Is the patient experiencing lithium toxicity, given their increased dosage to 750 milligrams (mg) twice daily, resulting in symptoms of lethargy, decreased motivation, and difficulty speaking, despite improved hallucinations and anxiety while taking lithium and previously taking Lurasidone (lurasidone hydrochloride)?

From the Guidelines

The patient should immediately consult with their healthcare provider to adjust their lithium dosage due to potential toxicity or excessive dosing, as evidenced by increased fatigue, decreased motivation, and difficulty speaking, which are concerning side effects that may outweigh the benefits of the current dose. These symptoms emerged after increasing lithium to 750 mg twice daily, suggesting a possible correlation between the dosage increase and the adverse effects. Although the medication has been effective in stabilizing hallucinations and improving anxiety, as noted in the patient's report of stabilized hallucinations and improved anxiety 1, the new side effects indicate that the current dose may be too high. The patient should not stop lithium abruptly but should discuss these symptoms with their psychiatrist and possibly have their lithium blood levels checked to determine the best course of action.

Some key points to consider in this situation include:

• The patient's difficulty speaking, which could be related to lithium, as suggested by the patient themselves, and is a concerning side effect that warrants prompt medical attention.
• The continued feelings of hopelessness, which may indicate that despite symptom improvement, the patient's depression requires additional treatment approaches beyond lithium adjustment.
• The importance of regular monitoring of serum lithium concentrations, as recommended by the American Academy of Sleep Medicine, to prevent lithium toxicity, which can occur at doses close to therapeutic concentrations 1.
• The need for the patient to work closely with their healthcare provider to find a balance between the benefits of lithium in managing their condition and minimizing its adverse effects, considering the very low quality of evidence available for lithium treatment in similar cases 1.

Given the potential risks associated with lithium toxicity, as highlighted by the black box warning and the need for prompt and accurate serum lithium determinations 1, it is crucial for the patient to prioritize their safety and well-being by seeking immediate medical guidance.

From the FDA Drug Label

ADVERSE REACTIONS Lithium toxicity: The likelihood of toxicity increases with increasing serum lithium levels. Diarrhea, vomiting, drowsiness, muscular weakness and lack of coordination may be early signs of lithium toxicity, and can occur at lithium levels below 2 mEq/l. Fine hand tremor, polyuria and mild thirst may occur during initial therapy for the acute manic phase, and may persist throughout treatment. Transient and mild nausea and general discomfort may also appear during the first few days of lithium administration Neuromuscular: Tremor, muscle hyperirritability (fasciculations, twitching, clonic movements of whole limbs), ataxia, choreo-athetotic movements, hyperactive deep tendon reflexes Central Nervous System: Blackout spells, epileptiform seizures, slurred speech, dizziness, vertigo, incontinence of urine or feces, somnolence, psychomotor retardation, restlessness, confusion, stupor, coma, acute dystonia, downbeat nystagmus Miscellaneous: Fatigue, lethargy, transient scotomata, dehydration, weight loss, tendency to sleep

The patient's symptoms of tiredness, less motivation, difficulty speaking, and hopelessness could be related to lithium toxicity or side effects, as the drug label lists similar symptoms such as drowsiness, muscular weakness, slurred speech, somnolence, psychomotor retardation, fatigue, and lethargy 2. It is essential to monitor the patient's serum lithium levels and adjust the dosage accordingly to avoid toxicity. The patient should be cautioned to watch for early symptoms of lithium toxicity and to discontinue the drug and inform the physician should they occur 2.

From the Research

Patient Symptoms and Lithium Dosage

• The patient has been experiencing increased tiredness and decreased motivation since increasing their lithium dosage to 750 mg twice daily about a week ago.
• The patient reports that their hallucinations have stabilized and anxiety has improved, but they feel somewhat hopeless and have difficulty speaking, which they attribute to lithium 3, 4.
• Sleep has been good, except for a period in April when they took Lurasidone due to restlessness.

Potential Side Effects of Lithium

• Lithium can cause a range of side effects, including thyroid disorders, hypercalcaemia, and nephrogenic diabetes insipidus 3.
• The patient's symptoms of tiredness and decreased motivation could be related to lithium's effects on the thyroid gland, as hypothyroidism is a common side effect of lithium treatment 3, 4.
• Difficulty speaking could be a result of lithium's effects on the nervous system, as tremor is a common side effect of lithium 4.

Dosing Schedule and Side Effects

• The patient's twice-daily dosing schedule may be contributing to their side effects, as a twice-daily schedule has been shown to produce higher renal adverse effects compared to a once-daily schedule 5.
• A once-daily dosing schedule may be a viable method to reduce the side effects of lithium and improve patient compliance 5.

Interactions with Other Medications

• The patient's use of Lurasidone in April may have interacted with their lithium treatment, although there is no direct evidence to suggest a significant interaction between these medications 6, 7.
• The patient's lithium treatment may be effective in stabilizing their hallucinations and improving their anxiety, but the side effects and potential interactions with other medications need to be carefully managed 3, 4, 7.