eMedicine Specialties > Psychiatry > Adult
Bipolar Affective Disorder: Treatment & Medication
Updated: Sep 10, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
The treatment of bipolar disorder is directly related to the phase of the episode, eg, 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.
- Inpatient hospital treatment: The indications for hospitalization in a person with bipolar disorder include the following:
- Danger to self: A patient, 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.
- Danger to others: Patients with bipolar disorder can 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.
- Total inability to function: Occasionally, depression is so profound that the person cannot function at all. Leaving such a person alone would be dangerous and not therapeutic.
- Totally out of control: This is true especially 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.
- Medical conditions that warrant medication monitoring: 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.
- Partial hospitalization or a day-treatment program
- In general, these patients have severe symptoms but have a level of control and a stable living environment.
- For example, a patient with severe depression who has thoughts of suicide but no plans to act upon them and who has a high degree of motivation can get well when given a great deal of interpersonal support, especially during the day, and with the help of a very involved and supportive family. The family needs to be home every night and should be very concerned with the patient's care. Partial hospitalization also offers a bridge to return to work. Returning directly to work often is difficult for patients with severe symptoms, and partial hospitalization provides support and interpersonal relationships.
- Outpatient treatment: Outpatient treatment has 4 major goals.
- First, 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.
- Second, monitor and support the medication. Medications make an incredible difference. The key is to get the benefits and avoid 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.
- Third, 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.
- The fourth aspect involves education. The clinician must help educate both the patient and the family about bipolar illness. They 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. See Patient Education.
- Somatic health issues in individuals with bipolar disorder are ubiquitous, under-recognized, and suboptimally treated.21 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. These patients often have difficulty obtaining primary physician care.22
Surgical Care
No surgical procedure is indicated. Historically, treatment was attempted with psychosurgery, such as prefrontal lobotomy. Lobotomy is no longer used in the clinical care of patients with bipolar disorder.
Consultations
A consultation with a psychiatric colleague or a psychopharmacologist is always appropriate if the patient does not respond to conventional treatment and medication.
Diet
Unless the patient is on monoamine oxidase inhibitors (MAOIs), no special diet is required. Patients should be advised not to make significant changes in their salt intake because increased salt intake may lead to reduced serum lithium levels and reduced efficacy, and reduced intake may lead to increased levels and toxicity.
Activity
Patients in the depressed phase are encouraged to exercise. Propose a regular exercise schedule for all patients, especially those with bipolar disorder. Both the exercise and the regular schedule are keys to surviving this illness. However, increases in exercise level, with increased perspiration, can lead to increased serum lithium levels and lithium toxicity.
Medication
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. Atypical antipsychotics are being used increasingly for treatment of both acute mania and mood stabilization. The broad range of antidepressants and electroconvulsive therapy are used for an acute depressive episode (ie, major depression). Finally, another set of medications is chosen for the maintenance and preventive phases of treatment.
Clinical experiences have shown that, if treated with mood-stabilizing drugs, patients with bipolar disorder have fewer episodes of mania and depression. These medications serve to stabilize the patient's mood, as the name implies. They also can dampen extremes of mania or depression.
Atypical antipsychotics 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 documented23 as is the use of long-acting antipsychotics to help with the maintenance phase24 .
Atypical antipsychotics are being used increasingly for treatment of both acute mania and mood stabilization. These include ziprasidone, quetiapine, risperidone, aripiprazole, olanzapine, and asenapine.
The current consensus is that the most effective treatment for acute mania is a combination of second-generation antipsychotic medications and mood-stabilizing medications.25
This table shows FDA-approved bipolar treatment regimens.26
Table. FDA-Approved Bipolar Treatment Regimens
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Table
| Generic Name | Trade Name | Manic | Mixed | Maintenance | Depression |
|---|---|---|---|---|---|
| Valproate | Depakote | X | |||
| Carbamazepine extended release | Equetro | X | X | ||
| Lamotrigine | Lamictal | X | |||
| Lithium | X | X | |||
| Aripiprazole | Abilify | X | X | X | |
| Ziprasidone | Geodon | X | X | ||
| Risperidone | Risperdal | X | X | ||
| Asenapine | Saphris | X | X | ||
| Quetiapine | Seroquel | X | X | ||
| Chlorpromazine | Thorazine | X | |||
| Olanzapine | Zyprexa | X | X | X | |
| Olanzapine/fluoxetine Combination | Symbyax | X |
| Generic Name | Trade Name | Manic | Mixed | Maintenance | Depression |
|---|---|---|---|---|---|
| Valproate | Depakote | X | |||
| Carbamazepine extended release | Equetro | X | X | ||
| Lamotrigine | Lamictal | X | |||
| Lithium | X | X | |||
| Aripiprazole | Abilify | X | X | X | |
| Ziprasidone | Geodon | X | X | ||
| Risperidone | Risperdal | X | X | ||
| Asenapine | Saphris | X | X | ||
| Quetiapine | Seroquel | X | X | ||
| Chlorpromazine | Thorazine | X | |||
| Olanzapine | Zyprexa | X | X | X | |
| Olanzapine/fluoxetine Combination | Symbyax | X |
Mood stabilizers
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.27
Lithium carbonate (Duralith, Eskalith, Lithobid)
Considered a first-line agent for long-term prophylaxis in bipolar illness, especially for classic bipolar disorder with euphoric mania. Also can be used to treat acute mania, although cannot be titrated up to an effective level as quickly as valproic acid. Evidence suggests that lithium, unlike any other mood stabilizer, may have a specific antisuicide effect. Monitoring blood levels is critical with this medication.
Adult
Maintenance, preventive use: 400-1200 mg (0.6-1 mmol/L) PO qd
Acute manic episode: 600-2400 mg (0.8-1.2 mmol/L) PO qd
Pediatric
<6 years: Not established
6-12 years: 15-60 mg/kg/d PO divided tid/qid; not to exceed adult dose
>12 years: Administer as in adults
Increases toxicity of thiazide diuretics, haloperidol, phenothiazines, neuromuscular blockers, carbamazepine, fluoxetine, and ACE inhibitors
Documented hypersensitivity; renal disease or damage (renal function and clearance are critical in maintaining proper levels); history or evidence of brain damage; cardiovascular disease; generalized severe debilitation
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Patient should have adequate renal function as evidenced by elevated creatinine levels or BUN levels, and they should drink plenty of fluids to prevent dehydration; excessive sodium loss can produce lithium toxicity (avoid excessive sweating); use lower doses in elderly individuals; do not perform ECT when being administered; avoid rapid increases in dosing
Anything causing hyponatremia increases levels and could cause toxicity; toxicity is closely related to serum levels and can occur at therapeutic doses; serum lithium determinations are required to monitor therapy
Anticonvulsants
Have been effective in preventing mood swings associated with bipolar disorder, especially in patients known as rapid cyclers. For the depressed phase, mood stabilizers, such as lithium and lamotrigine, are preferred because antidepressants may propel a patient into a manic episode or exacerbate irritability in mixed-symptom mania. Gabapentin, although not a mood stabilizer, also may have anxiolytic properties. The most widely used anticonvulsants have been carbamazepine, divalproex sodium, and lamotrigine. More recently, topiramate and oxcarbazepine also are being tried.
Carbamazepine (Tegretol)
Effective in patients who have not responded to lithium therapy. Also can act to inhibit seizures induced through the kindling effect, which is thought to occur by way of repeated limbic stimulation. Has been effective in treating patients who have rapid-cycling bipolar disorder or those who have not been responsive to lithium therapy.
Adult
Initial: 200 mg PO qd in divided doses with increments of 100 mg 2 times/wk; if adverse effects occur, decrease dose by 200 mg
Dose range: 300-1600 mg PO qd
Serum level range: 17-50 mmol/L (4-12 mcg/mL)
Manic episode: 200-1800 mg PO qd
Plasma level: 4-12 mcg/mL
Pediatric
<6 years: Not established
6-12 years: 100 mg PO bid or 10 mg/kg/d divided bid initially, then increase to 100 mg/d every wk
Maintenance: 20-30 mg/kg/d PO divided bid/qid; not to exceed 1000 mg/d
>12 years: Administer as in adults to achieve 4-12 mcg/mL plasma level
Halothane coadministration may cause hepatocellular damage; grapefruit juice, influenza vaccine, isoniazid, cimetidine, erythromycin, and phenelzine increase plasma levels; phenytoin, alprazolam, clonazepam, primidone, and phenobarbital decrease both CBZ level and levels of interacting agents; fluoxetine increases level; decreases levels of imipramine, phenothiazines, haloperidol, theophylline, thyroid hormones, ritonavir, saquinavir, contraceptives, risperidone, thiothixene, cyclosporine, corticosteroids, doxycycline, trazodone, doxepin, and amitriptyline; increases plasma levels of diltiazem and verapamil; can reduce its own level by "autoinduction;" coadministration with lithium or loxapine increases toxicity of both CBZ and the interacting agents; coadministration with clozapine further increases bone marrow toxicity and resulting agranulocytosis
Documented hypersensitivity; administration of MAOIs within last 14 d; history of liver disease, cardiovascular disease, and blood dyscrasias
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
A very small, but significant, risk of causing agranulocytosis or aplastic anemia exists.
During drug initiation, avoid using hazardous equipment or driving; other depressants and alcohol may lead to increased dizziness and sleepiness; keep in a dry place; drinking grapefruit juice while taking CBZ elevates blood levels; report any indications of blood dyscrasias (eg, easy bruising, sore throats, fever, rash)
Valproate sodium, valproic acid (Depakene, Depakote)
Has proven effectiveness in treating and preventing mania. Classified as a mood stabilizer and can be used alone or in combination with lithium. Useful in treating patients with rapid-cycling bipolar disorders and has been used to treat aggressive or behavioral disorders. A combination of valproic acid and valproate has been effective in treating persons in manic phase, with a success rate of 49%.
Adult
250 mg PO tid, initially in increments until a serum level of 350-700 mmol/L (50-100 mcg/mL) has been achieved
Maintenance: 750-3000 mg PO qd in divided doses
Manic episode: Loading dose of 20 mg/kg/d PO
Stat dose: 20 mg/kg PO, with next dose in 12 h; then 10 mg/kg bid
Maintenance: 500-3500 mg PO qd to achieve plasma level of 50-125 mcg/mL
Pediatric
10-15 mg/kg/d PO initially in 1-3 divided doses; increase by 5-10 mg/kg/d PO qwk until therapeutic plasma level achieved
Maintenance: 30-60 mg/kg/d PO divided bid/tid
Coadministration with cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may significantly reduce valproate levels; in pediatric patients, protein binding and metabolism of valproate decrease when taken concomitantly with salicylates; coadministration with carbamazepine may result in variable changes of carbamazepine concentrations, with possible loss of seizure control; valproate may increase diazepam and ethosuximide toxicity (monitor closely); valproate may increase phenobarbital and phenytoin levels, while either one may decrease valproate levels; valproate may displace warfarin from protein binding sites (monitor coagulation tests); may increase zidovudine levels in patient seropositive for HIV; valproate inhibits the metabolism of lamotrigine and increases the risk of Stevens-Johnson syndrome (a lamotrigine dose has to be titrated up more slowly when used with valproate)
Documented hypersensitivity, hepatic disease/dysfunction
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor for hepatic toxicity (obtain liver function tests prior to initiating therapy and thereafter); serum ammonia levels may increase independently of other liver functions and may cause altered mental status; check platelet count and bleeding times prior to therapy and during treatment; valproic acid inhibits cytochrome P-450 metabolism system (pay attention to any drugs that use this system); monitor for symptoms of pancreatitis and pancreatic enzymes because hemorrhagic pancreatitis has been reported
Lamotrigine (Lamictal)
Anticonvulsant that appears to be effective in the treatment of the depressed-phase in bipolar disorders.
Adult
12.5-37.5 mg/d PO, initially, gradually titrated in 25-mg increments not more often than weekly; effective dose usually 100-400 mg/d qd or divided bid
Pediatric
2-15 mg/kg/d PO divided bid initially
Acetaminophen increases renal clearance and decreases effects; similarly, phenobarbital and phenytoin increase metabolism, causing a decrease in levels; concurrent administration with valproic acid increases lamotrigine levels
Documented hypersensitivity; lactation; renal impairment; hepatic and cardiac problems
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Can cause adverse CNS effects, including dizziness, sedation, ataxia, nystagmus, and diplopia; dermatological problems include hypersensitivity rash, Stevens-Johnson syndrome, and angioedema; renal involvement can produce hematuria; caution in impaired renal or hepatic function; fatal hypersensitivity reactions to lamotrigine are more likely to occur with rapid dose increments (caution when coadministered with valproate)
Antipsychotics
Asenapine (Saphris)
Mechanism of action unknown. Efficacy thought to be mediated through a combination of antagonist activity at dopamine 2 and serotonin (5-HT2) receptors. Exhibits high affinity for serotonin 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5, 5-HT6, and 5-HT7 receptors; dopamine D2, D3, D4, and D1 receptors; alpha1- and alpha2-adrenergic receptors; and histamine H1 receptors, with moderate affinity for H2 receptors. In vitro assays suggest antagonistic activity elicited at these receptors. Indicated for acute treatment of manic or mixed episodes associated with bipolar I disorder (with or without psychotic features).
Adult
Day 1: 10 mg SL bid
Day 2 and subsequent days: 5 mg SL bid; if patient responds favorably, continue beyond initial acute phase (currently no recommendations for duration of therapy)
Pediatric
Not established
Metabolized via UGT1A4 and CYP450 (predominantly isoenzyme 1A2); weak inhibitor of CYP2D6; coadministration with other drugs that prolong QTc interval may result in life-threatening arrhythmias (eg, class 1A antiarrhythmics [quinidine, procainamide], class 3 antiarrhythmics [amiodarone, sotalol], antipsychotics [ziprasidone, chlorpromazine, thioridazine], and antibiotics [gatifloxacin, moxifloxacin]); concurrent use of CNS-acting drugs or alcohol may increase toxicity
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects while treating schizophrenia include akathisia, oral hypoesthesia, and dizziness; common adverse effects while treating bipolar disorder include drowsiness, dizziness, and movement disorders other than akathisia; may cause neuroleptic malignant syndrome, tardive dyskinesia, hyperglycemia (monitor patients with diabetes mellitus for worsening of glucose control), and weight gain; may cause hypotension and syncope, especially early in treatment because of its alpha1-antagonistic activity; may cause leukopenia, neutropenia, and agranulocytosis; may prolong QTc interval (avoid with history of cardiac arrhythmias and other conditions that increase risk for Torsade de Pointes [eg, bradycardia, hypokalemia, hypomagnesemia]); may increase risk of hyperprolactinemia, seizures, cognitive/motor impairment, and dysphagia; may disrupt body temperature regulation; not recommended with severe hepatic impairment (ie, Child-Pugh C); inherent suicide risk with population treated warrants close supervision when changing drug therapy
Boxed warning: Use of antipsychotic drugs to treat elderly patients with dementia-related psychosis has been found to increase risk of death (not approved for dementia-related psychosis)
More on Bipolar Affective Disorder |
| Overview: Bipolar Affective Disorder |
| Differential Diagnoses & Workup: Bipolar Affective Disorder |
 Treatment & Medication: Bipolar Affective Disorder |
| Follow-up: Bipolar Affective Disorder |
| References |
| « Previous Page | Next Page » |
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Further Reading
Keywords
bipolar depression, bipolar disorder, bipolar symptoms, bipolar treatment, manic depression, affective disorder, mood disorder, bipolar affective disorder, bipolar disorder, bipolar I, bipolar II, subthreshold bipolar disorders, bi polar disorder, bipolar treatment, bipolar symptoms, manic-depressive disorder, manic-depressive illness, MDI, manic depression, BPI, BPII, schizophrenia, psychosis, mood disorders, cyclothymia, suicide, mania
electroconvulsive therapy, ECT, electroshock, hypomania, psychomotor agitation, grandiosity, inflated self-esteem, racing thoughts, flight of ideas, distractibility, hypersomnia, insomnia, depression, Mental Status Examination, MSE, aggression
