Bipolar Mood Disorder Case 3 Management Discussion Abdullah Al-Subaie F.R.C.P (C) Professor of Psychiatry

Differential Diagnosis 1 Idiopathic Basal Ganglia Calcification ------- personality and/or behavior, to psychosis and dementia Cancer Epilepsy Fahr disease AIDS Medications (eg, antidepressants, baclofen, bromide, bromocriptine, captopril, cimetidine, corticosteroids, cyclosporine, disulfiram, hydralazine, isoniazid, levodopa, methylphenidate, metrizamide, procarbazine, procyclidine)

Differential Diagnosis 2 Circadian rhythm desynchronization Cyclothymic disorder Oppositional defiant disorder (in children) Substance abuse disorders (eg, with alcohol, amphetamines, cocaine, hallucinogens, opiates)

Workup 1 The basic principle remains, "do not miss a treatable medical cause for the mental status.“ The condition necessitates use of a number of medications that require certain body systems to be working properly. The basic principle remains, "do not miss a treatable medical cause for the mental status.“ Second, the condition necessitates use of a number of medications that require certain body systems to be working properly. For example, lithium requires an intact genitourinary (GU) system and can affect certain other systems, and certain anticonvulsants can suppress bone marrow. Third, because bipolar illness is a lifelong disorder, performing certain baseline studies is important to establish any long-term effects of the medications. A number of infections, especially chronic infections, can produce a presentation of depression in the patient. Any of the encephalitides can dramatically manifest as changes in mental status.

Workup 2 Because bipolar illness is a lifelong disorder, performing certain baseline studies is important. A number of infections, especially chronic infections, can produce a presentation of depression in the patient. The basic principle remains, "do not miss a treatable medical cause for the mental status.“ Second, the condition necessitates use of a number of medications that require certain body systems to be working properly. For example, lithium requires an intact genitourinary (GU) system and can affect certain other systems, and certain anticonvulsants can suppress bone marrow. Third, because bipolar illness is a lifelong disorder, performing certain baseline studies is important to establish any long-term effects of the medications. A number of infections, especially chronic infections, can produce a presentation of depression in the patient. Any of the encephalitides can dramatically manifest as changes in mental status.

Workup 3 A complete blood count (CBC) with differential  To rule out anemia as a cause of depression. Treatment, with certain anticonvulsants, may depress the bone marrow-hence the need to check the red blood cell (RBC) and white blood cell (WBC). Lithium may cause a reversible increase in the WBC count.

Workup 4 Erythrocyte sedimentation rate Fasting glucose  To look for any underlying disease process such a lupus or an infection. Fasting glucose Atypical antipsychotics have been associated with weight gain and problems with blood glucose regulation in patients with diabetes.

Workup 5 Electrolytes Hyponatremia can manifest as a depression. Treatment with lithium can lead to renal problems and electrolyte problems. Low sodium levels can lead to higher lithium levels and lithium toxicity. Lithium toxicity can lead to renal impairment.

Workup 6 Calcium Proteins Hyperparathyroidism, produces depression. Certain antidepressants, such as nortriptyline, affect the heart. Proteins Low serum protein levels in depressed patients may be a result of not eating. Low serum protein levels increase the availability of certain medications because these drugs have less protein to which to bind.

Workup 7 Thyroid hormones Creatinine and blood urea nitrogen To rule out hyperthyroidism (mania) and hypothyroidism (depression). Treatment with lithium can cause hypothyroidism, which may also contribute to the rapid cycling of mood. Creatinine and blood urea nitrogen Kidney failure can present as depression. Treatment with lithium can affect urinary clearances, and serum creatinine and blood urea nitrogen (BUN) levels can increase.

Workup 8 Substance and Alcohol Screening Substance abuse can present as either mania or depression. A number of patients with bipolar affective disorder also have a drug or alcohol addiction. Performing a substance screen helps make this dual diagnosis

Workup 9 Other Laboratory Tests Urine copper level testing is used to rule out Wilson disease, which produces mental changes. This disease is a rare condition that is easily missed. Antinuclear antibody testing is used to rule out lupus. An HIV test because AIDS causes changes in mental status, including dementia and depression. A VDRL test may be indicated. Syphilis, especially in its later stage, alters mental status.

Workup 10 Magnetic Resonance Imaging Electrocardiography The total value of performing magnetic resonance imaging (MRI) in a patient with bipolar disorder remains unclear; however, To establishes a baseline in such a chronic illness. Some investigators report that patients with mania have hyperintensity in their temporal lobes. Electrocardiography Many antidepressants, Lithtium and some of the antipsychotics, can affect the heart and cause conduction problems.

Workup 11 Electroencephalography EEG provides a baseline and helps rule out any neurologic problems such as seizure disorder and brain tumor. In electroconvulsive therapy (ECT), EEG monitoring during ECT is used to detect occurrence and duration of seizure. Some EEG findings may indicate anticonvulsant effectiveness. Specifically, to valproate. Some patients may have seizures when on medications, especially antidepressants. In addition, lithium can cause diffuse slowing.

Outlines of Treatment 1 The treatment is directly related to the phase of the episode and the severity of that phase. Most patients recover from the first manic episode, but their course beyond that is variable. The treatment of bipolar disorder is directly related to the phase of the episode (ie, depression or mania) and the severity of that phase. For example, a person who is extremely depressed and exhibits suicidal behavior requires inpatient treatment. In contrast, an individual with a moderate depression who still can work would be treated as an outpatient. Fortunately, most patients recover from the first manic episode, but their course beyond that is variable. A consultation with a psychiatric colleague or a psychopharmacologist is always appropriate if the patient does not respond to conventional treatment and medication. All patients with bipolar disorder need outpatient monitoring for both medications and psychotherapy. In addition, they need education. The schedule must be regular, with great flexibility if they need extra sessions. No surgical care is indicated for bipolar disorder. Historically, treatment was attempted with psychosurgical procedures, such as prefrontal lobotomy. Lobotomy is no longer used in the clinical care of patients with bipolar disorder.

Outlines of Treatment 2 All patients with bipolar disorder need education, outpatient monitoring for both medications and psychotherapy. The schedule must be regular, with great flexibility if they need extra sessions. ECT may be needed but no surgical care is indicated for bipolar disorder

Indications of Inpatient Treatment Danger to self A depressed patient may have suicidal ideation, attempts or plans. A person who is depressed enough to not eat might be at risk of death. A person in extreme mania who foregoes sleep or food may be in a state of serious exhaustion. The indications for inpatient treatment in a person with bipolar disorder include the following: Danger to self Danger to others Total inability to function Total loss of control Medical conditions that warrant medication monitoring A patient with bipolar disorder, especially one in a depressive episode, may present with a significant risk for suicide. Serious suicide attempts and specific ideation with plans constitute clear evidence of the need for constant observation and preventive protection; however, in other situations, the danger to the person may come from other aspects of the disease. For example, a person who is depressed enough to not eat might be at risk of death. Alternately, a person in extreme mania who foregoes sleep or food may be in a state of serious exhaustion. Patients with bipolar disorder can also become a threat to others. For example, a patient experiencing a severe depression believed the world was so bleak that she planned to kill her children to spare them from the world’s misery. In the other extreme, a delusional patient having a manic episode believed everyone was against him; he searched for a rifle in order to defend himself and to get them before they got him. Occasionally, depression is so profound that the person cannot function at all. Leaving such a person alone would be dangerous and not therapeutic. Sometimes, patient’s behaviors are totally out of control; this is a particular concern during a manic episode. In this situation, patients’ behaviors are so beyond limits that they destroy their career and can be harmful to those around them. Some patients with bipolar disorder have other medical conditions for which medication monitoring is warranted. For example, patients with certain cardiac conditions should be in a medical environment where the effects of the psychotropic medications can be monitored and observed closely. In the clearest case of the bipolar/depressed phase, the patient is suicidal and homicidal in a few situations (this can result in homicide followed by suicide). In these scenarios, commitment is in order and indicated. In other situations, the depression has led to an inability to work, eat, and function; hospitalization is also indicated in these cases. In the situation of a patient in bipolar/manic phase, there often is less clear and dramatic evidence of homicide or suicide, but a pattern of very poor judgment and impairment emerges. Because of the behavior during the manic phase, the person often does major damage to finances, career, and position in the community. This type of self-destructive mania calls for containment with good documentation and family support.

Indications of Inpatient Treatment Danger to others A patient experiencing a severe depression may believe the world was so bleak that he planns to kill his children to spare them from the world’s misery. A delusional patient having a manic episode may believes everyone was against him; he searches for a rifle in order to defend himself and to get them before they got him. The indications for inpatient treatment in a person with bipolar disorder include the following: Danger to self Danger to others Total inability to function Total loss of control Medical conditions that warrant medication monitoring A patient with bipolar disorder, especially one in a depressive episode, may present with a significant risk for suicide. Serious suicide attempts and specific ideation with plans constitute clear evidence of the need for constant observation and preventive protection; however, in other situations, the danger to the person may come from other aspects of the disease. For example, a person who is depressed enough to not eat might be at risk of death. Alternately, a person in extreme mania who foregoes sleep or food may be in a state of serious exhaustion. Patients with bipolar disorder can also become a threat to others. For example, a patient experiencing a severe depression believed the world was so bleak that she planned to kill her children to spare them from the world’s misery. In the other extreme, a delusional patient having a manic episode believed everyone was against him; he searched for a rifle in order to defend himself and to get them before they got him. Occasionally, depression is so profound that the person cannot function at all. Leaving such a person alone would be dangerous and not therapeutic. Sometimes, patient’s behaviors are totally out of control; this is a particular concern during a manic episode. In this situation, patients’ behaviors are so beyond limits that they destroy their career and can be harmful to those around them. Some patients with bipolar disorder have other medical conditions for which medication monitoring is warranted. For example, patients with certain cardiac conditions should be in a medical environment where the effects of the psychotropic medications can be monitored and observed closely. In the clearest case of the bipolar/depressed phase, the patient is suicidal and homicidal in a few situations (this can result in homicide followed by suicide). In these scenarios, commitment is in order and indicated. In other situations, the depression has led to an inability to work, eat, and function; hospitalization is also indicated in these cases. In the situation of a patient in bipolar/manic phase, there often is less clear and dramatic evidence of homicide or suicide, but a pattern of very poor judgment and impairment emerges. Because of the behavior during the manic phase, the person often does major damage to finances, career, and position in the community. This type of self-destructive mania calls for containment with good documentation and family support.

Indications of Inpatient Treatment Total inability to function Leaving such a person alone would be dangerous and not therapeutic. Total loss of control The patient’s behaviors may go totally out of control to harm themselves & others and may destroy their career & social position. The indications for inpatient treatment in a person with bipolar disorder include the following: Danger to self Danger to others Total inability to function Total loss of control Medical conditions that warrant medication monitoring A patient with bipolar disorder, especially one in a depressive episode, may present with a significant risk for suicide. Serious suicide attempts and specific ideation with plans constitute clear evidence of the need for constant observation and preventive protection; however, in other situations, the danger to the person may come from other aspects of the disease. For example, a person who is depressed enough to not eat might be at risk of death. Alternately, a person in extreme mania who foregoes sleep or food may be in a state of serious exhaustion. Patients with bipolar disorder can also become a threat to others. For example, a patient experiencing a severe depression believed the world was so bleak that she planned to kill her children to spare them from the world’s misery. In the other extreme, a delusional patient having a manic episode believed everyone was against him; he searched for a rifle in order to defend himself and to get them before they got him. Occasionally, depression is so profound that the person cannot function at all. Leaving such a person alone would be dangerous and not therapeutic. Sometimes, patient’s behaviors are totally out of control; this is a particular concern during a manic episode. In this situation, patients’ behaviors are so beyond limits that they destroy their career and can be harmful to those around them. Some patients with bipolar disorder have other medical conditions for which medication monitoring is warranted. For example, patients with certain cardiac conditions should be in a medical environment where the effects of the psychotropic medications can be monitored and observed closely. In the clearest case of the bipolar/depressed phase, the patient is suicidal and homicidal in a few situations (this can result in homicide followed by suicide). In these scenarios, commitment is in order and indicated. In other situations, the depression has led to an inability to work, eat, and function; hospitalization is also indicated in these cases. In the situation of a patient in bipolar/manic phase, there often is less clear and dramatic evidence of homicide or suicide, but a pattern of very poor judgment and impairment emerges. Because of the behavior during the manic phase, the person often does major damage to finances, career, and position in the community. This type of self-destructive mania calls for containment with good documentation and family support.

Indications of Inpatient Treatment Medical conditions that warrant medication monitoring Such as cardiac and renal conditions where the effects of the psychotropic medications can be monitored and observed closely. The indications for inpatient treatment in a person with bipolar disorder include the following: Danger to self Danger to others Total inability to function Total loss of control Medical conditions that warrant medication monitoring A patient with bipolar disorder, especially one in a depressive episode, may present with a significant risk for suicide. Serious suicide attempts and specific ideation with plans constitute clear evidence of the need for constant observation and preventive protection; however, in other situations, the danger to the person may come from other aspects of the disease. For example, a person who is depressed enough to not eat might be at risk of death. Alternately, a person in extreme mania who foregoes sleep or food may be in a state of serious exhaustion. Patients with bipolar disorder can also become a threat to others. For example, a patient experiencing a severe depression believed the world was so bleak that she planned to kill her children to spare them from the world’s misery. In the other extreme, a delusional patient having a manic episode believed everyone was against him; he searched for a rifle in order to defend himself and to get them before they got him. Occasionally, depression is so profound that the person cannot function at all. Leaving such a person alone would be dangerous and not therapeutic. Sometimes, patient’s behaviors are totally out of control; this is a particular concern during a manic episode. In this situation, patients’ behaviors are so beyond limits that they destroy their career and can be harmful to those around them. Some patients with bipolar disorder have other medical conditions for which medication monitoring is warranted. For example, patients with certain cardiac conditions should be in a medical environment where the effects of the psychotropic medications can be monitored and observed closely. In the clearest case of the bipolar/depressed phase, the patient is suicidal and homicidal in a few situations (this can result in homicide followed by suicide). In these scenarios, commitment is in order and indicated. In other situations, the depression has led to an inability to work, eat, and function; hospitalization is also indicated in these cases. In the situation of a patient in bipolar/manic phase, there often is less clear and dramatic evidence of homicide or suicide, but a pattern of very poor judgment and impairment emerges. Because of the behavior during the manic phase, the person often does major damage to finances, career, and position in the community. This type of self-destructive mania calls for containment with good documentation and family support.

Outpatient Treatment Goals 1 Look at areas of stress and find ways to handle them: The stresses can stem from family or work, This is a form of psychotherapy. Monitor and support the medication: Patients are ambivalent about their medications and they resent that they need them. The job is to address their feelings and allow them to continue with the medications. Outpatient treatment has 4 major goals, as follows: Look at areas of stress and find ways to handle them. The stresses can stem from family or work, but if they accumulate, they propel the person into mania or depression. This is a form of psychotherapy. Monitor and support the medication. Medications make an incredible difference. The key is to obtain the benefits while avoiding adverse effects. Patients are ambivalent about their medications. They recognize that the drugs help and prevent hospitalizations, yet they also resent that they need them. The job is to address their feelings and allow them to continue with the medications. Develop and maintain the therapeutic alliance. This is one of the many reasons for the practitioner to deal with the patient’s ambivalence about the medications. Over time, the strength of the alliance helps keep the patient’s symptoms at a minimum and helps the patient remain in the community. Provide education (see Patient Education). The clinician must help educate both the patient and the family about bipolar illness. Patients and families need to be aware of the dangers of substance abuse, the situations that would lead to relapse, and the essential role of medications. Support groups for patients and families are of tremendous importance. Psychotherapy helps patients with bipolar disorder. Schöttle and colleagues looked at psychotherapy for patients, family, and caregivers. They found that although results were heterogeneous, most studies found relevant positive results in regard to decreased relapse rates, improved quality of life, increased functioning, or more favorable symptom improvement.[55] Somatic health issues in individuals with bipolar disorder are ubiquitous, underrecognized, and suboptimally treated.[56] Therefore, practitioners must pay attention to patient’s medical conditions, including cardiovascular concerns, diabetes, endocrine problems, infections, urinary complications, and electrolyte imbalances. In view of the possible medical complications, medical follow-up is important. Persons with bipolar disorder often have difficulty obtaining primary physician care.[57]

Outpatient Treatment Goals 2 Develop and maintain the therapeutic alliance: Over time, the strength of the alliance helps keep the patient’s symptoms at a minimum and helps the patient remain in the community. Provide education (see Patient Education): Both the patient and the family need to be aware of the dangers of substance abuse, the situations that would lead to relapse, and the essential role of medications. Outpatient treatment has 4 major goals, as follows: Look at areas of stress and find ways to handle them. The stresses can stem from family or work, but if they accumulate, they propel the person into mania or depression. This is a form of psychotherapy. Monitor and support the medication. Medications make an incredible difference. The key is to obtain the benefits while avoiding adverse effects. Patients are ambivalent about their medications. They recognize that the drugs help and prevent hospitalizations, yet they also resent that they need them. The job is to address their feelings and allow them to continue with the medications. Develop and maintain the therapeutic alliance. This is one of the many reasons for the practitioner to deal with the patient’s ambivalence about the medications. Over time, the strength of the alliance helps keep the patient’s symptoms at a minimum and helps the patient remain in the community. Provide education (see Patient Education). The clinician must help educate both the patient and the family about bipolar illness. Patients and families need to be aware of the dangers of substance abuse, the situations that would lead to relapse, and the essential role of medications. Support groups for patients and families are of tremendous importance. Psychotherapy helps patients with bipolar disorder. Schöttle and colleagues looked at psychotherapy for patients, family, and caregivers. They found that although results were heterogeneous, most studies found relevant positive results in regard to decreased relapse rates, improved quality of life, increased functioning, or more favorable symptom improvement.[55] Somatic health issues in individuals with bipolar disorder are ubiquitous, underrecognized, and suboptimally treated.[56] Therefore, practitioners must pay attention to patient’s medical conditions, including cardiovascular concerns, diabetes, endocrine problems, infections, urinary complications, and electrolyte imbalances. In view of the possible medical complications, medical follow-up is important. Persons with bipolar disorder often have difficulty obtaining primary physician care.[57]

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Pharmacologic Therapy 1 Appropriate medication depends on the stage the patient is experiencing. A number of drugs are indicated for an acute manic episode, primarily the antipsychotics, valproate, and. The choice of agent depends on the presence of symptoms such as psychotic symptoms, agitation, aggression, and sleep disturbance. Appropriate medication depends on the stage of the bipolar disorder the patient is experiencing. Thus, a number of drugs are indicated for an acute manic episode, primarily the antipsychotics, valproate, and benzodiazepines (eg, lorazepam, clonazepam). The choice of agent depends on the presence of symptoms such as psychotic symptoms, agitation, aggression, and sleep disturbance. (See the list of medications for bipolar disorder in the Table below.) For patients with bipolar affective disorder in the depressed phase, the Medscape Reference article Depression provides antidepressant guidelines. Bauer and colleagues suggest 2 approaches. First, in a patient with bipolar depression who is not currently being treated with a mood-stabilizing agent (de novo depression, first or subsequent episode), options include quetiapine or olanzapine, with carbamazepine and lamotrigine as alternatives. Antidepressant are options for short-term use, but it remains controversial if it is better to administer them in combination with mood-stabilizing agents or as monotherapy. Most clinicians use antidepressants and an antimanic agent in combination. Second, if the patient is already optimally treated with a mood-stabilizing agent (appropriate dose, good compliance) such as lithium, an option would be lamotrigine. No evidence suggests additional benefit from antidepressants if a patient is already being treated with a mood stabilizer, but this often tried in practice.[58] One cautionary note of interest, Post and colleagues have found that the more different antidepressant trials the patient with bipolar disorder has received, the less responsive they become to treatment.[59] Lithium is the drug commonly used for prophylaxis and treatment of manic episodes. A recent study suggests that lithium may also have a neuroprotective role.[60] However, it is also associated with increased risk of reduced urinary concentrating ability, hypothyroidism, hyperparathyroidism, and weight gain. The consistent finding of a high prevalence of hyperparathyroidism should prompt physicians to check patient calcium concentrations before and during treatment. Lithium is not associated with a significant reduction in renal function in most patients, and the risk of end-stage renal failure is low.[61] Lithium therapy may serve to protect and preserve the hippocampal volumes, in contrast to patients with major depression (ie, unipolar), who show diminished hippocampal volumes.[62] Atypical antipsychotics are being used increasingly for treatment of both acute mania and mood stabilization. The broad range of antidepressants and ECT are used for an acute depressive episode (ie, major depression). Ansari and Osser have developed a very useful algorithm to treat a bipolar patient in a depressed phase.[63] Finally, another set of medications is chosen for the maintenance and preventive phases of treatment. Diazgranados and colleagues have reported that for patients with treatment-resistant bipolar depression, impressive and swift antidepressant effects occurred when a single intravenous (IV) dose of an N -methyl-D -aspartate (NMDA) antagonist was administered.[64] Increasingly, the role of glutamate in mood disorders is being researched, and experimental evidence shows that the NMDA receptor antagonist ketamine may be helpful in short-term treatment of depression, even in the context of bipolar disorder. Although antidepressant medications are most often prescribed for patients with bipolar disorder who are experiencing an acute depression, a study found that antidepressants were not statistically superior to placebo or other current standard treatment for bipolar depression.[65] Clinical experiences have shown that patients with bipolar disorder have fewer episodes of mania and depression when treated with mood-stabilizing drugs. These medications serve to stabilize the patient’s mood, as the name implies. They can also dampen extremes of mania or depression. Kessing et al found that, in general, lithium was superior to valproate.[66] Clinical experiences have shown that patients with bipolar disorder have fewer episodes of mania and depression when treated with mood-stabilizing drugs.[67]These medications serve to stabilize the patient’s mood, as the name implies. They also can dampen extremes of mania or depression. Atypical antipsychotics (including ziprasidone, quetiapine, risperidone, aripiprazole, olanzapine, and asenapine) are also now frequently used to stabilize acute mania, or even to treat bipolar depression in some cases. The role of mood stabilizers and antipsychotic medications in maintaining patients with bipolar disorder is well documented,[68] as is the use of long-acting antipsychotics to help with the maintenance phase. According to a multiple treatments meta-analysis of treatments for acute mania, haloperidol, risperidone, and olanzapine are the most efficacious treatments, significantly outperforming primary mood stabilizers and other antipsychotic medications.[69] In the treatment of depression associated with bipolar disorder II, Swartz and associates report that 95% of relevant trials were published later than 2005. They noted compelling evidence for the efficacy of quetiapine and preliminary support for the efficacy of lithium, antidepressants, and pramipexole. Mixed support was noted for lamotrigine.[70] As outlined in a clinical practice guideline from the American Psychiatric Association,[71] benzodiazepines have sedative effects, which may make them useful adjunctive medications until antimanic medications take effect. Additionally, the guideline states that manic symptoms may be treated with chlorpromazine, which was deemed superior to placebo in a randomized trial and was deemed comparable to lithium (for controlling manic and psychotic symptoms) in acute treatment comparison trials. Children and adolescents who have bipolar disorder are particularly challenging to treat. Hamrin and Iennaco have conducted an extensive literature review using research findings on medication effectiveness in this population and have developed guidelines and recommendations for medications and management approaches.[72] The US Food and Drug Administration (FDA) has approved several bipolar treatment regimens (see the Table below).[73] Caution in polyantipsychotic therapy in bipolar disorder Brooks et al assessed the safety and tolerability associated with second-generation antipsychotic polytherapy in bipolar disorder.[74] The study sought to evaluate the safety and tolerability of second-generation antipsychotic (SGA) polytherapy compared with monotherapy in patients with bipolar disorder receiving open naturalistic treatment in the 22-site Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). After controlling for illness onset, age, baseline illness severity, and medication load, patients who were prescribed polytherapy compared with monotherapy had more dry mouth, sexual dysfunction, and constipation and were almost 3 times as likely to incur more psychiatric and medical care. No association with greater global functioning scores or percentage of days spent well was noted. The study concluded that although polytherapy was fairly common in bipolar disorder, it was associated with increased side effects and increased health service use but not with improved clinical status or function. Therefore, polytherapy in bipolar disorder may incur important disadvantages without clear benefit, warranting careful consideration before undertaking such interventions.

Pharmacologic Therapy 2 Depressed Patient In a patient with bipolar depression who is not on a mood-stabilizing agent, options include quetiapine or olanzapine, with carbamazepine and lamotrigine as alternatives. However, most clinicians use antidepressants and an antimanic agent in combination. If the patient is already optimally treated with a mood-stabilizing agent such as lithium, an option would be lamotrigine.