A 36-year-old woman comes to the office for follow-up of a mood disorder. The patient has a history of several depressive episodes that started in her twenties. Two years ago, she was hospitalized after staying up for several nights without sleeping and claiming that she had special powers to "end global poverty and climate change." Her symptoms responded well to treatment and she has remained on the same drug regimen since then. However, the patient now has new-onset constipation, dry skin, and hair loss. She is also concerned about a weight gain of 2.27 kg (5 lb) over the last 3-4 months despite eating healthy, low-calorie foods. Blood pressure is 110/70 mm Hg and pulse is 55/min. The patient appears tired, but physical examination is otherwise normal. The diagnosis is established and her current condition is attributed to adverse effects from one of her medications. Which of the following is the most likely culprit drug?
Mood stabilizers in bipolar disorder | ||
Indications | Adverse effects | |
Lithium |
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Valproate |
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Carbamazepine |
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Lamotrigine |
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SIADH = syndrome of inappropriate antidiuretic hormone secretion. | ||
This patient's weight gain, hair loss, and mild bradycardia are most likely due to lithium-induced hypothyroidism. Lithium is a mood stabilizer primarily used in the treatment of bipolar disorder. It can cause hypothyroidism by interfering with normal synthesis and release of thyroid hormone. The compensatory increase in TSH release by the pituitary can lead to goiter in some patients. Lithium-induced hypothyroidism is treated with standard levothyroxine (T4) replacement and does not require discontinuation of lithium therapy.
Long-term lithium therapy is also associated with adverse effects on renal function (eg, nephrogenic diabetes insipidus, chronic tubulointerstitial nephropathy), requiring regular monitoring of blood lithium levels and renal function (blood urea nitrogen and creatinine). Lithium use during pregnancy has been associated with Ebstein anomaly of the tricuspid valve, but the absolute risk is small.
(Choices A and D) Carbamazepine and lamotrigine are anticonvulsants that are also used as mood stabilizers in bipolar disorder. Carbamazepine can cause aplastic anemia. Lamotrigine is associated with a risk of rash, including potentially life-threatening Stevens-Johnson syndrome.
(Choice B) Citalopram is a selective serotonin reuptake inhibitor (SSRI) antidepressant. Sexual dysfunction is the most common long-term side effect. SSRIs are not used as monotherapy in bipolar disorder and are not associated with hypothyroidism.
(Choice C) Clozapine, a second-generation antipsychotic indicated for treatment-refractory schizophrenia, is associated with agranulocytosis and requires regular monitoring of the absolute neutrophil count. Although clozapine can cause weight gain and constipation, it is not a first-line treatment for mood disorders and would not explain this patient's other hypothyroid features (eg, dry skin, hair loss, bradycardia).
(Choice F) Risperidone is a second-generation antipsychotic that can cause weight gain and hyperprolactinemia (eg, galactorrhea, amenorrhea). It is not associated with hypothyroidism.
(Choice G) Trazodone is an antidepressant that has significant sedating effects and is most commonly used to treat depression-related insomnia. Other adverse effects include priapism (prolonged painful erection) and anticholinergic effects (eg, dry mouth, constipation).
Educational objective:
Hypothyroidism and nephrogenic diabetes insipidus are the most common adverse effects of long-term lithium therapy. Serum TSH and renal function (blood urea nitrogen and creatinine) should be monitored routinely.