Elsevier

Psychiatry Research

Volume 256, October 2017, Pages 267-274
Psychiatry Research

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

https://doi.org/10.1016/j.psychres.2017.06.069Get rights and content

Highlights

  • After the first 3 years, antipsychotic treatment for schizophrenia is less effective.

  • 20 years sustained of antipsychotic treatment does not improve work function in schizophrenia.

  • Many non-medicated schizophrenia patients show adequate work functioning after the acute phase of illness.

Abstract

To assess the long-term effectiveness of antipsychotic medications in facilitating work functioning in patients with schizophrenia we conducted longitudinal multifollowup 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.

Introduction

Work functioning and factors related to work functioning in patients with schizophrenia have long been important in regard to outcome for these patients. This includes psychosocial functioning and the economic impact to the country through job loss by patients with schizophrenia (Rosenheck et al., 2006). Programs to enhance social rehabilitation, and facilitate work functioning for patients with schizophrenia have increased in number and in sophistication (Bond et al., 2012, McGurk et al., 2013, McGorry et al., 2013, Mueser et al., 2013).

A major factor is psychopharmacological treatment with the belief that antipsychotic medications may facilitate work functioning for some or many patients with schizophrenia (Tandon et al., 2008, Alonso et al., 2009). However, until recently, the research on antipsychotic medications and work functioning have almost all been based on short-term (under 3-years) studies.

Research on the efficacy of antipsychotics administered to acute schizophrenia with flagrant psychosis has provided data indicating that antipsychotics, during the early most acute phase, are very effective in reducing severity of psychosis of many patients with schizophrenia (Gilbert et al., 1995, Buchanan et al., 2010), although other approaches also have some effectiveness (Ciompi and Hoffmann, 2004, Bola et al., 2009, Seikkula et al., 2011). In addition, there are a very large number of double-blind studies showing that during the first year and a half patients on placebo have a relatively high rate of relapse. However, several major studies, including the double-blind 2-year, Northwich Park Study by Johnstone, Mcmillan, Frith, Benn and Crow (Johnstone et al., 1990) found better work functioning in unmedicated psychotic patients.

The long-term evidence on the effects of antipsychotics beyond the first 3 years of administration is relatively sparse (Barnes and Badre, 2016). A comprehensive meta-analysis by Leucht, Davis and colleagues, noted that “the meta-regression suggested that antipsychotic drugs might lose their effectiveness with time” (Leucht et al., 2012b). They also noted that studies beyond 3-years would be important to the field, observing that “nothing is known about the effects of antipsychotic drugs compared to placebo after 3 years (Leucht et al., 2012a).

Recent longitudinal research has provided evidence of improvement in psychosis and in recovery for some or many unmedicated patients with schizophrenia as one moves past the 2-year period. This long term research on antipsychotic medication treatment includes that of Wunderink (Wunderink et al., 2013), the Northern Finland Birth Cohort Studies (Moilanen et al., 2013), the Danish OPUS trials (Wils et al., 2016) the study of Jung, Lincoln and colleagues (Jung et al., 2016) and our longitudinal research from the Chicago Followup Study (Harrow and Jobe, 2007, Harrow and Jobe, 2013, Jobe and Harrow, 2010, Harrow et al., 2012, Harrow et al., 2014). These and other studies have led to questions by R. Murray (Murray et al., 2016), by Barnes and Badre (2016) and others (Buchsbaum et al., 1992, Howes et al., 2012) concerning the long-term effects of antipsychotics on functioning.

The current longitudinal study directly measures work functioning over prolonged periods for a) patients with schizophrenia in long term antipsychotic treatment vs b) patients with schizophrenia not on antipsychotics, focusing on the long-term effects of antipsychotics on work functioning, using statistical controls and data on symptom level, and on premorbid achievements to control for inter-subject differences.

This study also examines whether the 2 major types of symptoms in schizophrenia, positive and negative symptoms, and whether major prognostic factors, influence work functioning. Previous research provide strong evidence concerning the importance of neurocognitive impairment in schizophrenia for poorer work functioning (Green, 1996, Green et al., 2000).

Since mood disordered patients who are psychotic at the acute phase (e.g., some bipolar patients and some psychotic MDD) are sometimes treated with antipsychotics, the long-term work functioning of these patients, used as a control group, also was assessed.

The following objectives were addressed:

  • 1.

    To provide clues on whether long-term use of antipsychotics facilitates work functioning, or in contrast interferes with work functioning in schizophrenia and psychotic mood disorders.

  • 2.

    To provide long-term data on whether negative symptoms and/or psychosis interfere with work functioning in schizophrenia.

  • 3.

    To provide long-term data on whether patients with schizophrenia not in medication treatment can show effective work functioning.

  • 4.

    To study whether long-term treatment of schizophrenia with antipsychotic medications improves their work functioning.

Section snippets

Method

The present research, derived from the Chicago Followup Study, involves a prospective, longitudinal multi-followup research program studying functioning, outcome, and recovery in major psychotic disorders (Harrow et al., 1990, Harrow et al., 2005, Harrow et al., 2012, Harrow et al., 2014, Harrow and Jobe, 2007, Harrow and Jobe, 2013, Jobe and Harrow, 2010). The 139 patients included 70 initially psychotic schizophrenia patients (61 patients with schizophrenia and 9 schizoaffective patients) and

Work functioning: Patients with schizophrenia prescribed antipsychotic medications versus those not on antipsychotic medications (Insert Fig. 1 and Table 2)

Fig. 1 presents data on work adjustment for patients with schizophrenia continuously prescribed antipsychotic medications (group 1, n=25) and for those not on antipsychotic medications throughout the last 18 years (group 3, n=15).

Table 2 reports the detailed data on work functioning, presenting the chi-square and effect sizes-odds ratios at the 6 followups over 20 years for the patients with schizophrenia continually prescribed antipsychotics vs those schizophrenia patients not prescribed

Discussion

Recent summaries of the literature by Leucht and colleagues (Leucht et al., 2012b) have noted that there is still not strong evidence of positive effects of treatment with antipsychotic medications beyond the first 3 years of treatment (Leucht et al., 2012a). Despite this, the great majority of workers in the field view antipsychotics positively for both short-term and long-term treatment.

However, important theoretical discussions by major theorists have questioned the long-term efficacy of

Funding Information

Supported, in part, by USPHS Grants MH-26341 and MH-068688 from the National Institute of Mental Health, USA (Dr. Harrow) and a Grant from the Foundation for Excellence in Mental Health Care (Dr. Harrow).

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