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  • Impact of Bipolar Disorder Bipolar disorder is a common psychiatric illness, with a worldwide prevalence of approximately 3 – 5%. 1-3 The incidence is equal in men and women and there is no significant differences based on race or ethnicity. 4 Disease onset commonly occurs in late adolescence or early adulthood. Unfortunately, accurate diagnosis of bipolar disorder may take as long as 5 to 10 years after onset. 5 Bipolar disorder is associated with a high rate of suicide. About a third of the individuals with this illness attempt suicide and 10% to 15% succeed. In addition, high recurrence rates of bipolar disorder result in significant morbidity. 1,5 The disease has a high rate of recurrence. 1 Morbidity and mortality in bipolar disorder results in a high economic burden. 6,7 See section on Personal and Socioeconomic Impact for futher details. References on next slide
  • Bipolar Patients Are Symptomatic Almost Half Their Lives 1,2 Judd and colleagues prospectively studied the natural history of 146 patients with bipolar I disorder during long-term follow-up. They found that patients were symptomatic for almost half of the 12.8 years’ mean follow-up period. Depression was the most frequent symptom during this period, followed by mania/hypomania and rapid cycling or mixed episodes. References Judd LL, et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 2002;59:530-537. Judd LL, et al. The comparative phenotype and long term longitudinal episode course of bipolar I and II: a clinical spectrum or distinct disorders. J Affective Disorders 2003; 73:19-32.
  • Unmet Needs And Limitations Of Current Therapy For Bipolar Disorders While improved therapies for the treatment of bipolar disorders continue to be made available, unmet needs still exist. Among the most salient are the development of pharmacologic agents that, in addition to acting as mood stabilisers, effectively treat bipolar depression, while at the same time being well tolerated. Pharmacologic agents currently available for the treatment of bipolar disorders include mood stabilisers, antipsychotics (typical and atypical), antidepressants, and benzodiazepines. Unfortunately, there are limitations associated with some agents that are currently prescribed. Due to these treatment limitations, it becomes the responsibility of physicians to incorporate a patient-focused educational component into their treatment plans. With the addition of this component, patients better understand that current treatments for bipolar disorders may require changes in lifestyle, changes in treatment expectations, and an acceptance of treatment limitations themselves. Meanwhile, research and development continues for pharmacologic agents that are characterised by effective treatment of the mania and depression associated with bipolar disorders, mood stabilising properties, and are well tolerated. Author: Eduard Vieta, MD Note: Quetiapine is currently licensed for ‘the treatment of depressive episodes associated with bipolar disorder’, in the United States and some additional countries only.
  • Definition and Classification Overview Bipolar disorder is one of the most severe forms of mental illness and is characterised by mood swings. It is a single disease with two poles of mood. It affects both sexes equally in all age groups and its worldwide prevalence is approximately 3 – 5%. 1-4 The clinical course of illness can vary from mild depression to a severe form of mania. The condition has a high rate of recurrence and if untreated, it has an approximately 15% risk of death by suicide. It is the third leading cause of death among people aged 15–24 years and is a burden on society and families. 1-7 Social and occupational functioning is impaired. 8 Appropriate diagnosis and treatment can improve symptoms and social and occupational functioning. 9-12 References Shastry BS. Bipolar disorder: an update. Neurochemistry International 2005; 46 (4): 273-279. Pini S, et al. Prevalence and burden of bipolar disorders in European countries. Eur Neuropsychopharmacol 2005;15(4):425-434. Hirschfeld RMA, et al. Screening for bipolar disorder in the community. J Clin Psychiatry 2003;64:53-59. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) . Washington, DC: American Psychiatric Association, American Psychiatric Press; 2000:382-401.
  • Bipolar Disorder is Multidimensional Bipolar disorder is characterised by dramatic mood swings. These "mood swings" or episodes may last for a few hours, days, weeks or even months. This schematic illustrates the multidimensionality of the disease and indicates that the first presentation is usually with depression rather than mania. This is one of the reasons for misdiagnosis of bipolar depression – a physician may not recognise bipolar disorder unless questions regarding a previous history of mania have been asked. Between full-blown manic and depressive episodes, patients may also experience subsyndromal depression or hypomania. Resolution of an episode, on its own or with treatment, results in a normal mood state (euthymia) being maintained until the next episode. Some patients may meet the criteria for both a manic and a depressive episode in the same period, resulting in a mixed state. Not every patient will experience all these episodes. Longitudinal assessment of bipolar disorder is critical in order to achieve correct diagnosis.
  • Bipolar Spectrum Disorders Classification 1 There are several subtypes of bipolar disorder: Bipolar I disorder Bipolar II disorder Cyclothymia Rapid cycling bipolar disorder Bipolar disorder not otherwise specified (NOS) Patients with bipolar I disorder must have experienced at least one manic or mixed episode. An initial episode of mania is considered diagnostic, even without a history of depression. Subsequent episodes are likely to involve depression if effective treatment is not instituted. Patients with bipolar II disorder must have experienced one or more major depressive episodes with at least one hypomanic episode, but never a full mania. Subsyndromal symptoms may be present in both patients with bipolar I and bipolar II disorder. Cyclothymic disorder involves chronic, fluctuating mood disturbance. Patients with cyclothymia experience numerous periods of hypomanic and depressive symptoms that are insufficient in number and severity to satisfy criteria for bipolar I and II disorders. The required duration of this pattern of mood symptoms is 2 years (1 year in children/adolescents) for the DSM-IV diagnosis. A person is said to have rapid-cycling bipolar disorder when four or more episodes occur within a 12-month period. More modern descriptions of rapid cycling estimate its prevalence to be at least 20% of bipolar I patients and it has been noted to occur more often in women than men. Bipolar disorder not otherwise specified (NOS) is a category including patients who experience features that do not meet criteria for a particular bipolar disorder, eg, hypomanic episodes without depressive episodes or bipolar disorder as the result of a medical condition. Patients who have mania as a result of antidepressants will most likely have spontaneous episodes at follow-up. The most common example may be that of hypomanic symptoms lasting less than 4 days. Reference on next slide
  • Diagnosis and Assessment Overview Bipolar disorder is a paradox - biological in nature, yet psychological in expression. Physicians and patients often either fail to recognise it or are reluctant to acknowledge it. Bipolar disorder is often misdiagnosed. 1,2 Individuals who are misdiagnosed suffer with symptoms for an average of ten years before the condition is correctly diagnosed. 1-4 A large variety of psychiatric rating scales are available for assessment of Bipolar disorder (see slide 22 for more details). References 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 2003b;64:161-174. Evans DL. Bipolar disorder: diagnostic challenges and treatment considerations. J Clin Psychiatry 2000;61(suppl 13):26-31. Hirschfeld RM, et al. Screening for bipolar disorder in the community. J Clin Psychiatry 2003;64:53-59. Muller-Oerlinghausen B. Bipolar Disorder. Lancet 2002; 359:241-247.
  • Diagnosis The major symptoms and signs of bipolar disorder are mania and depression. Bipolar disorder is often misdiagnosed. Individuals who are misdiagnosed suffer with symptoms for an average of ten years before the condition is correctly diagnosed. 1-3 1 out of 3 patients are misdiagnosed and saw at least 4 physicians before receiving a correct diagnosis 1 References 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. 2003b;64:161-174. Evans DL. Bipolar disorder: diagnostic challenges and treatment considerations. J Clin Psychiatry. 2000;61(suppl 13):26-31. Hirschfeld RM, et al. Screening for bipolar disorder in the community. J Clin Psychiatry. 2003;64:53-59.
  • Diagnostic Challenges of Bipolar Disorder 1,2 Since the symptoms of bipolar disorder may overlap with other disorders such as major depressive disorder, mania secondary to another illness or treatment, or schizophrenia, patients often may be misdiagnosed. In addition, many individuals fail to report important information, either by choice or due to a lack of understanding of their symptoms, further complicating the accurate diagnosis of this illness. The presence of other disorders such as eating disorders, substance abuse, or anxiety disorders, may mask the bipolar disorder. Conversely, a patient may be misdiagnosed with a mood disorder when the symptoms are a result of a medical condition (eg, thyroid disorder, neurological condition). Bipolar disorder is particularly difficult to diagnose in children and adolescents, as the disease shares several characteristics of other illnesses associated with childhood/adolescence, eg, schizophrenia or attention-deficit hyperactivity disorder. Another problem with misdiagnosis of bipolar disorder, in this population, is the stigma that is associated with the illness. Clinicians may, therefore, avoid a psychiatric diagnosis for younger patients, especially if the illness is expected to have a lifelong course. References 1. Evans DL. Bipolar disorder: diagnostic challenges and treatment considerations. J Clin Psychiatry 2000;61(suppl 13):26-31. 2. Citrome L, Goldberg JF. The many faces of bipolar disorder. How to tell them apart. Postgrad Med. 2005 Feb;117(2):15-6, 19-23.
  • Bipolar Disorder: Unrecognised and Underdiagnosed 1,2 A study by Hirschfeld and colleagues shows that the prevalence of bipolar disorder may be higher than previously estimated. In this study, the Mood Disorder Questionnaire (MDQ) (a validated screening tool for bipolar I & II disorders) was sent to a sample of more than 125,000 adults in the United States. Results of the survey (with a 66.8% response rate) showed a positive screen rate for bipolar I and II disorders of 3.4% when weighted to match the 2000 US Census demographics. The rate rose to 3.7% when adjusted for a no response bias. Only about one fifth of the respondents who screened positive on the MDQ reported that they had previously received a diagnosis of bipolar disorder; 31% of these individuals were diagnosed with unipolar depression. Almost 50% of the respondents reported receiving no diagnosis of either unipolar depression or bipolar disorder and were therefore either undiagnosed or misdiagnosed. References 1. Hirschfeld RM, et al. Screening for bipolar disorder in the community. J Clin Psychiatry 2003;64:53-59. 2. Hirschfeld RM, et al. Perceptions and impact of bipolar disorder: how far have we really come? J Clin Psychiatry 2003;64:161-174.
  • Misdiagnosis of Bipolar Disorder This slide shows data from a study conducted by the National Depressive and Manic-Depressive Association (NDMDA) that found an initial diagnosis of bipolar disorder patients was often inaccurate. This study demonstrated that the most common misdiagnoses for patients with bipolar disorder include depression, anxiety, schizophrenia, cluster B, and alcohol abuse. Hirschfeld et al show that 40% of patients with bipolar disorder are misdiagnosed as having unipolar depression. Hirschfeld data also confirm the NDMDA data, showing a delay in proper diagnosis. In 35% of patients who were symptomatic for bipolar disorder, more than 10 years passed before a correct diagnosis was made. Hirschfeld RM, Vornik LA. Recognition and diagnosis of bipolar disorder. J Clin Psychiatry . 2004;65(suppl 15):5-9.
  • Psychiatric Rating Scales To more objectively define various types of mental illness and to standardise assessment of these disorders, mental health practitioners have developed a wide array of rating scales for psychiatric illness that can be utilised in a variety of settings. For example, the psychiatric researcher may select a battery of rating scales that will best identify those symptoms of mood disorders that change during use of a novel drug therapy. Alternatively, another group of rating scales may be selected that identify how change in psychosocial treatments affects an individual’s level of functioning and satisfaction with treatment. Careful selection and appropriate use of rating scales in a given situation will assist in obtaining information of patient outcomes that is accurate and useful for future care planning. A small sample of the these assessment scales is described below: Young Mania Rating Scale (YMRS) 1 The Young Mania Rating Scale (YMRS) is an 11-item instrument used to assess the severity of manic symptoms.The YMRS was developed in 1978, and inter-rater reliability for the scale is high.The choice of items was made on the basis of published descriptions of the core symptoms of the manic phase of bipolar disorder and includes abnormalities that exist over the entire range of illness, from mild to severe. Depressive symptoms are not assessed. The severity rating for each of the 11 items is based on the patient's subjective report of his or her condition over the previous 48 hours and on the clinician's behavioral observations during the interview, with emphasis on the clinician's observations. Continued on next slide
  • Features of Bipolar Mania Overview Manic symptoms can be categorised as affective (related to emotion or mood), cognitive (involving comprehension, judgment, memory, and reasoning), physical (such as changes in appetite or energy levels), and psychotic (especially in more severe mania or depression). Irritability is a key symptom across all acute phases of bipolar disorder (manic, mixed, and depressive). Reference American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR). Washington, DC: American Psychiatric Association, American Psychiatric Press; 2000:382-401.
  • Symptom Domains of Bipolar Disorder There is a wide constellation of symptoms associated with bipolar disorder. These can be separated into 4 major domains: (1) manic mood and behavior; (2) dysphoric or negative mood and behavior; (3) psychotic symptoms; and (4) thought/cognitive dysfunction. Manic mood and behavior is characterized by euphoria, grandiosity, pressured speech, impulsivity, excessive libido, recklessness, social intrusiveness, and diminished need for sleep. Dysphoric or negative mood and behavior is characterized by depression, anxiety, irritability, hostility, and violence or suicide. Psychotic symptoms include delusions and hallucinations. Cognitive symptoms include racing thoughts, distractibility, disorganization, and inattentiveness. Slide courtesy of Keck PE Jr.; adapted from Goodwin FK, Jamison KR. Manic-Depressive Illness. Oxford University Press: New York, NY; 1990.
  • Features of Manic and Mixed Manic Episodes 1 Manic symptoms can be categorised as affective (related to emotion or mood), cognitive (involving comprehension, judgment, memory, and reasoning), physical (such as changes in appetite or energy levels), and psychotic (especially in more severe mania or depression). Irritability is a key symptom across all acute phases of bipolar disorder (manic, mixed, and depressive). The signs and symptoms of mania can last from several days to weeks or months. Mixed states are characterised as symptoms of mania and depression present nearly every day for at least 1 week to a degree that meets criteria (except for duration) for a major episode of each. Mixed states are considered to reflect variants of mania rather than depression. Reference American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR). Washington, DC: American Psychiatric Association, American Psychiatric Press; 2000:382-401.
  • Features of Hypomania 1 Symptoms of hypomania are the same as mania, but milder in intensity. Hypomania is defined by the DSM-IV as a distinct period of persistently elevated, expansive, or irritable mood, lasting for at least 4 days*, that is different from usual non-depressed mood. However, by definition, this does not lead to the impairment of daily functioning or hospitalisation. *The duration of hypomania symptoms may be less than 4 days, which is not captured by the DSM. Reference American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR). Washington, DC: American Psychiatric Association, American Psychiatric Press; 2000:362-368.
  • Features of Bipolar Depression Overview Bipolar depression is associated with affective, cognitive, and physical symptoms such as sadness, suicidal ideation, and low energy. 1 For the patient, bipolar disorder magnifies common human experiences to larger-than-life proportions. Among its symptoms are exaggerations of normal sadness and fatigue, joy and exuberance, sensuality and sexuality, irritability and rage, energy and creativity. The clinical course of the disease can vary from a mild depression and a brief hypomania to a severe form of mania or depression. 2-5 Episodes of depression last longer than episodes of mania. 3 Symptoms of bipolar depression can vary from mild to severe depression. 1,4,5 Irritability is a key symptom across all acute phases of bipolar disorder, including the depressive phase. Psychotic symptoms may be present in bipolar depression. 1 Irritability is a key symptom across all acute phases of bipolar disorder, including the depressive phase. 1 Psychotic symptoms may be present in bipolar depression. 1-5 Symptoms of depression last longer than symptoms of mania and patients are more likely to present during a depressive episode. 1,3,4,5 References on next slide
  • Symptoms of Bipolar Depression 1 Bipolar depression is associated with affective, cognitive, and physical symptoms such as sadness, suicidal ideation, and low energy. Irritability is a key symptom across all acute phases of bipolar disorder, including the depressive phase. Psychotic symptoms may be present in bipolar depression. The symptoms of bipolar depression can lead to an increased risk of alcohol and substance abuse. Efforts to understand the high prevalence of suicidality among bipolar patients have focused on a number of factors, including: the extent and severity of depression cognitive constructs related to depression, such as hopelessness and demoralisation mixed states, which could represent the amalgam of a depression-driven self-destructive vulnerability with the impulsivity and propensity toward action imposed by concomitant mania or hypomania. Additional factors linked with suicide risk in bipolar patients include comorbid alcohol abuse or dependence, previous suicide attempts, and a heightened vulnerability to stressful interpersonal interactions. Other Features of Bipolar Depression 2 Biochemical features of bipolar depression include increased cortisol, decreased somatostatin (SRIF), an increase in the level of corticotropin-releasing factor (CRF) in the cerebrospinal fluid (CSF), and an increase in thyroid hormone levels. Cellular changes in the central nervous system include hypometabolism, a decrease in the number and activity of glial cells, and an increase in the size of the amygdala. References on next slide
  • Frequency of Depressive Symptoms In a study of long-term symptomatic status by Judd, et al., patients with bipolar I disorder were symptomatic for 47.3% of weeks during a 12.8 year follow-up period. Depressive symptoms occurred for 31.9% of weeks and predominated over manic/hypomanic symptoms which occurred for 8.9% of weeks (67.4 % vs. 18.8% of symptomatic weeks) and over cycling/mixed symptoms which occurred for 5.9% of weeks (12.4% of symptomatic weeks). Thus, depression symptoms predominated over manic symptoms (3:1) or cycling/mixed symptoms (5:1). 1 In a similar study by Judd, et al., patients with bipolar II disorder patients were symptomatic for 53.9% weeks during a 13.4 year follow-up period. Again depressive symptoms dominated over hypomanic and mixed/cycling. Depressive symptoms occurred for 50.3% of weeks (93.3% of symptomatic weeks), hypomanic symptoms occurred for 1.3% of weeks (2.4% of symptomatic weeks). Cycling/mixed symptoms occurred during 2.3% of weeks (4.3% of symptomatic weeks). 2 References Judd LL, et al. The long-term history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 2002;59:530-7. Judd LL, et al. Long-term symptomatic status of bipolar I vs bipolar II disorders. Int J Neuropsychopharmacol 2003;6:127-137.
  • Psychosis 1-3 During an episode of mania or depression, the patient may develop symptoms of psychosis. People with psychosis can become unreasonably fearful and suspicious, and develop severe paranoia. References Shastry BS. Bipolar disorder: an update. Neurochemistry International 2005; 46 (4): 273-279. Muller-Oerlinghausen B. Bipolar Disorder. Lancet 2002; 359:241-247. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR). Washington, DC: American Psychiatric Association, American Psychiatric Press; 2000:362-368.
  • Personal and Socioeconomic Impact of Bipolar Disorder Overview Bipolar disorder is a leading cause of disability worldwide. 1-5 Bipolar disorder imposes a high economic burden. 3-7 Bipolar disorder has a serious social and occupational impact on the individual. 8,9 Bipolar disorder is associated with social stigma. 8 Bipolar disorder is associated with a high risk of suicide. 9-14
  • Social Stigma Associated With Bipolar Disorder 1 The World Federation for Mental Health (WFMH) global bipolar disorder consumer survey revealed that: Almost half (47%) of all people with bipolar disorder feel that their disease has had a highly negative impact on their quality of life. More than a third (35%) of respondents stated they have been discriminated against as a result of their condition, usually within the context of everyday social relationships. The WFMH, partnered with AstraZeneca, to conduct this survey of 687 people with bipolar disorder across seven countries (Canada, Germany, Greece, Italy, Spain, United Kingdom, United States). : U.S (n=(203), Canada (n=99), U.K. (n=100), Germany (n=102), Spain (n=75), Italy (n=100) and qualitative in Greece (n=8). The survey also revealed that: 26% of respondents do not disclose their condition. Fear of social stigma is a key reason The vast majority (79%) of respondents in all countries say successful treatment would lead to significant quality of life changes in terms of increased functionality/improved lifestyle such as, maintaining a job, having relationships, living independently, and achieving goals. - 71% of people with bipolar disorder who were surveyed believe that the public does not understand their illness. This ignorance may be causing the stigma that many feel. 687 people with bipolar disorder were interviewed via the internet and face-to-face, across seven countries. For more information regarding the WFMH international activities, including World Mental Health Day (October 10), visit www.wfmh.org and/or www.moodswing.org. Reference on next slide
  • The burden of bipolar disorder Bipolar disorder is the sixth leading cause of disability worldwide in those aged 15 – 44 years. 1,2 Data indicate that the direct and indirect economic and health burden of bipolar disorder is substantial. 3 (See next slide) In a study of patients with bipolar disorder hospitalised for a manic episode, 43% patients were unable to resume normal work, while 21% were working at their expected level of employment prior to the episode despite the absence of affective symptoms in almost 80% of the study group. 4 Of the ten leading causes of disability worldwide in 1990, measured in years lived with a disability, five were psychiatric, including bipolar disorder. Globally, it is estimated that 14.1 million people (3%) are affected. 5 The projections show that psychiatric and neurological conditions could increase their share of the total global burden by almost half, from 10.5% to almost 15% in 2020. This is a bigger proportionate increase than that for cardiovascular diseases. References on next slide
  • Mortality Rates in Bipolar Disorder Untreated bipolar disorder is associated with high rates of suicide. 1 Up to half of all individuals with bipolar disorder have been estimated to make at least one suicide attempt in their lifetime. 2,3 One study using the Schedule for Affective Disorders and Schizophrenia (SADS) suicide subscale in 129 patients with bipolar disorder, observed the highest rate of suicidality in individuals with bipolar depression (79.3%) compared with diagnoses of depressive-mania (56.3%) and pure mania (2.3%). 4 Similar studies have also highlighted the higher frequency of suicide attempts during depressive episodes in the bipolar population. 5,6 References Sachs GS et al. Unmet needs in bipolar disorder. J Clin Psychopharmacology 2003; 23(3)Suppl 1: S2-S8. Goodwin FK, Jamison KR. Manic-Depressive Illness. New York: Oxford University Press; 1990. Robins LN, Regier DA. In: Psychiatric Disorders in America: The Epidemiologic Catchment Area Study. New York, NY: Free Press; 1991. Dilsaver SC, et al. Suicidality, panic disorder and psychosis in bipolar depression, depressive-mania and pure mania. Psychiatry Re 1997;73:47-56. Rihmer Z, et al. Depression and suicide on Gotland: an intensive study of all suicides before and after a depression-training programme for general practitioners. J Affect Disord 1995;35:147-152. Slama F, et al. Bipolar patients with suicidal behavior: toward the identification of a clinical subgroup. J Clin Psychiatry 2004;65:1035-1039.
  • Suicide and Bipolar Disorder The risk of suicide in patients with bipolar disorder is >20 times higher than in general population. 1 There are multiple risk factors for suicide, which pose treatment challenges for clinicians. 2,3 25-50% of patients with bipolar disorder attempt suicide at least once in their life. 2 Patients with a history of suicide attempts experience a more severe and complex course of illness. 3 References Tondo L, et al. Suicidal behaviour in bipolar disorder. CNS Drugs 2003; 17(7): 491-511. Jamison KR. Suicide and bipolar disorder. J Clin Psychiatry 2000;61 (Suppl 9): 47-51. Leverich GS, et al. Factors associated with suicide attempts in 648 patients with bipolar disorder in the Stanley Foundation Bipolar Network. J Clin Psychiatry 2003; 64(5): 506-515.
  • Management of Suicide in Bipolar Disorder 1-3 It is important to recognise suicide risk in bipolar depression. 1,2 A comprehensive and ongoing ‘risk assessment’ is recommended Risk factors for suicide should be considered, which include: substance and alcohol abuse family history of suicide rapid cycling history of hospitalisation for depression References Jamieson KR. Suicide and bipolar disorder. J Clin Psychiatry 2000;60(Suppl 9): 47-51. Leverich GS, et al. Factors associated with suicide attempts in 648 patients with bipolar disorder in the Stanley Foundation Bipolar Network. J Clin Psychiatry 2003; 64(5): 506-515. Dunner DL. Correlates of suicidal behavior and lithium treatment in bipolar disorder. J Clin Psychiatry 2004; 65(Suppl 10): 5-10.
  • Costs of Non-adherence to Treatment The rate of non-adherence to pharmacotherapy may be as high as 64%. Nonadherence is associated with an increase in the frequency and duration of hospitalisation, and is the most common cause of relapse. 1 A study that used pharmacy records to assess adherence found that 68% of patients with bipolar disorder were hospitalised within 90 days of discontinuing their medication. 2 Increased hospitalisation translated to higher treatment costs. Therefore, effective and well-tolerated treatments are necessary to improve adherence and reduce the economic and family burden of bipolar disorder. 3,4 References Colom F, et al. Clinical factors associated with treatment noncompliance in euthymic bipolar patients. J Clin Psychiatry 2000;61:549-555. Unutzer J, et al. The use of administrative data to assess quality of care for bipolar disorder in a large staff model HMO. Gen Hosp Psychiatry 2000;22:1-10. Durrenberger S, et al. Economic grand rounds: the high costs of care for four patients with mania who were not compliant with treatment. Psychiatr Serv 1999;50:1539-1542. Perlick DA, et al. Impact of family burden and affective response on clinical outcome among patients with bipolar disorder. Psychiatr Serv 2004;55:1029-1035.
  • Treatment of Bipolar Disorder Overview Successful control of bipolar disorder involves the effective treatment of acute episodes of mania, acute episodes of bipolar depression, and the ongoing prevention of relapses. Impaired occupational and social functioning can result in difficulties with work-related performance, leisure activities, and interpersonal relationships with family and friends. Therefore, symptomatic remission together with a return to healthy levels of functioning is the ultimate goal of therapy. There is a need for treatments that are both efficacious and well tolerated in order to optimise patient satisfaction and adherence with therapy. Side effects that interfere with social functioning are also important to avoid. A range of agents is available that are approved either for specific uses in bipolar disorder, or for uses in patients with other disorders, such as schizophrenia (antipsychotics), seizures (anticonvulsants), and unipolar depression (antidepressants). Lithium, the first drug found to be effective for bipolar disorder, was approved by the US FDA for the treatment of acute mania in 1970. A number of other treatment options have since been used in bipolar disorder. Different agents are often used in combination to treat the various aspects of bipolar disorder. 1,2 Nonadherence is the most important modifiable factor that increases the risk of relapse. In studies with patients with schizophrenia, discontinuation of antipsychotic medication increased risk of relapse by almost 5-fold. Nonadherence accounts for ~40% of relapses. 3-5 References on next slide
  • Therapeutic Challenges 1,2 Like many neuropsychiatric disorders, bipolar disorder has no cure. There are significant therapeutic challenges specific to bipolar disorder and its successful treatment. Noncompliance results when the patient rejects medication or lacks insight into his or her illness, leading to a discontinuation of medication. It may also be related to successful symptom treatment resulting in medication discontinuation. Many patients find the side effects and medication management issues (blood draws) difficult to manage. Others may miss the feelings associated with the symptoms of a manic, hypomanic, or mildly depressed state. Symptom overlap among diagnostic categories makes treatment decisions more challenging. As previously mentioned, individuals may be misdiagnosed, therefore mistreated, causing significant distress and possibly precipitating more severe symptoms and unnecessary medication side effects. Efficacy across the symptom picture in both the short- and long-term is a significant challenge. Suicidal tendencies are a serious concern for persons who are in treatment as well as those who are not receiving appropriate care. Safety and tolerability of medication treatments are major concerns related to noncompliance and are therefore ultimately related to the long-term management of the disorder. Comorbid conditions such as eating disorders, primary mood disorders, substance abuse disorders not only interfere with diagnosis and treatment but also add to the cost of care. References on next slide
  • Disease Management Goals 1 In treating individuals with bipolar disorder, experts, families, and patients themselves strive to reach several goals. The overall goal of management of bipolar disorder is to decrease the morbidity and mortality of the illness. Once an acute episode has been successfully treated, it is important to maintain a therapy that works. Treatment in any phase, acute or maintenance, must be selected to increase patient compliance. New episodes must be identified early and functional impairment must be minimised, with encouragement toward routine activity and sleep patterns. Patients, their caregivers, and healthcare providers must also be aware of individual stressors and be educated about bipolar disorder and its management. Reference American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry. 2002;159(4 suppl):1-50.
  • Objectives of Treatment for Bipolar Disorder Successful control of bipolar disorder involves the effective treatment of acute episodes of mania, acute episodes of bipolar depression, and the ongoing prevention of relapses. Impaired occupational and social functioning can result in difficulties with work-related performance, leisure activities, and interpersonal relationships with family and friends. Therefore, symptomatic remission together with a return to healthy levels of functioning is the ultimate goal of therapy. There is a need for treatments that are both efficacious and well tolerated in order to optimise patient satisfaction and adherence with therapy. Side effects that interfere with social functioning are also important to avoid. There is currently no cure for bipolar disorder and no single agent appears to be completely effective in all phases of the disease and in all patients. The therapeutic challenge is to select clinically effective treatments that are efficacious and well tolerated so that patients can get better and stay well. Treatments associated with mood instability (eg, induction of mania, treatment-emergent depression, cycle acceleration) should be avoided wherever possible.
  • Issues Identified by Patients to Optimise Outcome 1 Medications should be: Fast acting Efficacious Have few troubling side effects Inexpensive Patient-physician communication should be improved in order to: Encourage patient participation Identify, understand, address patient needs Provide more effective listening Ask direct / targeted questions Involve patients in their treatment including: Treatment decisions made jointly with physician Patients given an active role in their healthcare show improved outcome versus those not involved Peer to peer support for patients helps to: Improves treatment adherence Reduce hospitalisation Provide hope for future Reference 1. Lewis L. Patient perspectives on the diagnosis, treatment, and management of bipolar disorder. Bipolar Disord 2005: 7 (Suppl. 1): 33–37.
  • Definitions of Remission, Recovery, Relapse, and Recurrence The relapse-remitting course of bipolar disorder has prompted the need to define events such as the resolution of an episode and the onset of a new one. Many definitions have evolved for use in treatment and research settings, but the criteria for remission, recovery, relapse, and recurrence, as used in general clinical practice, remain poorly defined. 1 Remission is a period in which the patient no longer meets affective syndrome criteria and is either asymptomatic or has no more than minimal symptoms. Recovery (from an episode) refers to a period of sustained remission. Relapse is the return of symptoms satisfying the full syndrome criteria for an episode that occurs during remission, but before recovery. Recurrence is the appearance of a "new episode" and can only occur during a recovery, not during remission. These distinctions are important when clinicians are attempting to differentiate between new episodes and an index episode that is not fully resolved. Reference Frank E, et al. Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Arch Gen Psychiatry. 1991;48:851-855.
  • Treatment Modalities in Bipolar Disorder A number of treatment modalities for bipolar disorder are currently in use, either alone or in combination. The main categories include: Pharmacotherapy Psychotherapy (includes psychoeducation, cognitive behavioral therapy [CBT], and interpersonal and social rhythm therapy [IPSRT]) Electroconvulsive therapy (ECT) The first two modalities will be described in the subsequent slides.
  • Ideals of Effective Pharmacotherapy There is currently no cure for bipolar disorder and no single agent appears to be completely effective in all phases of the disease and in all patients. The therapeutic challenge is to select clinically effective treatments that are efficacious and well tolerated so that patients can get better and stay well. Treatments associated with mood instability (eg, induction of mania, treatment-emergent depression, cycle acceleration) should be avoided wherever possible. Clinical effectiveness can include a number of factors, including: Bimodal efficacy in a broad range of symptoms experienced during manic episodes and depressive episodes, and effective in the prevention of relapses during long-term maintenance therapy Efficacy in a range of settings (inpatient, outpatient, etc.) Rapid onset of action (within 1 week) Efficacy despite comorbidity Efficacy and tolerability when combined with other agents Safety and tolerability, particularly the absence of treatment-stopping side effects Ease of use, eg, no need for blood monitoring Enhanced adherence to treatment
  • Common Pharmacological Treatments for Bipolar Disorder A range of agents is available that are approved either for specific uses in bipolar disorder, or for uses in patients with other disorders, such as schizophrenia (antipsychotics), seizures (anticonvulsants), and unipolar depression (antidepressants). Lithium, the first drug found to be effective for bipolar disorder, was approved by the US FDA for the treatment of acute mania in 1970. A number of other treatment options have since been used in bipolar disorder. Different agents are often used in combination to treat the various aspects of bipolar disorder. 1,2 References Bowden CL. Key treatment studies of lithium in manic-depressive illness: efficacy and side effects. J Clin Psychiatry 1998;59(suppl 6):13-19. Post RM, et al. Beyond lithium in the treatment of bipolar illness. Neuropsychopharmacology 1998;19:206-219.
  • FDA-approved Bipolar Disorder Treatments 1 As you can see from this chart, most FDA-approved therapies for bipolar disorder are not indicated for bipolar depression. The olanzapine/fluoxetine combination is approved for treatment of acute depression. Quetiapine is FDA-approved as monotherapy for treatment of acute mania and for acute depression. The most recent FDA approval of quetiapine for acute depression makes it the only single agent approved for the treatment of both poles of bipolar disorder. With the exception of olanzapine/fluoxetine combination (OFC), SSRIs are not FDA approved for the treatment of any phase of bipolar disorder. Note: The immediate release formulations of divalproex and carbamazepine are not approved for bipolar disorder. Please note that this chart does not imply comparable efficacy or safety profiles. Abbreviations: DR, delayed release; ER, extended release. Reference Physicians’ Desk Reference ® . 60th ed. Montvale, NJ: Medical Economics Co; 2006.

Transcript

  • 1. Internal Use Only Gangguan Bipolar dan Manajemen TerapiRihadiniPsikiaterRSJD Dokter Amino Gondohutomo SemarangSER/023/Aug08-Aug09/WW
  • 2. PendahuluanSER/023/Aug08-Aug09/WW
  • 3. Apa itu gangguan bipolar? Gangguan bipolar merupakan penyakit gangguan perasaan seumur hidup, kronis, dan sangat menyengsarakan, ditandai oleh episode yang berulang baik mania maupun depresi Gejala-gejalanya yaitu rasa sedih dan lelah yang lebih dari orang normal. Perasaan senang dan antusias, sensualitas dan seksualitas, iritabilitas dan berpacu, energi dan kreativitas yang lebih dari orang normal pada umumnya3 SER/023/Aug08-Aug09/WW
  • 4. Dampak dari gangguan bipolar 1. Gangguan bipolar memiliki prevalensi yang tinggi dengan estimasi 3%-5% 2. Angka kejadian yang sama-sama setara antara laki-laki dan wanita 3. Tidak ada perbedaan signifikan atas dasar suku atau etnis 4. Awal mula penyakit antara 15 tahun sampai 24 tahun, tetapi diagnosa yang akurat diperlukan 5 sampai dengan 10 tahun 5. 1/3 pasien penderita gangguan bipolar ini ada usaha untuk melakukan bunuh diri dan 10%-15%-nya berhasil bunuh diri 6. Laju kekambuhannya mencapai angka 90% 7. Beban ekonomi yang sangat tinggiSource: Shastry 2005; Pini 2005; Hirschfeld 2003; Goodwin and Jamison 1990; Evans 2000; Murray 1997; Woods 2000 4 SER/023/Aug08-Aug09/WW
  • 5. Pasien gangguan bipolar hampir separuh hidupnyamengalami gejala-gejala 6% 9% 32% 53% n = 146; 12.8-year follow-up Minggu-minggu tanpa gejala Minggu-minggu manik/hipomanik Minggu-minggu gejala depresi Minggu-minggu campur antara manik-depresiSource: Judd, et al. 2002; Judd, et al. 20035 SER/023/Aug08-Aug09/WW
  • 6. Kebutuhan dan keterbatasan terapi saat ini padagangguan bipolar  Adanya kebutuhan akan preparat mood stabiliser yang dapat memberikan terapi depresi  Keterbatasan dari terapi pada saat ini meliputi:  Munculnya EPS dan tardive dyskinesia, penambahan berat badan yang berlebihan, dan penurunan kemampuan kognitif umumnya ada pada kebanyakan antipsikotik  Banyak pasien tidak merasakan adanya manfaat dari penggunaan mood stabiliser ini dalam periode jangka panjangEduard Vieta 6 SER/023/Aug08-Aug09/WW
  • 7. Definisi dan klasifikasi gangguan bipolar Gangguan bipolar adalah suatu penyakit yang ditandai adanya dua buah kutub perasaan: manik dan depresi Perubahan perasaan ini atau disebut episode dapat bertahan selama beberapa jam, hari, minggu atau bahkan beberapa bulan. Berdasarkan kriteria diagnosa, ada beberapa tipe gangguan bipolar yaitu:  Gangguan bipolar tipe I  Gangguan bipolar tipe II  Cyclothymia  Gangguan bipolar tidak spesifik (NOS) Source: Shastry 2005; Pini 2005; Hirschfield 2003; American Psychiatric Association 2000; Murray 1997; Evans 2003; Goodwin 19907 SER/023/Aug08-Aug09/WW
  • 8. Perkembangan episode gangguan bipolar Mania Subsyndromal Mania (Hypomania) Mania MaintenanceSubsyndromal Depression (Dysthymia) Depression 8 SER/023/Aug08-Aug09/WW
  • 9. Macam-macam tipe gangguan bipolar(menurut DSM IV)  Gangguan bipolar tipe I ≥1 episode manik atau bercampur yang berat  Gangguan bipolar tipe II ≥1 episode depresi yang berat diikuti adanya episode hipomanik (tidak sampai episode manik seluruhnya)  Cyclothymia Beberapa periode hipomanik dan gejala depresi selama ≥2 tahun (tidak pernah episode depresi mayor atau episode manik)  Gangguan bipolar dengan perubahan yang cepat (Rapid Cycling) empat episode atau lebih selama periode 12 bulan  Gangguan bipolar tidak spesifik Beberapa gejala klinis tidak memenuhi ketentuan gangguan bipolar spesifik tertentu, misalnya gangguan bipolar yang muncul akibat kondisi suatu terapi pengobatan American Psychiatric Association 20009 SER/023/Aug08-Aug09/WW
  • 10. Menurut PPDGJ III Tipe-tipe GangguanSuasana Perasaan (Mood/Afektif) Episode Manik Gangguan afektif bipolar: Gangguan afektif bipolar, episode kini manik (dengan gejala psikotik/ tanpa gejala psikotik) Gangguan afektif bipolar, episode kini depresif berat (dengan gejala psikotik/ tanpa gejala psikotik) Episode Depresif Gangguan Depresif berulang Gangguan suasana perasaan menetap Gangguan suasana perasaan lainnya Gangguan suasana perasaan YTT10 SER/023/Aug08-Aug09/WW
  • 11. Gejala klinis Gangguan Afektif Bipolar  Episode berulang (sekurang-kurangnya 2 kali)  Gangguan ini pada waktu tertentu terdiri dari peninggian suasana perasaan, peningkatan enersi dan aktivitas (mania atau hipomani) dan  pada waktu lain berupa penurunan suasana perasaan serta pengurangan energi dan aktivitas (depresi)  Khas penyembuhan sempurna antar episode  Episode mani biasanya tiba-tiba, berlangsung antara 2 minggu sampai 4-5 bulan (rata-rata 4 bulan )  Episode depresi cenderung berlangsung lebih lama (rata-rata sekitar 6 bulan )  Episode pertama bisa timbul pada setiap usia dari masa kanak sampai tua  Remisi cenderung makin lama makin pendek, depresi menjadi lebih sering dan lebih lama berlangsungnya setelah usia pertengahan Source: Hirschfield 2003; Evans 2000; Muller-Oerlinghausen 200211 SER/023/Aug08-Aug09/WW
  • 12. Diagnosa  Adanya tanda-tanda utama dan gejala-gejala yang khas yaitu manik dan depresi  Diagnosa memerlukan waktu hingga 10 tahun  Kesalahan diagnosa umum terjadi  1 dari 3 pasien pernah mengalami kesalahan diagnosa dan sebelumnya datang ke 4 dokter sebelum diagnosanya ditegakkan secara benar Source: Hirschfield 2003; Evans 200012 SER/023/Aug08-Aug09/WW
  • 13. Pedoman Diagnosis Gangguan Afekti Bipolar,Episode kini manik tanpa gejala psikotik Memenuhi kriteria mania tanpa gejala psikotik : Berlangsung sekurang-kurangnya satu minggu dan cukup beratsehingga mengacaukan seluruh pekerjaan biasa dan aktivitas sosial Perubahan suasana perasaan disertai energi yang meninggi Dan beberapa gejala khususnya percepatan berbicara, kebutuhan tidur berkurang, grandiositas dan terlalu optimistik Harus ada sekurang-kurangnya satu episode afektif lain (hipomanik, manik, depresif atau campuran)13 SER/023/Aug08-Aug09/WW
  • 14. Pedoman Diagnosis Gangguan Afekti Bipolar,Episode kini manik dengan gejala psikotik Lebih berat dari bentuk mania tanpa gejala psikotik Harga diri membumbung dan gagasan kebesaran berkembang menjadi waham dan iritabilitas serta kecurigaan menjadi waham kejar, Waham kebesaran Gagasan yang takabur Percepatan berbicara Aktifitas dan eksitasi fisik yang hebat  agresi, agitatis Waham dan halusinasi yang serasi atau tidak serasi afek14 SER/023/Aug08-Aug09/WW
  • 15. Pedoman Diagnosis Gangguan Afekti Bipolar,Episode kini depresif tanpa gejala psikotik Episode sekarang harus memenuhi kriteria episode depresi berat tanpa gejala psikotik Suasana perasaan depresif, kehilangan minat dan kegembiraan, berkurangnya enersi (mudah lelah dan berkurangnya aktivitas) Gejala lain yang lazim:a) Konsentrasi dan perhatian kurangb) Harga diri dan kepercayaan diri kurangc) Gagasan tentang perasaan bersalah dan tidak bergunad) Pandangan masa depan yang suram dan pesimistise) Gagasan atau perbuatan membahayakan diri atau bunuh dirif) Tidur terganggug) Nafsu makan berkurang15 SER/023/Aug08-Aug09/WW
  • 16. Pedoman Diagnosis Gangguan Afekti Bipolar,Episode kini depresif dengan gejala psikotik Memenuhi kriteria tersebut diatas disertai Waham, halusinasi atau stupor depresif Waham biasanya tentang dosa, kemiskinan atau malapetaka yang mengancam Halusinasi auditorik atau olfatorik biasanya suara yang menghina atau menuduh atau bau kotoran atau daging yang membusuk Retardasi motorik berat dapat menuju stupor16 SER/023/Aug08-Aug09/WW
  • 17. Tantangan dalam diagnosa gangguan bipolar Gejala-gejala yang ada seringkali tumpang tindih dengan gangguan/penyakit lain sehingga mengakibatkan kesalahan diagnosa Pasien menolak dikatakan sakit Kondisi adanya penyakit penyerta, misalnya gangguan cemas, gangguan pola makan, penggunaan zat-zat psikotropika. Kejadian pada anak-anak dan remaja (adanya faktor kesalahan diagnosa dan stigma) Source: Evans 2000; Citrome and Goldberg 200517 SER/023/Aug08-Aug09/WW
  • 18. Gangguan bipolar: Tidak dikenali dandidiagnosa yang lain Kuisioner/Survey Gangguan Perasaan (Berdasarkan populasi penduduk USA) Didiagnosa secara benarTidak didiagnosa secara sebagai gangguan bipolarbenar, melainkan sebagai 20% penyakit lain 49% 31% Tidak didiagnosa secara benar, melainkan sebagai depresi sajaSource: Hirschfeld 200318 SER/023/Aug08-Aug09/WW
  • 19. Kejadian Salah Diagnosa pada Gangguan Bipolar Berdasarkan NDMDA Diagnosa Awal 60% 60 Depresi 50 Persentasi (%) Cemas 40 26% Skizofrenia 30 18% 17% Gangguan kepribadian 14% 20 Penyalahgunaan Alkohol 10 0NDMDA = National Depressive and Manic-Depressive Association; N = 400Hirschfeld RM, et al. J Clin Psychiatry. 2004;65(suppl 15):5-9. 19 SER/023/Aug08-Aug09/WW
  • 20. Instrumen psikiatrik yang digunakan Young Mania Rating Scale (YMRS) Montgomery Asberg Depression Rating Scale (MADRS) Hamilton Rating Scale for Depression (HAM-D) Hamilton Rating Scale for Anxiety (HAM-A) The Clinical Global Impressions scale (CGI) yang dimodifikasi untuk digunakan pada kasus gangguan bipolar (CGI-BP)20 SER/023/Aug08-Aug09/WW
  • 21. Sekilas tentang Bipolar mania1. Gejala manik dapat dikategorikan sebagai gangguan afektif (berkenaan dengan emosi atau perasaan), kognitif (meliputi secara keseluruhan aspek kognitif, penilaian, memori dan penjelasan), fisik (perubahan nafsu makan atau energi) dan psikotik (khususnya pada kondisi manik atau depresi yang lebih berat)2. Perasaan mudah tersinggung (iritabilitas) merupakan gejala kunci pada semua episode gangguan bipolar, baik pada manik, campuran, maupun depresi)3. Gejala-gejala hipomanik sama seperti manik tetapi lebih ringan dalam hal intensitasnyaSource: American Psychiatric Association 200021 SER/023/Aug08-Aug09/WW
  • 22. Symptom Domains of Bipolar Disorder Manic Mood and Behavior Dysphoric or Negative Mood and Behavior • Euphoria • Grandiosity • Depression • Pressured speech • Anxiety • Impulsivity • Irritability • Excessive libido • Hostility • Recklessness BIPOLAR • Violence • Social intrusiveness • Diminished need DISORDER • Suicide for sleep Thought/Cognitive Dysfunction Psychotic Symptoms Racing thoughts Delusions Distractibility Hallucinations Disorganization InattentivenessSlide courtesy of Keck PE Jr.; adapted from Goodwin FK, Jamison KR.Manic-Depressive Illness. Oxford University Press: New York, NY; 1990. 22 SER/023/Aug08-Aug09/WW
  • 23. Ciri-ciri Episode Manik dan Campuran Affective Cognitive Physical Pure Mania Racing thoughts Rapid or pressured speech Elevated, euphoric, or Distractibility irritable mood Poor insight Increased energy Expansive Disorganization Decreased need for sleep Grandiose Impulsive Impaired attention Increased libido Impaired comprehension Overly active, social, or hostile behavior Dysphoric/Mixed Mania Psychotic Recklessness, bizarre behavior, Depression/Anxiety destruction co-mixed Delusions of property Irritability Hallucinations Hostility or violence Sleep and endocrine Sensory hyperactivity abnormalitiesSource: American Psychiatric Association 200023 SER/023/Aug08-Aug09/WW
  • 24. Ciri-ciri Hipomanik Hipomanik merupakan komponen penting dari gangguan bipolar tipe II dan gangguan cyclothymic Suatu periode berbeda dari perasaan yang naik, ekspansif, atau mudah tersinggung, yang bertahan selama 4 hari Selama periode munculnya gangguan perasaan tadi, setidaknya 3 dari gejala manik akan tetap ada dan menonjolSource: American Psychiatric Association 200024 SER/023/Aug08-Aug09/WW
  • 25. Ciri-ciri Bipolar Depresi Bipolar depresi dikaitkan dengan gejala-gejala afektif, kognitif dan fisik seperti perasaan sedih, ide untuk melakukan bunuh diri, dan kurangnya tenaga (energi) Gejala-gejala gangguan bipolar depresi ini bisa sangat bervariasi dari depresi yang ringan hingga berat Perasaan mudah tersinggung merupakan gejala kunci dari gangguan bipolar termasuk didalamnya adalah fase depresi Gejala-gejala psikotik dapat muncul pada gangguan bipolar depresi Gejala-gejala depresi bertahan lebih lama dibandingkan manik Pasien umumnya datang atau berobat ke dokter pada periode episode depresi tersebut.Source: American Psychiatric Association 200025 SER/023/Aug08-Aug09/WW
  • 26. Ciri-ciri gangguan bipolar depresi Affective Cognitive Physical (alam persaan) (pikiran) Change in: Sadness Poor self-esteem Sleep Apathy Poor concentration Endocrine function Anhedonia Indecisiveness Appetite and/or weight Irritability Suicidal ideas Activity Anxiety Self-blame Energy Hopelessness Slow thought and speechSource: American Psychiatric Association 200026 SER/023/Aug08-Aug09/WW
  • 27. Perbandingan gejala depresi pada bipolar tipe I dan tipe II Campuran Campuran 4.5% 13% Manik/ hipomanik Manik / 2.5% Depresi hipomanik Depresi 67% 20% 93%Gangguan Bipolar Tipe I Gangguan Bipolar Tipe II n=146 n=86Judd, et al. 2002, Judd, et al. 2003 27 SER/023/Aug08-Aug09/WW
  • 28. Psikosis pada gangguan bipolar Selama suatu episode manik atau depresi, pasien gangguan bipolar ada kemungkinan mengalami ciri psikotik Gejala-gejalanya termasuk rasa takut yang tidak beralasan, rasa curiga atau paranoidSource: Shastry 2005; Muller-Oerlinghausen 2002; American Psychiatric Association 200028 SER/023/Aug08-Aug09/WW
  • 29. Sekilas tentang dampak personal dan sosialekonomi dari gangguan bipolar Salah satu yang menyebabkan ketidakmampuan mengerjakan sesuatu (disability) Memiliki dampak ekonomi yang tinggi Berdampak pada pekerjaan individu dan hubungan sosial yang serius Dikaitkan dengan stigma sosial Adanya risiko bunuh diri Source: Shastry 2005; Pini 2005; Murray 1997; Woods 2000; Wyatt 1995; Begley 2001; Gupta 2002; World Federation of Mental Health 2005; Sachs 200329 SER/023/Aug08-Aug09/WW
  • 30. Stigma sosial sehubungan dengan gangguan bipolar Seberapa dalam anda merasakan stigma / diskriminasi; Bagaimana sebenarnya stigmatisasi tersebut? responden 100 (%) 80 n=737 pasien gangguan bipolar 60 40 20 0 l s ia a a os d is rja asi ga arg an tas si so t e p ia g n me na an kr i t pe rimin ah asili n g e lu d is g a an mi d ter San at rja eta ri k ng rum n f ya tkan ke ke k bu n t da pe atka Dis Pe Hu ng a da atif ap ap eg nd nd pn Me Me a Sik Source: World Federation for Mental Health 2005 30 SER/023/Aug08-Aug09/WW
  • 31. Disability yang disebabkan gangguan bipolar  Peringkat 6 penyebab ketidakmampuan di seluruh dunia Ketidakmampuan 6th Gangguan bipolar  Memiliki risiko tinggi penyakit kardiovaskular 7th Akibat Perang dan kanker  Memiliki dampak 8 th Akibat Kebrutalan ekonomi yang tinggi ($45.2 milyar di USA 9th Skizofrenia pada tahun 1991)Wyatt and Henter 1995; Murray and Lopez 1997; Woods 2000; Murray 1996; Dion 1988 31 SER/023/Aug08-Aug09/WW
  • 32. Angka kematian pada kasus gangguan bipolarRasio angka ***kematian 30 *p<0.05; ***p<0.001 Tidak diterapisehubungan n=220 pasien gangguan bipolar Diterapi 25denganpopulasi 20secara umum 15 10 5 *** *** * *** *** 0 ar ab r n m a ri la aa ny ul di as eb ku sk ak in uh pl ny as va La el eo un pe ov ec ro N B di K ua eb ar em er K C SSource: Sachs, et al. 2003; Goodwin 1990; Robins & Regier 1991; Dilsaver, et al. 1997; Rihmer, et al. 1995; Slama, et al. 2004 32 SER/023/Aug08-Aug09/WW
  • 33. Bunuh diri dan gangguan bipolar  Risiko bunuh diri pada pasien dengan gangguan bipolar ternyata 20% lebih besar dibandingkan populasi secara umum  Terdapat beberapa faktor risiko untuk melakukan bunuh diri, dimana menjadi tantangan tersendiri bagi para klinisi  25%-50% pasien dengan gangguan bipolar setidaknya pernah mencoba bunuh diri sekali dalam hidup mereka  Pasien dengan riwayat percobaan bunuh diri mengalami perjalanan penyakit yang lebih kompleks dan lebih berat Source: Tondo, et al. 2003; Jamison 2000; Leverich, et al. 200333 SER/023/Aug08-Aug09/WW
  • 34. Manajemen risiko bunuh diri pada gangguan bipolar  Kenali dengan benar fase depresi gangguan bipolar  Direkomendasikan untuk melakukan tambahan penilaian risiko yang lebih lengkap dan berkelanjutan  Mempertimbangkan faktor-faktor risiko yang mendorong pasien untuk melakukan bunuh diri  Penyalahgunaan zat dan alkohol  Adanya riwayat keluarga yang meninggal akibat bunuh diri  Perubahan yang cepat (rapid cycling)  Adanya riwayat pernah dirawat karena depresi Source: Jamison 2000; Leverich, et al. 2003; Dunner 200434 SER/023/Aug08-Aug09/WW
  • 35. Harga yang harus dibayar karenaketidakpatuhan terhadap terapi Tidak patuh terhadap terapi  Cukup tinggi hingga 64%  Merupakan penyebab utama kekambuhan dan meningkatkan risiko kembali masuk rumah sakit (hospitalization)  Lebih lanjut meningkatkan biaya terapi Obat-obatan yang memiliki efikasi yang baik dan ditoleransi baik oleh pasien sangat diperlukan untuk meningkatkan kepatuhan pasien terhadap terapi dan mengurangi risiko beban ekonomi dan keluarga akibat gangguan bipolar iniSource: Durrenberger, et al. 1999; Unutzer, et al. 2000; Colom, et al. 2001; Perlick, et al. 200435 SER/023/Aug08-Aug09/WW
  • 36. Sekilas tentang terapi gangguan Bipolar  Untuk dikatakan berhasil dalam mengendalikan gangguan bipolar diperlukan terapi yang efektif baik manik dan depresi dan mencegah terjadinya kekambuhan  Sampai saat ini belum ada terapi yang dapat menyembuhkan gangguan bipolar tersebut. Belum ada preparat yang dikatakan efektif pada semua fase penyakit dan pada semua pasien.  Sejumlah modalitas terapi untuk gangguan bipolar yang sampai sekarang masih digunakan, baik monoterapi maupun dikombinasikan, yaitu:  Farmakoterapi  Psikoterapi  Terapi elektro-konvulsif atau lebih dikenal ECT  Ketidakpatuhan terhadap terapi meningkatkan risiko kekambuhanSource: Bowden 1998; Post RM, Frye MA, et al. 1998; Weiden & Zygmunt 1997; Robinson et al. 1999; Lacro, et al. 200236 SER/023/Aug08-Aug09/WW
  • 37. Tantangan Terapi Gangguan Bipolar Tidak ada obat yang dapat menyembuhkan gangguan bipolar Angka ketidakpatuhan sangat tinggi Adanya gejala-gejala yang tumpang tindih Permasalahan efikasi baik pada periode akut dan jangka panjang  Pada semua gejala-gejala  Pada semua fase gangguan bipolar (menstabilkan perasaan/mood)  Dorongan untuk bunuh diri Faktor keamanan dan toleransi pasien terhadap obat Adanya penyakit penyertaBrady 2000; McIntyre 200437 SER/023/Aug08-Aug09/WW
  • 38. Tujuan Manajemen Terapi Gangguan Bipolar Menurunkan angka kesakitan (morbiditas) dan kematian (mortalitas) Mempertahankan terapi yang efektif Meningkatkan kepatuhan pasien Mengidentifikasi pasien baru sejak awal Meminimalkan hendaya fungsional Menganjurkan aktivitas rutin dan pola tidur yang teratur Memberikan perhatian lebih terhadap adanya stresor Memberikan arahan dan didikan kepada pasien dan keluarganyaAPA Practice Guidelines 200238 SER/023/Aug08-Aug09/WW
  • 39. Tujuan Terapi Gangguan Bipolar Fase-fase pengobatan Episode Akut Rumatan (Manik atau Depresi) Tujuan yang ingin dicapai Mengatasi gejala- Mengatasi Mempertahankan remisi gejala akut Gejala sisa & mencegah kekambuhan Melihatnya sebagai satu penyakit; bukan dua39 SER/023/Aug08-Aug09/WW
  • 40. Ikhtiar mengoptimalkan terapi Pengobatan Hubungan pasien dan dokter  Pasien berpartisipasi dlm  Bekerja cepat proses penyembuhannya  Efektif  Identifikasi, memahami, dan  Memiliki efek samping rendah merespon kebutuhan pasien  Tidak mahal  Lebih aktif mendengar Keterlibatan pasien Dukungan sesama pasien  Pasien mengambil keputusan  Meningkatkan kepatuhan bersama dengan dokternya pasien  Mengurangi hospitalisasi  Pasien terlibat secara aktif dalam  Memberikan harapan sembuh proses penyembuhannyaLewis 2005 40 SER/023/Aug08-Aug09/WW
  • 41. Definisi Remisi, Pulih, Kambuh, and Ulangan Remisi Pulih Kambuh Ulangan Pasien tidak Periode dimana Gejala yang Perulangan lagi memiliki remisi kembali muncul suatu episode gejala sesuai dipertahankan sama dengan kriteria fase remisi gangguan afektif Tidak ada gejala / minimalSource: Frank, et al. 199141 SER/023/Aug08-Aug09/WW
  • 42. Modalitas Terapi pada Bipolar Disorder Farmakoterapi Terapi Gangguan Bipolar Electroconvulsive Psikoterapi Therapy (ECT)42 SER/023/Aug08-Aug09/WW
  • 43. Panduan dalam memilih farmakoterapi efektifyang ideal Efikasi spektrum luas Tolerabilitas baik • Efikasi yang Bimodal • Ditoleransi baik oleh • Mencegah kekambuhan pasien • Onset kerja yang cepat • Tidak menyebabkan: • Dapat sebagai monoterapi – Efek samping yang atau dikombinasikan mengganggu dengan preparat lain atau – Mencetuskan modalitas lain depresi/manik • Efektif pada kondisi – Mempercepat adanya penyakit penyerta perubahan – Hendaya fungsional – Berat badan berlebihan43 SER/023/Aug08-Aug09/WW
  • 44. Farmakoterapi yang umum pada gangguan bipolar Mood Stabilisers Tradisional Antipsikotik atipik • Lithium • Aripiprazole • Divalproex • Clozapine • Lamotrigine • Olanzapine • Carbamazepine • Quetiapine • Risperidone • Ziprasidone Antidepresan • Bupropion Antipsikotik tipik • Monoamine oxide inhibitors (MAOIs) • Haloperidol • Selective serotonin reuptake • Chlorpromazine inhibitors (SSRIs) • Serotonin and norepinephrine • Thiothixine reuptake inhibitors (SNRIs) Note: Some of these agents are not approved for treatment of bipolar disorder44 SER/023/Aug08-Aug09/WW
  • 45. FDA-approved Bipolar Disorder Treatments Agents Manic Mixed Maintenance Depression MOOD STABILiseR STABILISER Lithium Lithium + √ – + √ – DivalproexDR Divalproex DR + √ – – – DivalproexER Divalproex ER + √ + √ – – CarbamazepineER Carbamazepine ER + √ + √ – – ANTYPICALS ATYPICALS – Risperidone Risperidone + √ + √ – – Olanzapine Olanzapine + √ + √ + √ – Quetiapine + √ – – √ √ Ziprasidone Ziprasidone + √ + √ – – Aripiprazole Aripiprazole + √ + √ + √ – OTHER Lamotrigine Lamotrigine – – + – Olanzapine/fluoxetine Olanzapine/fluoxetine – – – √ Drugs listed in order of approval for a bipolar disorder indication. This chart does not imply comparable efficacy or tolerability profiles. Physicians’ Desk Reference®. 60th ed. Montvale, NJ: Medical Economics Co; 200645 SER/023/Aug08-Aug09/WW
  • 46. CANMAT Update 2007 (Canadian Network for Mood and Anxiety Treatments) Recommendations for pharmacological treatment of acute bipolar mania Options TreatmentsFirst-line Lithium, divalproex, olanzapine,, quetiapine monotherapy, risperidone aripiprazole, ziprasidone, lithium or divalproex + risperidone, lithium or divalproex + quetiapine, lithium or divalproex + olanzapineSecond-line Carbamazepine, oxcarbazepine, ECT, lithium + divalproexThird-line Haloperidol, chlorpromazine, lithium or divalproex + haloperidol, lithium + carbamazepine, clozapineNot recommended Monotherapy with gabapentin, topiramate, lamotrigine, verapamil, tiagabine, risperidone + carbamazepineYatham LN, et.al., Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: update 2007,Bipolar Disorders 2006: 8: 721–73946 SER/023/Aug08-Aug09/WW
  • 47. CANMAT Update 2007 (Canadian Network for Mood and Anxiety Treatments) Recommendations for pharmacological treatment of acute bipolar I depression Options Treatments First-line Lithium, lamotrigine, lithium or divalproex + SSRI, olanzapine + SSRI, lithium + divalproex, lithium or divalproex + bupropion, Quetiapine monotherapy* Second-line Quetiapine + SSRI, lithium or divalproex + lamotrigine Third-line Carbamazepine, olanzapine, divalproex, lithium + carbamazepine, lithium + pramipexole, lithium or divalproex + venlafaxine, lithium + MAOI, ECT, lithium or divalproex or AAP + TCA, lithium or divalproex or carbamazepine + SSRI + lamotrigine, adjunctive EPA, adjunctive riluzole, adjunctive topiramate Not recommended Monotherapy with gabapentin*) Disclaimer: indication of bipolar depression is under evaluation by BPOM and has not been approvedYatham LN, et.al., Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: update 2007,Bipolar Disorders 2006: 8: 721–739 47 SER/023/Aug08-Aug09/WW