Antipsychotic medication treatment for mild hallucinations in Parkinson's disease: Positive impact on long-term worsening.

To test if antipsychotic medication treatment of Parkinson's disease (PD) patients with mild hallucinations and retained insight delays deterioration to delusions or hallucinations without insight. We identified subjects at the time they developed their first hallucination, based on documented progression in their UPDRS thought disorder (TD) score from <2 to 2 ("benign" hallucinations with insight retained). We registered TD scores at follow-up visits and their hallucination treatment: antipsychotic medication, PD medication reduction, or observation. The primary outcome measure was the time from the first TD = 2 until the TD score worsened to 3 (hallucinations with loss of insight) or 4 (delusions, psychosis). The effect of antipsychotic medication treatment on transition hazard rate was modeled by proportional hazards regression (Cox model) with antipsychotic medication use as a time-dependent covariate. Of 64 patients, 31 received antipsychotic medication during the study (mean group follow-up 31 months). Of the 38 subjects who reached endpoint, eight subjects had been treated with antipsychotic medication compared to 30/33 in those not treated with antipsychotic medication. Antipsychotic medication treatment reduced the risk of deterioration [hazard ratio = 0.156, CI = (0.067-0.363), P < 0.0001] compared to treatment without antipsychotic medications. The median time from the introduction of antipsychotic medication to the conversion from TD = 2 to TD > 2 was 39 months in subjects on antipsychotic medication compared to 12 months in patients treated otherwise. Until randomized treatment trials provide definitive information, early antipsychotic medication treatment for mild hallucinations should be considered with the combined goal of improving current hallucinations and reducing risks of later deterioration.