Is Treating Schizophrenia with Antipsychotics Worth the Risk?


Three-quarters of patients who discontinue antipsychotic treatment experience relapse within 12-18 months. However, there are no current clinical guidelines describing treatment continuation or discontinuation beyond 1-2 years.

Christoph Correll, MD

Christoph Correll, MD

Despite the possible adverse effects of long term antipsychotic use, the efficacy and impact on quality of life for patients is generally favorable, according to a recent meta-analysis.

Researchers from Long Island, New York completed a risk-benefit analysis using the existing literature in order to study the long term positive and negative effects of schizophrenia treatment and chronic antipsychotic use. Studies included in the analysis lasted between 26 and 52 weeks, comparing second-generation antipsychotics and placebo for the prevention of relapses.

The researchers noted that 75% of patients who discontinue antipsychotic treatment experience relapse within 12-18 months. However, there are no current clinical guidelines describing treatment continuation or discontinuation beyond 1-2 years.

The greatest risk for relapse was non-adherence to medication, according to the investigators after they reviewed longitudinal studies. Adherence, or lack thereof, also explained up to a third of the effect of cannabis on the number of relapses, they said.

The study authors also looked a dose-reduction and dose-discontinuation study. In its first phase, antipsychotic discontinuation had to be adjusted to reduction only, due to too many relapses. After the second phase, the reduction group had twice as many relapses as the control group, although about 20 percent discontinued the medication without relapse. However, the researchers wrote that these findings have been cited as reasons behind the hypothesis that antipsychotics could postpone, rather than prevent, a relapse.

An analysis of 11 studies examining physical morbidity and mortality in patients receiving antipsychotics showed a shorter life expectancy in the patients compared to others by 14.5 years. The researchers attributed this to growing life expectancy overall, plus a gap in healthcare received by schizophrenia patients.

“To what extent antipsychotic treatment moderates the association between schizophrenia and poor health care utilization is not yet well understood,” researchers wrote.

The risk for developing tardive dyskinesia (TD) using first generation antipsychotics is about 3-5% per year of exposure for the first 5 years, but lower in second-generation antipsychotics, the researchers wrote. Some studies also purport that TD patients are at a greater risk for relapse after antipsychotic reduction or discontinuation.

“Overall, tardive dyskinesia is the clearest adverse clinical consequence in brain functioning of long‐term antipsychotic treatment, which may be related to dopamine supersensitivity in a subgroup of vulnerable individuals,” the study authors continued. “This risk should be evaluated when considering long‐term antipsychotic treatment, and preventive strategies utilized.”

Another important factor in schizophrenia mediation is possibly the use of psychosocial interventions, the researchers found—in particular, cognitive behavioral therapy. It can reduce positive, negative, and overall symptoms in patients taking antipsychotics.

These interventions may improve the long term risk benefit ratio of patients taking antipsychotics because they improve recovery focused outcomes and decrease burdens linked to the medication.

“The importance of the information for treating clinicians is that, based on our review of the available literature, the benefits of long-term maintenance antipsychotic treatment for people with a confirmed diagnosis of schizophrenia generally outweigh the risks that have been discussed and examined,” study author Christoph Correll, MD told MD Magazine®.

The study, “What is the risk‐benefit ratio of long‐term antipsychotic treatment in people with schizophrenia?” was published online in World Psychiatry.

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