Effect of Early Dysphoric Response and Cannabis Use on Discontinuation of Olanzapine or Risperidone in Patients With Early Psychosis

An early dysphoric response following treatment with antipsychotic medication may lead to discontinuation of antipsychotic medication and thereby to relapse and rehospitalisation. Also cannabis use has found to be related to non-adherence to therapy. In the present study we examined whether 1) an early dysphoric response to antipsychotic medication, 2) cannabis use were related to discontinuation of antipsychotic medication in patients with early psychosis, and 3) whether there were differences in discontinuation between olanzapine compared with risperidone.

This study was a 1-year open extension of a previous double-blind randomized controlled trial comparing olanzapine (n=63) and risperidone (n=65) in patients with early psychosis due to schizophrenia according to DSM IV criteria, performed in 4 centres in the Netherlands. In the previous trial [2] we found no differences between olanzapine and risperidone in early dysphoric response to study medication, nor in the use of cannabis. However, it was hypothesised that both these variables would lead to earlier discontinuation. Discontinuation of olanzapine and risperidone was assessed after 1 year when patients were interviewed with the Life Chart Schedule.

Early subjective response was defined as the difference between the total score on the Subjective Well-being under Neuroleptics Scale (SWN) between start of treatment and after 6 weeks treatment. Early dysphoric response was defined as an SWN difference score less than the median. Cannabis use after 6 weeks treatment was assessed with self reports.

3 different survival curves were executed; 1) ‘early dysphoric response’ vs. ‘early non-dysphoric response’, 2) cannabis use vs. non use, and 3) olanzapine vs. risperidone. Differences between groups were tested with a log rank test.

The mean doses of study medication were 11.0 mg per day for olanzapine and 3.0 mg per day for risperidone at the end of the double blind trial.

After 1 year, 15 patients were lost to follow-up, and 75 of the 113 patients with follow-up data had discontinued the treatment: 39/58 patients stopped olanzapine and 36/55 patients stopped taking risperidone (P=0.84). Discontinuation rates are comparable to those found in the CATIE study [1]. The mean time to discontinuation was 5.8 (SD 4.9) months for the total group. 1) Time to discontinuation due to any reason was significantly longer for the group with an early non-dysphoric response (7.3 months, SD 4.8) compared to the group with an early dysphoric response (4.1 months, SD 4.4) (log-rank chi squared=13.3, d. f.=1, P=0.0003). 2) Patients who did not use cannabis after 6 weeks treatment had a significantly longer mean time on the study medication (mean 6.4 months, SD 5.0) compared to cannabis users (4.3 months, SD 4.2) (log-rank chi squared=4.98, d. f.=1, P=0.03). 3) We found no statistical difference in discontinuation between olanzapine (mean 5.6 months, SD 4.9) and risperidone (mean 5.9 months, SD 4.9). Reasons for discontinuation were not significantly different for olanzapine (19/58 inefficacy, 5/58 weight gain, 2/58 extrapyramidal symptoms, 6/58 sedation, 7/58 other) vs. risperidone (14/55 inefficacy, 1/55 weight gain, 5/55 extrapyramidal symptoms, 9/55 sedation, 7/55 other).

In conclusion, we have found that time on medication was associated with early dysphoric response and use of cannabis, whereas no significant difference in time on medication was found between olanzapine and risperidone. Improving the subjective response to medication by adjusting dose or type of medication may increase time on medication.

References

• 1 Lieberman JA, Stroup TS, McEvoy JP. et al . Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.  N Engl J Med. 2005;  353 1209-1223
• 2 Van Nimwegen L, de Haan L, van Beveren JM. et al . Effect of olanzapine and risperidone on subjective well-being and craving for cannabis in patients with schizophrenia or related disorders: a double blind comparison.  Can J Psychiatry. 2008;  53 400-405

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