Lithium

Is lithium safe?

Lithium is a medicine you can take safely for decades, but only with regular blood tests and some care with everyday things such as painkillers and dehydration. For bipolar disorder it remains a first-line long-term treatment in NICE guidelines, and it is one of the few psychiatric drugs with trial evidence that it reduces suicide. We score it 51, close to warfarin, another old and effective drug where a small change in blood level can cause harm.

The score reflects safety, not usefulness. A low-ish number here does not mean lithium is a poor choice. For many people its benefits clearly outweigh the risks, and stopping it suddenly carries risks of its own.

Why the blood level matters so much

The US label's boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary is short: lithium toxicity is closely related to blood levels and can occur at doses close to therapeutic ones. The target for maintenance treatment is 0.8 to 1.0 mEq/L (US label), and NICE suggests 0.6 to 0.8 mmol/L for people starting lithium for the first time. Toxicity starts at about 1.5, and some people show signs within the normal range.

Blood level	What it means (US label)
0.8 to 1.2 mEq/L	Target range for an acute manic episode
0.8 to 1.0 mEq/L	Target range for maintenance
1.5 mEq/L or more	Toxic
Above 3 mEq/L	Risk of seizures, coma and permanent brain damage

Lithium is cleared by the kidneys along with sodium. Anything that makes the body hold on to sodium and water, such as sweating, vomiting, diarrhoea, fever or a low-salt diet, also makes it hold on to lithium. NICE advises people to keep drinking fluids after exercise, in hot weather or when ill, and to seek medical advice if they get diarrhoea or vomiting.

Medicines that raise lithium levels

This is where many problems start, because the drugs involved are very common:

• NSAIDs such as ibuprofen, naproxen and diclofenac, including over-the-counterOver-the-counterA medicine you can buy without a prescription, in a pharmacy or shop, with directions on the pack for safe use without a doctor.More in the glossary packs
• ACE inhibitors and ARBs such as lisinopril and losartan
• Diuretics, especially thiazides
• Metronidazole and related antibiotics

The label asks for more frequent blood tests and a dose review whenever one of these is started, stopped or changed. Lithium can also cause serotonin syndromeSerotonin syndromeA reaction caused by too much serotonin in the body, usually from combining medicines that raise it. Symptoms range from shivering to high fever.More in the glossary with antidepressants such as sertraline, triptans, tramadol and fentanyl, and, rarely, a serious encephalopathy with antipsychotics. Tell every prescriber and pharmacist that you take lithium.

Kidneys and thyroid

Long-term lithium affects two organs most. In the kidneys it can reduce the ability to concentrate urine, causing thirst and frequent urination, sometimes to the level of nephrogenic diabetes insipidus. Over years, some people develop chronic kidney disease. The label says kidney function should be checked before and during treatment, and lithium should be avoided when creatinine clearance is below 30 mL/min.

Lithium collects in the thyroid and can slow it down, so hypothyroidism is a recognised effect; occasionally the thyroid becomes overactive instead. The label calls for thyroid tests before starting, at 3 months and every 6 to 12 months; NICE says every 6 months, together with kidney function and calcium, because long-term use can also raise calcium and affect the parathyroid glands. Hypothyroidism is usually treated with thyroid hormone while lithium continues.

The suicide evidence

Bipolar disorder carries a high risk of suicide. A 2013 BMJ meta-analysis of 48 randomised trials with 6,674 participants found lithium was linked to fewer suicides than placebo (odds ratio 0.13) and fewer deaths from any cause (0.38). The authors concluded it is an effective treatment for reducing suicide risk in mood disorders. NICE recommends offering lithium as the first-line long-term medicine for bipolar disorder.

Overdose and toxicity

There is no antidote. Activated charcoal does not bind lithium, and severe poisoning is treated with haemodialysis. Symptoms can be delayed by up to a day because lithium takes time to reach the brain. Early signs include worse tremor, unsteadiness, drowsiness, slurred speech, blurred vision and diarrhoea or vomiting. Get urgent medical help if they appear. US Poison Help is 1-800-222-1222.

Who should be careful

Talk to your doctor or pharmacist before starting or changing any medicine, including over-the-counterOver-the-counterA medicine you can buy without a prescription, in a pharmacy or shop, with directions on the pack for safe use without a doctor.More in the glossary painkillers, if you take lithium. Extra care applies to older adults, people with kidney, heart or thyroid disease, anyone on a low-salt diet or planning a big change in exercise, and anyone pregnant or planning a pregnancy. NICE advises tapering over at least 4 weeks, and preferably up to 3 months, if lithium is stopped, because stopping abruptly raises the risk of relapse.

How we scored it

Dependence (95) and track record (95) are strong: lithium is not addictive and has decades of evidence. Overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (25) is weak because toxic and therapeutic levels are so close, and interactions (30) suffer because common painkillers and blood pressure drugs raise levels. Serious side effects (45) and regulatory warnings (40) reflect the boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary and the kidney and thyroid effects that make regular monitoring essential.