Ms. W, age 27, presents with a chief concern of “depression.” She describes a history of several hypomanic episodes as well as the current depressive episode, prompting a bipolar II disorder diagnosis. She is naïve to all psychotropics. You plan to initiate a mood-stabilizing agent. What would you include in your initial workup before starting treatment and how would you monitor her as she continues treatment?
Mood stabilizers are employed to treat bipolar spectrum disorders (bipolar I, bipolar II, and cyclothymic disorder) and schizoaffective disorder, bipolar type. Some evidence suggests that mood stabilizers also can be used for treatment-resistant depressive disorders and borderline personality disorder.1 Mood stabilizers include lithium, valproate, carbamazepine, oxcarbazepine, and lamotrigine.2-5
This review focuses on applications and monitoring of mood stabilizers for bipolar I and II disorders. We also will briefly review atypical antipsychotics because they also are used to treat bipolar spectrum disorders (see the September 2013 issue of Current Psychiatry at CurrentPsychiatry.com for a more detailed article on monitoring of antipsychotics).6
There are several well-researched guidelines used to guide clinical practice.2-5 Many guidelines recommend baseline and routine monitoring parameters based on the characteristics of the agent used. However, the International Society for Bipolar Disorders (ISBD) guidelines highlight the importance of monitoring medical comorbidities, which are common among patients with bipolar disorder and can affect pharmacotherapy and clinical outcomes. These recommendations are similar to metabolic monitoring guidelines for antipsychotics.5
Reviews of therapeutic monitoring show that only one-third to one-half of patien
taking a mood stabilizer are appropriately monitored. Poor adherence to guideline recommendations often is observed because of patients’ lack of insight or medication adherence and because psychiatric care generally is segregated from other medical care.7-9
Baseline testing
The ISBD guidelines recommend an initial workup for all patients that includes:
• waist circumference or body mass index (BMI), or both
• blood pressure
• complete blood count (CBC)
• electrolytes
• blood urea nitrogen (BUN) and creatinine
• liver function tests (LFTs)
• fasting glucose
• fasting lipid profile.
In addition, medical history, cigarette smoking status, alcohol intake, and family history of cardiovascular disease, cerebrovascular disease, hypertension, dyslipidemia, and diabetes mellitus should be documented. Rule out pregnancy in women of childbearing potential.2 The Figure describes monitoring parameters based on selected agent.
Agent-specific monitoring
Lithium. Patients beginning lithium therapy should undergo thyroid function testing and, for patients age >40, ECG monitoring. Educate patients about potential side effects of lithium, signs and symptoms of lithium toxicity, and the importance of avoiding dehydration. Adding or changing certain medications could elevate the serum lithium level (eg, diuretics, angiotensin-converting enzyme [ACE]-inhibitors, nonsteroidal anti-inflammatory drugs [NSAIDs], COX-2 inhibitors).
Lithium can cause weight gain and adverse effects in several organ systems, including:
• gastrointestinal (GI) (nausea, vomiting, abdominal pain, loss of appetite, diarrhea)
• renal (nephrogenic diabetes insipidus, tubulointerstitial renal disease)
• neurologic (tremors, cognitive dulling, raised intracranial pressure)
• endocrine (thyroid and parathyroid dysfunction)
• cardiac (benign electrocardiographic changes, conduction abnormalities)
• dermatologic (acne, psoriasis, hair loss)
• hematologic (benign leukocytosis).
Lithium has a narrow therapeutic index (0.5 to 1.2 mEq/L), which means that small changes in the serum level can result in therapeutic inefficacy or toxicity. Lithium toxicity can cause irreversible organ damage or death. Serum lithium levels, symptomatic response, emergence and evolution of adverse drug reactions (ADRs), and the recognition of patient risk factors for toxicity can help guide dosing. From a safety monitoring viewpoint, lithium toxicity, renal and endocrine adverse effects, and potential drug interactions are foremost concerns.
Lithium usually is started at a low, divided dosages to minimize side effects, and titrated according to response. Check lithium levels before and after each dose increase. Serum levels reach steady state 5 days after dosage adjustment, but might need to be checked sooner if a rapid increase is necessary, such as when treating acute mania, or if you suspect toxicity.
If the patient has renal insufficiency, it may take longer for the lithium to reach steady state; therefore, delaying a blood level beyond 5 days may be necessary to gauge a true steady state. Also, anytime a medication that interferes with lithium renal elimination, such as diuretics, ACE inhibitors, NSAIDs, COX-2 inhibitors, is added or the dosage is changed, a new lithium level will need to be obtained to reassess the level in 5 days, assuming adequate renal function. In general, renal function and thyroid function should be evaluated once or twice during the first 6 months of lithium treatment.
Subsequently, renal and thyroid function can be checked every 6 months to 1 year in stable patients or when clinically indicated. Check a patient’s weight after 6 months of therapy, then at least annually.2