A 74-year-old woman was admitted to hospital for drowsiness and confusion, Glasgow Coma Scale was 12 of 15. On admission she received lithium, escitalopram, levompromazine, lormetazepam, metformin, repaglinide, lisinopril, irbesartan, furosemide and spironolactone. Three months before admission, lisinopril dosage had been increased and irbesartan added for hypertension. On admission, lithium, diuretics, levomepromazine and escitalopram was withdrawn and risperidone was added, but neurological status deteriorated. Potentially interacting drugs (lisinopril, irbesartan and risperidone) was stopped to accellerate lithium excretion and eliminate neurotoxic symptoms and this led to neurological improvement. The addition of an angiotensin-II receptor antagonist (irbesartan) several weeks before admission may have contributed to lithium intoxication.

A case report of a 60-year-old woman with bipolar affective disorder and hypertension was admitted to hospital with normal renal, liver and thyroid functions. She was administered valproate, lithium, clonazepam and valsartan and experienced an adverse event possibly due to lithium-valsartan interaction.

A 77-year-old woman with manic-depressive psychosis on a regimen of lithium carbonate and diazepam was treated with losartan due to high blood pressure. This led to a rise in lithium plasma levels, possibly due to retention of lithium caused by the angiotensin II antagonist, losartan.  

WHAT IS KNOWN AND OBJECTIVE: Hypothyroidism is a common clinical side effect of lithium treatment, whereas parkinsonism is a very rare adverse event. A number of case series of clinical signs of reversible and permanent parkinsonism due to lithium toxicity have been previously published, but never in association with hypothyroidism. We describe a rare clinical case of concurrent reversible parkinsonism and severe hypothyroidism due to lithium toxicity. CASE SUMMARY: The patient was a 74-year-old woman chronically treated with carbonate lithium (300 mg, twice daily) and clomipramine (75 mg, once daily); she also received valsartan (160 mg) plus hydrochlorothiazide (12.5 mg), once daily. The patient was visited after a 1-week history of progressively worsening and disabling parkinsonism. Laboratory tests showed elevated values of lithium and thyroid stimulating hormone (TSH) serum concentrations as well as reduced circulating thyroid hormone serum concentrations. Lithium treatment was discontinued; treatment with levothyroxine and saline solution i.v. was readily performed, and valsartan plus hydrochlorothiazide were replaced with amlodipine (5 mg, once daily). Within a few days, the patient showed a rapid improvement in overall clinical condition, but complete resolution of neurologic symptoms occurred only after about 5 months. WHAT IS NEW AND CONCLUSION: Lithium toxicity may present with concurrent hypothyroidism and parkinsonism. In the present case, interaction with valsartan and hydrochlorothiazide most likely played an important role. In patients who receive chronic therapy with lithium, prescribers should monitor lithium serum concentration both periodically and immediately at the onset of signs and symptoms, potentially related to lithium toxicity

This case of a 51-year-old woman with a history of bipolar disorder admitted to hospital for a manic relapse, supports the potential risk of concurrent angiotensin-II receptor antagonist and lithium therapy as it led to lithium toxicity. The patients medication was before admission, L-tryptophan, lorazepam, glyburide, estrogens, ciprofloxacin, lithium and valsartan. The serum lithium concentration rose and fluctuated and dose was decreased. A potential drug interaction with valsartan was recognized, and her antihypertensive medication was switched to sustained-release diltiazem to prevent fluctuating lithium concentrations. Her serum lithium concentration dropped and her delirium and ataxia were resolved at this time. Lithium dose was increased to the concentration prior to admission.

OBJECTIVES: Lithium is often the mood stabilizer of choice for the treatment of type I bipolar disorder. However, side effects as well as the narrow therapeutic dosing range often complicate its use. Lithium toxicity can be fatal and its serum level needs to be closely monitored, especially at the time of introduction and titration, or whenever combined with potentially interacting drugs, such as inhibitors of angiotensin-converting enzyme (ACE-I) or angiotensin receptor 1 (AT1 ) blockers. ACE-I and AT1 blockers can increase serum lithium levels, leading to acute lithium toxicity upon their introduction or titration. METHODS: Here, we report a case of lithium toxicity during concomitant treatment with valsartan, an AT1 blocker, in a patient who previously displayed a stable serum lithium level. The patient was observed for a few weeks and the serum lithium concentration was measured regularly. RESULTS: In contrast to previous reports, the toxicity in our patient occurred not upon introduction or titration of lithium or valsartan but after subtle modifications in daily dosing schedule for lithium. Just before the onset of toxicity, lithium had been split into two doses, whereby half of the lithium daily dose was administrated concomitantly with valsartan. We presumed that this combination had led to simultaneous concentration peaks of valsartan and lithium, promoting lithium retention within a sharp time window. CONCLUSIONS: Our observation points to the need for caution not only during the introduction and titration of ACE-I/AT1 blockers in lithium-treated patients, but also whenever the temporal pattern of drug administration is modified