Should the Australian Therapeutic Goods Administration recommend rapid dosing of lithium carbonate in acute mania?

To the Editor

The Product Information (PI) for lithium carbonate 250 mg tablets (Lithicarb), published by the Australian Therapeutic Goods Administration (TGA, 2017), contains a suggested dosing regime for the rapid initiation of lithium in patients with acute mania. According to this regime, daily doses of 1500–2000 mg are reached by day 3 of treatment. The document states, ‘a programme has been established aimed at obtaining high serum levels as rapidly as is safely possible’. However, no references are provided to determine the source of this information.

We were surprised by this TGA recommendation because it stands in contrast to many published guidelines for lithium initiation in acute mania, including the recent Royal Australian and New Zealand College of Psychiatrists (RANZCP) clinical guideline for mood disorders (Malhi et al., 2015). Here, in order to reduce the risk of acute lithium toxicity, cautious lithium carbonate initiation (e.g. a starting dose of 500 mg/day) is recommended. This is followed by assessment of lithium blood levels after 5 days of treatment, and further careful titration aims at serum trough levels of 0.8–1.2 mmol/L for full antimanic efficacy.

Of course, the ‘empirical titration’ method results in considerable delays until an antimanic lithium effect can be achieved. In clinical practice, most manic patients are prescribed second-generation antipsychotic medications, in addition to lithium, for acute symptom and behavioural control. However, in order to keep polypharmacy to a minimum, the question whether lithium could be initiated more rapidly remains valid.

Sinaert et al. (2013) recently reviewed 65 studies that reported 38 distinct predictive algorithms to guide rapid lithium dosing in acutely manic patients. Undertaken mostly in the 1980s and 1990s, before second-generation antipsychotics became widely available, these studies examined a wide variety of predictor parameters such as body weight, height, gender or creatinine clearance. However, the authors concluded that none of these approaches had been sufficiently studied to provide a safe alternative to empirical titration and cautioned clinicians on rapid lithium dosing.

Until more reliable methods to predict lithium pharmacokinetics and pharmacodynamics in individual patients are developed, perhaps through genetic investigation or blood biomarker discovery, clinicians will need to consider the rapid lithium dosing recommendations published by the Australian TGA with reservation. Furthermore, the TGA should review their PI in light of current guidelines to reduce the widespread reluctance to prescribe this effective drug, which may in part be due to inconsistent information and advice.