What is the next step in managing a 24-year-old female patient with bipolar disorder, currently euthymic, with a recent lithium (lithium) level of 0.5mmol/L, who has been experiencing fatigue, decreased motivation, and difficulty speaking after increasing lithium to 750mg twice daily and reducing Risperidone (risperidone) to 2mg daily?

From the Guidelines

The patient's lithium dose should be temporarily reduced back to the previous level of 450mg BID until new lithium levels are obtained, given the recent onset of fatigue, decreased motivation, and speech difficulties, which could indicate lithium toxicity or a swing toward depression. The patient's bipolar disorder symptoms have improved with the increased lithium dose and reduced Risperidone, with stabilized manic symptoms and psychotic features (visual and auditory hallucinations) 1. However, the new symptoms that have appeared, including fatigue, decreased motivation, and speech difficulties (word stumbling), are concerning and warrant immediate attention. The speech difficulties are particularly concerning as dysarthria can be an early sign of lithium toxicity 1.

Given the potential for lithium toxicity, even at therapeutic levels, and the recent dosage increase, it is essential to monitor the patient's lithium levels closely and adjust the dose as needed 1. The American Academy of Child and Adolescent Psychiatry recommends regular monitoring of lithium levels, renal and thyroid function, and urinalyses every 3-6 months 1. In this case, given the patient's new symptoms, more frequent monitoring may be necessary.

Additionally, these symptoms could represent a swing toward depression, which is common in bipolar disorder 1. A comprehensive evaluation should be performed to distinguish between medication side effects and emerging depression, with appropriate adjustments to the treatment regimen based on the findings. The patient's Risperidone dose was recently reduced, which may also be contributing to the new symptoms 1.

Some key points to consider in the patient's management include:

• Regular monitoring of lithium levels and adjustment of the dose as needed
• Close monitoring of the patient's symptoms and adjustment of the treatment regimen as needed
• Consideration of the potential for lithium toxicity, even at therapeutic levels
• Comprehensive evaluation to distinguish between medication side effects and emerging depression
• Adjustment of the Risperidone dose as needed to manage the patient's symptoms.

From the Research

Patient's Current Condition

The patient is a 24-year-old female with bipolar disorder, currently experiencing manic episodes with psychotic symptoms. She has been taking lithium and risperidone, with recent adjustments to her medication dosages.

Medication Adjustments

• The patient's lithium dosage was increased to 750mg twice daily from 450mg BID after a lithium level result of 0.5mmol/L was received on 5/4/2025.
• The patient had previously reduced her risperidone dosage to 2mg daily from 4mg daily due to feeling that the higher dose was too much for her.

Current Symptoms

• The patient reports that her symptoms of mania, including flight of ideas, talkativeness, and increased energy, have stabilized.
• She also reports that her visual and auditory hallucinations have improved.
• However, the patient has been experiencing fatigue, decreased motivation, and difficulty speaking over the past 2 days.

Potential Side Effects of Lithium and Risperidone

• The combination of lithium and risperidone can increase the risk of neurotoxicity and nephrotoxicity, as reported in a case study 2.
• Lithium can cause renal adverse effects, including increased urinary frequency, which may be dose-related 3.
• The risk of lithium toxicity can be minimized by monitoring serum lithium levels and adjusting dosages accordingly 4.
• A single daily dose of lithium may be a viable option to reduce side effects and improve patient compliance 3, 5.

Considerations for Future Treatment

• The patient's lithium dosage and serum levels should be closely monitored to minimize the risk of toxicity and adverse effects.
• The patient's risperidone dosage should be adjusted as needed to manage her psychotic symptoms while minimizing potential side effects.
• Alternative treatment options, such as a different mood stabilizer, may be considered if the patient experiences persistent or severe side effects from lithium or risperidone.
• Regular monitoring for signs of lithium-induced nephrogenic diabetes insipidus (Li-NDI) and lithium nephropathy (Li-NP) is essential, and preventive measures such as using a once-daily dosing schedule and targeting the lowest effective serum lithium level should be taken 6.