A Wolf in Dog s clothing: unmasking Bipolar Depression

1. A Wolf in Dog�s clothing: unmasking Bipolar Depression Dr Gregor Schutz

2. Key Points Bipolar Depression is common It is easily missed It has serious implications Treatment protocols are significantly different from Unipolar Depression (UPD) Treating it within UPD paradigm can lead to iatrogenic harm Managing it within a bipolar paradigm can be rewarding for patient and clinician

3. Overview Case study Definitions and Descriptions Epidemiology Current accuracy of diagnosis Implications of missing diagnosis Risk Co-morbidity Functioning Barriers to Diagnosis Screening and Diagnosis in Primary Care

4. Case study Kate is a 36 year old married mother of 3. She described a 7 month history of worsening mood characterised by poor appetite, initial and terminal insomnia, anhedonia and thoughts of hopelessness and worthlessness. During the initial month she was reviewed by her GP and prescribed escitalopram 10mg In the subsequent months she took 2 deliberate overdoses of prescribed medication but did not seek medical attention

5. Case study Her escitalopram was increased to 20mg. This initially helped but after 10 days her mood crashed with constant thoughts of suicide, irritability and tearfulness. This culminated in a serious suicide attempt in which she attempted to gas herself. She was admitted to a private psychiatric hospital

6. Case study Kate�s sister suffers depression She describes her mother as erratic and may have had periods of mood elevation. Her maternal grandmother had periods of uncharacteristic behavior with excessive spending Kate has a long history of mood problems dating back to her teens when she began to suffer �black moods.� She was first diagnosed with depression in the post-natal period and over the years has been prescribed antidepressants with partial or temporary benefit. She had not been seen by a psychiatrist or had any psychiatric admissions.

7. Case study On specific questioning Kate reported that her low moods alternate with brief periods of elevated moods lasting a few days at a time. During these times she feels invincible, has racing thoughts, is intensely creative and cleans everything. She also has reduced need for sleep. She had also been cautioned previously for taking money from her workplace � out of character In a typical month she will have a short period of elevated mood followed by a �crash� into a depressed mood This was confirmed by her husband and sister. She had never reported these symptoms to her doctor

8. Case Study Given diagnosis of BMD-II Kate and her family were provided with psycho-education They felt that the diagnosis was accurate and explained some of her chaotic moods Escitalopram ceased, Sodium Valproate commenced Mood continued to improve, �highs� became attenuated.

9. Mood Disorders: DSM-IV Classification DSM-IV divides mood disorders into depressive disorders (unipolar depression), bipolar disorders, and 2 disorders with etiologiesinduced by substance intake or a general medical condition. Depressive disorders include major depressive disorder (MDD), dysthymic disorder, and depressive disorder not otherwise specified (NOS). Depressive episodes are distinguished from bipolar disorders by the absence of any history of a manic, mixed, or hypomanic episode. Bipolar disorders include bipolar I disorder (BPD I), bipolar II disorder (BPD II), bipolar disorder NOS, and cyclothymic disorder. These diagnoses require the current presence of, or a history of, manic episodes, mixed episodes, or hypomanic episodes, usually accompanied by a history of major depressive episodes (MDEs).DSM-IV divides mood disorders into depressive disorders (unipolar depression), bipolar disorders, and 2 disorders with etiologiesinduced by substance intake or a general medical condition. Depressive disorders include major depressive disorder (MDD), dysthymic disorder, and depressive disorder not otherwise specified (NOS). Depressive episodes are distinguished from bipolar disorders by the absence of any history of a manic, mixed, or hypomanic episode. Bipolar disorders include bipolar I disorder (BPD I), bipolar II disorder (BPD II), bipolar disorder NOS, and cyclothymic disorder. These diagnoses require the current presence of, or a history of, manic episodes, mixed episodes, or hypomanic episodes, usually accompanied by a history of major depressive episodes (MDEs).

10. Definitions and Epidemiology

12. Manic Episode: Diagnostic Criteria Elevated, expansive, or irritable mood for 1 week or longer, plus 3 or more of the following Inflated self-esteem or grandiosity Decreased need for sleep Pressured speech Racing thoughts/flight of ideas Distractibility Psychomotor agitation/increased goal-directed activity Excessive involvement in high-risk activities Recognition of the 4 key types of episodes of bipolar disorder is the first step in ensuring an accurate diagnosis. Each mood episode has its own distinct criteria, and the episodes exist in various combinations in each of the bipolar disorders. The first of the additional criteria, inflated self-esteem or grandiosity, frequently reaches delusional proportions. Decreased need for sleep, when the patient sleeps or rests for just a few hours and then feels fully refreshed, is an almost invariable symptom of mania. It is not unusual for patients experiencing severe manic episodes to go for days without sleeping. Pressured speech of mania tends to be loud, rapid, dramatic, and difficult tointerrupt. It is frequently characterized by clanging; sound rather than sense determines word choice. Racing, disjointed thoughts are a very common symptom; in severe mania, the patient may be completely incoherent. No stimulus is too inconsequential to escape notice by the patient with severe mania. He or she may be completely unable to distinguish between what is meaningful and what is irrelevant. Patients experiencing mania often involve themselves in innumerable simultaneous goal-directed activities. However, these activities are often entirely unrealistic in the context of the patient�s life. A hallmark of mania is excessive involvement in pleasurable activities thathave a high potential for dangerous or negative consequences. Examplesof such activities include participation in promiscuous sexual activity and extremely high-risk sports.Recognition of the 4 key types of episodes of bipolar disorder is the first step in ensuring an accurate diagnosis. Each mood episode has its own distinct criteria, and the episodes exist in various combinations in each of the bipolar disorders. The first of the additional criteria, inflated self-esteem or grandiosity, frequently reaches delusional proportions. Decreased need for sleep, when the patient sleeps or rests for just a few hours and then feels fully refreshed, is an almost invariable symptom of mania. It is not unusual for patients experiencing severe manic episodes to go for days without sleeping. Pressured speech of mania tends to be loud, rapid, dramatic, and difficult tointerrupt. It is frequently characterized by clanging; sound rather than sense determines word choice. Racing, disjointed thoughts are a very common symptom; in severe mania, the patient may be completely incoherent. No stimulus is too inconsequential to escape notice by the patient with severe mania. He or she may be completely unable to distinguish between what is meaningful and what is irrelevant. Patients experiencing mania often involve themselves in innumerable simultaneous goal-directed activities. However, these activities are often entirely unrealistic in the context of the patient�s life. A hallmark of mania is excessive involvement in pleasurable activities thathave a high potential for dangerous or negative consequences. Examplesof such activities include participation in promiscuous sexual activity and extremely high-risk sports.

13. Manic Episode: Diagnostic Criteria Marked impairment in functioning / usual social activities OR Requires hospitalisation OR Psychotic symptoms Recognition of the 4 key types of episodes of bipolar disorder is the first step in ensuring an accurate diagnosis. Each mood episode has its own distinct criteria, and the episodes exist in various combinations in each of the bipolar disorders. The first of the additional criteria, inflated self-esteem or grandiosity, frequently reaches delusional proportions. Decreased need for sleep, when the patient sleeps or rests for just a few hours and then feels fully refreshed, is an almost invariable symptom of mania. It is not unusual for patients experiencing severe manic episodes to go for days without sleeping. Pressured speech of mania tends to be loud, rapid, dramatic, and difficult tointerrupt. It is frequently characterized by clanging; sound rather than sense determines word choice. Racing, disjointed thoughts are a very common symptom; in severe mania, the patient may be completely incoherent. No stimulus is too inconsequential to escape notice by the patient with severe mania. He or she may be completely unable to distinguish between what is meaningful and what is irrelevant. Patients experiencing mania often involve themselves in innumerable simultaneous goal-directed activities. However, these activities are often entirely unrealistic in the context of the patient�s life. A hallmark of mania is excessive involvement in pleasurable activities thathave a high potential for dangerous or negative consequences. Examplesof such activities include participation in promiscuous sexual activity and extremely high-risk sports.Recognition of the 4 key types of episodes of bipolar disorder is the first step in ensuring an accurate diagnosis. Each mood episode has its own distinct criteria, and the episodes exist in various combinations in each of the bipolar disorders. The first of the additional criteria, inflated self-esteem or grandiosity, frequently reaches delusional proportions. Decreased need for sleep, when the patient sleeps or rests for just a few hours and then feels fully refreshed, is an almost invariable symptom of mania. It is not unusual for patients experiencing severe manic episodes to go for days without sleeping. Pressured speech of mania tends to be loud, rapid, dramatic, and difficult tointerrupt. It is frequently characterized by clanging; sound rather than sense determines word choice. Racing, disjointed thoughts are a very common symptom; in severe mania, the patient may be completely incoherent. No stimulus is too inconsequential to escape notice by the patient with severe mania. He or she may be completely unable to distinguish between what is meaningful and what is irrelevant. Patients experiencing mania often involve themselves in innumerable simultaneous goal-directed activities. However, these activities are often entirely unrealistic in the context of the patient�s life. A hallmark of mania is excessive involvement in pleasurable activities thathave a high potential for dangerous or negative consequences. Examplesof such activities include participation in promiscuous sexual activity and extremely high-risk sports.

14. Hypomanic Episode: Diagnostic Criteria Elevated, expansive, or irritable mood for at least 4 days plus 3 or more of the following Inflated self-esteem or grandiosity Decreased need for sleep Pressured speech Racing thoughts/flight of ideas Distractibility Psychomotor agitation/increased goal-directed activity Excessive involvement in high-risk activities

15. Hypomanic Episode: Diagnostic Criteria Unequivocal uncharacteristic change in functioning Changes are observable by others No psychosis or marked impairment of functioning Not requiring hospitalisation

17. Depressed mood and/or loss of interest or pleasure ? 2 weeks duration Associated symptoms Physical: insomnia/hypersomnia, appetite/weight change, decreased energy, psychomotor change Psychological: feelings of guilt or worthlessness, poor concentration/indecisiveness, thoughts of death/suicidal intentions (SI) Major Depressive Episode: DSM-IV Criteria

18. Major Depressive Episode: DSM-IV Physical Sleep disorder Appetite change Fatigue Psychomotor retardation Psychological Low self esteem/guilt Poor concentration/indecisiveness Thoughts of death/SI

20. Mixed Episode: Diagnostic Criteria Criteria met for both manic episode + MDE for ?1 week Symptoms Are sufficient to impair functioning or Necessitate hospitalization or Are accompanied by psychotic features A mixed episode consists of at least 1 week during which criteria for both a manic episode and a major depressive episode (MDE) are met nearly every day. Mood tends to alternate rapidly between euphoria, sadness, and irritability. Symptoms must be sufficient to impair social or occupational functioning or to require hospitalization. Alternatively, hospitalization must be required. Common symptoms include agitation, appetite disturbance, insomnia, psychosis, and suicidal ideation. Relative to manic episodes, mixed episodes are more commonly characterized by dysphoria and disorganization; therefore, patients experiencing mixed episodes may be more likely to seek help than those experiencing purely manic episodes. Mixed episodes may be more common in younger and older persons with bipolar disorder and may be more likely to occur in male than in female individuals.A mixed episode consists of at least 1 week during which criteria for both a manic episode and a major depressive episode (MDE) are met nearly every day. Mood tends to alternate rapidly between euphoria, sadness, and irritability. Symptoms must be sufficient to impair social or occupational functioning or to require hospitalization. Alternatively, hospitalization must be required. Common symptoms include agitation, appetite disturbance, insomnia, psychosis, and suicidal ideation. Relative to manic episodes, mixed episodes are more commonly characterized by dysphoria and disorganization; therefore, patients experiencing mixed episodes may be more likely to seek help than those experiencing purely manic episodes. Mixed episodes may be more common in younger and older persons with bipolar disorder and may be more likely to occur in male than in female individuals.

21. Bipolar I or II � what is difference? Bipolar I disorder: Manic or mixed episode May have other mood episodes Bipolar II disorder Hypomanic episode AND Major depressive episode Never had manic or mixed episode

23. Course Specifiers 1) Rapid cycling : ?4 episodes/year 2 month well interval required without a change in polarity Antidepressant induced switches do not count 2) Full inter-episode recovery 3) Seasonal pattern

24. Bipolar Disorders: Epidemiology Although estimates vary, data from community samples estimate the lifetime prevalence of bipolar I disorder (BPD I) at up to 1.6%. The lifetime prevalence of bipolar II disorder (BPD II) alone is approximately 0.5%. There is no apparent differential incidence of bipolar disorder based on race or ethnicity. However, there is some evidence of a greater tendency to overdiagnose schizophrenia instead of bipolar disorder in some ethnic groups. BPD I is believed to be equally common in men and women. BPD II, on the other hand, may be more common in women. In men with bipolar disorder, the first episode is likely to be manic; in women, the first episode is likely to be depressive.Although estimates vary, data from community samples estimate the lifetime prevalence of bipolar I disorder (BPD I) at up to 1.6%. The lifetime prevalence of bipolar II disorder (BPD II) alone is approximately 0.5%. There is no apparent differential incidence of bipolar disorder based on race or ethnicity. However, there is some evidence of a greater tendency to overdiagnose schizophrenia instead of bipolar disorder in some ethnic groups. BPD I is believed to be equally common in men and women. BPD II, on the other hand, may be more common in women. In men with bipolar disorder, the first episode is likely to be manic; in women, the first episode is likely to be depressive.

25. Bipolar Disorders: Epidemiology (cont.) Hypomanic episodes in BPD II immediately precede or follow MDEs in 60% to 70% of cases First-degree relatives may have increased rates of BPD I, BPD II, and MDD Recurrent in >90% of cases First-degree relatives have increased rates of BPD I, BPD II, and MDD Bipolar I disorder (BPD I) is recurrent in more than 90% of cases. Approximately 60% to 70% of manic episodes occur immediately before or after a major depressive episode (MDE). Each individual tends to develop a pattern in which manic and depressive episodes precede and follow each other. In the absence of treatment, individuals with BPD I will suffer an average of 4 episodes in a 10-year period. In the case of bipolar II disorder (BPD II), approximately 60% to 70% of hypomanic episodes occur immediately before or after an MDE. Both BPD I and BPD II show tendencies to run in families, although this tendency is more evident in BPD I. First-degree biological relatives of individuals with BPD I have increased rates of BPD II and major depressive disorder (MDD), and twin and adoption studies provide convincing evidence of genetic predisposition. Some studies also suggest that first-degree relatives of individuals with BPD II have increased rates of BPD II, BPD I, and MDD.Bipolar I disorder (BPD I) is recurrent in more than 90% of cases. Approximately 60% to 70% of manic episodes occur immediately before or after a major depressive episode (MDE). Each individual tends to develop a pattern in which manic and depressive episodes precede and follow each other. In the absence of treatment, individuals with BPD I will suffer an average of 4 episodes in a 10-year period. In the case of bipolar II disorder (BPD II), approximately 60% to 70% of hypomanic episodes occur immediately before or after an MDE. Both BPD I and BPD II show tendencies to run in families, although this tendency is more evident in BPD I. First-degree biological relatives of individuals with BPD I have increased rates of BPD II and major depressive disorder (MDD), and twin and adoption studies provide convincing evidence of genetic predisposition. Some studies also suggest that first-degree relatives of individuals with BPD II have increased rates of BPD II, BPD I, and MDD.

30. Bipolar Spectrum Continuum of mood states that goes beyond currently defined disorders to include other variations in mood that impact on functioning and risk Multiple variations of mood, lability, impulsivity, irritability, energy levels and drives, cognitions and behaviours Adds to overall lifetime prevalence of 5-6%

33. How common is Bipolar Depression in Primary Care? Patients with BMD spend much greater percentage of time in depression than with mania/hypomania � especially BMD-II > 50 % of BMD has initial presentation with depression Up to 30% of depression/anxiety seen in primary care is Bipolar � especially BMD-II

35. Accuracy of Diagnosis Psychiatrists and GP�s frequently miss diagnosis 50 - 70% of patients misdiagnosed as having UPD, even though they had previously had manic or hypomanic episode Another sample � 10% had BMD, only 10% of those were accurately diagnosed Mean time to diagnosis of 7.5 years 30% of patients had 10 year delay in diagnosis 50% of patients saw ?3 clinicians prior to diagnosis

36. Effects of not detecting BMD Personal Iatrogenic harm Lack of appropriate interventions Continued chaotic existence Unfavorably altered course and outcome Worsening of illness over time Risk of suicide 15% to 25% for un/underRx patients � especially in depressed phase Exacerbation of co-morbidity Societal Family breakdown Cost, including lost productivity Institutionalization Legal issues Bipolar disorder is not always easy to diagnose. However, accurate diagnosis is crucial, because failure to diagnose the condition correctly and treat it optimally can result in a myriad of negative personal and societal consequences. Without proper diagnosis and treatment, many patients with bipolar disorder lead chaotic lives, with the severity of their illness gradually worsening over time. The mortality rate for untreated bipolar disorder is extremely high; in fact, it exceeds those for most types of heart disease and some forms of cancer. The suicide rate has been estimated to be between 15% and 25% for untreated or inadequately treated patients. Societal consequences include the costs associated with both treatment and lost productivity, the potential for institutionalization, and for problems with the legal system.Bipolar disorder is not always easy to diagnose. However, accurate diagnosis is crucial, because failure to diagnose the condition correctly and treat it optimally can result in a myriad of negative personal and societal consequences. Without proper diagnosis and treatment, many patients with bipolar disorder lead chaotic lives, with the severity of their illness gradually worsening over time. The mortality rate for untreated bipolar disorder is extremely high; in fact, it exceeds those for most types of heart disease and some forms of cancer. The suicide rate has been estimated to be between 15% and 25% for untreated or inadequately treated patients. Societal consequences include the costs associated with both treatment and lost productivity, the potential for institutionalization, and for problems with the legal system.

37. Iatrogenic harm AD�s are commonly used - 50% of BMD depressed patients are being treated with AD monotherapy When given without a mood stabiliser AD�s can induce switch into manic or mixed episode or more severe rapid cycling Ghaemi et al � 1/3 misDx and given AD monotherapy � 1/4 developed new or accelerated rapid cycling Increase risks, including suicide, especially in adolescents Increased risk of later poor response to mood stabilisers FDA recommended screening all patients for BMD prior to starting AD

38. Lack of specific interventions Fail multiple trials of AD�s Some respond initially and effect wears off soon after Patients with Bipolar Depression present as complex management issues � majority require poly-pharmacy

39. Major Issues that impede diagnosis Depression is high profile, Bipolar is less so Poor insight is common in all phases of Bipolar Patients may consider hypomanic episodes as normal � also frequently pleasurable and not likely to present to clinician as �symptoms.� When depressed, patients may not recall hypomanic episodes � memory is mood-congruent Denial/Stigma may cause clinicians to under diagnose and clients may not accept the diagnosis Over-reliance on cross-sectional presentation Over-reliance on patient self-report

40. Major Issues that impede diagnosis Commonly have co-morbid diagnoses � substance abuse, anxiety � may obscure bipolarity Compared with people in the community, Bipolar patients are 6 times more likely to be alcoholic. >70% of cocaine users have a psychiatric diagnosis, most commonly BMD. Patients with difficult impulsive behaviour and affective instability can be labeled as having personality disorders. Adolescents and young adults are often diagnosed with ADHD People often do not have clear cut, discrete mood episodes Psychotic features are often mistaken for Schizophrenia

41. DETECTING BIPOLARITY 2 main groups Those who have actually had prior manic or hypomanic episode Those who have not, but have markers of bipolarity, which may not have fully revealed itself yet

42. Assessment Procedures Don�t need to make diagnosis at single session Diagnostic accuracy can be doubled by more extensive assessment Conduct a thorough clinical interview Cross-sectional and longitudinal Conduct careful observations of the client in session Obtain a longitudinal history of mood episodes � very helpful to display graphically � often helps patient see patterns, make sense of history

43. Assessment Procedures Collateral information is essential � families report manic symptoms twice as often as patients themselves � also employer, friends, other allied health workers Consider screening tools Consider self-monitoring tools (eg: mood diary) Priorities Functioning Risk Always evaluate risks broadly To self � suicide, accidental harm, financial, medical, sexual, reputation To others

44. SUICIDE RISK Must Be Continually Monitored Presence of suicidal or homicidal ideation, intent, plans Access to means Mental state characterised by significant agitation, hopeless and helpless themes Mixed states Substance abuse History of previous attempts Family history or recent exposure LOW THRESHOLD TO REFER TO SPECIALIST, CRISIS SERVICES

45. Diagnosis: 5 Factors Gary S. Sachs, M.D. Abbott Talk 1 Core SyllabusGary S. Sachs, M.D. Abbott Talk 1 Core Syllabus

46. AGE OF ONSET

47. FAMILY HISTORY History of BMD in family members raises alarm in any patient with MDE Obtain a family history of illness. Remember to ask detailed questions beyond �Has anyone been diagnosed with�� Look for relatives that committed suicide, extremely impulsive or odd behaviour abused substances were hospitalised

48. LIFE HISTORY Overall unpredictable behaviour Relationship breakdowns Uncharacteristic spending / legal problems Multiple jobs and moves Not clearly related to personality factors

49. CO-MORBIDITIES Increased overall medical co-morbidity High levels of co-morbid anxiety � especially panic disorder Significantly increased rates of substance abuse

50. COURSE OF ILLNESS Overall � more complex and tempestuous course Post-partum onset Seasonal exacerbations More episodes of illness, less periods of wellness between episodes, increased severity of episodes Partial/No response to AD�s � multiple trials Rapid response to AD�s which rapidly fades Switches into mixed/hypomanic states

51. EPISODE SIGNS AND SYMPTOMS Questions for detecting mania/hypomania Features that distinguish Unipolar from Bipolar depressive episode

52. Questions for Detecting Hypomania Do you have days of energy or ideas that come and go abruptly? On those days of energy, are you productive? Creative? Feel unconquerable? Convinced of your self-worth, talents abilities? Positive about the future? Talkative? Distinctly more social? Irritable? On those days of energy, do your thoughts feel as if they�re racing?

53. Questions for Detecting Hypomania At these times, do you need less sleep? Continue to be productive? How many consecutive days does this period of increased energy and change in mood last? Do others notice the change in your mood or energy level?

54. Questions for Detecting Hypomania During these �up� times, do you do things that you later regret? Make plans you find impossible to complete? Take on tasks that you later suddenly lose interest in? Are you particularly more depressed or lethargic immediately before or after these periods of energy? Does it feel like you �crash�? Does your body seem as if made of lead? Do you need excessive sleep?

56. Bipolar Spectrum Symptoms / Signs Hyperactivity Impulsivity Irritability/Hostility Psychosis Anxiety Dysphoria The spectrum of symptoms that make up bipolar disorder may also be seen individually or combined in other conditions, such as personality disorders.The spectrum of symptoms that make up bipolar disorder may also be seen individually or combined in other conditions, such as personality disorders.

57. DISTINGUISHING FEATURES

58. SPECIFIC SCREENING MEASURES MOOD DISORDER QUESTIONNAIRE BIPOLARITY INDEX

62. Differential Diagnosis NOT EVERYTHING THAT LOOKS BIPOLAR IS BIPOLAR General medical condition Substances � including medications Schizophrenia ADHD Personality disorder

63. MANAGEMENT Collaborative model � GP, psychiatrist, psychologist Engagement and strong therapeutic alliance is key � with patient and supports Monitoring medication � adherence, side effects, toxicity, metabolic effects Lifestyle interventions � sleep, appetite, substances Managing co-morbidity