Table 2.

Areas of controversy surrounding long-acting injectable antipsychotic medications

LAI perception		Controversies affected
Negative	Positive	Benefits of LAIs	Target population	When to initiate	HCP training	Patient interaction
LAIs result in injection-site reactions [16]	SGA-LAIs have improved formulations over FGA-LAIs, with fewer injection-site reactions [16]	X			X	X
LAIs have intolerable side effects [16, 39, 42]	AE frequency and AE-related discontinuations are the same or lower for LAIs than for OAs [22, 42, 44], and mortality is lower for LAIs than for OAs [51, 52]	X			X	X
Patients on an LAI experience breakthrough psychosis [48, 49]	The rate of breakthrough psychosis is similar among LAIs and OAs [49], and the benefit-risk ratio supports use of LAIs [27]; when breakthrough occurs, it is clear whether or not medication was taken	X		X	X	X
Patients on LAIs can also become nonadherent to LAI use [35]	Adherence rates are higher and discontinuation rates are lower for LAIs than for OAs [22, 32, 42], nonadherent patients can be immediately identified if a dosing appointment is missed [76], and relapses are delayed because of longer half-lives of LAIs [36]	X	X		X
Many HCPs lack experience/knowledge of LAIs; therefore, target population should remain limited [10]	HCPs can be educated [78]; HCPs with LAI prescribing experience are supportive of LAI use [60]		X		X
Dosing of an LAI is difficult to adjust, and it would be dangerous to treat patients without knowing if the most appropriate medication has been selected [59]	Per drug prescribing information and recommendations, a short trial with an OA or short-duration LAI should occur to assess tolerability and efficacy, followed by a transition to the LAI formulation of the same drug [60]		X	X	X
Providers do not have the proper resources or background to set up the complicated infrastructure needed to administer LAIs [14, 54, 77]	The long-term nature of the disease is worthy of training professionals and setting up a coordinated care team to improve outcomes, including a decrease in hospitalizations and mortality [16, 22, 37, 51]; a coordinated care team can be organized by collaborating with experts and specialty clinics [62, 63]		X	X	X
Suggesting an LAI early on in treatment will impede patient autonomy [87]	Early treatment success correlates with patient acceptance of treatment and improved adherence [3, 18]		X	X	X
Initial recommendation of an LAI can negatively impact the patient’s level of trust with the physician [70]	Surveys have found that patients actually felt better about their relationships with providers while taking an LAI because of more interactions at checkups and injection administration [65]; shared care decisions and collaborative care can be developed early on to keep the patient involved throughout the long-term treatment journey [62, 64], and earlier use of LAIs is associated with better outcomes than later initiation [66–68]		X	X	X	X
LAI treatment can be complicated, and it is best to wait until after multiple relapses to see whether it should be initiated [92]	Relapse has a significant negative impact on the patient; LAIs can reduce the number of relapses/hospitalizations, and an effective treatment should be initiated as soon as possible [45, 46, 93]	X	X	X	X	X
There are few SGA-LAI options, and it is difficult to coordinate managing LAI-related side effects [16, 39, 42, 69]	HCPs can be educated on the benefits of SGA vs FGA-LAIs regarding increased tolerability and how there are several SGA options [22, 28, 42, 94]	X			X	X
Patients are adherent to OAs, and there is no reason to use an LAI since the long-acting medication is only for the chronically ill [14, 23]	Adherence to OAs is overestimated, and adherence is higher/discontinuation lower with LAIs than with OAs; missed doses of an LAI can be identified immediately [32]	X	X		X	X
Patients do not want to take an LAI/injectable medication [69, 71]	There are no data to support that patients are opposed to LAIs; patients who were encouraged to take an LAI by their physician demonstrated improvements [69, 78]				X	X
Patients do not feel that they are sick/need treatment or are unaware of how the disease will impact their daily lives [12, 13]	Educational material and involvement of family members can promote a shared decision-making process and address FAQs [62, 79]		X			X
There is patient anxiety over side effects of LAIs, and the patient should not be placed under additional stress by suggesting this treatment option [12, 13, 18]	Planned discussion and educational material can provide insight into the improved tolerability (and efficacy) of LAIs over OAs; the positive perceptions of patients currently taking LAIs (e.g., mild side effects, relapse prevention, less anxiety) should be shared [18, 65]	X	X			X
Cognitive/mental state of patients is impaired, and any effort to support LAI use will appear like coercion [81]	Providing educational material and a recommendation does not involve a threat and is not coercion [88]		X		X	X
Use of a financial incentive to take an LAI is immoral and can also negatively affect the clinician–patient relationship [87]	Healthcare incentives exist for other changed behavior to promote good health (e.g., quitting smoking, exercising more); therefore, recommending an effective and safe treatment, such as an LAI, should be considered no different and can improve the clinician–patient relationship [86]	X			X	X
Physicians/payers cannot afford to provide financial incentives to patients	Financial incentives may affect costs related to patients visiting clinics for medication and checkups because of use of LAIs; however, the financial incentive itself does not appear to affect healthcare cost [86], and LAIs are cost-effective because they reduce hospitalizations costs vs OAs [14, 37]				X	X

AE adverse event, FAQs frequently asked questions, FGA first-generation antipsychotic, HCP healthcare provider, LAI long-acting injectable, OA oral antipsychotic, SGA second-generation antipsychotic