Summary of DSM-IV-TR Classification of Bipolar Disorders According to the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders , 4th edition (DSM-IV-TR), bipolar disorder can be divided into four classifications: Bipolar I Disorder, Bipolar II Disorder, Cyclothymic Disorder, and Bipolar Disorder Not Otherwise Specified. Bipolar I Disorder is characterized by one or more manic or mixed episodes usually accompanied by major depressive episodes. Bipolar II Disorder focuses on one or more major depressive episodes accompanied by at least one hypomanic episode. A diagnosis of Cyclothymic Disorder is made when a patient experiences at least 2 years of numerous periods of hypomanic symptoms that do not meet the criteria for a manic episode and numerous periods of depressive symptoms that do not meet the criteria for a major depressive episode. Bipolar Disorder Not Otherwise Specified is characterized by bipolar features that do not meet the criteria for any of the specific bipolar disorders described above or for bipolar symptoms about which there is inadequate or contradictory information. Each classification of bipolar disorder is further defined by the presence (or history) of manic episodes, mixed episodes, or hypomanic episodes, usually accompanied by the presence (or history) of major depressive episodes. First, ed. Diagnostic and Statistical Manual of Mental Disorders . 4th ed. Text Rev. Washington, DC: American Psychiatric Association; 2000:345-428.
Symptoms of Bipolar Disorder —Heavy Impact on Daily Life Recently, 3,059 subjects from a large epidemiologic study of bipolar disorder, matched to scores on the Mood Disorder Questionnaire and US Census data, were surveyed using the Social Adjustment Scale-SR, Sheehan Disability Scale, and the Family History Screen to evaluate the psychological and social impact of bipolar I and II in the general population Note that this group is a subset of patients from the 85,358 reported in the prevalence study The results from this survey not only provided a clear picture of the personal and societal impact of bipolar disorder, but also confirmed the usefulness of the MDQ MDQ-positive subjects reported significantly more difficulty with work (1.96% vs 1.46%), social/leisure interactions (2.4% vs 1.87%), and extended family interactions (2.22% vs 1.66%), and more days of disruptive symptoms (6.41 vs 2.62) than MDQ-negative subjects Patients with a positive screen were significantly more likely to be fired or laid off, or be arrested, jailed, or convicted of a crime other than drunk driving Symptoms of bipolar disorder can have a devastating impact on patients and their families and places a heavy burden on society Cal a brese. J Clin Psychiatry . 2003;64:425-432.
Electroconvulsive therapy (ECT) is considered a mood-stabilizing treatment. It tends to be used for patients who are suicidal or severely ill and cannot wait for medications to work, or have a history of nonresponse to treatments. Lithium has been the main treatment for acute mania for over 40 years. Lithium appears to be effective for individuals with euphoric mania, but is less effective in mixed manic episodes and in rapid-cycling bipolar disorder. First-generation antipsychotic treatments have been prescribed to combat the psychotic symptoms sometimes associated with manic episodes of bipolar I disorder. Antipsychotics are also used to treat symptoms of anxiety, insomnia, and agitation often associated with manic episodes, even when no psychosis occurs. Antipsychotics are used both as monotherapy and as adjuncts to mood stabilizers for the initial treatment of acute mania. However, intolerable side effects associated with conventional antipsychotics, such as EPS and tardive dyskinesia (TD), can increase patient health burden and have a negative impact on compliance. Valproic acid and its salts (divalproex sodium and sodium valproate), originally developed as an anticonvulsant to treat seizures, have been used to treat bipolar disorder for a number of years. While data support its efficacy in treating euphoric and mixed manic episodes, the data to support efficacy in prophylaxis are considerably weaker. Preliminary research suggests that several other anticonvulsants (eg, lamotrigine, gabapentin, and topiramate) may also possess mood- stabilizing properties. Second-generation antipsychotics have a greatly improved side-effect profile over conventional antipsychotics in terms of EPS and TD liability. Currently, olanzapine is the only atypical agent approved for use in acute mania. Although atypical agents show improvements over conventional agents, concerns remain regarding the emergence of drug-specific side effects such as excessive weight gain, diabetes, lipid abnormalities, QTc prolongation, and somnolence. Aripiprazole is a novel antipsychotic with a unique mechanism of action. This new agent shows promise as a treatment with efficacy against acute mania and an improved safety and tolerability profile. 1. Nemeroff CB. An ever-increasing pharmacopoeia for the management of patients with bipolar disorder. J Clin Psychiatry . 2000;61(suppl 13):19-25. 2. McElroy SL, Keck PE Jr. Pharmacologic agents for the treatment of acute bipolar mania. Biol Psychiatry . 2000;48:539-557. This slide provides a historic overview of current therapies used to treat acute mania and potential treatments that may help to improve treatment outcomes.
Rajiv Tandon, M.D. 2001 Pfizer Talk 1
Identical to previous slide, but with additional of PBO and LTG 12 & 18 month relapse rates in lower left inset. On the combined primary outcome measure: Lamotrigine was significantly superior to placebo on time to intervention for any mood episode Lithium was also superior to placebo. There was no significant difference between lamotrigine and lithium. P-values on the slide are unadjusted for study. When these combined analyses were adjusted for study (stratified) p-values were: LTG vs. PBO p=0.002 Li vs. PBO p<0.001 Li vs. LTG p=0.644 Source: SCAB2003 & SCAB2006
Identical to previous slide, but with additional of PBO and LTG 12 & 18 month relapse rates in lower left inset. This analysis examines time to intervention for depressive episodes only. Manic and hypomanic events and other dropouts were censored in the analysis. On this measure: Lamotrigine was superior to placebo in prolonging time to intervention for a depressive event Lithium did not separate statistically from placebo, only reaching a statistical trend despite the large sample size (larger than any other previous lithium sample) There was no significant difference between lamotrigine and lithium. P-values on the slide are unadjusted for study. When these combined analyses were adjusted for study (stratified) p-values were: LTG vs. PBO p=0.004 Li vs. PBO p=0.076 Li vs. LTG p=0.281 Source: SCAB2003 & SCAB2006
This analysis examines time to intervention for manic or hypomanic episodes only. Depressive events and other dropouts were censored in the analysis. On this measure: Lithium was superior to placebo in prolonging time to intervention for a manic event. Lamotrigine was also superior to placebo in prolonging time to intervention for a manic event. Lithium was superior to lamotrigine in prolonging time to intervention for a manic event. P-values on the slide are unadjusted for study. When these combined analyses were adjusted for study (stratified) p-values were: LTG vs. PBO p=0.149 Li vs. PBO p<0.001 Li vs. LTG p=0.024 This alternative analysis provides additional evidence that the efficacy of lamotrigine against mania is less robust than its effect against depression. Source: SCAB2003 & SCAB2006
NP From Bip Depr ECNP GSK 9 20 03 NDMDA, National Depressive and Manic-depressive Association References Goodwin FK, Jamison KR. Manic-depressive illness. New York: Oxford University Press, 1990. Hirschfeld RM, Lewis L, Vornik LA. Perceptions and impact of bipolar disorder: how far have we really come? Results of the National Depressive and Manic-depressive Association 2000 survey of individuals with bipolar disorder. J Clin Psychiatry 2003; 64: 161-174. Lish JD, Dime-Meenan S, Whybrow PC, et al. The National Depressive and Manic-depressive Association (DMDA) survey of bipolar members. J Affect Disord 1994; 31: 281-294.
Bipolar Disorder—3.4% of the US Population Screened Positive by MDQ The Mood Disorder Questionnaire is a screening tool that can be used to identify patients most likely to have bipolar disorder 1,2 In 2001, a large-scale epidemiologic survey (n=85,358) was conducted using the MDQ to screen respondents for the presence of symptoms of bipolar disorder (based on DSM-IV criteria) 3 The overall prevalence rate (weighted to match US census data) for patients with symptoms of bipolar disorder was estimated to be 3.4%, or about 7 million adults 3 When adjusted for response bias, the estimated prevalence rate rises to 3.7%, or 7.6 million adults 3 Symptoms were much more common among younger rather than older people (those aged 18 to 24 years vs those over 65), and in households with incomes less than $20,000 3 1. Hirschfeld. Prim Care Companion J Clin Psychiatry. 2002;4:9-11. 2. Hirschfeld et al. Am J Psychiatry. 2000;157:1873-1875. 3. Hirschfeld et al. J Clin Psychiatry. 2003;64:53-59.
This new research reveals on untapped point of entry for patients to receive either a diagnosis or a referral to a mental health professional who can make a correct diagnosis. The research team looked at the number of patients who had received a diagnosis of either bipolar disorder or depression from a community physician, and then compared that with the number of patients who were identified as having bipolar disorder through the Mood Disorder Questionnaire. As you can see, nearly half of the patients identified by the questionnaire received a diagnosis for neither bipolar disorder or depression from their community physician.
Treatment of Bipolar Disorder An UPDATE Rajiv Tandon, MD Chief of Psychiatry State of Florida Tallahassee, Florida, U.S.A.
Summary of DSM-IV-TR Classification of Bipolar Disorders * Symptoms do not meet criteria for manic and depressive episodes. Bipolar features that do not meet criteria for any specific bipolar disorders At least 2 years of numerous periods of hypomanic and depressive symptoms* One or more major depressive episodes accompanied by at least one hypomanic episode FEMALE>MALE One or more manic or mixed episodes, usually accompanied by major depressive episodes MALE=FEMALE Bipolar Disorder Not Otherwise Specified Cyclothymic Bipolar II Bipolar I First, ed. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text Rev. Washington, DC: American Psychiatric Association; 2000:345-428.
ON THE OTHER HAND Depression Following Antidepressant Discontinuation in Bipolar Patients (Chart Review) Weeks After Improvement % Well ( Not Depressed) Altshuler et al., J Clin Psychiatry, 2001; 62:612-616. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 13 26 39 52 Discontinued Antidepressant n=25 Continued Antidepressant n=19
Maintenance Treatment with Divalproex Time to Any Affective Episode Bowden et al., Arch Gen Psychiatry 2000 0 0.2 0.4 0.6 0.8 1.0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Weeks Survival Divalproex Lithium Placebo P = .33
Time to Intervention for a Mood Episode Lamotrigine vs Lithium vs Placebo Goodwin et al., 2003 submitted 12 Mon. 18 Mon. Index Manic or Depressed LTG v. PBO, p < 0.001 Li v. PBO, p < 0.001 LTG v. Li, p = 0.629
Time to Intervention for Depression Goodwin et al., 2003 submitted 12 Mon. 18 Mon. Index Manic or Depressed LTG v. PBO, p = 0.009 Li v. PBO, p = 0.120 LTG v. Li, p = 0.325
Time to Intervention for Mania LTG v. PBO, p = 0.034 Li v. PBO, p < 0.001 LTG v. Li, p = 0.030 Goodwin et al., 2003 submitted Index Manic or Depressed 12 Mon. 18 Mon.
For breakthrough episodes, first optimize the maintenance medication dose
Consider adding an antipsychotic
If this does not work, consider adding lithium, divalproex, carbamazepine, or oxcarbazepine
Clozapine or ECT should be considered for treatment-refractory patients
APA Practice Guidelines Am J Psychiatry . 2002;159(4)supplement.
Approach to the Patient With Bipolar Depression
Is the patient already in treatment with a mood stabilizer?
Then optimize the dose of the mood stabilizer
Then add antidepressant
APA Practice Guidelines Am J Psychiatry . 2002;159(4)supplement.
Approach to the Patient with Bipolar Depression Then...
For less severely ill patients
initiate lithium or lamotrigine
For more severely ill patients
initiate lithium and an antidepressant
For those with psychosis or at high suicide risk
APA Practice Guidelines Am J Psychiatry . 2002;159(4)supplement.
Emerging Trends Pharmacotherapy of Acute Mania
Combination treatment the rule, not the exception
Continued use of Lithium and Divalproex as cornerstones of treatment
Increasing use of atypical antipsychotics for acute treatment and ?for maintenance
BIPOLAR DISORDER The Major Challenge: Misdiagnosis Goodwin & Jamison (1990); Hirschfeld et al (2003); Lish et al (1994) NDMDA survey of its bipolar members Rate of misdiagnosis 1994 2000 73% 69%
Most frequent misdiagnosis: Unipolar depression
Treatment as unipolar depression can lead to worsening of symptoms by switching into mania or cycle acceleration
Steps to Increase Recognition of Bipolar Disorder and to Improve Diagnosis
Education of physicians about the illness, particularly how it presents itself in clinics
Ask patients directly about history of symptoms of Bipolar Disorder
Involve family members in clinical evaluations
Increase patients’ and families’ awareness of the illness
Screen for Bipolar Disorder, especially in depressed patients
Screening for Bipolar Disorder Mood Disorder Questionnaire
A brief, simple, self-report questionnaire for bipolar disorder--13 yes-no items regarding bipolar disorder
Well validated in psychiatric clinical and general population samples
Translated into several languages
Hirschfeld RMA, et al. Am J Psychiatry. 2000; 157:1873-1875
Bipolar Disorder — 3.4% of the US Population Screened Positive by MDQ * Weighted to match US census data. Weighted Percent * Overall Prevalence Age Group Income Hirschfeld et al. J Clin Psychiatry. 2003; 64:53-59.
Physician Diagnoses Among MDQ Positives in the Community Dx with bipolar disorder Dx with depression but not bipolar disorder Neither bipolar disorder nor depression Dx 20% 31% 49% Hirschfeld RMA, et al. J Clin Psychiatry . 2003;64:53-59. 80% of patients who screened positive for BP were not diagnosed w/ BP