Prescribing and monitoring lithium therapy: summary of a safety report from the National Patient Safety Agency

Why read this summary?

Lithium is a commonly prescribed drug for treating bipolar disorder and unipolar (refractory) depression. Over 800 000 prescriptions for lithium salts were dispensed in England in 2008.1

Lithium has a narrow therapeutic range and may be affected by changes in renal function and fluid balance (for example, when a person is dehydrated or pregnant).2 Its tolerability profile also provides challenges for prescribing, as adverse effects such as fine tremor may be confused with the coarse tremor seen in toxicity. Lithium treatment increases the risk of clinical hypothyroidism and renal insufficiency (both acute and chronic). Thus tailoring doses for individual patients, with careful monitoring of lithium concentrations, estimated glomerular filtration rate, and thyroid stimulating hormone, is essential.

Treatment is usually started by a psychiatrist, with longer term care and monitoring by a general practitioner, who can be guided by the relevant quality outcome framework (QOF) target for lithium monitoring in the general practitioner contract. The 2006 guidelines from the National Institute for Health and Clinical Excellence (NICE) set out clear standards for lithium monitoring, including measurement of serum lithium concentrations every three months and assessment of thyroid and renal function every six months.3 These guidelines are more stringent than the current quality outcome framework targets for England.

A quality improvement programme showed that mental health trusts often do not have electronic systems that reliably communicate test results between the laboratory and the clinical team or between primary and secondary care.4 It also showed the shortcomings in the monitoring standards of QOF and NICE and a lack of understanding among patients of side effects and signs of toxicity.4

The National Patient Safety Agency (NPSA) received 567 incident reports between October 2003 and December 2008 relating to poor lithium management, including two cases of severe harm where failures in monitoring led to lithium toxicity and admission to hospital in a critical condition. In addition, litigation data over the past 10 years show two deaths and 12 cases of severe harm, again where system failures in monitoring led to patient harms.

A typical incident report to the NPSA reads: “Emergency admission of patient for lithium toxicity in a critical condition. Unfortunately his lithium levels were out of date. The last level was within the therapeutic range, hence his lithium was re-authorised. Unfortunately, it appeared his outpatient appointments had been subject to cancellations hence his lithium levels were not being regularly monitored. Patient at time of report was being ventilated.”

This summary is based on a patient safety alert issued in December 2009 by the NPSA in collaboration with the Prescribing Observatory for Mental Health and the National Pharmacy Association to improve the safety of lithium therapy, with key actions for staff (www.nrls.npsa.nhs.uk/resources/type/alerts/?entryid45=65426&p=1).5

What can we do?

• The NPSA asked healthcare organisations to review their local systems for ensuring that blood test results are communicated between laboratories and prescribers. The NPSA has also provided practitioners with a standard patient information pack, which includes a patient held record book to track lithium serum concentrations and relevant clinical tests.

• Individual practitioners who are monitoring patients taking lithium should:

  • -Issue repeat prescriptions only when they are satisfied that it is safe to do so, as informed by the serum lithium concentration and the results of biochemical monitoring

  • -Monitor serum lithium concentrations every three months, aiming for therapeutic concentrations (guidance range 0.6-1.0 mmol/l)3 at which side effects can be tolerated with no toxic effects (the box lists side effects of treatment and signs of toxicity). Higher concentrations may be required for younger patients with predominantly manic symptoms6

  • -Monitor older patients carefully for clinical features of toxicity (box), as they can experience toxicity even at the upper end of the guidance range7

  • -Monitor thyroid and renal function every six months and more often if renal function is impaired. If serum urea and creatinine concentrations become raised seek advice from a renal physician and/or psychiatrist as there are trade-offs between risks of renal impairment and unmanaged bipolar disorder

  • -Monitor patients carefully for clinical and biochemical evidence of hypothyroidism. Be especially vigilant for women starting lithium at age 40-59 years, whose risk is much greater than the average risk for men (>20% v 4.5%).8 The clinical symptoms overlap with those of depression so can easily be missed

  • -Ask patients to use the lithium record book and explain its importance. The record book will be the key record for all the health professionals they encounter in different settings, with up to date information on the type and dose of lithium they are taking, side effects they can expect, how these differ from more serious signs of toxicity that they must look out for, and what may cause toxicity (box; record available at www.nrls.npsa.nhs.uk/resources/type/alerts/?entryid45=65426)

  • -Consider the potential for concomitant medication (such as angiotensin converting enzyme inhibitors; thiazides and related diuretics; and non-steroidal anti-inflammatory drugs) to reduce the renal excretion of lithium and precipitate toxicity. Use of concomitant medication that may affect lithium therapy should be accompanied by more frequent monitoring of the serum lithium concentration.

Further details are given in the NICE guidelines3 and see figure⇓.

National Patient Safety Agency’s information booklet for patients taking lithium: front cover plus section 7. The whole booklet is available from www.nrls.npsa.nhs.uk/resources/type/alerts/?entryid45=65426

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What else do we need to know?

In developing the patient safety alert, the NPSA was aware of variation in the prescribing and monitoring of lithium treatment across primary and secondary care, with different approaches to shared care. Health services research to identify cost effective models of care and sharing of good practice would be welcome.

How will we know when practice has become safer?

Healthcare organisations were given until December 2010 to implement the actions in this patient safety alert and are required to report compliance at that point. By 6 October 2010, only a fifth (70) of the 356 organisations required to take action had reported compliance to the Central Alerting Service. The NPSA will continue to monitor incidents reported by staff. The current quality improvement programme of lithium monitoring will continue, with further clinical audits to measure performance against the standards noted above.