, worsening
`of affective symptoms may occur, including
`rapid cycling, which is sometimes refractory
`to drug therapy.” Women who have worsen-
`ing of symptoms postpartum may have an
`increased risk of recurrence.
`
`Comorbid Conditions
`
`Studies of primary care patients with major
`depressive disorders have demonstrated a ten-
`dency toward certain comorbid conditions. In
`one study,” more than 42 percent of patients
`meeting the criteria for a major depressive dis-
`order (including bipolar disorder) had life-
`time histories of substance abuse. In another
`
`study,” the frequency of substance abuse was
`39 percent in adolescents who had symptoms
`of bipolar disorder. Another study” revealed a
`high prevalence of moderate to severe anxiety
`disorders in association with bipolar disorder,
`as well as a high prevalence of psychosocial
`morbidity.
`‘
`While many patients with bipolar disorder
`show gradual improvement in the first several
`years after diagnosis, a substantial subgroup
`experiences poor adjustment in one or more
`
`mood disorders.” One study revealed a 13 per-
`cent risk of bipolar disorder among offspring of
`persons with the disorder.” The risk of unipo-
`lar depression was 15 percent, and the risk of
`schizoaffective disorder was 1 percent.” The
`mode of inheritance remains unclear, and no
`
`algorithm exists to predict the risk of bipolar
`disorder.“ Because of the familial association,
`
`genetic counseling should be offered to patients
`and their families as part of comprehensive
`educational and supportive approaches.
`
`Clinical Presentations
`
`Patients with symptoms of a mood disorder
`often do not meet the full criteria for bipolar
`disorder. Many patients with bipolar disorder
`are diagnosed as having depression. If agitation
`is prominent, hypomanic symptoms may be
`misunderstood as representing an anxiety state.
`Accurate diagnosis of bipolar disorder requires
`obtaining a comprehensive psychiatric history.
`
`CHILDREN
`
`Hyperactivity is the most common behav-
`ioral manifestation of mania in children.”
`
`irritability or
`Manic children may exhibit
`temper tantrums.” The differential psychi-
`atric diagnoses include attention-def1cit/
`hyperactivity disorder, conduct disorder and
`schizophrenia."
`
`ADOLESCENTS
`
`Manic symptoms in adolescents are similar
`to those in adults. Florid psychosis can be a
`presentation of bipolar disorder in adoles-
`cents. Included in the differential diagnosis of
`mania in adolescents are substance abuse and
`
`schizophrenia, which may be challenging to
`distinguish from bipolar disorder. The normal
`risk-taking behavior in some adolescents must
`be distinguished from the reckless nature of
`manic symptoms.
`
`DURING PREGNANCY
`
`The course of bipolar disorder during preg-
`nancy is variable. Management requires sus-
`tained collaboration between the patient’s
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`
`diography in pati
`rests with the clini
`
`
`
`If necessary, an
`good general healt
`as other drugs use
`lar disorder, can
`
`in
`ell
`
`
`
`areas of functioning.“ In a study of psychi-
`atric patients who were evaluated 30 to 40
`years after the index hospitalization for mania,
`24 percent of the sample was considered to be
`occupationally incapacitated.”
`
`Treatment
`URGENT AND EMERGENT
`
`If a patient with symptoms of acute mania
`presents to the office, a psychiatrist should be
`consulted, and the patient should be evaluated
`urgently. The family physician must know the
`legal requirements in the community for
`transferring a patient with acute mania from
`the office to the hospital. Often, police must be
`involved. It is inappropriate to expect family
`members to transport the patient from the
`office to the hospital, because family members
`may not appreciate the irrationality of manic
`thinking and the unpredictability of manic
`behavior.
`
`The family physician and psychiatrist have
`the responsibility to inform, educate and sup-
`port family members in terms of the possible
`need for the family to petition the court for
`the patient’s admission to a psychiatric unit. It
`is important to recognize, and to try to allay,
`the guilt and regret family members often feel
`in these circumstances.
`
`Patients with newly diagnosed bipolar dis-
`order require a medical evaluation along with
`a psychiatric evaluation. Table 3“ lists the rec-
`ommended laboratory tests for patients eval-
`uated on an inpatient or an outpatient basis.
`Computed tomography or magnetic reso-
`nance imaging and electroencephalography
`are second—line options in the evaluation of
`treatment—resistant patients. These studies are
`not routinely required without a specific clin-
`ical reason. Similarly, the need for electrocar-
`
`results are available. If the need to begin treat-
`ment is urgent, medication can be given even
`before laboratory specimens are obtained.
`
`COLLABORATIVE ONGOING CARE
`
`Given the chronic nature of bipolar disor-
`der and its impact on the entire family, it is
`
`TABLE 3
`
`Laboratory Evaluation of Patients
`Presenting with Bipolar Disorder
`
`Inpatient
`Complete physical examination
`Serum levels of lithium, valproic acid (Depakene),
`carbamazepine (Tegretol) and selected tricyclic
`antidepressants (if relevant)
`Thyroid function tests
`Complete blood count and general chemistry
`screening
`Urinalysis if lithium therapy is initiated
`Electrocardiography in patients older than 40 years
`Urine toxicology for substance abuse
`Pregnancy test (if relevant)
`Outpatient
`Complete physical examination
`Serum levels of lithium, valproic acid,
`carbamazepine and selected tricyclic
`antidepressants (if relevant)
`Thyroid function tests
`Complete blood count and general chemistry
`screening
`Urinalysis if lithium therapy is initiated
`Pregnancy test (if relevant)
`Second—line tests; urine toxicology for substance
`abuse and electrocardiography in patients older
`than 40 years
` —
`Adapted with permission from Steering Committee.
`Treatment of bipolar disorder. The Expert Consensus
`Guideline Series.
`J Clin Psychiatry 1996,'57(suppI
`72A):3—88.
`
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`Bipolar Disorder
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`important for the patient’s family physician
`and psychiatrist to develop an effective and
`collaborative relationship. Informed collabo-
`ration depends on an agreed method of com-
`munication in a frequency that meets the
`needs of each physician.“ A Canadian model
`brings psychiatrists and counselors into family
`practice offices for shared care.’-”
`At the onset of bipolar disorder, the family
`physician might seek psychiatric consultation
`for differential diagnosis and treatment rec-
`ommendations. Often,
`the psychiatrist
`assumes responsibility for initial manage-
`ment until
`the patient’s clinical pattern is
`determined. During follow—up, both physi-
`cians should monitor the patient for signs of
`psychosis, mood swings, violence and self-
`harmful behaviors. As the patient’s illness sta-
`bilizes and management becomes routine, the
`physicians can renegotiate, with each other
`and with the patient, responsibility for ongo-
`ing care.
`When the patient’s oondition has become
`stable, the psychiatrist may not need to see the
`patient as often, although the frequency of fol-
`low-up psychiatric visits depends on the
`course of the illness, the patient’s adherence to
`treatment, medication requirements, the need
`for ongoing psychotherapy and patterns of
`care in a particular geographic area. It
`is
`important for the patient's family physician
`and psychiatrist
`to coordinate medication
`prescriptions and follow—up laboratory tests
`such as determination of serum drug levels. In
`addition, counseling and family therapy are
`important components of management and
`may be rendered by the family physician, psy-
`chiatrist and/or psychologist.
`
`MEDICATION
`
`Recommendations for drug therapy in
`patients with bipolar disorder are summa-
`rized in Table 4.23
`
`Medication is the key to stabilizing bipolar
`disorder. Initial treatment of mania consists of
`
`lithium or valproic acid (Depakene). If the
`patient is psychotic, a neuroleptic medication
`
`
`
`is also given. Long—acting benzodiazepines
`may be used for treating agitation. However,
`in patients with a substance-abuse history,
`benzodiazepines should be used with caution
`
`TABLE 4
`
`Recommendations for Drug Therapy in Patients
`with Bipolar Disorder
`
`Considerations for prescribing mood stabilizers
`Lithium: For classic, euphoric mania; for mixed manic episode; when a mood
`stabilizer alone is used to treat depression; when the mood stabilizer must be
`given in a single evening dose; in patients with liver disease, excessive alcohol
`use or cocaine use; and in patients older than 65 years
`Valproic acid (Depakene): For classic, euphoric mania; for mixed manic episode;
`for mania with rapid cycling; for long-term maintenance therapy in patients
`who do not tolerate lithium because of the "flat" feeling lithium causes; in
`patients with structural central nervous system disease, renal disease and
`cocaine use; and in patients older than 65 years
`Carbamazepine (Tegretol): For mixed manic episode; for mania with rapid cycling;
`in patients with structural central nervous system disease or renal disease
`An antipsychotic agent
`High- or medium-potency antipsychotic agents are used as adjunctive
`treatment for mania with psychosis or psychotic depression.
`A benzodiazepine
`Sleep and sedation in mania or hypomania; insomnia in depression
`
`The combination of a mood stabilizer, an antidepressant
`and an antipsychotic
`Psychotic depression
`
`The combination of a mood stabilizer and an antidepressant
`Nonpsychotic depression
`A mood stabilizer alone
`
`Milder depression in bipolar I disorder
`
`Bupropion (wellbutrin)
`Bipolar depression
`Patient with high risk of manic switch or rapid cycling
`A selective serotonin reuptake inhibitor
`Bipolar depression
`
`Adapted with permission from Steering Committee. Treatment of bipolar disorder
`The Expert Consensus Guideline Series. J Clin Psychiatry 7 996,57(supp/ 72A):3—88.
`
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`TABLE 5
`
`Drug Interactions with Lithium
`Mana ement
`
`
`
`
`Avoid this combination or alter either
`dosage as needed; monitor lithium level
`
`
`
` Avoid this combination or reduThiazide diuretics Increased lithium level
`
`
`monitor lithium level
`
`Loop diuretics
`
`Increased or decreased
`lithium level
`
`Potassium-sparing diuretics Decreased lithium level
`
`Monitor lithium level and adjust dosage
`
`Nonsteroidal
`anti-inflammatory drugs
`
`Increased lithium level
`
`Use lower dosage of lithium; consider
`aspirin or sulindac
`
`Angiotensin—converting
`enzyme inhibitors
`
`Increased lithium level;
`toxicity reported
`
`Use lower dosage of lithium; monitor
`lithium level closely
`
`Calcium channel
`blockers
`
`Increased
`lithium l
`
`creased
`
`Monitor lithium level closely
`
`
`Adapted with permission from Devane CL, Nemeroff CB. 1998 Guide to psychotropic drug interactions.
`Primary Psychiatry 1998,'5.'36—75.
`
`because of the addictive potential of these
`agents.
`When the patient" with bipolar disorder
`becomes depressed, a selective serotonin reup—
`take inhibitor (SSRI) or bupropion (Well—
`butrin) is recommended.“ The use of tricyclic
`
`antideprjould be avoided because of
`the possibility of inducing rapid cycling of
`symptoms.
`Drug interactions are an important consid-
`eration when prescribing lithium (Table 5)3’
`valproic acid (Table 6)" and a selective sero-
`
`TABLE 6
`
`Drug Interactions with Valproic Acid (Depakene)
`
`Mana ement
`
`Phenobarbital
`
`Increased phenobarbital level
`
`Reduce dosage
`
`Magnesium— and aluminum— Increased valproic acid level
`containing antacids
`
`Monitor valproic acid level;
`reduce dosage
`
`Carbamazepine (Tegretol)
`
`Decreased valproic acid level; possible Monitor valproic acid level;
`increased carbamazepine level
`adjust dosage
`
`Aspirin and naproxen
`(Naprosyn)
`
`Increased valproic acid level
`
`Avoid salicylates or other drugs
`bound to plasma albumin
`
`Clonazepam (Klonopin)
`
`Increased sedation
`
`Use with caution
`
`Adapted with permission from Devane CL, Nemeroff CB.
`Primary Psychiatry 7998,'5.'36—75.
`‘
`
`7 998 Guide to psychotropic drug interactions.
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`tonin reuptake inhibitor (Table 7)9’ Informa-
`tion about starting and maintenance dosages
`for lithium, valproic acid and carbamazepine
`(Tegretol) is summarized in Table 8.23
`
`MONITORING ISSUES
`
`Treatment with mood stabilizers requires
`periodic laboratory tests to monitor the
`patient_1e drug (Table 9}.“ In
`
`addition, preventive care includes surveillance
`for possible comorbidities. Screening for sub-
`stance abuse and other mental health prob-
`lems should be conducted routinely. If pro-
`dromal symptoms of depression or mania are
`noted, interventions may include more fre-
`quent office visits, crisis telephone calls and
`intensive outpatient programs.” It is impor-
`tant that patients regulate their sleep. Insuffi-
`
`
`
`ctions with Selective Serotonin Reuptake Inhibitors
`
`Interaction
` Management
`
`Increased alprazolam levels
`Alprazolam (Xanax)
`Monitor; reduce dosage
`Increased TCA level
`TCAs
`Monitor TCA level
`
`Warfarin (Coumadin)
`
`Increased warfarin level with
`fluvoxamine (Luvox)
`
`MAO|s
`
`Serotonin syndrome
`
`Monitor prothrombin time (INR);
`reduce fluvoxamine dosage
`Combination of MAOI and SSRI
`is contraindicated
`
`Clozapine (Clozaril)
`
`Increased clozapine level with fluvoxamine
`
`Monitor clozapine level
`
`L—Tryptophan
`
`Serotonin syndrome
`
`Phenytoin (Dilantin)
`
`Possible phenytoin toxicity
`
`Combination of L-tryptophan
`and SSRI is contraindicated
`
`Monitor phenytoin level
`
`Monitor carbamazpine level
`
`Carbamazepine
`(Tegretol)
`
`Tolbutamide
`
`Theophylline
`
`Cimetidine (Tagamet)
`
`Type lc antiarrhythmics
`
`Beta-adrenergic blockers
`
`increased carbamazepine level with
`‘fluvoxarriine and fluoxetine (Prozac)
`
`Possible increased hypoglycemia
`
`Monitor blood glucose level
`
`Increased theophylline level with
`fluvoxamine
`
`Increased SSRI levels
`
`Increased antiarrhythmic level with
`fluoxetine, paroxetine (Paxil) and
`sertraline (Zoloft)
`Increased beta—blocker level and enhanced
`effects
`
`Monitortheophylline level
`
`Monitor clinically
`
`Monitor antiarrhythmic drug
`levels
`
`Use lower beta—b|ocker dosage
`
`Codeine
`
`Inhibited metabolism from fluoxetine,
`paroxetine and sertraline
`
`Use different SSRI
`
`St. John's wort
`
`Serotonin syndrome
`
`mm-
`
`Stop St. John's wort before
`beginning SSRI therapy
`
`SSRI = selective serotonin reuptake inhibitor," TCA = tricyclic antidepressant; /NR = International Normalized
`Ratio,‘ MAOI = monoamine oxidase inhibitor.
`
`Adapted with permission from Devane CL, Nemeroff CB. 1998 Guide to psychotropic drug interactions.
`Primary Psychiatry 7998,'5;36~75.
`
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`support and education. Because patients with
`bipolar disorder lose judgment early in the
`course of the illness and often engage in high-
`risk behavior, family members may be inter-
`acting with the legal system, t
`'
`health care system simult
`anger, grief and ambivalence
`
`
`
`cient and irregular hours of sleep often pre-
`cipitate mood disturbance.
`
`Family and Psychosocial Issues
`
`Significant issues for the patient and family
`members include the stigma that is frequently
`associated with mental illness and the need for
`
`
`
`TABLE 8
`
`Starting and Maintenance Dosages of Lithium, Valproic Acid and Carbamazepine and Common Side Effects
`
` *
`
`Cost
`
`Common side effects:
`
`Lithium
`
`900 mg per day; increase
`by 300 to 600 mg every
`2 to 3 days as tolerated
`
`Valproic acid (Depakene)
`20 mg per kg per day for
`mania; adjust dosage in
`3 to 5 days
`An alternative is 500 to 750
`
`mg daily; increase by 30
`to 50 percent every 2 to 3
`days as tolerated
`
`Carbamazepine (Tegretol)
`200 to 400 per day; increase
`by 200 mg daily every 2
`to 4 days
`
`(generi’c)§
`
`One 300-mg
`capsule: $0.19
`(0.06 to 0.10)
`
`900 to 1,800 mg per day; 1,200 mg
`may be given as a single bedtime
`dose if tolerated; otherwise,
`prescribe twice—daily dosing
`Therapeutic blood level: 0.8 to 1.5
`mEq per L
`
`Thirst, polyuria, cognitive complaints,
`tremor,]| weight gain, sedation, diarrhea,
`nausea (watch for dehydration, which
`can lead to toxicity), hypothyroidism
`(monitor TSH; give levothyroxine
`[Synthroid] if TSH is elevated)
`
`1,000 to 3,000 mg per day. Lower
`dosages may be used in hypomania.
`Sometimes it is appropriate to give
`as a single bedtime dose; otherwise,
`prescribe twice—daily dosing
`Therapeutic blood level: 50 to
`125 pg per mL
`
`400 to 1,200 mg daily; in an
`occasional patient, it is appropriate
`to give a single bedtime dose;
`otherwise, prescribe twice—daily
`dosing
`Therapeutic blood level: 4 to 12 pg
`per mL; not well established
`
`Tremor,“ sedation, diarrhea, nausea (use
`divalproex [Depakote]; give histamine
`H,-receptor blocker such as ranitidine
`[Zantac], 150 mg daily); weight gain,
`hair loss, mild elevation on liver
`function tests
`
`One 250—mg
`capsule:
`$1.24
`
`One 200—mg
`tablet: $0.44
`(0.29 to 0.33)
`
`Headache, nystagmus, ataxia, sedation,
`rash, leukopenia (do not combine with
`clozapine [Clorazi|]), mild elevation on
`liver function tests. Carbamazepine is
`associated with frequent drug—drug
`interactions related to induction of
`cytochrome P450 liver enzymes,
`resulting in lower drug levels of many
`other medications.
`
`TSH = thyroid-stimulating hormone.
`*—When initiating therapi/, consider lower dosages in patients with hypomania and in medi'cally ill or elderly patients.
`t—Consolidate doses to twice daily or once daily at bedtime if tolerated and efficacious.
`t—Many of the side effects are dose related. Tolerance can be enhanced by tailoring the dosage to each patient‘s tolerance and response.
`§—Estimated cost to the pharmacist for one tablet or capsule based on average wholesale prices rounded to the nearest dollar in Red
`book. ll/Iontvale, N.J.: Medical Economics Data, 7999. Cost to the patient will be higher, depending on prescription filling fee.
`|l~Tremor may be relieved with a beta—adrenergic blocker such as atenolol (Tenormin), in a dosage of 50 mg daily
`
`Adapted with permission from Steering Committee. Treatment of bipolar disorder The Expert Consensus Guideline Series. J Clin Psychia-
`try l996,'57(suppl 12A).'3-88.
`
`vwvw.aafp.org/afp
`
`CAN FAMILY PHYSICIAN
`VOLUME 62, NUMBER 6 / SEPTEMBER 15,2000
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`I Bipolar Disorder
`
`ings among family members as they cope with
`the difficulties.
`
`Family members must be educated about
`possible relapses, what to look for and how to
`handle different situations. The recklessness
`
`that accompanies mania can have devastating
`consequences—including sexually transmit-
`ted diseases, financial ruin, traumatic injuries
`and accidents. Risk-taking causes significant
`distress to patients and families, and such
`behavior is a problem for which family physi-
`cians, psychiatrists and mental health profes-
`sionals can intervene with appropriate med-
`ical, preventive, educational and social
`strategies (Table 10)H lnitial
`intervention
`includes education for the patient and family,
`
`including informational pamphlets, videos
`and involvement in support and patient advo-
`cacy groups.
`
`Patients who are manic or depressed may
`attempt suicide or homicide. The risk is
`increased in patients who are psychotic and
`have severe depressive symptoms concurrent
`with mania.” The lifetime suicide risk is 15
`
`in patients with bipolar disorder;
`percent
`patients at highest risk are young men in an
`
`TABLE 9
`
`Recommended Laboratory Tests for Monitoring Response
`to |.ithium, Valproic Acid and Carbamazepine
`
`Lithium
`
`Val roic acid De akene
`
`Carbamaze ine
`
`e retol
`
`Serum level every 1 to 2
`weel<s*
`CBC and liver function
`tests monthly
`
`Serum level every 1 to 2
`weeks*
`CBC and liver function
`tests monthly
`
`Serum level every 3 to 6
`months*t
`CBC and liver function
`tests every 6 to 12 months
`
`Serum level every 3 to 6
`months*
`CBC and liver function
`tests every 6 months
`
`First two months of therapy
`Serum level every 1
`to 2 weel<s*t
`
`Long—term therapy
`Serum level every 3 to
`6 months*t
`Thyroid function tests yearly
`(total T4, T4 uptake and TSH)‘r
`
`Renal function every 6 to 12
`months (serum urea nitrogen,
`creatinine and electrolytes);
`24-hour urine for volume and
`GFR only if specifically indicated,
`not routinely
`
`CBC = complete blood count; T4 = thyroxine; TSH = thyroid-stimulating hormone," GFR = glomerular filtration
`rate.
`
`*—Serum levels of mood stabilizers should be obtained whenever the dosage or clinical situation changes.
`t—Tests are strongly recommended by the committee that formulated the guidelines for treatment of bipo-
`lar disorder
`
`Adapted with permission from Steering Committee. Treatment of bipolar disorder The Expert Consensus
`Guideline Series. J Clin Psychiatry 1996,'57(supp/ 72A):3-88.
`
`SEPTEMBER 15, 2000 l VOLUME 62, NUMBER 6
`www.aafp.org/afp
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`TABLE 10
`
`Psychosocial Issues to Address in the Acute and Maintenance Phases
`of Bipolar Disorder
`
`Ac
`
`Maintenance phase
`
`
`
`Monitor suicidality, mood, substance use, sleep
`patterns and medication compliance.
`
`Inquire about suicidality, mood, medication compliance,
`life events, substance use, sleep and activity.
`
`Educate patient and family members about
`features and biologic nature of the illness and
`the importance of compliance with therapy.
`
`Encourage telephone contact and optimism
`regarding recovery. Set limits on impulsive
`behavior in patients with mania. Consider
`interpersonal or cognitive therapy for patients
`with depression. Hold family meetings to
`discuss issues.
`
`Educate patient and family members about use of
`medication, warning signs of relapse, management
`of stress, sleep hygiene, eating and exercising
`regularly, limited caffeine and alcohol intake and
`management of work and leisure activities.
`
`Long-range issues may include marital problems,
`employment and financial problems, peer
`relationships and modification of personality traits.
`
`Adapted with permission from Steering Committee. Treatment of bipolar disorder The Expert Consensus
`Guideline Series, J Clin Psychiatry 7996,'57(suppl 72A).'3-88.
`
`early phase of illness who have made previous
`suicide attempts or who abuse alcohol.” Fam-
`ily members must learn the warning signs of
`suicide and must be able to distinguish
`between the signs of mania and those of
`depression.
`Substance use should be discouraged.
`Even modest social drinking can lead to
`mood disturbance. In addition, substances
`such as alcohol can interact with medica-
`
`tions, disinhibit patients and contribute to
`risky behaviors.
`Guns should be removed from the house.
`
`Easy access to firearms can supply a ready
`means of suicide or accidental
`injury in a
`patient with impaired insight and judgment.
`If the patient or family has concerns about
`sexual