Recognition of Patients Who Would Benefit From LAI Antipsychotic Treatment: How to Assess Adherence

Christoph U. Correll, MD

Recognition and Prevention Program (RAP), The Zucker Hillside Hospital, Glen Oaks; the Department of Psychiatry and Molecular Medicine, Hofstra-North Sh​ore-Long Island Jewish School of Medicine, Hempstead; and the Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, New York

Long-acting injectable (LAI) antipsychotics are effective for certain patients with schizophrenia.1 A major factor in determining a patient’s candidacy for an LAI formulation is the level of past or expected medication adherence. Nonadherence, especially in patients with mental disorders, is a major threat to relapse prevention as well as symptomatic and functional improvement.2 Roughly half of patients with schizophrenia are nonadherent to their medication regimen,3 highlighting the urgency of this issue. Because many patients often exhibit partial adherence (taking their medications occasionally and erratically), adequately assessing patients’ adherence is key to identifying a majority of those who would benefit from LAI treatment.

AV 1. Risk of Hospitalization in Patients With Schizophrenia, by Gap in Antipsychotic-Taking (00:28)

Data from Weiden et al6

Adherence Measurement Issues

Research has shown that patients with schizophrenia have higher nonadherence rates (50%)2 than those with medical conditions, such as diabetes (33%), cardiovascular disease (23%), and cancer (21%).3,4 In schizophrenia studies, however, adherence rates vary due to numerous factors, including treatment duration, treatment setting, utilization of patient or caregiver reports (which generally underestimate nonadherence5), assessment tools used to measure adherence, and the threshold used for defining nonadherence. Even short gaps in medication-taking increase the rate of hospitalization (AV 1).6

Factors Affecting Adherence

To recognize patients who would benefit from an LAI antipsychotic, clinicians should identify factors that influence adherence, including specific characteristics of patients and their illness, medication factors, provider and system characteristics, and patients’ support networks.

Patient characteristics. Adherence can be affected by many patient factors including demographics and socioeconomic status. For example, unemployed patients or low-income patients who lack family support may not have resources to buy medications or transportation to get medications, which leads to nonadherence. Other factors include medication knowledge, illness insight, motivation for medication-taking, beliefs about treatment risks and benefits, perceived need for treatment, past experiences with medication, history of adherence, and self-stigma.7 Being aware of these factors can help clinicians to assess patients’ risk for nonadherence and tailor treatment programs accordingly, for instance, by adding psychoeducation for a patient with poor illness insight. Additionally, clinicians could try to address any barriers to receiving treatment by discussing community programs, such as social services, free clinics, or public transportation, with patients.

Illness characteristics. Patients in an earlier phase of illness who quickly remit are actually at a higher risk for discontinuing medication than those who experience less improvement. They might not yet accept that they have a chronic mental disorder that requires ongoing treatment7 and may believe that the treatment solved the problem and is no longer needed. Although relapse may convince them otherwise, unfortunately, many patients who have had multiple relapses remain chronically nonadherent.

Symptom type and severity play various roles in adherence as well. Patients with negative symptoms might not have the motivation to obtain or take medication; patients with cognitive dysfunction might not remember to take it; and patients who have severe psychotic symptoms may be paranoid about mental health professionals and medications or be too disorganized to take medication regularly. Additionally, patients with comorbid substance abuse and dependence often feel that medications might interfere with their desired drug or alcohol effects.

Medication characteristics. Patients who perceive that the medication is not effective might be more likely to stop taking it than those who feel the medication is helping them.7 Similarly, particularly burdensome side effects that interfere with patients’ functioning can also lead to nonadherence. Psychoeducation, motivational interviewing, and shared decision-making are vital to a patient’s positive outcome. Clinicians must understand which efficacy domains and side effects are most important to patients, and they must explain to patients what to expect from different treatment options.

Delivery system/formulation of the medication can affect adherence. For example, if caregivers report problems with patients “cheeking” pills, clinicians can prescribe dissolvable tablets so that they know that the medication is absorbed once it has been put in the mouth. Alternatively, the LAI formulations offer clinicians the opportunity, when patients have missed an appointment for their injection, to recognize nonadherence immediately and intervene in a timely manner, helping the patient get back on track. Moreover, blood drug levels with LAI antipsychotics do not drop off as abruptly as with oral medications, giving clinicians time to reach out to the patients or family members and get the patient back into treatment. Dosage frequency also affects adherence. For example, once-a-day dosing is easier to remember than two- or three-times-daily dosing. Once-monthly injections are even easier to remember and have the added advantage that patients do not need to hide having to take daily psychotropic medication if they do not have private living space. Moreover, conflict can be reduced with caregivers who may feel compelled to remind or check on the patient regarding medication adherence.

Provider and system characteristics. Patients’ adherence can be severely affected by organizational barriers, such as the complexity of the mental health care system and fragmentation versus continuity of care, physicians’ lack of knowledge of LAI formulations and their hesitance to discuss this treatment option and prescribe them, and drug administration issues, such as requiring trained team members to give the injections as well as storing the medications.7 Further, the availability of programs for patients, including psychoeducation, peer counseling, and adherence-training might influence adherence.8

Clinicians who work to ensure a seamless transition from acute to maintenance treatment and who foster a therapeutic alliance with patients to build a trusting and shared decision-making relationship lay groundwork for patients to feel more comfortable discussing issues that may affect adherence. This way, clinicians are more likely to find out about troublesome side effects or other issues that make consistent medication-taking problematic, and they can be in the position to provide advice and develop a viable treatment plan with the patients and people close to them.

Family and caregiver characteristics. Several components involving patients’ support systems should also be considered.7 Appropriate family support, when available, is crucial to maintaining adherence. For example, continuous social and family support significantly influenced patients’ medication adherence (P = .04).9 Additionally, families that are more involved in the care of patients are able to help quickly intervene and get the patient back into treatment should nonadherence become an issue.

Because families and caregivers play such an important role in patients’ treatment, clinicians should educate them about the nature of schizophrenia, as well as how to effectively remind patients to take their medication while still allowing patients to maintain a sense of autonomy in managing their own illness.


Methods for Monitoring Adherence and Potential Drawbacks

Adherence can be measured in many ways, many of which can be clustered into the following 4 categories7:

Patient-related methods
patient report, self-assessment questionnaires, diaries, informant report

Physician-observed methods
pill counts, prescription refill data, observed ingestion, clinical response or side effects

Physiologic methods
serum drug levels, biomarkers, hair analysis

Electronic methods
electronic pill trays, MEMS (such as on bottle caps), ingestible event markers (microchipped pills that transmit data)

All of these adherence measures have potential drawbacks, especially patient or family member reports, which can be quite unreliable; they might forget, hide information, or simply not know. Regarding pill counts, patients can remove pills and throw them away, rather than take them. Even the pharmacy records, MEMS caps, and electronic pill trays are rather undependable because they only signal that the patient picked up the prescription, opened the pill bottle, or took the medication out of a tray, not that the patient actually swallowed the pill.

While biomarkers do have the advantage of being objective rather than subjective measures, they also have drawbacks. Generally, biomarkers provide a cross-sectional, all-or-nothing assessment. Clinicians do not have a clear correlation between drug levels and medication dosage. “White coat compliance” also comes into play here; when patients realize that they will be assessed, they might take a medication just the day before the blood, saliva, or urine test, so that they appear adherent.10 Hair analysis might indicate whether the medication has been taken over the last few months, but this testing method is logistically challenging and impractical.

AV 2. Adherence Rates According to Various Methods Among Outpatients With Schizophrenia (N = 52) (00:29)

Data from Velligan et al10
Adherence = taking ≥80% of the prescribed drug

A study10 of adherence to oral antipsychotics over 12 weeks compared various measurement methods. Patient report and physician impression concluded the highest adherence rates while plasma blood levels found the lowest rate (AV 2).10 Although no method of measuring nonadherence is fully accurate, the use of multiple methods may increase accuracy.5

An ingestible, digital event marker system might be the most reliable method, but this tool is just emerging in psychiatry. It remains unclear if patients who may be paranoid will accept ingesting a medication that emits a signal to a receiver worn by the patient (eg, a patch) when it hits the gastric content. However, a pilot study11 has shown that stable patients with schizophrenia are able to differentiate the concept of this medication ingestion system from a delusion of influence over their body and mind. Nevertheless, more data are needed to replicate these findings.

Identifying Patients Eligible for LAI Use

Patients with poor social support, substance abuse disorders, or a history of florid psychosis and those in the earlier phases of their illness may be at risk for nonadherence.7 Poorly adherent or nonadherent patients are at a higher risk for hospitalization and may benefit from LAI treatment.12,13 For example, even small gaps in adherence of up to 10 days doubles the risk of hospitalization.6 Nonadherence to antipsychotics can also increase the risk for suicide attempts.14 When a patient does not respond to an adequate dosage, experiences relapse, or attempts suicide, clinicians must determine whether the medication is ineffective for that patient or whether the patient is not adherent. Clinicians should address or remove barriers to adherence to the extent possible,5 including giving psychoeducation about medication-taking practices and the effect of nonadherence on illness course and functioning (AV 3).15

AV 3. Assessing Patients for Nonadherence (02:30)

One way to remove some barriers to adherence is by administering an LAI antipsychotic. With this formulation, patients do not need to remember to take a pill every day (sometimes more than once a day), and the therapeutic alliance between the physician and patient is enhanced.12 Patients are also more likely to continue their medication and are less likely to be hospitalized than those taking oral antipsychotics.6,12,16 Additionally, for those patients at risk for suicide, they cannot overdose on a clinician-administered dose of an LAI antipsychotic.


As with medical disorders, nonadherence is common in psychiatric disorders, especially in patients with schizophrenia. Mental health care professionals need to be aware that their patients may not be taking medications as prescribed, regardless of what patients or caregivers/family members report, and that patients may be thinking of discontinuing medication at any point during treatment. Although reliably measuring adherence can be difficult, using a multimodal approach may offset the liabilities of the various information-obtaining techniques to get an accurate assessment of the patient. Assessing patients for nonadherence is a key step to determine their optimal form of treatment and to avoid frequent switching or deterioration. Psychoeducation and adherence interventions are crucial to improving outcomes. The use of LAI antipsychotics, along with psychosocial interventions, can improve nonadherence, thus improving the overall outcomes for patients with schizophrenia.

Clinical Points

  • Recognize that LAIs are a valuable treatment option for some patients with schizophrenia
  • Assess patients’ adherence using multiple methods to identify their eligibility for LAI treatment
  • Acknowledge that psychoeducation and a good therapeutic alliance are important parts of improving adherence and outcomes


LAI=long-acting injectable

MEMS= Medication Event Monitoring System


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