Patients and physicians

A total of 42 patients participated in the study—25 patients with MDD and 17 with schizophrenia (Table 1). More than half of the patients with MDD were female (64%) and more than half of the patients with schizophrenia were male (65%). The most common currently prescribed AAPs in patients with MDD were quetiapine and aripiprazole (both 24%) and for patients with schizophrenia, risperidone and olanzapine (both 24%). These AAPs were also the most commonly prescribed to each of the two patient groups within the last year. Of patients with MDD, 44% were diagnosed within the last 10 years while 35% of patients with schizophrenia were diagnosed within that time frame. Of patients with MDD, 48% reported living with a spouse or partner while only 4% reported living with roommates who were not family members. Patients with schizophrenia more often reported living with non-family roommates (29%) than living with a spouse or partner (24%).

Table 1 Patient characteristics at screening Full size table

Four psychiatrists participated in the study; all were male and they had an average of 21.5 years of experience in practice. In total during the last year, the psychiatrists treated approximately 600 patients with MDD (35% of whom used AAPs) and approximately 300 patients with schizophrenia (57% of whom used AAPs). All of the psychiatrists regularly prescribed quetiapine, aripiprazole, risperidone, olanzapine, lurasidone, and ziprasidone; 75% of them regularly prescribed clozapine and paliperidone; and 50.0% regularly prescribed asenapine.

Patient results

During the MDD group discussions and the schizophrenia interviews, exhaustive lists of TEAEs were developed. The first step was to gather a list of AEs from the patients via spontaneous elicitation, followed by queries to the patients from a target listing of TEAEs. Specific TEAEs reported by more than half of patients overall (across both patient types) included: weight gain (76%), cognitive issues including decreased ability to attend, concentrate, remember, or recall (79%), need to sleep/excessive sleep/excessive sleepiness (71%), low energy (67%), EPS (62%), and anxiety (55%) (Tables 2 and 3). The reporting rates of the TEAEs differed between the two groups of patients. For example, patients with MDD were most likely to report cognitive issues as a TEAE (92%) while patients with schizophrenia were most likely to report weight gain as a TEAE (94%). Patients with MDD also commonly reported somnolence (76%), weight gain (64%), low energy (56%), and EPS (52%). Along with weight gain, patients with schizophrenia commonly reported low energy (82%), EPS (77%), somnolence/sedation (71%), and anxiety (65%).

Table 2 Frequency, bother, and most bothersome atypical antipsychotic AEs reported by patients with MDD Full size table

Table 3 Frequency, bother, and most bothersome atypical antipsychotic AEs reported by patients with schizophrenia Full size table

Using the exhaustive list of TEAEs generated in each group or interview as a reference guide, patients reported those that they perceived as bothersome and, of those, further delineated the TEAEs they found to be “most bothersome” through a ranking process. Table 2 lists the frequencies of TEAEs reported by patients with MDD as well as those identified as bothersome and the bothersome TEAEs ranked as the top 3 “most bothersome”. Table 3 lists the frequencies of TEAEs reported by patients with schizophrenia. The table includes the TEAEs identified as bothersome, as well as those ranked in the top 3 “most bothersome.” Specific TEAEs reported as bothersome across the overall patient sample (across both patient groups) included cognitive issues (57%), weight gain and/or increased appetite (55%), low energy (48%), EPS (36%), and need to sleep/excessive sleep/excessive sleepiness (36%). Again, the pattern of results differed between the two patient groups. Patients with MDD were most likely to include cognitive issues, weight gain, and excessive sleepiness as bothersome issues (72, 44, and 36%, respectively). These same three TEAEs were also most likely to be selected as most bothersome by patients with MDD (52, 32, and 28% of patients, respectively) although the TEAE of low energy was also rated as most bothersome 28% of the time. In contrast, patients with schizophrenia were most likely to include weight gain (71%), low energy (71%), and EPS (59%) on the list of bothersome TEAEs, and then to select weight gain, low energy, and anxiety as the most bothersome symptoms (41, 35, and 35%, respectively).

There were other findings that were common across both patient groups. For instance, reduced sexual desire was mentioned as a TEAE by 44% of patients with MDD and by 47.1% of patients with schizophrenia; however, neither group was likely to endorse this TEAE as the most bothersome (8.0% for MDD and 11.8% for schizophrenia).

The burden or impact of TEAEs varied in the patient groups, although some generalities could be made. For example, cognitive issues were reported by both groups of patients although patients with MDD reported a more significant impact, including trouble holding conversations, trouble managing work or school, concern about “losing it” or having permanent memory problems, and having poor self-esteem resulting from “feeling stupid”. Participants in both groups noted concerns about gaining weight: small amounts gained quickly, and large amounts gained over a longer period. Most patients attributed weight gain to AAP use and patients in both groups noted that the weight gain resulted in physical problems, poor body image, and poor self-esteem. Additionally, whereas patients with schizophrenia verbalized that they would likely discontinue their medications because of significant weight gain and the related concern about the impact on existing and future cardiometabolic TEAEs, patients with MDD noted that they would rather live with the TEAEs associated with the medications than with extreme depressive symptoms. Both groups also noted increased fatigue, low energy, and sleepiness, usually immediately following AAP initiation and, especially in the case of patients with schizophrenia, these TEAEs were noted with each administration of medication. The impact of the somnolence/sedation was significant and similar in the two groups and included missing time with family and friends, missing social activities, lack of energy leading to not eating properly, poor self-esteem, and feelings of sedation that interfered with proper functioning. Patients in both groups reported EPS symptoms, including tremors and irregular jerky movements, but only patients in the schizophrenia group reported them as burdensome and impactful. Impact in these patients included the fear of others noticing tremors in public and interference with job duties. Patients in both groups noted change in sexual desire and functioning, and while most patients who reported this experienced decreased sexual desire effect, a few patients experienced increased desire. However, in both cases, most patients did not report an impact.

Physician results

As a group, the physicians also participated in the creation of an exhaustive list of TEAEs. Using the exhaustive list as an index, the physicians reported and then rated or ranked both clinically important and bothersome TEAEs (Table 4). Those considered most clinically important by at least 2 of the 4 psychiatrists were metabolic syndrome (100%), weight gain (50%), neutropenia (75%), hyperglycemia (50%), and QT prolongation (50%). TEAEs considered most bothersome to patients by at least 2 of the 4 psychiatrists were weight gain (100%), reduced sexual desire or performance (50%), EPS (50%), akathisia (50%), and hormonal issues (50%).

Table 4 Atypical antipsychotic AEs reported by physicians as clinically important and/or bothersome Full size table

The two TEAEs discussed most by physicians were weight gain and reduced sexual desire or performance. According to the physicians, weight gain was common and almost immediate, but in contrast to patient opinion, it was not always attributed to medication; rather, it was attributed to poor eating habits that were exacerbated during hospitalization or major depressive episode. The physicians believed that the weight gain created a negative impact that was generally more significant for women, but sometimes created a positive impact for individuals with poor appetite associated with MDD, because it helped achieve healthy body weight. Reduced sexual desire or performance was reportedly mentioned within the first visit following medication change or initiation. The physicians commented that it was not always due to AAP, and it was rare to see an improvement of this TEAE while on medication.

Patient and physician summary

A summary of frequently reported, bothersome, or clinically important AAP TEAEs conveyed by patients and psychiatrists is illustrated in Fig. 1. This figure shows that patients with MDD and schizophrenia used similar terms to describe their TEAEs and the most frequent and bothersome TEAEs reported by patients were mentioned by the psychiatrists as well. One exception was that the terminology and descriptions of some TEAEs differed between patients and clinicians, such as that of akathisia. Instead of using the clinical term, patients described experiences consistent with akathisia, including “very uncomfortable and shaking inside,” “can’t get comfortable,” “needing to move,” “can’t sit still,” “had to fidget,” and “jumping out of my skin.” Many TEAEs that were highly bothersome were also noted as frequently occurring, including weight gain, low energy, somnolence, cognitive issues, and EPS. TEAEs considered highly bothersome by patients and clinically significant by psychiatrists included weight gain and cognitive issues (MDD and schizophrenia) and EPS (schizophrenia), although the results indicate that cognitive issues are more bothersome than physicians think, especially for MDD patients. In contrast, many other TEAEs were considered clinically important by psychiatrists but not by patients, including metabolic syndrome, reduced sexual function, QT prolongation, hormonal changes, akathisia, neutropenia, seizures, and hypotension. It should be noted that some of these TEAEs (e.g., QT prolongation, neutropenia) are not amenable to self-reporting by the patient and therefore, should not necessarily be considered unimportant by the patient. However, although the patients cannot self-report these specific TEAEs, they were discussed as part of the exhaustive list.