Utilizing data from the Chicago Follow-up Study, researchers followed 139 initially psychotic patients over 20 years. Published in Psychiatry Research, the study reports that while antipsychotics were beneficial during acute hospitalizations, patients not prescribed antipsychotics had significantly better work functioning than those who were prescribed antipsychotics.

“Negative evidence on the long-term efficacy of antipsychotics have emerged from our own longitudinal studies and the longitudinal studies of Wunderink, of Moilanen, Jääskeläinena and colleagues using data from the Northern Finland Birth Cohort Study, by data from the Danish OPUS trials the study of Lincoln and Jung in Germany, and the studies of Bland in Canada,” the authors write. These longitudinal studies have not shown positive effects for patients with schizophrenia prescribed antipsychotic for prolonged periods. In addition to the results indicating the rarity of periods of complete recovery for patients with schizophrenia prescribed antipsychotics for prolonged intervals, our research has indicated a significantly higher rate of periods of recovery for patients with schizophrenia who have gone off antipsychotics for prolonged intervals.”

Authors of this study draw attention to previous research that has pointed out the lack of evidence on the effectiveness of antipsychotics after 3-years. The present article adds to previous research presented in the Danish OPUS trial which demonstrated improved functioning and higher rates of employment after ten years in patients off antipsychotics.

The authors of this longitudinal study aimed to measure work functioning in patients with schizophrenia on long-term antipsychotic treatment compared to patients with schizophrenia not on antipsychotics controlling for symptom level and premorbid achievements.

Using data from the Chicago Follow-up Study, a study examining functioning, outcome, and recovery in psychotic disorders, 139 patients (psychotic schizophrenia, n= 70; control sample (psychotic mood disordered), n = 69) were followed over a 20-year period. Patients were recruited and initially assessed during an acute phase of hospitalization and followed up at 2 years, 4.5 years, 7.5 years, 10 years, 15 years, and 20 years.

Of the 70 patients classified as having schizophrenia, 58 were followed up at the 20 year period, 30 were assessed at all 6 follow ups (2, 4.5, 7.5, 10, 15, and 20 years), and 32 were assessed at 5 follow-up periods. Two patients were assessed at 4 follow-ups and 6 at less than 4 follow-ups. 25 patients were always prescribed antipsychotics and 15 were not prescribed antipsychotics from the 2-year follow-up onward. These two comparison groups were used in assessing the long-term differences between patients on vs. off antipsychotics.

The chart above presents the work functioning of patients continuously prescribed antipsychotics (n= 25) vs those not on antipsychotics over the last 18 years (n=15). As the figure shows, the only time point where there was no significant difference between the on work functioning between the two groups was during the 2-year period.

At each of the remaining time points, the unmedicated group performed significantly better on work functioning (.000 -.016 ). From the 4.5 year assessment on, over 65% of patients not on antipsychotics were working half-time or more.

Moreover, patients continuously prescribed antipsychotics were significantly more likely to have negative symptoms than those not prescribed antipsychotics at 4.5 years and 20-year follow-up and those with negative symptoms were less likely to be working at 4 of the 6 follow up periods.

When controlling for prognosis, patients with poor prognosis not on antipsychotics had better work functioning than those with poor prognosis prescribed antipsychotics. No significant differences were found between the medicated and unmedicated groups with good prognostic potential, which the authors point out may be due to the small number of patients with a good prognosis.

When controlling for premorbid achievements, those with poor premorbid achievements not on antipsychotics had significantly better work functioning than those prescribed antipsychotics with poor premorbid developmental achievement. Among the small number of those with good premorbid achievements, more of those not on antipsychotics were working than those taking the drugs.

When combining all results on symptom and functioning of the 70 patients with schizophrenia across all six follow-ups, results did not support the use of antipsychotics to improve functioning and the odds ratio conducted by the authors demonstrated that those not on antipsychotics were 1.76 times more likely to have adequate work functioning compared to those on antipsychotics.

The results of this study add to the growing literature demonstrating a lack of long-term positive effects of antipsychotics for patients identified as having schizophrenia. The researchers add that in other published papers, they have reported a higher rate of recovery in those off antipsychotics.

Overall, the results of this study make clear that after the 2-year mark (at which the differences are not significant), those off-antipsychotics have better outcomes. The authors write:

“The data indicate that any hypothesis based on the view that antipsychotics facilitate work functioning are extremely doubtful since the results for work functioning were running strongly (at significant levels) in the opposite direction.“

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Harrow, M., Jobe, T. H., Faull, R. N., & Yang, J. (2017). A 20-Year multi-followup longitudinal study assessing whether antipsychotic medications contribute to work functioning in schizophrenia. Psychiatry Research, 256, 267-274. (Abstract)