Clinical Practice Guidelines for Management of Bipolar Disorder

Participants of expert group on CPG for Bipolar Affective Disorder Vidhyadhar Watve, Mrugesh Vaishnav, Vivek Kirpekar, D.K. Sharma, Mahendra Jain, Asim Kumar Mallick, C.L. Narayan, Anup Bharti, Madhu Nijhawan. INTRODUCTION Bipolar disorder (BPAD) is a serious mental disorder characterized by episodes of depression, hypomania/mania and mixed episodes, with interepisodic recovery. However, many patients with BPAD continue to exhibit residual symptoms in the interepisodic period. The illness usually starts in adolescence or early adulthood and has significant negative impact on the life of the sufferer and their caregivers. Patients with BPAD encounter educational difficulties, job related problems, interpersonal difficulties, psychosocial dysfunction, disability, marital problems, multiple suicidal attempts, completed suicide and medication side effects. Additionally patients with BPAD have high rates of physical and psychiatric comorbidity. The prevalence rates of BPAD vary from country to country. A large multinational study suggests that lifetime prevalence of BPAD-I ranges from 0-1% with a mean of 0.6 (SD-0.4). The prevalence rate of BPAD-II ranges from 0 to 1.1% with a mean of 0.4 (SD-0.3). Additionally a significant proportion of patients have been shown to have subthreshold BPAD with a range of 0.1 to 2.4% with a mean of 1.4 (SD-0.8). There is no nationwide study to evaluate the prevalence rates of BPAD in India. In a country like India, patients have limited resources, poor knowledge about the disorder and treatment; have inadequate access to the health care facilities, which makes treatment of BPAD a challenge. Indian Psychiatric Society (IPS) made first attempt to formulate Clinical Practice Guidelines (CPGs) for management of BPAD in 2005. Since then, over the last one decade there have been several developments, especially in the form of emergence of new evidence for some of the pharmacological agents. Accordingly, these new guidelines attempt to update the previous guidelines published by IPS. These guidelines should be read along with the earlier version of the CPGs, published by IPS in 2005. ASSESSMENT AND EVALUATION [TABLE-1]Table 1: Components of assessment and evaluationAssessment of patients is an ongoing process and comprehensive assessment of a patient involves the assessment of patients themselves and their caregivers. The role of taking a proper history from the patient and all the available resources cannot be over-emphasized. In addition to the history taking, proper attention must be paid to the mental status examination. Diagnosis of BPAD is to be made on the basis of current diagnostic criteria, because a diagnosis based on diagnostic criteria can be considered more reliable, facilitates communication among various clinicians and paves the way for management on the basis of evidence based recommendations. It is important to remember that especially during the initial part of the illness, the symptoms may be confusing and at times it may be difficult to distinguish symptoms of mania from other psychiatric syndromes like schizophrenia, acute and transient psychosis and other psychiatric disorders. A possibility of substance induced disorder or disorder secondary to organic causes is to be considered, when the symptoms are atypical or there is evidence of the use of substance or underlying organic causes. Occasionally establishing the definite diagnosis of BPAD may require time. The assessment may cover history of number of previous episodes, type of first episode in lifetime, predominant polarity of illness, duration and severity of episodes, inter-episodic recovery, presence or absence of suicidal behaviour, violence and agitation, seasonal variation in onset of symptoms, presence of rapid cycling and features of ultra-rapid cycling. Assessment of current episode may also focus on the issues of severity of symptoms, suicidality and agitation. Understanding the role of various psychosocial stressors and biological rhythms in onset of illness, precipitation of relapse and continuation of symptoms need to be understood thoroughly. A thorough assessment includes assessment of comorbid psychiatric and medical conditions. It is important to remember that many a times; comorbidity is not very evident during the acute episode of illness. The comorbid conditions become more evident when the patient has come out of the acute episode of the illness. Evaluation of comorbid substance abuse needs to consider the type and frequency of substance abuse. If the patient does not provide adequate information about the substance use pattern, but there is high index of suspicion, urine or blood screens (with prior consent) can be used to confirm the existence of comorbid substance use/dependence, wherever such facilities are available. Functional impairment in various domains of life including impact of the illness on the family functioning and psychosocial impact of the illness on the caregivers is not to be neglected. A thorough physical examination need to be done to rule out presence of any physical illness and also to rule out episodes secondary to physical illnesses. This may be supplemented by the judicious use of investigations. Depending on the feasibility, unstructured clinical assessments need to be supplemented by documentation of severity and extent of symptoms on appropriate standardized rating scales. Patients with bipolar disorders also have cognitive deficits. Accordingly, depending on the need, detailed cognitive testing may be undertaken. The use of neuroimaging may be indicated in those with atypical features, neurological signs, non-response to treatment and having first episode of illness at a later age and elderly. Caregiver's assessment may involve evaluation of their knowledge about illness, knowledge about treatment, their attitudes and beliefs regarding treatment, the impact of the illness on them and their personal and social resources in the form of burden, distress, stigma, personal and marital life etc. In case patient has received treatment in the past, then it is important to record the type of medications used, response to treatment, duration of use of treatment, side effects experienced and reasons for discontinuation. Importance of ongoing assessment cannot be underestimated. With progress in treatment, new issues like response to treatment, side effects, treatment adherence, marriage, pregnancy, disability, other health-care needs, ease of access to treatment team and therapeutic alliance may need to be assessed from time to time. FORMULATING A TREATMENT PLAN [FIGURE 1]Figure 1: Initial evaluation and management plan for schizophreniaFigure 2: Management of Hypomania/ Mania/Mixed EpisodeFigure 3: Management of Bipolar DepressionFormulation of treatment plan will involve decision making about the treatment setting, treatments to be used and areas to be addressed. Treatment plan need to be formulated in consultation with patients, caregivers and other members involved in the treatment team. Treatment plans may be guided by the needs and be practical, feasible and flexible. Further, the treatment plan is be re-evaluated from time to time and be modified as per the needs. CHOICE OF TREATMENT SETTINGS In general, most of the patients with BPAD are managed on the outpatient setting. However, some patients may require inpatient care. Whenever possible patient admitted to the inpatient setting should have accompanying family caregivers. In case inpatient care is required and such facilities are not available, than the patient and/or family need to be informed about the need for inpatient care and patient may be referred to the nearest available inpatient facility and admission may be facilitated. OPTIONS FOR MANAGEMENT OF BIPOLAR DISORDER Treatment options for management of BPAD can be broadly classified as mood stabilizers, antidepressants, antipsychotic medications, electroconvulsive therapy (ECT), adjunctive medications and psychosocial interventions [Table-2]. Use of various treatment options is guided by the phase of illness (mania/hypomania/depression/mixed) in which patient presents to the clinician and past treatment history.Table 2: Options for management for Bipolar disorderPHARMACOLOGICAL MANAGEMENT OF BIPOLAR DISORDER The mainstay of management of BPAD is mood stabilizers. The available mood stabilizers include lithium, valproate, lamotrigine, carbamazepine/oxcarbazepine and topiramate. Lithium Lithium is the oldest mood stabilizer used in the management of BPAD. It has been found to be efficacious in management of acute episode of either polarity and has been found to be efficacious in prevention or relapse of episodes of either polarity. Additionally, it has been shown to have a role in prevention of suicide in patients with BPAD. Prior to starting lithium, history need to be reviewed for the presence of physical illnesses like renal dysfunction, thyroid dysfunction and cardiac conduction abnormalities. Additionally information needs to be reviewed for presence of dermatological In case of last is to be and required urine need to be Further, prior to starting lithium, patients need to be about the various side effects of lithium, use of and of medications which can Patients also need to be informed to Whenever is it need to be in in and the need to be with of of are about of starting or the are be done of of treatment or in the However, the may be earlier patient features of The of lithium, which are usually required for management of acute are in the range of 0.6 to and for range from 0.6 to that as as 0.4 to may be for are with of the is patient may be to a to the side effects and the medication may be need to be in during the initial of therapy and thyroid need to be or during the first of renal and thyroid may be in to in patients and more indicated Lithium is usually in patients have bipolar depression, predominant polarity of illness is that of depression, of illness, cycling of illness, of mixed age of onset for presence of family history of BPAD and presence of family history of 3: prior to starting of and and and have been found to be in the management of BPAD. It has been found to be efficacious in management of acute mania and mixed The evidence for in acute is not as as that for It is also efficacious in prevention of mania and depression, when used during the with lithium, prior to starting valproate, clinicians need to the medical history for presence of any and Prior to starting of valproate, patient is to be about the side effects, especially about and symptoms of and need to be to to the clinicians at the these and symptoms Prior to starting valproate, it is important to the patient for and In last need to be and required urine need to be done to rule out is with and it may be a to evaluate the blood and prior to starting of and is in or and with of side effects and However, some of the have also rapid of with initial of and have shown that it is which is is but most patients not require such high The therapeutic which are considered to be efficacious vary from to the of is the need to be to or to the side effects and In case is may be However, it is important to remember that the of is about than the and the is to be are to be done of starting or in the of The need to be in case patient is the patient is the may be to There is evidence to that patients with or mixed rapid cycling episode later age of onset of illness, duration of illness, and of illness to for response to include presence of comorbid use mental and and and comorbid prior to starting of and The role of in management of BPAD has been and it has been shown to be efficacious in management of bipolar and prevention of relapse of However, the most side of includes including and The can any time during the but are more during the initial phase of treatment and when used along with suggests that the of can be by of the Accordingly, lamotrigine, patients need to be informed about the possibility of and to the in case is the is more and with symptoms like or may be may be at the of for initial then it may be at the of during the and that can be per depending on the therapeutic has been shown to be efficacious in the management of acute bipolar mania and prevention of Prior to starting clinician needs to focus on the history of blood and is considered, patients need to be informed about the and symptoms of dysfunction, dysfunction and and to to the these symptoms prior to starting of may include and renal used in may also be in of the of starting of is in and the of is the of may be and the is about but it can vary from patient to patient and may be to The therapeutic have not been in patients with BPAD and the of which is for disorders is with and the need to be done of of treatment or of There is of in the form of for but suggests that it may be of some as or therapy in patients with The from the of therapy with in patients with bipolar which have the role of in management of mania have negative the last decade or many large and have the role of various atypical like and etc. in the management of bipolar depression, bipolar mania and for phase from these that like and are in the management of acute There is evidence for use of and and in the management of bipolar There is evidence for in the management of acute episode of bipolar and or as adjunctive medications to or have been shown to be efficacious in prevention of relapse of and like have been shown to be in prevention of mania as or as adjunctive medications to or therapy There is evidence to that when or is with in the management of acute the is and the onset of is than that for Accordingly, depending on the severity of may be There is evidence for use of in the management of acute mixed episode and bipolar for use of are shown in of use of in patients of have the of like and to and current of evidence suggests that the of these are difficult to distinguish from the of these agents. Accordingly, these are considered to be adjunctive which may be in management of acute Further, there is evidence to the role of in the management of and other medications like have been in as or on agents. However, available the evidence is not to these medications as first in management of bipolar mania and have been used in the management of bipolar However, over the last or use of in patients with bipolar has as a in of the of from suggests that use of along with mood stabilizers is to use of of a mood stabilizer and a and is not with of of the which have not found to be have involved one to use of an is to be the various antidepressants, has been to be with of induced However, it is important to remember that should not be used as and in those with rapid cycling disorder and mixed The duration of treatment to consider it to be an for an acute episode is about In case of bipolar depression, a is considered as an adequate MANAGEMENT OF BIPOLAR DISORDER management as an to has been shown to be of significant during the management of acute phase of bipolar and phase of illness. the various psychosocial the use of and interpersonal and social therapy cognitive therapy and family These psychosocial interventions have been shown to be with of functioning and treatment The of all these involve the patients about their illness, the early of social the interpersonal issues and and medication and treatment for patients and or family of may be considered for the patient and family members The is to be to the patient and family about the illness. may be about the of the illness, treatment possible side effects of medications and of treatment etc. may also be with an to out their and may also the important of treatment and early of new It is important to remember that is not a and prior to of the previous may be and need to be to the needs of the patient and the caregivers. and social therapy This therapy is based on the that rhythms in patients with BPAD are to and any of rhythms can an Accordingly, it on the social rhythms or of the patient and the interpersonal of the patients that can more in their social The is to the patient as to can the of a new episode Patients are informed that new episodes can be by poor medication adherence, life and of social Patients are with as to can interpersonal and issues in the social are also to a and attention to the to which can their and can the impact of these to stressors on their of and social therapy therapy therapy has been shown to be efficacious in the management of bipolar and during the phase of The of is to the patient about the illness, them cognitive for with their illness and psychosocial stressors and out of the medication and treatment the symptoms to interventions an part of treatment in Indian setting. are involved in treatment decision of treatment and of However, family members can also to relapse to poor or to of relapse and poor have shown that family interventions can the of medication and the frequency of interventions the and patients to the with mood episodes, the of having episodes, the need to continue with medications, the family about the in patients and and with and establishing a of for life and it is that patients with BPAD are at for and side effects to use of medications, all the patients need to be about life and to the of side effects and and These include physical and from and other etc. may be and to the needs of patients and their Treatment and treatment is very important for management of patients with BPAD. evidence suggests that of the patients with BPAD become with medication and out of all need to be made to the medication and treatment which can in the are in which can medication OF OF BIPOLAR DISORDER Management of BPAD will on the phase of illness in which patient presents to the bipolar depression, bipolar first episode mixed episode or clinical In addition to the phase of illness, which may in about the pharmacological include past history of episodes, type of comorbidity substance past treatment history side and clinical symptoms of etc. In based on the of various pharmacological treatments are as first and agents. of an on the basis of current polarity and past history can be of as in most is in the The of management in the acute phase are shown in may focus on out a comprehensive assessment about the treatment of the patient and about the treatment setting, about the of medication in with the patient and the family by taking the clinical and treatment related and psychosocial interventions at the as to provide comprehensive If patient is or other all are to be made to the a patient is on and presents with or mixed symptoms, these need to be of the of inpatient care are shown in Management in the acute for inpatient care during acute treatment need to be made in consultation with the patient and or family members and need to be Whenever mood stabilizers are used, the required need to be done prior to starting of mood stabilizers, of medications are to be and other need to be from time to time as indicated for various mood stabilizers. The evidence for of various in management of of illness depression, vary and it is important to be of the an update on the available of evidence for of of several and for bipolar OF The of management in episode is to the and of patients at the Depending of the severity of symptoms, inpatient care may be If patient is on then is to be In of pharmacological first for management of mania may involve use of or valproate, or as like and have also been used in the Indian These are very in the management of and However, these are with high of However, there is some evidence to that or with an antipsychotic may be more than any of these when used these is to have onset of Accordingly, it can be that the mania is be However, mania is and with significant than therapy need to be Use of adjunctive for duration may be Patients medications and are may be like or a of antipsychotic If a patient with a then the first in the management involves of the ongoing The can be done by the of like and If and may be used, depending severity of the If the used in of significant clinical of first need to be to the ongoing may include to or to antipsychotic medication not used the antipsychotic used may be considered patient is very not to a of of medications, has history of response to in the past, and those mixed interventions like of patient and family and family be at the interventions like or on the should be considered when patient is MANAGEMENT OF BIPOLAR The of management is to of functioning and to to the various mood stabilizers, there is evidence to that and may be used as the first medications in the management of bipolar If the patient presents with a the initial is to the medication and adequate If is not an initial is to the mood stabilizer which the patient is If the patient is not on any mood than or may be the suggests that may also be There is evidence for use of and If the patient does not to with mood or of these with may be Use of the use of mood stabilizer or an atypical antipsychotic is to be may be used as per the in the form of may also be considered when the is of to may be considered, is in presence of of to symptoms, symptoms, patient is when use of various is limited to medical illnesses. There is evidence to the of and DISORDER cycling disorder is by having or more episodes in a These episodes should be from other by or for at or a to an episode of polarity. have been for of Accordingly, the first in the management of is to evaluate the patients for underlying medical conditions which may be to the medications, use of has been shown to for Affective of there is evidence to that or may be used as the first agents. mood stabilizers which can be considered include If patient does not to then of mood stabilizers or a of mood stabilizer and antipsychotic medication may be TREATMENT FOR BIPOLAR DISORDER The of treatment is to the of episode of either the residual symptoms and the functioning of the In of evidence for treatment is available for and In evidence has also for use of and in prevention of of and However, these may be because of of side effects. has been shown to be in prevention of has been shown to be efficacious in prevention of episodes, but not for prevention of and has been shown to be of in prevention of of episodes, but not for has also been shown to be in prevention of it is to and because of side and have also the of and in with various use of there is evidence to the role of adjunctive psychosocial in the management of BPAD. may also be considered in patients have to during their acute The of management during the phase of treatment is to continue the medication during the acute phase of illness. Accordingly, the during the acute clinicians may the clinical which may the of episodes and side effects. If the patients have more episodes then one may lithium, or for more episodes one may consider or In of and may be It is important to that patients with mood disorders are more to side effects like with use of especially Patients have been with a of and antipsychotic or and antipsychotic the need for use of antipsychotic need to be on the basis of of needs to be considered bipolar therapy during the phase is to be considered for those have not to the of during the phase of illness. encounter clinical which either require attention or can treatment Management of these is in related to AND MANAGEMENT of medications used for the management of BPAD are with many side effects, which require The side effects with are in the clinical guidelines for The made for of side effects with various atypical may also be in patients with antipsychotic medications are Use of is with multiple side effects. These side effects can be classified on the basis of those during the early or phase of and frequency and very of these side effects can be managed with in of medication or to a as the first effects of management for the side effects with lithium, and are shown in Management of side effects of mood OF the lithium, and has a therapeutic Lithium and may be and are medical The therapeutic range for from 0.4 to effects of are usually when the of the life side effects may and symptoms of with lithium, and are shown in Management of is an acute and involves of lithium, the an and use of are more than However, in patients with renal may be considered in as and symptoms of of lithium, and of also involve use of However, there are no guidelines for the Management of involves and use of and of There are no of