May 2006, Vol 28, No. 5 |
Update Article
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Advances in bipolar affective disorderPaul T C Lam 林達聰 HK Pract 2006;28:208-214 Summary Knowledge of bipolar affective disorder has advanced rapidly in recent years. Progress has been made in the areas of classification, phenomenology, pharmacotherapy, psychoeducation and psychotherapy. Under-recognition and delay in diagnosis are major issues, as well as the need to differentiate bipolar from unipolar depression, which requires different treatment methods. Better awareness and understanding of the disorder can improve treatment results and enhance quality of life in patients with this chronic and relapsing condition. 摘要 有關雙相情感性疾病 — 躁狂抑鬱症，近年在疾病分類，症狀學，藥物治療、心理教育和心理治療各範疇都有快速的發展。誤診及診斷延誤是重要的問題，此外還要分辨躁狂抑鬱症和單相抑鬱症，因為治療方法各不相同。提高對此病的警覺性以及加深認識，可以改善療效，同時提升慢性和突發性雙相情感性疾病病人的生活質量。 Introduction Bipolar affective disorder has been increasingly recognised as being more prevalent than previously thought. Many patients had been wrongly diagnosed for many years by specialists and family doctors. Definition The DSM IV (Diagnostic and Statistical Manual, Fourth Edition, American Psychiatric Association, 1994) defines mania as a distinct period of abnormally and persistently elevated, expansive or irritable mood, lasting at least 1 week (any duration if hospitalization is necessary). There must be persistence of three or more of the following symptoms to a significant degree:
MARKED occupational or social dysfunction. Hypomania (in DSM IV) Hypomania is defined as a distinct period of persistently elevated, expansive or irritable mood, lasting throughout at least 4 days, that is clearly different from the usual (non-depressed) mood and persistence of three or more of the symptoms necessary for a manic episode. There should be SIGNIFICANT occupational or social dysfunction. Cyclothymic disorder (in DSM IV) Cyclothymic disorder is defined as the presence of numerous periods with hypomanic symptoms and numerous periods with depressive symptoms that do not meet criteria for a major depressive episode, for at least 2 years. During the above 2-year period, the person has not been without the symptoms for more than 2 months at a time. No major depressive episode, manic episode, or mixed episode has been present during the first 2 years of the disturbance. Bipolar disorder not otherwise specified (in DSM IV) There is also a category of bipolar disorder not otherwise specified (in DSM IV), defined as:
Prevalence Bipolar I disorder (in DSM IV) is defined as a mania (or mixed) mood episode with or without depressive episode. The population at risk is 1%.1,2 Bipolar II disorder (in DSM IV) is defined as a period of hypomania with major depressive episodes. The population at risk is about 1%.3,4 Bipolar III disorder is an ill-defined term (not a DSM IV diagnosis) including substance or drug induced bipolar disorder, depression in hyperthymic personality and depressed patients with a strong family history of bipolar disorder. Rapid cycling bipolar disorder (not a DSM IV diagnosis) is defined as four or more mood episodes per year. It comprises 15% of all bipolar patients and occurs more frequently in women. It is less responsive to treatment and carries a greater morbidity and functional impairment.5 The population at risk in the U.S. for bipolar spectrum disorder exceeded 3.7%.6,7 Certain limitations of the DSM IV diagnostic criteria have been raised.8 For example, a duration of 4 days required for the diagnosis of hypomnia is felt to be too long. Patients who have hyppomanic symptoms for a shorter duration do not differ from those who have symptoms for a longer duration.9 Recently an International Consensus group has suggested a 2 day symptomatic period.10 In DSM IV clinical descriptions of the bipolar spectrum disorders are brief and the relevance of family history is not mentioned. Bipolar vs unipolar It is important to differentiate between bipolar vs unipolar depression because the treatment is different. First and foremost, bipolar patients have a history of mania or hypomania. Such mood episodes may occur many years ago and may have been long forgotten. Often the patient needs specific prompting and direct questioning about the symptoms of mania or hypomania before he or she can recall such a period of mood change. At times the information may come from the relative or observer. Patients with bipolar disorder often have cyclothymic, extroverted personality, whereas patients with unipolar disorder tend to be dysthymic and introverted. For bipolar disorder, the sex ratio is equal and the illness starts early, from teens to thirties. In unipolar depression women have a higher risk and the age of onset is later, from thirties to fifties. Postpartum onset is more common with bipolar disorder. The onset of illness is more abrupt, with numerous episodes of shorter duration (3-6 months) in bipolar disorder. Psychomotor retardation and hypersomnia is a feature of bipolar disorder. Bipolar patients have relatives with bipolar and unipolar depression, while unipolar patients run true in the family. Cyclic antidepressants and SSRI induce mood swings in bipolar patients, but will not do so in unipolar patients. Lithium has an acute antidepressant effect in bipolar patients, but will be ineffective when used alone in unipolar patients. Screening for bipolar disorder This should be initiated in patients with depressive symptoms, patients presenting with vague, unexplained, non-specific symptoms or patients with reverse vegetative symptoms such as hypersomnia or hyperphagia. To carry out an effective screening:
The Mood Disorder Questionnaire The Mood Disorder Questionnaire 11 is a frequently used tool for screening. To have a positive score, the patient need to answer "Yes" to 7 or more symptoms in question 1, with several of these occurring during the same period of time and causing a moderate or serious problem in social or occupational life. The MDQ has a sensitivity of 0.73, (i.e., 7 out of 10 bipolar patients are detected.) It has a specificity of 0.90, (i.e., 9 out of 10 patients without bipolar disorder are successfully excluded).12 Conditions that can mimic bipolar disorder should be borne in mind, and these include general medical conditions such as Cushing's disease, alcohol and substances of abuse, medications, schizophrenia, schizoaffective disorder, dissociative disorder and organic brain disorders.
Treatment The treatment of bipolar disorder varies with the phase of the illness. The following treatment algorithm is based on and modified mainly from the Canadian Network for Mood and Anxiety Treatments (CANMAT), guidelines for the management of patients with bipolar disorder: consensus and controversies (2005):13 Level 1 evidence: meta-analysis or replicated double-blind (DB), randomized controlled trial (RCT) that includes a placebo condition Level 2 evidence: at least one DB-RCT with placebo or active comparison condition Level 3 evidence: prospective uncontrolled trial with 10 or more subjects Level 4 evidence: anecdotal reports or expert opinion For treatment recommendation: First line: Level 1 or level 2 evidence plus clinical support for efficacy and safety Second line: Level 3 evidence or higher plus clinical support for efficacy and safety Third line: Level 4 evidence or higher plus clinical support for efficacy and safety Not recommended: Level 1 or level 2 evidence for lack of efficacy For treatment of acute agitation in mania (Plate I), three drugs are currently used. The choice of medication depends on anticipated side effects and history of previous acceptability and effectiveness of the drug in the specific patient. For example, if weight gain or risk of diabetes is a particular risk to a patient, Olanzapine should be avoided. If a patient had previously responded to a drug and tolerated it well, then the same drug should be the first choice. For monotherapy for bipolar mania (Plate II), a number of drugs are available with various level of evidence. Note that medications such as Haloperidol and Chlorpromazine, although highly effective, are only used as third line drugs, being replaced by newer antipsychotic drugs with a more favourable side effect profile. Monotherapy gives a response rate of about 50%, and sometimes combination therapy is required (Plate III). 20% to 25% more patients respond to combination therapy. The combination of Carbamazepine and Risperidone is not used because Carbamazepine, being an enzyme inducer, reduces the blood level of Risperidone by about 50%. In monotherapy for bipolar depression (Plate IV), Lithium and Lamotrigine are the drugs of first choice. With Lithium the blood level need to be closely monitored to target at but not exceeding 1 mmol/litre. A lower blood level may be effective after the patient has remitted. With Lamotrigine, the dose should be built up gradually and skin hypersensitivity should be closely monitored. Note that the cyclic antidepressants and SSRI have no place in the monotherapy for bipolar affective disorder. Quite often, monotherpay is inadequate and combination therapy is required (Plate V). In this situation, although the level of evidence for efficacy of Venlafaxine and Tricyclics are good (level 2), they are only indicated for third line treatment because of the significant risk of mood switch. Conversely, the combination of Quetiapine or Risperidone with SSRI only have an efficacy evidence level of 3, but they are used as second line treatment due to their lower proneness to induce mood swings. It is also highly likely that as more studies are conducted, the level of evidence for efficacy of such combinations will improve. Maintenance therapy is often required for bipolar patients. The recurrence rate after stopping medication is probably double that of some one on maintenance medication. The aim of maintenance therapy is to control symptoms, reduce subsyndromal symptoms, prevent suicide, improve quality of life, improve cognition, improve functional outcome and ensure treatment adherence. Patients with severe symptoms, recurrent episodes, suicidal acts or strong family history require maintenance therapy. Either monotherapy (Plate VI) or combination therapy (Plate VII) may be considered for maintenance: In combination therapy, Carbamzepine halves the level of Lamotrigine whilst Valproate doubles the level of Lamotrigine. Such combination should therefore not be used. Certain factors act against treatment adherence. Young, male, single patients with a lower education level with lack of psychosocial support do less well. Patients with psychosis, poor insight or co-morbid personality disorder or substance abuse also run an increased risk. The maintenance treatment of rapid cycling bipolar disorder (Plate VIII) presents a special challenge and often tests the skills of the clinician. Frequent contact with the patient is required and careful attention should be paid to early clues of mood change so that appropriate adjustment in medication can be made early. The suicide risk of bipolar patients (up to 20%) is higher than that for unipolar patients (15%) or schizophrenia (10%). Those at higher risk are patients with history of suicide attempts, family history of suicidal behaviour, severity / number of depressive episodes, alcohol / substance abuse, level of pessimism, level of aggression / impulsivity and younger age of onset. Psychoeducation and psychosocial therapy play an important role in treatment. Combining standard pharmacological treatment with psychotherapy has complementary benefits and improves the clinical outcome in bipolar disorder. Effective psychoeducation can reduce the number of manic and depressive episodes, reduces the need for hospitalization and improves adherence with treatment. Conclusion Bipolar affective disorder is a common psychiatric illness. The population at risk for bipolar spectrum disorder is quoted as above 3.7% of the population, but can be much higher with some other studies. The illness runs a chronic and debilitating course, typically recurrent with lifelong vulnerability. There is a 20% risk of suicide, which is higher than that for unipolar depression and schizophrenia. Diagnosis is often delayed for ten years or more. Treatment is often given late and sub-optimally. The treatment of bipolar depression is different from treatment of unipolar depression. Tricyclic antidepressants and SSRI should not be used in the monotherapy of bipolar depression for risk of causing mood switch. Typical antipsychotic drugs should also be avoided in the treatment of manic symptoms for fear of inducing depression. Multiple drugs are often necessary but caution has to be exercised to avoid drug interaction. Psychoeducation and supportive psychotherapy has proven to confer additional benefit and improve outcome of the illness. The family doctor has a significant part to play by 1) screening and early detection of this group of patients, 2) differentiating bipolar from unipolar depression, 3) treating patients with relatively mild symptoms, 4) providing psychoeducation and supporting psychotherapy and 5) referral of difficult patients to specialist clinics. Key messages
Paul T C Lam, MBBS (HK), FRCP, FHKAM(Med), FHKAM(Psych) Correspondence to: Dr Paul T C Lam, Room 1907, Lane Crawford House, 70 Queen's Road Central, Hong Kong. E-mail: drtclam@netvigator.com References
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