Is early dose reduction among first episode remitters better in long term? Jama Psy.Sept.2013.


Short term studies have shown that early antipsychotic discontinuation / dose reduction (DR)  to be associated with increased rates of relapse among first episode remitters. Such relapse rate is often many folds. Maintenance treatment (MT)  is recommended for atleast  for one year following the first episode. Relapse is the major outcome criteria on which the recommendations are based. Functional outcome and its relationship to medication reduction or discontinuation needs to be studied. Would early discontinuation or dose reduction would have any effect on long-term outcomes?

Lex Wunderink, Roeline M. Nieboer,  Durk Wiersma, Sjoerd Sytema and Fokko J. Nienhuis report the results from  seven year follow-up assessment  conducted in a cohort of patients with first episode psychosis who originally participated in an early-course drug discontinuation/ reduction trial ( against maintenance treatment).


symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS).Social functioning was assessed with the Groningen Social Disability Schedule (GSDS) . A patient with functional remission should function adequately in all 7 domains with none or only a minimal disability in any of them. Criteria for recovery were met when patients had symptomatic and functional remission for at least 6 months at the 7-year follow-up. To compare medication use, prescribed antipsychotics were converted to haloperidol equivalents. Of the 128 patients who participated in the original study, 103 patients (80.5%) were located and consented to participate in the 7-year follow-up .


Recovery rates were significantly higher in patients who received DR than in those who received MTSymptom remission after 7 years did not differ significantly across the original treatment strategies of DR and MT. Functional remission differed significantly in favor of DR . Symptomatic remission without functional remission was achieved by 38.8% of all patients.  28.2%  achieved neither symptomatic remission nor functional remission.


Only half of the eligible patients participated in the original study. Non participants were different. Raters were not blind.


The study show that less antipsychotic load might result in better functional capacity in the long-term.  It is possible that higher antipsychotic dose might compromise important mental functions.(alertness, curiosity, drive, and activity levels, and aspects of executive functional capacity).Another factor to consider is the likely positive psychological impact of having been in a DR strategy. It is interesting to note that at the 7-year end point, relapse rates were not significantly different between the groups. Maybe maintenance strategy postpones the relapses compared with the DR strategy but does not prevent them. Relapse rates in the DR arm wanes off after approximately 3 years of follow-up.

Comment:This study needs replication to draw conclusions given the limitations and the importance of these findings. Effects of reduction and interval dosing strategies   need to be studied with more  rigour.

Low dose appears desirable. Clinicians might be persuaded to use higher doses to manage behavioural problems/ distress. Are clinicians giving enough time on lower doses to see the benefit before titrating the dose up?

With low dosing / no dosing strategy 40% achieved functional recovery. Identifying them early is important, It is not clear how to identify them at first episode remission stage.


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