Anti-VEGF Treatment Linked to Increased Risk of Anxiety, Depression

AMD patients receiving vascular endothelial growth factor inhibitors (anti-VEGF) treatment for wet age-related macular degeneration (wAMD) often experience anxiety and depression related to treatment regardless of how many injections they have received.

According to the study on the psychological impact of anti-VEGF treatments on wAMD patients led by Hugo Senra, PhD, a clinical psychologist at the University of Manchester's Division of Pharmacy and Optometry, School of Health Sciences, "depression seemed to be more frequent in patients at early stages of anti-VEGF treatment" for wAMD.

Injections of intraocular anti-VEGF medications are often stressful for patients, primarily due to "anticipatory anxiety and expectations of pain and discomfort." There is extensive documentation about the "relationship between AMD and depression and anxiety," but only a limited number of "low number" studies which have considered the link between the prevalence of depression and anxiety in patients receiving anti-VEGF treatment, according to Senra.

The study involved 300 wAMD patients and 100 carers, and was designed to explore the "patient experience of receiving anti-VEGF treatment for wAMD, with a particular focus on patient sources of anxiety related to anti-VEGF treatment," and gather information about the level of psychological burden of these treatments on patients, by examining the "frequency of clinical levels of anxiety, depression and posttraumatic stress (PTS) among patients attending for treatment of AMD."

Senra stated that the study, due to the limitations of literature on the relationship between wAMD and depression/anxiety, was exploratory in nature, and was particularly interested in depression/anxiety related to specific stages of the anti-VEGF regimen. Patients enrolled in the study were placed into 3 groups based on the number of anti-VEGF injections they had received during their treatment (group 1: ≤ 3 injections, n=21; group 2: 4-12 injections, n=119; group 3: >12 injections, n=160).

Researchers divided patients into 3 subgroups based on best-corrected visual acuity (BCVA) testing and the World Health Organization's (WHO) classifications of visual impairment. Qualitative data on anxiety and depression were assessed using the 14-item, self-reporting Hospital Anxiety and Depression Scale (HADS), qualitative data on PTS symptoms was assessed by the 22-item self-reporting Impact of Events Scale-Revised (IES-R), and patient cognitive status was assessed using the Mini-Mental State Examination (MMSE). The burden of patient caregivers was assessed with the 19-item Burden Assessment Scale (BAS) which is designed to evaluate the burden of caring for persons with physical limitations.

Results determined that 168 out of the 300 patients (56.0%) had felt "some type of anxiety" related to the anti-VEGF treatments. The most common sources of anxiety were fear of going blind due to injections/needle (n=118, 39.3%), fear of the treatment not working/symptoms worsening (n=111, 37.0%), anticipatory anxiety (n=104, 34.6%), and fear of unknown outcomes and AMD progression (n=91, 30.0%). Fear of pain around injection, which Senra and colleagues had originally theorized might be a cause of anxiety in patients, was found to be a less common source of anxiety (n=10, 3.3%), despite the fact that data showed over one-third of patients (n=127) reported injection-related pain (42.3%), and "more than half of patients (53.7%) reported having expected more pain than they really experienced" during treatment. Data showed no significant difference in anxiety levels between the 3 patient groups.

Quantitative data showed that 17.3% (n=52) of total patients had clinical levels of anxiety as diagnosed by HADS-Anxiety scores, and that the number of patients experiencing anxiety was significantly higher in group 1 (n=14, 66.7%) than in groups 2 (n=64, 53.8%) and 3 (n=90, 56.3%).

A similar distinction between groups was found in quantitative data on clinical levels of depression, with patients in group 1 experiencing a greater frequency of clinical levels of depression (n=7, 33.3%) than patients in groups 2 (n=16, 13.4%) and 3 (n=13, 8.1%). Data on patient carers showed that " Most patient carers did not report an experience of burden while being carers of someone with wAMD" suggesting, as Senra and colleagues write, that "patients had no issues with social support" in connection with the disease.

Senra and colleagues suggest that, given the data from their study, physicians should speak to patients about their anxiety, communicate risks to mitigate unfounded patient fears, and be aware of the most common sources of anxiety related to wAMD treatment. In addition, they write, " Physicians should also be aware of the prevalence of undiagnosed anxiety and depression in their AMD patients and be alert to the opportunity to manage this."

The researchers suggested that regular screenings of wAMD patients receiving anti-VEGF with a standardized tool for detecting symptoms of anxiety and depression could help clinicians to better identify and treat such patients. "Development of new intervention tools, at both the patient and clinical level" may, according to Senra, reduce psychological symptoms and "improve the well-being of patients receiving anti-VEGF treatment."

The study was published in the March 2017 issue of the American Journal of Ophthalmology.