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Medical Monitoring in Patients With Bipolar Disorder: Clinical Recommendations
Edward S. Friedman, MD
From the Department of Psychiatry, University of Pittsburgh Medical Center and Western Psychiatric Institute & Clinic, Pittsburgh, Pa
This activity was supported by an educational grant from Eli Lilly and Company, Bristol-Myers Squibb Company and Otsuka America Pharmaceutical, Inc, and Pfizer Inc.
Objective
After completing this educational activity, you should be able to:
- Identify and develop an appropriate treatment strategy for patients with bipolar disorder and psychiatric and medical comorbidities
Patients with bipolar disorder should be assessed for a variety of medical issues at certain intervals. A planned regimen of patient monitoring is highly recommended to track fluctuations in weight, blood pressure, glucose levels, and lipid profile, as well as other monitoring as necessary. Different monitoring may be needed depending on whether the patient is treated with lithium, divalproex, carbamazepine, or atypical antipsychotics.
From our review of the literature and our desire to fully monitor our patients for clinically significant adverse effects, the following recommendations have been adopted by our research clinic.1,2 When treating patients with lithium, clinicians should first take baseline measurements and then monitor patients throughout the course of treatment. Baseline measurements should be taken of a patient’s electrolytes, including calcium, in addition to a complete blood cell count (CBC) with differential. An electrocardiogram (ECG) should be conducted for patients older than 40 years or if a cardiac risk is suspected. Other baseline tests that should be obtained before lithium is started include a urinalysis, a blood urea nitrogen (BUN) test, tests for creatinine (and creatinine clearance if a risk of renal impairment is suspected), and thyroid function tests (TFTs), which typically include obtaining measurements of thyroid-stimulating hormone (TSH), thyrotropin, thyroxine (T4), and triiodothyronine (T3). Finally, female patients should be given a pregnancy test, and all patients should be given a physical exam and have their general medical history taken. For patients taking lithium, follow-up monitoring after the dosage is stabilized should occur monthly (over the first 4 months) and every 6 months thereafter. These should include lithium serum levels, CBC and differential, creatinine, BUN, urinalysis, and TFTs.
For patients prescribed divalproex treatment, baseline checks should include liver function tests (LFTs), a prothrombin time (PT) and partial thromboplastin time (PTT) blood test to check extrinsic coagulation system, and a CBC with differential and with platelet count (PLT). In addition, patients should be given a lipase blood test (to check for pancreatitis or other pancreatic diseases), a pregnancy test, and a physical exam, and a general medical history should be taken. For divalproex treatment, follow-up monitoring includes LFTs, PT/PTT, CBC with differential and with PLT, a lipase blood test, and a pregnancy test, if necessary, performed after the stable dosage is achieved and then examined monthly for the first 6 months and then every 6 months thereafter.
Before starting carbamazepine, baseline tests should include CBC with PLT, LFTs, PT/PTT, tests for creatinine, a BUN test, a urinalysis, and tests of electrolytes. For women, a pregnancy test should be given, and both men and women should be given a physical exam and have a general medical history taken. For follow-up monitoring, CBC and drug level should be monitored every 7–14 days. LFTs should be done until the dosage is stable. Routine follow-up then would include CBC with PLT, LFTs, thyroid, tests of electrolytes, a pregnancy test, and blood level check monthly for the first 4 months and thereafter every 6–12 months.
The American Diabetes Association (ADA), the American Psychiatric Association (APA), the American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity issued a consensus statement that included guidelines for patient monitoring during atypical antipsychotic treatment.3 At baseline, clinicians are urged to obtain the patient’s medical history, weight, waist measurement, blood pressure, fasting glucose level, and lipid profile. During follow-up, weight should be monitored at 4, 8, and 12 weeks after initiating or changing atypical antipsychotic therapy; then every 4 months; then annually; and then every 5 years. Waist measurements should be taken at 12 weeks and then every 5 years. Blood pressure, fasting glucose level, and lipid profile should be monitored at 12 weeks, annually, and then every 5 years. If the patient gains ≥5% of his or her initial weight during treatment, the clinician should consider switching to a different medication. A final caveat is that, depending on the patient’s clinical status, more frequent assessments may be needed.
When taking the patient’s history, clinicians should look for a personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease. Clinicians could also test prolactin levels, because some antipsychotics have been found to be associated with hyperprolactinemia, which could lead to gynecomastia, galactorrhea, sexual dysfunction, infertility, oligomenorrhea, and amenorrhea.4 Additional tests for antipsychotics with cardiovascular contraindications include an ECG (unless a recent ECG is available), measurements of electrolytes (including calcium and magnesium), and a Holter monitor, if indicated.
When treating patients with atypical antipsychotics, clinicians may neglect to perform simple monitoring tasks to help track patient health. Physicians can inquire about binge eating or other forms of unhealthy eating, and—the most basic of all—check their patients’ weight. If the patient is psychiatrically stable, but has experienced weight gain or dyslipidemia, the medication could be switched. Clinicians could also participate in patients’ behavior modification programs to aid patients and improve their chances for remission as well as maintaining physical health.
The signs and symptoms of diabetes and diabetic ketoacidosis (DKA) should be familiar to health professionals, patients, family members, and caregivers.3 Patients at risk for DKA are difficult to identify based on clinical characteristics, such as age, body weight, race, or length of atypical antipsychotic treatment. Also, no clear association has been observed between a heavy body weight, atypical antipsychotic-related weight gain, and DKA. To prevent DKA, regular laboratory screening should be done, and the rapid onset of polyuria, polydipsia, weight loss, dehydration, rapid respiration, and acute abdominal symptoms (such as nausea, vomiting, and pain) should be watched for. All patients with diabetes should be referred to an ADA-recognized diabetes self-management education program, if available.
Conducting measures of medical health in patients with bipolar disorder is important for obtaining the best possible outcome of treatment. Baseline and follow-up health tests vary according to the type of treatment the patient is taking but should be regularly implemented.
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Date of Original Release/Review
This Brief Report was published in September 2007 and is eligible for AMA PRA Category 1 CreditTM through September 30, 2009. The latest review of this material was August 2007.
Drug Names
carbamazepine (Carbatrol, Tegretol, and others), divalproex (Depakote), lithium (Eskalith, Lithobid, and others)
Disclosure of off-label usage:
Dr. Friedman has determined that, to the best of his knowledge, no investigational information about pharmaceutical agents that is outside U.S. Food and Drug Administration-approved labeling has been presented in this activity.
References
- Kupfer DJ. The increasing medical burden in bipolar disorder [commentary]. JAMA 2005;293:2528–2530
- Fagiolini A, Frank E, Scott JA, et al. Metabolic syndrome in bipolar disorder: findings from the Bipolar Disorder Center for Pennsylvanians. Bipolar Disord 2005;7:424–430
- American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity. Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes. Diabetes Care 2004;27:596–601
- Haddad PM, Wieck A. Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management. Drugs 2004;64:2291–2314
