Medication Summary
Mood stabilizers, such as lithium carbonate, sodium divalproex, and carbamazepine, have traditionally been the mainstays of treatment of patients with bipolar disorder. However, atypical antipsychotics are increasingly used in bipolar disorder, with or without psychotic symptoms. This class of medications includes asenapine, risperidone, quetiapine, olanzapine, aripiprazole, ziprasidone, and clozapine. In 2018, the FDA approved lurasidone for the treatment of major depressive episodes associated with bipolar I disorder in children and adolescents aged 10 to 17 years. [65] Benzodiazepines may be used to improve sleep and to modulate agitation during hospitalization.
Potential problems include the possibility of neuroleptic malignant syndrome with treatment with valproate. [83]
Mood stabilizers
Class Summary
Mood stabilizers are indicated for control of manic episodes occurring in bipolar disorder. They include lithium carbonate, valproic acid or sodium divalproex, and carbamazepine.
Lithium (Lithobid)
Lithium is considered a first-line agent for long-term prophylaxis in bipolar illness, especially classic bipolar disorder with euphoric mania. It is also used to treat acute mania, though it cannot be up titrated to an effective level as quickly as valproic acid can. Evidence suggests that lithium, unlike any other mood stabilizer, may have a specific antisuicide effect. Monitoring of blood levels is critical with this medication.
Anticonvulsants
Class Summary
Anticonvulsants have been effective in preventing mood swings associated with bipolar disorder.
Valproic acid (Depacon, Depakene, Depakote)
Valproic acid 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. It is useful in treating 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%.
Carbamazepine (Equetro)
Carbamazepine's anticonvulsant action may involve depressing activity in the nucleus ventralis anterior of the thalamus, reducing polysynaptic responses and blocking posttetanic potentiation. Carbamazepine reduces sustained, high-frequency, repetitive neural firing. It is a potent enzyme inducer that can induce its own metabolism. Because of potentially serious blood dyscrasias, weigh benefit and risk before therapy.
Therapeutic plasma levels are 4-12 µg/mL for analgesic and antiseizure response. Serum levels peak in 4-5 h. Serum half-life is 12-17 h with repeated doses. Carbamazepine is metabolized in the liver to its active metabolite (epoxide derivative) with a half-life of 5-8 h. Metabolites are excreted in feces and urine.
Carbamazepine is effective in cases that do not respond to lithium therapy. It has been effective in treating rapid-cycling bipolar disorder.
Atypical Antipsychotics
Class Summary
Atypical antipsychotics are being used increasingly for treatment of both acute mania and mood stabilization.
Aripiprazole (Abilify, Abilify Discmelt)
Aripiprazole is an atypical antipsychotic that is approved for bipolar disorder in children aged 10-17 years. It can be used as monotherapy or adjunctively with lithium or valproate. For children younger than 10 years, the safety and efficacy has not been established. It is a partial dopamine D2 and serotonin 5HT1A agonist, and it antagonizes serotonin 5HT2A.
Risperidone (Risperdal, Risperdal Consta, Risperdal M-Tab)
Risperidone binds dopamine D2-receptor with a 20 times lower affinity than it has for 5-HT2 receptor. It is indicated for short-term (3-wk) treatment of acute mania associated with bipolar disorder. It may be used alone or combined with lithium or valproate. Risperidone is approved for bipolar mania in children aged 10-17 years.
Quetiapine (Seroquel, Seroquel XR)
Quetiapine is indicated for acute treatment of manic episodes that are associated with bipolar I disorder. It is approved for bipolar mania in children aged 10-17 years. Quetiapine may act by antagonizing dopamine and serotonin effects. It is a newer antipsychotic used for long-term management. Improvements over earlier antipsychotics include fewer anticholinergic effects and less dystonia, parkinsonism, and tardive dyskinesia.
Olanzapine (Zyprexa, Zyprexa Zydis, Zyprexa Relprew)
Olanzapine's mechanism of action for acute manic episodes associated with bipolar I disorder is unknown. It is approved by the US Food and Drug Administration (FDA) for adolescents with bipolar I disorder. It is available in tablet, oral disintegrating tablets (Zyprexa, Zydis), and intramuscular (IM) dosage forms. It is approved for children aged 13 years and older.
Ziprasidone (Geodon)
Indicated for acute bipolar mania, including manic and mixed episodes. Antagonizes dopamine D2, D3, 5-HT2A, 5-HT2C, 5-HT1A, 5-HT1D, alpha1 adrenergic. Has moderate antagonistic effect for histamine H1. Moderately inhibits reuptake of serotonin and norepinephrine. Although effective for bipolar disorder, the mechanism of action in bipolar disorder is unknown.
Asenapine (Saphris)
Asenapine is an atypical antipsychotic. It is indicated as monotherapy for the acute treatment of manic or mixed episodes associated with bipolar I disorder in pediatric patients aged 10-17 years. Its mechanism of action is unknown, but is thought that its efficacy is attributed to antagonism of dopamine-2 and serotonin-2a receptors.
Tables
| Behavior | Bipolar | DMDD | ADHD | Conduct Disorder |
|---|---|---|---|---|
| Self-esteem | Inflated | Deflated/irritable | Inflated and/or deflated | Inflated and/or deflated |
| Pleasure | Euphoric in mania Dyphoric in mixed or depressed state |
Variable | Often dysphoric or euthymic | Pleasure in violating societal norms, especially if not caught |
| Attention | Distractible | Distractible | Distractible | Normal to vigilant |
| Hyperactivity | Goal directed | Variable | Unproductive | Goal directed |
| Sleep | Episodic disturbances such as decreased need in mania | Often poor due to avoiding bedtime | Chronic poor sleep; often late bedtimes | Not known to be disrupted except with substance abuse |
| Speech | Pressured or rapid in mania; slow in depression | Rapid/normal rate | Often rapid; may be pressured | May be normal |
| Impulsivity | Externally driven/reactive | Reactionary | Internally driven | May engage in predatory or reactionary acts |
| Social | Often good | Often poor | Often poor | Often poor |
| Academic | Often good | Varies | Often poor | Often poor |
| Psychomotor activity | Agitated in mania or mixed states; retarded in depressed states | Easily agitated | Chronically agitated | Easily agitated |
| ADHD—attention deficit/hyperactivity disorder |
Medication |
Common Adverse Effects |
Pediatric Doses |
Special Concerns |
Lithium carbonate (Lithobid) |
GI distress, lethargy or sedation, tremor, enuresis, weight gain, alopecia, cognitive blunting |
10-30 mg/kg/d; dose must be adjusted by monitoring serum level and patient response; up-titrate on twice-daily schedule |
Hypothyroidism, diabetes insipidus, toxic in dehydration, polyuria, polydipsia, renal disease; drug-drug interactions and sodium intake may alter therapeutic serum levels Approved for patients 12 y and older |
Sodium divalproex/valproic acid (Depakote, Depakene) |
Sedation, platelet dysfunction, liver disease, alopecia, weight gain |
15-30 mg/kg/d; dose must be adjusted by monitoring serum levels; up-titrate on twice- or thrice-daily schedule |
Elevated liver enzymes or liver disease, drug-drug interactions, bone marrow suppression Approved for patients 12 y and older |
Aripiprazole (Abilify, Abilify Discmelt) |
Less likely to cause prolactinemia than risperidone; may cause Stevens-Johnson syndrome; as with other atypical antipsychotics, may cause tardive dyskinesia, dystonia, parkinsonism, hyperglycemia; use with caution in seizure disorders and cardiac disorders, including problems with cardiac contractility and electrical activity |
2 mg once daily can be increased to 5 mg, 10 mg, 15 mg, to a maximum of 30 mg to start titrate upwards at weekly to bimonthly intervals |
levels may need to be adjusted in patients who are concurrently receiving lamotrigine, topiramate, Depakote, lithium, or other serotonin-norepinephrine reuptake, selective serotonin reuptake, or cytochrome P450 inhibitors Do not administer if there is an unstable seizure disorder Approved for patients 12 y and older |
Carbamazepine (Equetro) |
Suppressed WBCs, dizziness, drowsiness, rashes, liver toxicity (rare) |
10-20 mg/kg/d; dose must be adjusted by monitoring serum blood levels; up-titrate on twice-daily schedule |
Drug-drug interactions, bone marrow suppression |
Asenapine (Saphris) |
Somnolence, oral paraesthesia |
2.5 mg SL q12h initially; may increase to 5 mg SL q12hr after 3 days and to 10 mg SL q12hr after 3 additional days |
Pediatric patients are more sensitive to dystonia with initial dosing when recommended escalation schedule not followed Approved for patients 10 y and older |
Risperidone (Risperdal, Risperdal Consta, Risperdal M-Tab) |
Weight gain, sedation, orthostasis |
0.25 mg bid or 0.5 mg at bedtime initially; titrate as tolerated to target dosage of 2-4 mg/d; not to exceed 6 mg/d |
Galactorrhea, extrapyramidal symptoms Approved for patients 10 y and older |
Quetiapine (Seroquel, Seroquel XR) |
Sedation, orthostasis, weight gain |
50 mg bid initially; titrate as tolerated to target dosage of 400-600 mg/d |
Decrease dosage with hepatic impairment, may cause neuroleptic malignant syndrome or hyperglycemia Approved for patients 10 y and older |
Olanzapine (Zyprexa, Zyprexa Zydis, Zyprexa Relprevv) |
Weight gain, dyslipidemia, sedation, or orthostasis |
2.5-5 mg at bedtime initially; titrate as tolerated to target dosage of 10-20 mg/d |
Metabolic syndrome, extrapyramidal symptoms |
Clonazepam (Klonopin) |
Sedation, abnormal coordination, ataxia |
0.01-0.04 mg/kg/d PO at bedtime or divided bid |
Caution with renal/hepatic impairment and asthma |
Fluoxetine (Prozac) |
Headache, nausea, insomnia, anorexia, anxiety, asthenia, diarrhea, somnolence |
10 mg PO qd; may consider increasing to 20 mg/d after 1 wk |
Long half-life; potential to exacerbate manic symptoms when not coadministered with an antimanic or mood-stabilizing agent |
Ziprasidone (Geodon) |
Akathisia, nausea |
Off-label: 20 mg PO at bedtime; can increase to 40 mg (not to exceed 60 mg), usually in 2 divided doses for children |
Risk of sudden cardiac death due to torsades des pointes due to prolonged QT prolongation, which makes this medication undesirable for individuals with a family history of cardiac sudden death related to cardiac conduction abnormalities |
WBC—white blood cell. |
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