Improving Treatment Adherence in Patients With Schizophrenia

John M. Kane, MD

Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, and the Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY

In any area of medicine and regardless of the diagnosis, ensuring that the average patient maintains medication adherence for an extended period of time is a tremendous challenge. Among people taking antipsychotics, antidepressants, or nonpsychiatric drugs, those taking antipsychotics—many of whom have schizophrenia—were found to have the lowest adherence rate.1 Nonadherence to a prescribed medication regimen is one of the biggest obstacles to patients achieving and maintaining remission in schizophrenia treatment. Both patients and clinicians tend to underestimate the degree to which patients are actually missing doses of their medication.2–4 Partial adherence in patients with schizophrenia may begin early in treatment and increase over time. Some patients begin to have difficulty with adherence within 7 to 10 days of discharge from the hospital, and, after 2 years, 75% of patients may be only partially adherent with their medication regimen.5

Risk Factors for Partial Adherence and Nonadherence

Patients with schizophrenia have difficulty taking medication as prescribed for a number of reasons (AV 1AV 1).6 People with schizophrenia often have poor insight into or acceptance of their condition and/or may not believe in the benefits of medication7; cognitive dysfunction can affect decision making. The treatment regimen may be complicated, involving several medications with differing instructions for administration. Comorbidities, particularly substance use disorders,8 may also interfere with medication adherence. Individuals with schizophrenia may have poor social support networks, with no one regularly available to help them take medication correctly. Unpleasant side effects may compel some patients to be partially adherent or nonadherent.

Unfortunately, antipsychotics are often not successful in alleviating all of the signs and symptoms of schizophrenia, such that, while the positive symptoms may be reduced or eliminated, many of the negative symptoms and cognitive deficits remain. This partial symptom control may mean that patients mistakenly believe that the medication is not helping, although it has helped in some areas. Patients may feel demoralized and depressed by the persistent presence of some symptoms, and the negative symptoms themselves may contribute to a lack of motivation to take medicine. Sometimes patients are not sufficiently educated about why, how, and when to take antipsychotic medication. Follow-up by the treating physician may also be inadequate; some individuals are discharged from the inpatient setting and never connect with an outpatient clinic. Patients may miss appointments due to lack of a strong relationship with the health care provider, lack of payment ability, or lack of transportation. The cost of medications may also be a factor in poor adherence or nonadherence.

Consequences of Nonadherence

The consequences of nonadherence and partial adherence can be severe and include relapse and rehospitalization. Morken et al9 found that 69% of patients with poor adherence (≥1 week without medication in 2 years) relapsed compared with 18% of those with good adherence.

Many clinicians may believe that, if a patient misses a dose here and there, the overall treatment effectiveness will remain stable. However, an assessment10 comparing prescription refill data for over 4,000 patients showed that gaps in medication refills as short as 1 to 10 days were associated with an increased risk of rehospitalization (AV 2AV 2). Because the rate of rehospitalization increased linearly as interruptions in taking medication became longer, it appears that patients significantly increased their risk of relapse within a relatively short time after discontinuing their medication.

Partial adherence and nonadherence have implications beyond relapse and rehospitalization. A study11 of atypical antipsychotic discontinuation among patients with schizophrenia found that a 30-day gap in treatment was associated with a relative risk for suicide attempts approximately 4 times higher than when treatment was not interrupted.

Assessing and Improving Adherence

Reliable methods of measuring adherence exist, such as checking blood levels or physiologic markers or using electronic medication monitors, but these methods are expensive, time consuming, and invasive.12 Unfortunately, simply asking patients about their treatment adherence is unreliable. However, asking patients to describe problems they are having or expect to have with taking medication regularly may be more effective than asking a yes-or-no question about adherence.13 Also, discussions with family members about adherence can help ascertain difficulties. When available, a medication tracking system such as a statewide database of prescription refill data should be used.

Strategies for improving medication adherence include identifying patients’ risk factors for poor adherence, assessing their cognitive functioning, discussing their attitudes and beliefs about the illness and about taking medication, implementing psychoeducation for patients and their families, and, if possible, getting patients into support groups or peer-to-peer counseling. Cost and access issues should be addressed. Medication regimens should be as simple as possible without sacrificing efficacy, and patients should be involved in decision-making and treatment-strategy development, which may help foster a commitment to taking the medication. The use of atypical antipsychotic agents rather than older agents, perhaps in long-acting depot formulations, may improve adherence in some patients.

Second-generation antipsychotics vs first-generation antipsychotics. Second-generation or atypical antipsychotics have increasingly replaced first-generation antipsychotics in the treatment of schizophrenia. In comparing the 2 classes, a meta-analysis by Leucht et al14 analyzed the results of randomized, controlled studies and found that, overall, the second-generation drugs were associated with a 35% relative reduction in relapse rates compared with the older drugs. However, whether the reduced relapse rates were due to improved adherence or some other factor was unclear. Data15–17 suggesting improved adherence rates for atypical antipsychotics exist, but this issue requires further investigation. Even patients who take atypical antipsychotics may need additional interventions to improve adherence.

Long-acting medications could help improve adherence in some patients. Unfortunately, no transdermal medications or very long-acting oral medications are currently available for treating schizophrenia, so the most viable strategy is the use of long-acting depot, or injectable, formulations.

Long-acting depot antipsychotics. Long-acting depot antipsychotics not only provide a convenient dosing regimen so that the patient does not have to remember to take pills every day, but also minimize therapy disruptions by ensuring medication delivery in a reliable way. The blood drug level is predictable and stable, so clinicians can better control the amount of medication in the patient’s system than with oral formulations. Another advantage of depot agents is that, if an injection appointment is missed, the clinician has an immediate awareness of nonadherence and can call the patient's family or conduct a home visit. In contrast, when patients taking oral medications are missing doses, the doctor may not be aware of the adherence issue—the patient may not report it or may deny it. Because the injectable formulation will remain in the patient's system a little longer than an oral medication will after a dose is missed, the clinician has time to resolve the situation before the risk of relapse increases significantly.


The benefits of long-acting injectable medications may take time to become apparent. A 2-year study18 comparing relapse rates for the oral and injectable formulations of a typical antipsychotic found little difference during the first year. In the second year, the injectable formulation demonstrated a superior decrease in relapse rates than the oral formulation. A prospective study19 with an average follow-up rate of 3.6 years compared rates of rehospitalization among patients with schizophrenia taking either an oral or depot first- or second-generation antipsychotic. The depot drug was associated with less rehospitalization during follow-up than the oral antipsychotics.

Many clinicians may be reluctant to recommend long-acting injectable drugs because they think the patient would decline, but it is often the doctor’s reluctance that leads to the underuse of the long-acting injectable agents rather than the patient’s refusal or resistance. A discussion about the potential advantages of long-acting depot medications may convince many patients to agree to try them. In fact, many patients prefer long-acting injectable medications once they have had a chance to experience them (AV 3AV 3).20–26 Discussion about the benefits of adherence is still necessary, however, as patients must be present to receive injections.27

For Clinical Use


  • Be aware of the high probability of nonadherence among your patients with schizophrenia
  • With each patient, identify risk factors for nonadherence, discuss attitudes and beliefs about the illness and its treatment, and implement psychoeducation for the patient and the family or caregiver
  • If available, use prescription refill databases to help monitor patient adherence to medication
  • Use long-acting injectable antipsychotics when possible to improve patients’ adherence


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