More Than 50% of Antipsychotics Prescribed Off Label

Liam Davenport December 30, 2014

More than half of the prescriptions for antipsychotics in the United Kingdom are prescribed to individuals with no diagnosis of a serious mental illness (SMI), a major study of primary care records has revealed.

Investigators at University College London also found that off-label antipsychotic prescribing is more likely to occur in women, older people, and socially and economically disadvantaged individuals.

“In this study of antipsychotic prescribing in a large primary care database representative of the UK, approximately half of the prescriptions for first-generation and second-generation antipsychotics are issued to people who have no record of SMI…in their clinical notes,” the researchers, led by Louise Marston, PhD, write.

“Furthermore, they are more likely to be prescribed to older people, who may be more sensitive to adverse effects such as movement disorders and cardiometabolic risk,” they add.

The study was published online December 18 in BMJ Open.

Serious Side Effects

International and national guidelines urge caution concerning the use of antipsychotics; for patients who do not have a diagnosis of psychosis, their use is recommended only in a limited number of cases.

The drugs are associated with serious adverse effects, including extrapyramidal symptoms with first-generation antipsychotics and weight gain and lipid/glucose dysregulation with second- generation agents. Moreover, antipsychotics may be linked to increased rates of stroke and all-cause mortality in patients with dementia.

However, the researchers note that the drugs may be prescribed off label, potentially to “augment antidepressants in complex or treatment-resistant cases of obsessive compulsive disorder, anxiety and personality disorders.”

For the study, the team examined routine clinical care and administration data from a UK primary care database, the Health Improvement Network. Specifically, they determined the proportion of individuals prescribed antipsychotics between 2007 and 2011 with a diagnosis of psychosis and bipolar disorder; other diagnoses, including depression, anxiety, and dementia; or none of these diagnoses.

A total of 47,724 individuals were prescribed antipsychotic agents during the study period, including 13,941 who received first-generation drugs and 27,966 who were prescribed second-generation agents. The median length of follow-up was 2.4 years.

Women were significantly more likely to be prescribed antipsychotics than men, at an incidence rate ratio (IRR) of 1.092. Prescribing rates were also significantly higher among older people, at an IRR for those aged more than 80 years vs those aged 40 to 49 years of 2.234, and among those living in the most deprived areas, at an IRR vs those living in the least deprived areas of 3.487.

The proportion of patients prescribed first-generation antipsychotics with an SMI diagnosis, which was defined as schizophrenia, bipolar affective disorder, or other nonorganic psychosis, ranged from 27% for haloperidol (Haldol, Janssen Pharmaceuticals, Inc) to 35% for chlorpromazine (multiple brands). For second-generation antipsychotics, the proportion with an SMI diagnosis ranged from 36% for quetiapine (Seroquel, AstraZeneca Pharmaceuticals LP) to 62% for olanzapine (multiple brands).

Among individuals with no SMI diagnosis, antipsychotics were most often prescribed for anxiety, depression, dementia, and sleep and personality disorders. For example, for haloperidol, the proportion of patients with those diagnoses was 16%, 27%, 31%, 15%, and 3%, respectively. The respective proportions for risperidone (Risperdal, Janssen Pharmaceuticals, Inc) were 14%, 22%, 12%, 11%, and 4%.

Aside from when prescribing antipsychotics for attention-deficit/hyperactivity disorder and dementia, the median doses used tended to be lower and of shorter duration than when used for schizophrenia, for example.

Warnings Ignored?

Discussing the substantial proportion of dementia patients prescribed antipsychotics identified in the study, the researchers note: “Reducing the potential harm associated with antipsychotics in dementia has been emphasised as a priority by organizations such as the Department of Health in England and the US Food and Drug Administration.”

“Our findings suggest that further effort is required to decrease primary care antipsychotic prescriptions in dementia and that assessing time trends in antipsychotic prescribing in this group is an important area for future research.”

Speculating on the possible explanations for the high rate of antipsychotic prescribing to people without a psychotic diagnosis, the team dismisses the notion that it is due to psychotic disorders going unrecorded in the notes, either because of patient preference or to avoid stigma.

“It may be that clinicians and/or mental health professionals quite frequently add antipsychotics to the treatment plan for people with non-psychotic disorders, either for agitation, poor sleep or anxiety or due to their general reputation as tranquilizing medications,” the authors note.

“Since there were no major differences in the median doses and duration of treatment according to the likely indication, these patterns of prescribing warrant some attention in terms of monitoring side effects, particularly weight gain, extra-pyramidal side effects and metabolic impacts such as hyperprolactinaemia, glucose dysregulation and effects on lipid profiles.”