From the Guidelines
When managing patients with bipolar disorder and comorbid conditions in primary care, it is crucial to consider potential drug interactions that may impact morbidity, mortality, and quality of life, particularly with medications for hypertension, high cholesterol, diabetes, heart disease, and cancer.
Key Considerations
- Lithium can interact with antihypertensives, such as ACE inhibitors, ARBs, and diuretics, potentially causing lithium toxicity by reducing its renal clearance, as noted in various studies 1.
- NSAIDs should be avoided with lithium due to the risk of increased lithium levels and potential toxicity.
- For patients with cardiovascular disease, valproate and carbamazepine may interact with statins, increasing the risk of myopathy, while carbamazepine can reduce the effectiveness of many cardiovascular medications through enzyme induction 1.
- In diabetic patients, both valproate and certain atypical antipsychotics (especially olanzapine and clozapine) can worsen glycemic control and require more frequent monitoring 1.
- For cancer patients, tamoxifen's effectiveness may be reduced by strong CYP2D6 inhibitors like fluoxetine or paroxetine, which are sometimes used for bipolar depression, highlighting the need for careful medication management 1.
Medication Management
- Regular monitoring of drug levels (especially for lithium, valproate, and carbamazepine), renal and hepatic function, and electrolytes is essential, particularly when starting or adjusting medications.
- Valproate and lamotrigine generally have fewer problematic interactions and may be preferred in medically complex patients.
- Beta-blockers (not metoprolol) should be used with caution in patients with drug-induced tachycardia (antidepressant, anti-psychotic drugs) 1.
Patient-Specific Considerations
- Patients with hypertension and psychiatric disorders require careful management of blood pressure, with consideration of the potential interactions between antihypertensive medications and psychiatric medications 1.
- The risk of pharmacologic interactions, ECG abnormalities, and postural BP changes must be considered in patients with bipolar disorder and comorbid conditions.
- Additional risk factors should be managed according to the cardiovascular risk profile (SCORE/ASCVD calculator), as outlined in the 2020 International Society of Hypertension Global Hypertension Practice Guidelines 1.
From the FDA Drug Label
ZYPREXA may cause serious side effects, including: High blood sugar (hyperglycemia). High fat levels in your blood (increased cholesterol and triglycerides), especially in teenagers age 13 to 17 or when used in combination with fluoxetine in children age 10 to 17. Weight gain, especially in teenagers age 13 to 17 or when used in combination with fluoxetine in children age 10 to 17.
The potential drug-drug interactions to consider in a primary care setting for a patient with bipolar disorder and various medical conditions such as hypertension, high cholesterol, diabetes, heart disease, possibly breast or prostate cancer are:
- Hyperglycemia: Patients with diabetes should be monitored for worsening glycemic control when taking olanzapine 2.
- Dyslipidemia: Patients with high cholesterol should be monitored for increases in total cholesterol, triglycerides, LDL-cholesterol, and decreases in HDL-cholesterol when taking quetiapine 3.
- Weight gain: Patients should be monitored for weight gain, especially those with a history of weight-related issues or medical conditions such as hypertension, diabetes, or heart disease.
- Cardiovascular risks: Patients with heart disease should be monitored for potential cardiovascular risks associated with atypical antipsychotics, such as orthostatic hypotension and QT interval prolongation. It is essential to carefully evaluate the potential benefits and risks of using atypical antipsychotics in patients with bipolar disorder and various medical conditions, and to monitor them closely for potential drug-drug interactions and adverse effects.
From the Research
Drug-Drug Interactions in Bipolar Disorder
When treating a patient with bipolar disorder who has various medical conditions such as hypertension, high cholesterol, diabetes, heart disease, possibly breast or prostate cancer, several drug-drug interactions should be considered:
- Hypertension: Patients with bipolar disorder are more likely to have comorbid hypertension 4, 5, 6. Antihypertensive medications may interact with mood stabilizers or antipsychotics used to treat bipolar disorder.
- High cholesterol: Individuals with bipolar disorder are at increased risk of developing hyperlipidemia 4. Statins used to treat high cholesterol may interact with certain antipsychotics or mood stabilizers.
- Diabetes: Patients with bipolar disorder are more likely to have comorbid diabetes 6, 7. Medications used to treat diabetes may interact with antipsychotics or mood stabilizers.
- Heart disease: Individuals with bipolar disorder are at increased risk of developing cardiovascular disease 5, 8. Medications used to treat heart disease may interact with antipsychotics or mood stabilizers.
- Breast or prostate cancer: There is limited research on the interaction between bipolar disorder treatments and cancer medications. However, it is essential to consider potential interactions between mood stabilizers or antipsychotics and cancer treatments.
Common Comorbidities
Patients with bipolar disorder often have multiple comorbid medical conditions, including:
- Metabolic disorders (e.g., hypertension, hyperlipidemia, diabetes) 4, 7
- Cardiovascular disease 5, 8
- Respiratory diseases (e.g., chronic obstructive airways disease) 6, 8
- Musculoskeletal diseases (e.g., chronic pain) 6, 8
- Endocrine disorders (e.g., thyroid disorders) 6, 8
Treatment Considerations
When treating patients with bipolar disorder and comorbid medical conditions, it is crucial to: