Psychiatrists are increasingly prescribing second-generation antipsychotics for conditions including anxiety, depression, and insomnia, according to an article published in BMC Psychiatry.

Wang J, Jiang F, Yang Y, et al. Off-label use of antipsychotic medications in psychiatric inpatients in China: a national real-world survey. BMC Psychiatry. 2021;21(1):375.

 

But off-label prescriptions can come with risks. How can psychiatrists help prevent harm to patients from off-label medications?

 

Rationale for off-label prescribing

It lets prescribers expose patients to the latest possible treatments, offer alternatives when other treatments have failed, and offer patients access to a drug of interest in a class approved for the indication. And in light of social/institutional pressures, off-label prescribing can yield quick control of a condition.

However, off-label prescribing can increase the risks of adverse effects and may be ineffective. Moreover, inappropriate off-label prescribing can open up physicians to legal consequences.

A lack of clinical trials in psychiatry makes off-label prescriptions an important option. Healthcare professionals have been shown to have some knowledge of the practice based on medical school and residency training. Additionally, peer-reviewed research articles on off-label uses are available for reference.

Shakeel S, Nesar S, Rehman H, et al. Patterns and predictors of off-label drug prescribing in psychiatric practice: A qualitative study. Pharmacy (Basel). 2021;9(4):203.

 

 

Off-label antipsychotics

FDA indications of antipsychotics have grown over the years. For instance, risperidone and aripiprazole were greenlighted to treat behavioural disturbance related to autism spectrum disorders, and several second-generation antipsychotics have FDA indications for the adjunctive treatment of major depressive disorder and for bipolar depression.

Off-label prescribing is likely more common than on-label prescribing for second-generation antipsychotics. According to the BMC Psychiatry article, 60.7% of atypical antipsychotics are prescribed off-label. The following conditions are among those treated with off-label antipsychotics:

• Behavioural/psychological symptoms of dementia

• Anxiety disorders

• Borderline personality disorder

• Obsessive-compulsive disorder

• PTSD

• ADHD

• Depression

• Substance use disorders

• Eating disorders

• Insomnia

Results of a study published in Acta Psychiatrica Scandinavica indicated that, among individuals receiving off-label prescriptions of antipsychotics in a Finnish cohort, 70.1% had been diagnosed with depression and 40.1% had been diagnosed with anxiety.

Pirhonen E, Haapea M, Rautio N, et al. Characteristics and predictors of off-label use of antipsychotics in a general population sample. Acta Psychiatr Scand. 2022;146(3):227–239.

 

Investigators found that individuals who were prescribed off-label antipsychotics tended to be of lower socioeconomic status, had lower levels of education, had higher rates of somatic and psychiatric comorbidities, and exhibited substance use disorder.

But in patients taking antipsychotics for indications such as schizophrenia and bipolar disorder, those taking off-label medications exhibited less comorbidity, higher socioeconomic status, and were more educated.

Risperidone, quetiapine, and olanzapine are the atypical antipsychotics most commonly prescribed off-label.

Maglione M, Maher AR, Hu J, et al. Off-label use of atypical antipsychotics: An update [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2011. (Comparative Effectiveness Reviews, No. 43.) Results.

 

 

Clinical findings

But clinical studies have shown that adverse effects can still result from low doses.

Data from different trials show that even at quetiapine doses of about 100 mg per day, body weight rose after 6 and 12 months of use, in addition to increases in blood pressure, BMI, and blood glucose levels.

Unlike selective serotonin reuptake inhibitors, however, low-dose quetiapine did not predict type 2 diabetes. Its long-term effects need to be further explored.

Because the use of off-label antipsychotic medications requires more research to establish effects, psychiatrists may want to approach the practice gingerly, according to the Acta Psychiatrica Scandinavica authors.

“The potentially harmful effects of even small doses of AP should be acknowledged in clinical practice,” they wrote, “and proper follow-up and monitoring of long-term effects and, for example, metabolic effects, should be done more systematically.”