A 20-Year multi-followup longitudinal study assessing whether antipsychotic medications contribute to work functioning in schizophrenia

Abstract

To assess the long-term effectiveness of antipsychotic medications in facilitating work functioning in patients with schizophrenia we conducted longitudinal multi followup research on 139 initially psychotic patients. The 70 patients with schizophrenia and 69 initially psychotic mood disordered control patients were followed up 6 times over 20 years. We compared the influence on work functioning of patients with schizophrenia continuously prescribed antipsychotics with patients with schizophrenia not prescribed antipsychotics, using statistical controls for inter-subject differences. While antipsychotics reduce or eliminate flagrant psychosis for most patients with schizophrenia at acute hospitalizations, four years later and continually until the 20 year followups, patients with schizophrenia not prescribed antipsychotics had significantly better work functioning. The work performance of the patients who were continuously prescribed antipsychotics was at a low rate and did not improve over time. Multiple other factors also interfere with work functioning. The data suggest that some patients with schizophrenia not prescribed antipsychotics for prolonged periods can function relatively well. Multiple other factors are associated with poor post-hospital work performance. The longitudinal data raise questions about prolonged treatment of schizophrenia with antipsychotic medications.

What is the risk‐benefit ratio of long‐term antipsychotic treatment in people with schizophrenia?

“…However, recovery rates were twice as likely in the initial dose‐reduction group (40.4% vs. 17.6%, p=0.004), driven not by symptomatic remission (69.2% vs. 66.7%, p=0.79), but by functional remission (46.2% vs. 19.6%, p=0.01), and 8 of the 11 patients off antipsychotics for 2 years were in the original dose‐reduction condition. These results have been cited as important evidence that antipsychotics could postpone rather than prevent relapse, while impacting negatively on functional recovery in the long‐term.…”

“…Most, but not all, of the studies with follow‐up >3 years reported worse outcomes associated with continued antipsychotic use. However, these results are inconclusive, given small and selective patient samples and extensive risk of bias. Conversely, long‐term register studies of much larger and representative national cohorts of patients diagnosed with schizophrenia confirmed significantly less treatment failure and suicide‐related mortality in antipsychotic‐treated patients compared to those not treated with antipsychotics.…”

“…There has been an emerging body of literature on the long‐term effects of antipsychotics questioning their necessity. Long‐term animal studies of antipsychotic exposure, naturalistic cohorts, and treatment discontinuation studies have been cited by some authors who claim that antipsychotics do not improve outcomes in the long term, and that there may even be iatrogenic adverse consequences of long‐term antipsychotic treatment. Others suggest that there is insufficient evidence supporting iatrogenic effects.…”

Long‐term antipsychotic treatment of schizophrenia: does it help or hurt over a 20‐year period?

“…We also compared a good‐prognosis sample of patients prescribed antipsychotics for 15‐20 years with a good‐prognosis sample of patients not prescribed antipsychotics for 15‐20 years. In both comparisons, those patients not on antipsychotics for 15‐20 years had fewer symptoms and better outcomes after the first 2‐3 years.…”

“…These studies have been conducted by eight different investigator groups. They include those by Wunderink et al in the Netherlands, our own Chicago Followup Study, the Suffolk County study of Kotov et al in the US, and the long‐term data provided by the Danish OPUS trial, the AESOP‐10 study in England, the Finnish Birth Cohort Study, the Alberta Hospital Follow‐Up Study in Western Canada, and the international follow‐up study by Harrison et al. These research programs included samples studied from 7 to 20 years.…”