What are the treatment options for a patient with bipolar disease, taking lamotrigine (28 mg twice daily), valproate (200 mg twice daily), and olanzapine (Zyprexa, 2.5 mg nightly), who is experiencing agitation and depression?

From the Guidelines

For a patient with bipolar disorder experiencing agitation and depression while on lamotrigine 28 mg twice daily, valproate 200 mg twice daily, and olanzapine (Zyprexa) 2.5 mg nightly, I recommend optimizing the current medication regimen before considering alternatives. First, consider increasing lamotrigine gradually to a therapeutic dose of 100-200 mg twice daily, as the current dose is likely subtherapeutic, as suggested by studies on bipolar disorder treatment 1. Similarly, valproate levels should be checked, aiming for a therapeutic range of 50-125 μg/mL, which may require dose adjustment to 500-1000 mg twice daily for most adults, according to the practice parameter for the assessment and treatment of children and adolescents with bipolar disorder 1. For persistent depression, adding an antidepressant like bupropion (150-300 mg daily) or an SSRI with mood stabilizer coverage could be beneficial, as noted in the treatment of bipolar disorder 1. For agitation, a modest increase in olanzapine to 5-10 mg may help, though monitor for metabolic side effects, as antipsychotic medications are effective in managing agitation in patients with bipolar disorder 1. Regular monitoring should include CBC, liver function, valproate levels, and metabolic parameters. These medications work synergistically - lamotrigine primarily addresses depression, valproate stabilizes mood and reduces mania/agitation, and olanzapine helps with acute agitation and psychotic symptoms. Adjusting doses to therapeutic levels often improves symptom control before adding new medications, as the primary treatment for early-onset bipolar disorder involves traditional mood stabilizers and/or atypical antipsychotic medications 1.

Some key points to consider:

• The current dose of lamotrigine is likely subtherapeutic and should be increased gradually to a therapeutic dose of 100-200 mg twice daily.
• Valproate levels should be checked and adjusted to a therapeutic range of 50-125 μg/mL.
• Adding an antidepressant like bupropion or an SSRI with mood stabilizer coverage may be beneficial for persistent depression.
• A modest increase in olanzapine to 5-10 mg may help with agitation, but monitor for metabolic side effects.
• Regular monitoring of CBC, liver function, valproate levels, and metabolic parameters is necessary.

The treatment of bipolar disorder involves a combination of medications and psychotherapies, and the primary goal is to stabilize mood and reduce symptoms, as noted in the practice parameter for the assessment and treatment of children and adolescents with bipolar disorder 1.

From the FDA Drug Label

1.4 ZYPREXA IntraMuscular: Agitation Associated with Schizophrenia and Bipolar I Mania 1.5 ZYPREXA and Fluoxetine in Combination: Depressive Episodes Associated with Bipolar I Disorder 5.16 Use in Combination with Fluoxetine, Lithium, or Valproate

The patient is taking zyprexa (olanzapine) 2.5 mg nightly, which is indicated for agitation associated with schizophrenia and bipolar I mania and depressive episodes associated with bipolar I disorder. The patient is also taking valproate, and the label mentions use in combination with valproate.

• The patient's current medication regimen includes lamotrigine, valproate, and zyprexa, which suggests that the patient's agitation and depression are being managed with these medications.
• However, the label does not provide specific guidance on adjusting the dose of zyprexa in combination with lamotrigine and valproate for agitation and depression in bipolar disease. 2

From the Research

Management of Agitation and Depression in Bipolar Disorder

The patient's current medication regimen includes lamotrigine, valproate, and zyprexa, which are commonly used to manage bipolar disorder.

• The patient's agitation can be managed using a step-wise approach, starting with non-coercive de-escalation strategies and moving on to pharmacologic interventions as necessary 3.
• The use of ketamine, benzodiazepines, and antipsychotics should be considered for managing agitation 3.
• Nurses can use validated techniques such as frequent and sufficient reality orientation, validation therapy, and strategies that improve the individual's quality of life to manage agitation 4.

Treatment of Bipolar Depression

• The treatment of bipolar depression is a priority due to the significant risk of suicide in bipolar patients when depressed 5.
• Lamotrigine is one of the treatments with the best evidence for efficacy in managing bipolar depression, and it is already part of the patient's medication regimen 5.
• The combination of an atypical antipsychotic (such as zyprexa) and an SSRI or lamotrigine may provide a useful first-line treatment for depressed bipolar disorder patients 5.
• Other treatment options for bipolar depression include lithium, valproate, and quetiapine monotherapy, as well as olanzapine plus SSRI, and lithium or divalproex plus SSRI/bupropion 6.

Combination Therapy

• Combination therapy is commonly used in the treatment of bipolar depression, with many patients receiving more than one class of psychotropic substances 7.
• The patient's current medication regimen includes a combination of lamotrigine, valproate, and zyprexa, which is consistent with common combination therapy approaches for bipolar depression 7.
• The efficacy of many combination therapies has not been studied, and treatment should be individualized based on the patient's specific needs and response to treatment 7.