Atypical Antipsychotics vs. Traditional Medications

According to the National Institute of Mental Health (NIMH) in May 2014, results of a study published in JAMA showed that newer antipsychotic drugs like paliperidone (Invega) may not be more effective than traditional antipsychotics (e.g., haloperidol [Haldol]) in treating adults with schizophrenia. The NIMH reports that these findings are consistent with previous studies.

People with schizophrenia respond differently to medication and often have difficulty adhering to treatment—for several reasons. Therefore, it's important to find the "right" treatment for each patient—whether traditional (first-generation) or atypical (second-generation) antipsychotics, oral or long-acting injectable (LAI) drugs.

Currently, when oral medications are used to treat schizophrenia, atypical antipsychotic drugs are used more often than older medications. However, when it comes to LAIs, second-generation drugs are significantly more expensive, and, according to a number of studies, are not necessarily more effective. Newer medications also can cause significant weight gain—increasing the risk for related conditions like high cholesterol, heart disease, and diabetes. (Note: traditional antipsychotics—especially high-potency drugs—also can cause side effects. Lower doses often are better tolerated.)

In a clinical trial—called A Comparison of Long-Acting Injectable Medications for Schizophrenia (ACLAIMS) and conducted by researchers funded by the NIMH—311 adults with schizophrenia or schizoaffective disorder received either the newer, second-generation LAI drug paliperidone or a lower-than-normal dose of the older, first-generation LAI medication haloperidol. The effectiveness of each medication was determined by rates of the following:

  • Psychiatric hospitalization
  • Crisis stabilization
  • Increased outpatient visits
  • Continued need for oral antipsychotics after beginning LAI treatment
  • Adverse reactions
  • Clinical determination that the LAI provided no benefit

Metabolic markers, including weight gain, blood sugar levels, cholesterol, and prolactin (a reproductive hormone), were also monitored in study participants.

The ACLAIMS study did not find any evidence that paliperidone was better than haloperidol in reducing the following:

  • Psychiatric hospitalizations
  • Crisis stabilization measures
  • Outpatient visits
  • The number of patients who were unable to stop taking oral medication after beginning LAI therapy
  • Adverse side effects
  • The number of patients for whom LAI treatment was ineffective

According to researchers, more studies are needed to improve outcomes for people with schizophrenia. Goals include developing effective medications with fewer side effects, reducing related conditions like obesity—which can affect overall health, and improving cognitive function in people with schizophrenia.

Aripiprazole lauroxil (Aristada) is an extended release injection approved by the FDA in October 2015 to treat schizophrenia in adults. Aristada is injected by a health care provider every 4 to 6 weeks. The most common side effect of this medication is akathisia (severe restlessness that leads to agitation and anxiety).

Source: National Institute of Mental Health (NIMH); U.S. Food and Drug Administration (FDA)

Publication Review By: the Editorial Staff at

Published: 08 Jun 2014

Last Modified: 09 Oct 2015