Abstract
Antipsychotics are primarily labelled for the treatment of severe mental illness and have documented clinical utility in certain neurological disorders or palliative care. However, off-label use of antipsychotics is common and increasing, and prior studies on antipsychotic utilisation have not specifically assessed users in neurology, palliative care or general practice. We aimed to explore diagnoses associated with antipsychotic use, treatment patterns and characteristics of users without diagnoses relevant to antipsychotic treatment. Population-based study identifiying all users of antipsychotics in Denmark (pop 5.7 mio.) 1997-2018 in the Danish National Prescription Register (DNPR). Possible indications for antipsychotic therapy were evaluated using in- and outpatient contacts from the DNPR. Users were divided hierarchically into six groups: severe mental disorders (schizophrenia, bipolar-spectrum disorders), chronic mental disorders (dementias, mental retardation, autism), other mental disorders (depression-spectrum, anxiety and personality disorders, etc.), selected neurological diseases, cancer and antipsychotic users without any of these diagnoses. This last group was characterised regarding demographics, antipsychotic use, health care utilisation and likely antipsychotic treatment initiator in 2018. Altogether, 630 307 antipsychotic users were identified, of whom 127 649 had filled prescriptions during 2018. Users without diagnoses relevant to antipsychotic treatment comprised of the largest group (37%), followed by schizophrenia and bipolar-spectrum disorders (34%), other mental disorders (15%), dementia, autism and mental retardation (11%), cancer (2.2%) and neurological diagnoses (2.0%). Of 37 478 incident users in 2018, 39% had no diagnosis relevant to antipsychotic treatment, 7.9% had major depression, 7.7% neurotic/stress-related disorders and 7.5% dementia. Quetiapine was most commonly used, both overall (51%) and among users without diagnoses relevant to antipsychotic treatment (58%). Of 14 474 incident users in 2018 without diagnoses relevant to antipsychotic treatment, treatment was most likely initiated by a general practitioner (65%), with only 17% seeing a psychiatrist during the following year. As many as 18% of patients with adjustment disorders and 14% of those without relevant diagnoses for antipsychotic use, remained on antipsychotic treatment 5 years after their first prescription. Over one-third of antipsychotic users in Denmark did not have psychiatric, neurological or cancer diagnoses as possible indications for antipsychotic therapy. Many antipsychotics are initiated or prescribed in general practice, and a concerningly large subgroup without documented diagnoses relevant for antipsychotics continued to receive them. Rational prescribing, adequate side effect monitoring and further research into reasons for the observed antipsychotic use patterns and their risk-benefit ratio are needed.
Highlights
Antipsychotics are generally labelled for treatment of severe mental disorders, such as schizophrenia, mania and bipolar depression
We identified a total of 19 092 613 antipsychotic prescriptions in the Danish Register of Medicinal Product Statistics (DRMPS) from 1997 to 2018, filled by 630 307 individuals
The main findings of this nation-wide, 22-year antipsychotic utilisation study in 630 307 individuals filling 19 092 613 antipsychotic prescriptions are: (1) off-label antipsychotic use was highly prevalent; (2) most incident users were either diagnosed with non-severe mental illness or had no record of diagnoses relevant to antipsychotic treatment; (3) both overall and among patients without relevant diagnoses for antipsychotic use, quetiapine, used at low doses, was most frequently prescribed; (4) general practitioners most likely initiated antipsychotic treatment in users without relevant diagnoses for antipsychotic use and (5) long-term antipsychotic treatment was common in individuals with dementia, adjustment disorders and those without relevant diagnoses for antipsychotic use
Summary
Antipsychotics are generally labelled for treatment of severe mental disorders, such as schizophrenia, mania and bipolar depression. The use of antipsychotics can be clinically relevant in other psychiatric conditions that do not have a licensed indication, such as dementia, post-traumatic stress disorder or obsessive-compulsive disorder. IP address: 3.92.231.36, on 02 Nov 2021 at 12:29:10, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. Prior drug utilisation studies have found a considerable use of antipsychotics in other psychiatric conditions for which antipsychotics do not have an indication, including dementia, anxiety disorders and insomnia (Marston et al, 2014; Carton et al, 2015; Baandrup and Kruse, 2016). Antipsychotics are used in other medical specialties than psychiatry, e.g. for delirium (Marcantonio, 2017), for psychotic symptoms in epilepsy (Agrawal and Mula, 2019), treatment of headache disorders (Siow et al, 2005; Bendtsen et al, 2012), as antiemetics (Walsh et al, 2017) or in end-of-life care (Bush et al, 2017)
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