Decompensation in a 51-year-old woman with schizophrenia
Ms. A, age 51, has schizophrenia that for years had been stabilized with haloperidol. She recently became agitated and refuses to take medication. What could be causing these changes?
Given estrogen’s potentially protective effects, clinical trials have explored the role of estrogen as an adjuvant to antipsychotics for treating schizophrenia. Studies have shown that estrogen can improve psychotic symptoms in patients with schizophrenia.19,20 However, because estrogen administration can increase the risk of breast and uterine cancer, researchers are instead investigating selective estrogen receptor modulators (SERMs).14 These medications have mixed agonist and antagonist effects, with different effects on different tissues. Raloxifene is a SERM that acts as an estrogen agonist in some tissues, but an antagonist in uterine and breast tissue, which may minimize potential deleterious adverse effects (Table 221-24). Repeated randomized controlled trials have found promising results for use of raloxifene as an adjunctive treatment in peri- and postmenopausal women with schizophrenia, including those refractory to antipsychotic treatment.13,25-27
TREATMENT Address symptoms
The treatment team takes steps to address Ms. A’s perimenopausal symptoms. For mild to moderate hot flashes, primary interventions are nonpharmacologic.28 Because Ms. A primarily reports her hot flashes at night, she is given lightweight pajamas and moved to the coolest room on the unit. Both bring some relief, and her hot flashes appear to be less distressing. The treatment team decides to consult Endocrinology to further investigate the feasibility of starting raloxifene (Table 3) because of their experience using this medication to manage osteoporosis.
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The authors’ observations
Raloxifene is FDA-approved for treating osteoporosis and preventing invasive breast cancer.29 Because it is an estrogen antagonist in both breast and uterine tissues, raloxifene does not increase the risk of uterine or breast cancer. Large studies have shown rates of cardiovascular events are similar for raloxifene and placebo, and some studies have found that raloxifene treatment is associated with improvement in cardiovascular risk factors, including lower blood pressure, lower low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol.29 Raloxifene does, however, increase risk of venous thromboembolism, including deep vein thrombosis and pulmonary embolism, and fatal stroke.29,30 Overall, the risk remains relatively low, with an absolute risk increase of fatal stroke of 0.7 per 1,000 woman-years (number needed to harm [NNH]: 250) and an absolute risk increase of venous thromboembolic events of 1.88 per 1,000 women-years (NNH: 158).31 However, raloxifene may not be appropriate for patients with independent risk factors for these events. Despite this, a large meta-analysis found a 10% decrease in mortality for patients taking raloxifene compared with those receiving placebo.32 Raloxifene also can cause hot flashes, muscle cramps, and flu-like symptoms.29
Diagnosis of menopause and perimenopause is largely clinical, with hormone testing generally recommended for women age <45 in whom the diagnosis may be unclear.28 Thus, Ms. A’s vasomotor symptoms and absence of a menstrual cycle for at least 2 months were diagnostic of perimenopause; a 12-month cessation in menstrual cycles is required for a diagnosis of menopause.28
OUTCOME Improvement with raloxifene
Because Ms. A is at relatively low risk for a thromboembolism or stroke, the benefit of raloxifene is thought to outweigh the risk, and she is started on raloxifene, 60 mg/d. Over the next 2 weeks, Ms. A becomes increasingly interactive, and is seen sitting at a table talking with other patients on multiple occasions. She spends time looking at fashion magazines, and engages in conversation about fashion with staff and other patients. She participates in group therapy for the first time during this hospital stay and begins to talk about discharge. She occasionally smiles and waves at her treatment team and participates more in the daily interview, although these interactions remain limited and on her terms. She maintains this improvement and is transferred to a psychiatric facility in her home county for ongoing care and discharge planning.
