Monitoring Treatment and Managing Adherence in Schizophrenia

Stephen R. Marder, MD

Department of Psychiatry and Behavioral Sciences, David Geffen School of Medicine; VA Desert Pacific Mental Illness Research, Education, and Clinical Center; and the Semel Institute, University of California, Los Angeles

Poor treatment adherence is common at every stage of schizophrenia, from patients in their first psychotic episode to patients on maintenance treatment years into the illness. Nonadherence, which occurs in up to 72% of patients with schizophrenia,1 is associated with relapse, rehospitalization, and poor community functioning.2 To limit these negative consequences and optimize patients’ outcomes, clinicians should regularly assess their patients’ adherence, monitor adverse effects, and offer appropriate interventions.

Assessing Adherence

Clinicians often assess adherence by asking patients if they are taking their medications as prescribed; this can lead patients to say “yes” and may result in clinicians’ overestimation of patients’ adherence levels. Instead of asking direct questions, clinicians may use statements that diffuse defensiveness and open a discussion about adherence in a nonjudgmental way. For example, clinicians could say, “I understand that it’s difficult to remember to take medications, particularly every day,” or “It’s difficult to take your medications because it’s a reminder of your illness. How do you deal with that?” These types of statements can begin a dialogue that can help clinicians assess some of the patient’s barriers to taking medication.

AV 1. Barriers to Medication Adherence in Patients with Schizophrenia (00:41)


In addition to developing a therapeutic alliance with patients that facilitates open communication, clinicians should address the following signs of relapse and risk factors for poor adherence (AV 1).

Signs of relapse. When relapsing, patients with schizophrenia will typically experience a gradual decline (over perhaps a month) into a psychotic episode. The early signs often mirror symptoms of the individual’s previous episodes and can include symptoms like suspiciousness, argumentativeness, sleeplessness, or depression. When patients have previously attained remission and then present with worsened symptoms such as these, clinicians should discuss treatment adherence and promptly address any barriers to help to avoid a relapse.

Substance use. Substance abuse in patients with schizophrenia is associated with treatment nonadherence as well as a greater severity of illness, more hospitalizations, more relapses, and more missed appointments than in those who do not abuse substances.1,3 Common substances used by patients with schizophrenia include alcohol, marijuana, cocaine, and nicotine,4 all of which can have negative consequences for patients. For example, using marijuana and cocaine or amphetamines can exacerbate psychotic symptoms,5 alcohol and drug abuse can increase aggressive behavior,6 and smoking can make antipsychotic medication less effective.5 Additionally, an increase in substance use could cause symptom worsening that mimics nonadherence. Therefore, when assessing for nonadherence in patients whose symptoms are worsening, clinicians should also screen for substance use.

Cognitive impairment. Cognitive impairment, which is a key characteristic of schizophrenia, may affect adherence when patients are forgetful or lack insight into their illness. Forgetful patients may agree with the clinician about the importance of adherence, but the daily process of taking medications is difficult for them. Patients with poor insight may not understand why they must take medication, particularly when they feel well. Clinicians can discuss treatment-related attitudes, such as distrust or negative attitudes toward antipsychotics, to help patients understand the importance of taking their medication as prescribed.7

Complex regimens. Patients with schizophrenia often have comorbid psychiatric and medical problems. Therefore, they may have complex treatment regimens, which can complicate and hinder their adherence to treatment. Further, managing medications, especially if patients live alone, can be a challenge. To address this adherence barrier, clinicians can simplify the treatment regimen as much as possible by reducing the number of doses per day (by using extended-release formulations, for example) or reducing the number of different drugs (such as fixed-dose combination pills).8

Monitoring Side Effects

Adverse effects from antipsychotic treatment can be a risk factor for nonadherence, but they can lead to serious medical illnesses as well.9 Patients with schizophrenia tend to die 12 to 15 years earlier than the general population, from conditions like cardiovascular disease and hypertension.10 This difference could be because these illnesses are not detected early enough. Therefore, clinicians must monitor and treat adverse events, including metabolic, neurologic, and other events, before they contribute to nonadherence or serious health conditions.

Metabolic side effects. Clinicians who treat patients with schizophrenia should regularly monitor weight, BMI, waist circumference, and blood pressure, as well as fasting plasma glucose and fasting lipid levels.11 Both diabetes and obesity are more prevalent among individuals with schizophrenia than in the general population.11 When patients’ waist size is ≥35 inches (women) or ≥40 inches (men), their risks for high blood pressure, type II diabetes, dyslipidemia, and metabolic syndrome are increased.9 If patients gain ≥5% of their initial weight at any time during treatment, clinicians may want to consider switching to another antipsychotic agent.11

Fasting plasma glucose and lipid levels, as well as blood pressure should be assessed at baseline, 3 months after the patient starts antipsychotic medication, and then annually, or more frequently for patients at risk for developing diabetes or hypertension.11 Early elevations in triglyceride levels during the first 3 months of treatment can also indicate whether or not a patient is developing insulin resistance.

AV 2. Weight-Loss Intervention Study in Patients with Serious Mental Illness (00:36)

Data from Daumit et al12
Intervention = group and individual weight management counseling and group exercise sessions

An approach to controlling weight gain is lifestyle interventions. Because a sedentary lifestyle and poor diet often exacerbate the metabolic side effects of antipsychotics, patients with schizophrenia will benefit from lifestyle interventions that combine a healthy diet and exercise (AV 2).12,13

If switching medications to control weight gain is ineffective, clinicians can consider adding metformin, an oral antidiabetic drug that helps control glucose levels, in addition to lifestyle interventions. Metformin has been shown to reduce weight gain and other metabolic problems associated with SGAs.14 Patients should be given an explanation for why they need an additional medication to treat side effects, and not all patients will be able to manage an additional oral medication.


Neurologic side effects. In addition to metabolic side effects, neurologic side effects from antipsychotics can also contribute to nonadherence.9 Clinicians should routinely assess patients for akathisia and restlessness, tardive dyskinesia, signs of rigidity and tremor, and unusual arm swing or gait movements.15 When any of these adverse events are noted, clinicians can lower the medication dose, switch to another antipsychotic that is less likely to cause these effects, or use an adjunctive medication.

AV 3. Monitoring Side Effects and Addressing Adherence in a Patient with Schizophrenia (03:06)


Other side effects. Other adverse events that can hinder treatment adherence include sexual side effects, lactation caused by prolactin elevations, and sedation, which could contribute to weight gain or poor functioning. Fostering a good therapeutic alliance and creating an atmosphere where patients can freely discuss any problems will help clinicians intervene before patients stop taking their medication (AV 3). Additionally, patients experiencing sexual side effects often do not spontaneously report negative effects and may need to be specifically asked about libido and orgasm to elicit accurate responses.

Offering Appropriate Interventions to Improve Adherence

Once clinicians know what is contributing to nonadherence, they can focus on interventions. For patients with substance use problems, the focus will be on support to help them quit. For patients experiencing adverse effects, the intervention may include a dose change, an additional medication, or a switch to another antipsychotic. Other interventions to improve adherence include long-acting injectable antipsychotics, patient and family education, and psychotherapy.

Long-acting injectables. In some cases, the clinician may realize that a patient cannot reliably take oral medication; long-acting injectable antipsychotics may be a solution for these patients.16 Depot antipsychotics have been associated with a lower risk of rehospitalization than their counterpart oral formulations,17 and they have significantly reduced relapse rates (P = .0009), although data on adherence were limited.18 Long-acting injectables are a viable option for first-episode patients as well as for patients with adherence problems on oral medication.2

Patient and family education. Patient and family education has proven helpful for improving medication adherence.19 Patients need to understand the benefits and possible side effects of their treatment along with the risk of relapse if they discontinue their medication. Education and problem-solving skills can help family members be effective, understanding caregivers, which can help them provide support and encourage compliance at home. Families can be directed to the NAMI website for education, training, and support programs.

Psychosocial interventions. In addition to education, psychosocial interventions may improve adherence. For example, studies20 indicate that social skills training can improve medication management behaviors and cognitive-behavioral therapies can improve patients’ coping strategies, resulting in enhanced treatment adherence.21 Even simple interventions that use watches or alarms can remind patients exactly when to take their medication.


Patients with schizophrenia will likely be nonadherent at some point during their treatment, especially those with poor insight, cognitive impairment, or complex treatment regimens. To ascertain the factors contributing to nonadherence, clinicians should regularly assess patients’ symptoms, substance use, and treatment side effects. Because adverse effects are a common cause of patients discontinuing their medication, clinicians must monitor metabolic, neurologic, and other side effects throughout treatment. When patients experience side effects that hinder their adherence, clinicians can consider lowering the dose, switching to an agent with a more favorable side effect profile, implementing lifestyle interventions, or augmenting the current medication with an agent to counteract a particular side effect. Other interventions to improve adherence include using long-acting injectable antipsychotics, educating patients and their families, and implementing psychotherapy. Improving adherence requires nonjudgmental communication and diligent monitoring to help patients with schizophrenia achieve and maintain remission.

Clinical Points

  • Regularly assess patients’ treatment adherence by diffusing patients’ defensiveness and opening a dialogue in a nonjudgmental way
  • Screen patients for risk factors that can affect their treatment adherence, including substance use, cognitive impairment, and antipsychotic-induced side effects
  • Regularly monitor metabolic risk factors by tracking patients’ weight, BMI, waist circumference, fasting plasma glucose, and fasting lipids
  • Provide interventions to improve adherence, such as adjusting medications as necessary, implementing lifestyle changes, starting long-acting injectable antipsychotic treatment, educating patients and their families, and recommending psychotherapy

Drug Names

metformin (Glucophage, Glumetza, and others)


APA = American Psychiatric Association
BMI = body mass index
NAMI = National Alliance on Mental Illness
SGA = second-generation antipsychotic

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