Nonadherence with prescribed medications is very common among patients with any chronic condition. However, patients with schizophrenia may experience unique challenges, such as cognitive and mood disturbances, comorbid substance use, and other factors that are not typically faced by those without major psychiatric illness. There may also be socioeconomic issues, such as lower income, limited access to providers, and/or homelessness in patients with schizophrenia. Any or all of these factors may interfere with adherence. In my experience, approximately 50% of patients with schizophrenia have adherence issues, and this is consistent with the literature in this area.

Medication adherence is dynamic. A patient may be adherent with therapy for a period of time but later may become nonadherent. Therefore, it is important to ensure that past adherence continues to translate to current adherence. There are several strategies that clinicians can use to assess oral medication adherence, including pill counts and confirming medication refills; however, measuring the 12-hour plasma level of the oral antipsychotic is a useful objective test and can be employed on a periodic basis (eg, every 6 months) in the same manner that we might track serum levels of divalproex or lithium. A recent handbook on the use of plasma antipsychotic levels notes that, in adherent patients, 12-hour trough levels fluctuate less than 30% from their average plasma level on that dose. Fluctuations much greater than this (eg, ≥50% from the mean level) are typically due to nonadherence, absent other causative factors such as new exposure to a cytochrome P450 inducer. When a long-acting injectable version of their medication is available, the use of a long-acting injectable antipsychotic is a very effective approach to oral medication adherence, as a missed appointment equates to nonadherence.

The least effective strategy for adherence monitoring is directly asking the patient, “Are you taking your medication?” The answer to this question will almost always be “yes,” regardless of whether it is accurate. A better approach is to preface the discussion with a nonjudgmental statement explaining that nonadherence is common (eg, “People miss doses, it happens to everybody”) and then asking them to estimate the number of missed doses over the past month. On occasion, a third party, such as a family member, can substantiate adherence information. 

For many patients, nonadherence is a consequence of medication side effects, such as weight gain, cognitive impairment, sedation, and neurological adverse effects (eg, akathisia). Younger patients with first-episode schizophrenia may be particularly sensitive to side effects such as weight gain, cognitive issues, and sedation, as they may be more conscious of their body image and may have been highly functional until recently. The good news is that if side effects are the cause of nonadherence, there are numerous antipsychotic options that may be a better fit for that patient.  

Although the efficacy of psychosocial intervention for nonadherence is relatively limited, family education regarding the importance of consistent adherence is beneficial. In addition, the utilization of available technological innovations (eg, phone apps, text reminders, and pill boxes with alarms) can be helpful.

It is important to realize that clinicians may not be an accurate judge of their patients’ adherence, and they often misinterpret the lack of recent hospitalizations as evidence of routine oral medication adherence. Once nonadherence is identified as a potential issue, clinicians should apply a “full-court press” to facilitate medication adherence in their patients with schizophrenia.