Use of antipsychotics in Denmark 1997–2018: a nation-wide drug utilisation study with focus on off-label use and associated diagnoses

Abstract

Aims 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. Methods 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. Results 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. Conclusions 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.

Use of chlorprothixene and the risk of diabetes and major adverse cardiovascular events: A nationwide cohort study

“…To our knowledge, this is the first study to investigate the cardiometabolic safety of chlorprothixene in its most predominant role today—as anxiolytic or hypnotic used off‐label and at low doses 6,8 . Only one prior study has investigated the cardiovascular safety of chlorprothixene and found similar rates of MACE with use beyond one year 27 .…”

“…5 Despite the limited indications, chlorprothixene remains a commonly used antipsychotic in Scandinavia and in a number of other countries 6,7 with evidence of substantial off-label use. 8 Unlike most other first-generation antipsychotics, chlorprothixene has high affinity for 5-HT 2C -, H 1 -and M 3receptors (Table 1). 9 Antagonistic action at these receptors is responsible for some of the anxiolytic and hypnotic properties of chlorprothixene but has also been connected to the development of metabolic disturbances (impaired glucose metabolism or dyslipidaemia).…”

Comparison of antipsychotic drug use among Dutch Youth before and after implementation of the Youth Act (2010–2019)

“…For example, short-duration treatment of quetiapine in low dosages (i.e., 25-75 mg) is often used to treat insomnia in girls with diagnoses of anxiety disorder, eating disorder, borderline personality disorder, and depressive disorders [16]. A study on prescribing of antipsychotics in primary care in the UK found that low doses of quetiapine are also often prescribed to females diagnosed with anxiety or depression [17] and a recent Danish study reported increased use of low-dose quetiapine outside its approved indications [18]. It is possible that over the years, an increasing number of adolescent girls face unmet medical needs ending in crisis situations where quetiapine use is required.…”

Reversibility of Antipsychotic-Induced Weight Gain: A Systematic Review and Meta-Analysis

“…As weight gain and potential loss are important to many people, it should be shared that little is known about the reversibility of antipsychotic-induced weight gain. This lack of knowledge could affect the decision, especially when drugs are prescribed as off-label ( 3 ), where the potential benefits are less clear. Some may worry that patients with severe mental illness may reject the medication in fear of substantial and irreversible weight gain, and thereby put themselves at risk of relapse.…”

“…Shared decision making is the cornerstone of modern, evidence-based medicine and requires transparency about risks and benefits associated with any treatment decisions. Second generation antipsychotic medication is the mainstay of treatment of psychotic disorders ( 1 ) and is increasingly prescribed for other indications like bipolar disorder and severe depression and off-label indications such as sleeplessness and anxiety ( 2 , 3 ). Weight gain is a major adverse effect of second-generation antipsychotics, affecting quality of life ( 4 ), personal recovery, and somatic morbidity and is a common reason for antipsychotic discontinuation ( 5 ).…”