September 2010

Personalized Medicine
Even before genomic advances are ready for clinical use, "low-tech" aspects of personalized medicine can enhance psychiatric treatment.

Treating Patients with Schizophrenia: The Importance of Adherence
Antipsychotics can't work if patients don't take them. Nonadherance is a major cause of relapse among patients with schizophrenia.

Valproic Acid and Congenital Malformation
Exposure to valproic acid in the first trimester of pregnancy increases the risk of many congenital malformations in newborns.

In Brief
Bone Mineral Density Is Lower in Depressed than Nondepressed People; Few Adolescents Who Die by Suicide Have Had Recent Exposure to SSRIs

IV Ketamine Infusion Decreases Suicidal Ideation
In a study of treatment-resistant inpatients with major depressive disorder, a single IV infusion of ketamine rapidly decreased suicidal ideation.

SSRIs May Increase the Risk of Cataracts
In a pharmacoepidemiologic study, the use of selective serotonin reuptake inhibitor (SSRI) antidepressants was associated with a greater risk of cataracts among elderly patients.

Treating Patients with Schizophrenia: The Importance of Adherence

September 2010

Patients experiencing their first episode of schizophrenia have an 81.9% chance of relapse within 5 years.1 Conversely, only 13.7% of them experience a sustained recovery lasting 2 years or longer. The greatest predictor of relapse is medication nonadherence.

We recently described the high rate of treatment nonadherence among patients with schizophrenia in the US Veterans Affairs health care system (BTP 2010;33:28).2 Even patients receiving a long-acting injectable antipsychotic often did not return for ongoing treatment. Approximately 40% of first-episode patients are nonadherent and up to 60% have intermittent periods during which they do not comply fully with prescribed treatment.

Patients who stop maintenance antipsychotic medication for schizophrenia have a relapse rate approximately five times greater than those who continue to take these medicines.1 A medication gap as short as 10 days can double the risk of rehospitalization for schizophrenia.3 And as the length of time without an antipsychotic increases, the patient's risk of rehospitalization rises almost linearly. Still worse, nonadherence appears to increase the risk of suicide.

In first-episode schizophrenia patients, factors that predict nonadherence are lack of insight, negative attitudes towards medication, substance misuse, severe positive symptoms, parkinsonism, and executive dysfunction. In multi-episode patients, low income also contributes to nonadherence.2

To address this critical issue, Dr John Kane recommends measurement-based care—using quantitative measurements of symptom severity at baseline and throughout treatment—to increase adherence to a medication regimen and, presumably, improve outcome.3 In this approach, rating scales can provide target goals for treatment and evaluate progress made in achieving those goals. Treatment response after 2 weeks of a medication is a valuable predictor of how the patient will ultimately respond. Lack of response suggests the need to try a different treatment or, at a minimum, increase the dose of the original medicine. A 2003 meta-analysis suggested that the rate of relapse with second-generation antipsychotics is significantly lower than the rate of relapse with first-generation agents.4

Information technology may help to improve adherence rates. Home teleconferencing and text messaging, for example, can provide opportunities for patients and families to report early warning symptoms and signs of psychotic relapse. Kane also mentions a Medication Interest Model, which provides a framework for discussing treatments with patients and helping them achieve better adherence. Patients should come to appreciate that medicine makes them feel better and more able to achieve their goals. The clinician must take into account the medicine's cost to the patient and the cost-benefit ratio for the individual and family. It is also important to assess the drug's meaning for the patient and whether a perceived stigma associated with taking antipsychotics is contributing to nonadherence. Ultimately, the goal is to have a patient invested in taking the medicine to improve his or her treatment outcome.

Current medications for the treatment of schizophrenia are far from perfect. They don't help all patients, and they seldom alleviate all symptoms. And each drug carries many potential side effects. Nevertheless, most patients with schizophrenia function better and lead better quality lives when they take medicine than when they do not. Helping them to continue on a medication regimen remains an ongoing challenge.

1Robinson D: First-episode schizophrenia. CNS Spectr 2010;15(Suppl 6):4–7.

2Mohamed S, Rosenheck R, Harpaz-Rotem I, Leslie D, Sernyak MJ: Duration of pharmacotherapy with long-acting injectable risperidone in the treatment of schizophrenia. Psychiatr Q 2009;80:241–249.

3Kane JM: Maintenance strategies in schizophrenia. CNS Spectr 2010;15(Suppl 6):12–14.

4Leucht S, Barnes TR, Kissling W, Engel RR, Correll C, Kane JM: Relapse prevention in schizophrenia with new-generation antipsychotics: A systematic review and exploratory meta-analysis of randomized, controlled trials. Am J Psychiatry 2003;160:1209–1222.