Evidence of lithium underuse in bipolar disorder: analysis of lithium and antipsychotic consumption, prediction of future trends, regional disparities and indicators of rational and inappropriate use in Europe

Mental disorders represent a significant global burden. Despite increasing use of medications, there is no evidence that this burden is decreasing. Lithium has been one of the first-line treatments in bipolar disorder for many years. However, lithium prescribing has plateaued, while antipsychotic use increased over the past decades. This study assesses the current situation and historical trends in 11 European countries for lithium and antipsychotic medications, predicts future trends and presents key characteristics for assessing the appropriate or inappropriate use of lithium. Consumption data for lithium (ATC N05AN) and antipsychotics (ATC N05A) were collected from publicly available sources in European countries, spanning from 1997 to 2024. An analysis of past trends in DID (defined daily dose per 1000 population per day) prescriptions for lithium and antipsychotics was performed and predictions were made until 2030, using ARIMA(0,1,0) models. For each country, the lithium treatment coverage for the prevalence of bipolar disorder was calculated, along with the ratio of antipsychotic to lithium use. Identified similarities and differences were compared between countries and between northern and southern European regions to generalise prescribing patterns. Based on these results, the prescribing behaviour of lithium in the analysed countries was classified as good, moderate or poor. Data were available for 11 countries, including Croatia, Denmark, Estonia, Finland, Germany, Iceland, Italy, the Netherlands, Norway, Spain and Sweden. In all countries, lithium consumption plateaued or declined, while antipsychotic use increased. Projections suggest a continuation of observed trends. Treatment coverage was very low, with the highest rate in Sweden (32.6%) and the lowest in Estonia and Croatia (5.3%). Comparably good prescribing behaviour was observed in the Netherlands, Sweden, Denmark and Iceland. Moderate prescribing was observed in Germany, Spain, Finland and Norway, while poor compliance with lithium prescribing was reported in Italy, Croatia and Estonia. Lithium prescribing is influenced by adherence to guidelines, concerns about side effects and practicability, monitoring infrastructure, clinician training and prescribing preferences. However, antipsychotics also come with severe adverse effects, require extensive monitoring and cause higher healthcare costs compared to lithium. Lithium is increasingly being replaced by antipsychotics in the treatment of bipolar disorder, despite a constant recommendation in guidelines. Lithium remains significantly underused in all countries analysed. A clear north-south shift in prescribing behaviour is observed, with a suggested west-east shift. Northern countries show higher lithium consumption and a lower antipsychotic-to-lithium ratio, reflecting greater adherence to guidelines and more rational prescribing. In contrast, southern countries show lower lithium and higher antipsychotic use. Overall, there is little progress in improving prescribing practices. Withholding lithium from eligible patients is both medically and economically irresponsible. To reduce the burden of mental disorders, effective and evidence-based treatment strategies need to be prioritised, which is currently failed.