Medication Summary
Appropriate medication for managing bipolar disorder, or manic-depressive illness (MDI), depends on the stage the patient is experiencing. The choice of agent depends on the presence of symptoms such as psychotic symptoms, agitation, aggression, and sleep disturbance. Drug categories include mood stabilizers, anticonvulsants, and antipsychotics.
Anxiolytics, Benzodiazepines
Class Summary
By binding to specific receptor sites, benzodiazepines appear to potentiate the effects of gamma-aminobutyric acid (GABA) and facilitate inhibitory GABA neurotransmission and the action of other inhibitory transmitters.
Lorazepam (Ativan)
Lorazepam is an anxiolytic hypnotic with an intermediate onset of effects and a relatively intermediate half-life. By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, it may depress all levels of the central nervous system (CNS), including the limbic and reticular formation.
Clonazepam (Klonopin)
Clonazepam is a long-acting benzodiazepine that increases presynaptic GABA inhibition and reduces monosynaptic and polysynaptic reflexes. It suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters.
Mood stabilizers
Class Summary
Lithium is the drug commonly used for prophylaxis and treatment of manic episodes. A 2012 study suggested that lithium may also have a neuroprotective role. [83] However, this agent is also associated with an 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. [88] 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. [89]
Furthermore, recognizing that patients with bipolar disorder are at risk for suicide, lithium may also have some anti-suicidal action. A report from Lewitka and Bauer suggest that lithium may be an option for patients with affective disorders who are at risk for suicide. However, they caution that lithium is still a medication that requires careful assessment and monitoring. Patient adherence is essential. [43] Many female patients with bipolar disorder will discontinue their lithium medication when they become pregnant. [120]
Lithium carbonate (Lithobid)
Lithium is considered a first-line agent for long-term prophylaxis in bipolar illness, especially for classic bipolar disorder with euphoric mania. It also can be used to treat acute mania, although it cannot be titrated up to an effective level as quickly as valproate can. Evidence suggests that lithium, unlike any other mood stabilizer, may have a specific antisuicide effect.
Monitoring blood levels is critical with this medication. Serum levels should be determined twice weekly during the acute phase, and until the serum level and clinical condition of the patient has been stabilized.
Anticonvulsants
Class Summary
Anticonvulsants have been effective in preventing mood swings associated with bipolar disorder, especially in those 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, valproate, and lamotrigine. More recently, topiramate and oxcarbazepine also are being tried.
Note that the Department of Veterans Affairs/Department of Defense (VA/DoD) do not recommend lamotrigine, topiramate, and gabapentin in patients with mania or mixed episodes. [3]
Carbamazepine (Equetro, Epitol, Carbatrol, Tegretol, Tegretol XR)
Carbamazepine is effective in patients who have not had a clinical response to lithium therapy and who have rapid-cycling bipolar disorder. Its efficacy is not well established for long-term use; therefore, periodically reevaluate the long-term risks and benefits of carbamazepine for individual patients. This drug can also act to inhibit seizures induced through the kindling effect, which is thought to occur by way of repeated limbic stimulation.
Valproate sodium, valproic acid, divalproex sodium (Depakene, Depakote, Depakote ER, Depacon, Stavzor)
Valproate has proven effectiveness in treating and preventing mania. It is classified as a mood stabilizer and can be used alone or in combination with lithium. This agent is 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%.
Lamotrigine (Lamictal, Lamictal ODT, Lamictal XR)
Lamotrigine is an anticonvulsant that appears to be effective in the treatment of the depressed phase in bipolar disorders. It is used for the maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in adults treated for acute mood episodes with standard therapy.
Topiramate (Topamax, Qudexy XR, Trokendi XR, Topamax Sprinkle)
Topiramate has an off-label indication for the treatment of bipolar disease. In a small retrospective review, marked improvement occurred in 62% of patients when topiramate was added to their current regimen. [115] . It is unclear if topiramate's efficacy occurs only as adjunctive treatment. More studies are needed to examine potential benefits of this drug in treating bipolar disorders. Unlike conventional neuroleptics, topiramate is not associated with weight gain.
Antipsychotics, 2nd Generation
Class Summary
Second-generation, or atypical, antipsychotics are increasingly being used for treatment of both acute mania and mood stabilization in patients with bipolar I disease.
Asenapine (Saphris)
Asenapine is indicated as monotherapy for the acute treatment of manic or mixed episodes that are associated with bipolar I disorder. It is also indicated as adjunctive therapy with lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar I disease. The efficacy of asenapine is thought to be mediated through a combination of antagonist activity at dopamine 2 and serotonin (5-HT2) receptors.
Ziprasidone (Geodon)
Ziprasidone is approved for the treatment of acute or mixed episodes that are associated with bipolar disorder. It can be used as maintenance treatment or as an adjunct to lithium or valproate.
Quetiapine (Seroquel, Seroquel XR)
Quetiapine is indicated for acute treatment of manic (immediate release and extended release [XR]) or mixed (XR) episodes that are associated with bipolar I disorder. It can be used as monotherapy or adjunctively with agents such as lithium or divalproex.
Risperidone (Risperdal, Risperdal Consta, Risperdal M-Tab)
Risperidone is indicated for short-term treatment of acute manic or mixed episodes that are associated with bipolar I disorder. It can be used alone or in combination with lithium or valproate. Risperidone can be used in adults and adolescents aged 10-17 years with bipolar I disorder.
Aripiprazole (Abilify, Abilify Maintena, Aristada)
Aripiprazole is indicated for the acute and maintenance treatment of manic or mixed episodes associated with bipolar I disorder. It can be used alone or in combination with lithium or valproate. Aripiprazole may be mediated through a combination of partial agonist activity at D2 and 5-HT1A receptors and antagonist activity at 5-HT2A receptors.
Olanzapine (Zyprexa, Zyprexa Zydis)
Olanzapine is used for the acute and maintenance treatment of manic or mixed episodes associated with bipolar I disorder. It can be used alone or in combination with lithium or valproate. Olanzapine can be used in adults and adolescents aged 13-17 years with bipolar I disorder.
Olanzapine and fluoxetine (Symbyax)
The drug combination includes olanzapine, a second-generation antipsychotic, and fluoxetine, a selective serotonin reuptake inhibitor. This drug is indicated for the acute treatment of depressive episodes associated with bipolar I disorder in adults. The clinical effects of this agent have not been studied in patients younger than 18 years.
Clozapine (Clozaril, FazaClo ODT, Versacloz)
Clozapine has an off-label indication for treatment of acute manic episodes associated with bipolar disorder and treatment of refractory bipolar mania. This agent demonstrates weak D2 receptor and D1 receptor blocking activity. Clozapine also acts as an antagonist at adrenergic, cholinergic, histaminergic, and serotonergic receptors.
Paliperidone (Invegaj, Invega Sustenna, Invega Trinza)
Paliperidone may be used for refractory, moderate to severe mania alone or in combination with lithium or valproate. This agent is typically reserved for patients who decline electroconvulsive therapy (ECT) and who do not respond to medication combinations involving lithium or valproate plus aripiprazole, haloperidol, or another first-generation antipsychotic.
Cariprazine (Vraylar)
Precise mechanism by which cariprazine works for bipolar disorder is unknown. Efficacy could be mediated through a combination of partial agonist activity at central dopamine (D2) and serotonin 5-HT1A receptors. It is indicated for manic, mixed, and/or depressive episodes associated with bipolar 1 disorder.
Lurasidone (Latuda)
Lurasidone’s mechanism of action for treating bipolar depression is unknown. However, its efficacy could be mediated through a combination of central dopamine D2 and serotonin Type 2 (5HT2A) receptor antagonism. It is indicated for treatment of adults with major depressive episodes associated with bipolar I disorder as either monotherapy or as adjunctive treatment with lithium or valproate.
Serotonin-Dopamine Activity Modulators (SDAM)
Class Summary
Elicits antagonistic activity at central serotonin and dopamine receptors.
Olanzapine/samidorphan (Lybalvi)
Indicated for treatment of schizophrenia in adults. It is also approved for bipolar I disorder as monotherapy or as an adjunct to lithium or valproate. Olanzapine acts through a combination of dopamine and serotonin type 2 antagonism. Samidorphan is an opioid antagonist and mitigates weight gain associated with olanzapine.
Lumateperone (Caplyta)
Combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors. Indicated for depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate.
Antipsychotics, 1st Generation
Class Summary
First-generation antipsychotics, also known as conventional or typical antipsychotics, are efficacious for treating both psychotic and nonpsychotic manic and mixed episodes, as well as hypomania. These agents are strong dopamine D2 antagonists. However, each drug in this class has various effects on other receptors, such as 5-HT2 serotonin, alpha1, histaminic, and muscarinic receptors.
Loxapine (Adasuve)
The mechanism of action for loxapine is unknown, but it is theorized to antagonize central dopamine D2 and serotonin 5-HT2a receptors. The inhaled dosage form is indicated for acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults.
Haloperidol (Haldol)
Haloperidol is used for the acute treatment of mania or mixed episodes in patients with bipolar disorder. It can be used alone or in combination with lithium or valproate in an adult patient. Haloperidol blocks postsynaptic dopamine receptors (D2) in the mesolimbic system and increases dopamine turnover by blockade of the D2 somatodendritic autoreceptor
Antipsychotics, Phenothiazine
Class Summary
Phenothiazine antipsychotics, which are classified as first-generation antipsychotics, are efficacious for treating both psychotic and nonpsychotic manic and mixed episodes, as well as hypomania.
Chlorpromazine
Chlorpromazine is used to treat manic and mixed episodes in patients with bipolar I disorder. It can be used alone or in combination with lithium or valproate. Chlorpromazine blocks postsynaptic dopamine receptors (D2) in the mesolimbic system and increases dopamine turnover by blockade of the D2 somatodendritic autoreceptor
Antiparkinson Agents, Dopamine Agonists
Class Summary
Dopamine agonists are non-ergot agents that bind to D2 and D3 dopamine receptors in the striatum and substantia nigra.
Pramipexole (Mirapex, Mirapex ER)
Pramipexole is used as add-on therapy for patients whose condition is refractory to combination therapy and have bipolar depression. Pramipexole is a non-ergot, full dopamine agonist that binds to D2 and D3 dopamine receptors.
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What is bipolar disorder? Bipolar disorder, sometimes known as manic depression, is a type of mental disorder where people experience periods of extreme lows, known as depression, as well as periods of extreme highs, or manic episodes. Courtesy of Osmosis.org (https://www.osmosis.org/).
Tables
Generic Name |
Trade Name |
Manic |
Mixed |
Maintenance |
Depression |
Valproate |
Depakote |
X |
X |
|
|
Carbamazepine extended release |
Equetro |
X |
X |
|
|
Lamotrigine |
Lamictal |
|
|
X |
|
Lithium |
|
X |
|
X |
|
Aripiprazole |
Abilify |
X |
X |
X |
|
Ziprasidone |
Geodon |
X |
X |
X |
|
Risperidone |
Risperdal |
X |
X |
X |
|
Asenapine |
Saphris |
X |
X |
X |
|
Quetiapine |
Seroquel |
X |
X |
X |
X |
Chlorpromazine |
Thorazine |
X |
|
|
|
| Cariprazine | Vraylar | X | X | X | X |
Olanzapine |
Zyprexa |
X |
X |
X |
X* |
Olanzapine/fluoxetine combination |
Symbyax |
|
|
|
X |
| Lurasidone | Latuda | X | |||
| Lumateperone | Caplyta | X | |||
FDA = United States Food and Drug Administration. *In combination with fluoxetine Source: Prescribing information for individual drugs; Gutman DA, Nemeroff C.Medscape Education. Atypical antipsychotics in bipolar disorder.Available at: http://www.medscape.org/viewarticle/554128. Accessed: June 27, 2007. [81] |
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