Do early antipsychotic responders differ much from non responders in follow up? Schizophr Res(Nov:2012)


Agid et al’s (2003) meta-analysis  reported that larger symptom reduction occurred during the initial two than subsequent two weeks of treatment with antipsychotic medication  suggesting that antipsychotic effects begin simultaneously with the drug attaining its therapeutic levels in the first few days. Individual-level clinical trial analysis showed that incremental change in the first two weeks exceeds that in the subsequent two weeks of medication (Leucht et al., 2005). Studies  show that early-response is superior to early non-response on many outcomes (e.g., functioning, remission rate,  health care costs; Ascher-Svanum et al., 2008; Kinon et al., 2008).

These studies suggest that early-response is a marker of subsequent clinical response. This raises few questions:  Are there any differences between early- (i.e. within 2 weeks) and delayed- (i.e. 3–4 weeks) symptom response groups ?  Do early response and non- response groups differ on subsequent symptom response beyond three months?

Levine and team address these questions using a double blind placebo controlled study data.The trial was conducted from March 1997 to July 2001 at 14 academic centers in North America and Western Europe. Individuals with schizophrenia/schizoaffective/schizophreniform psychosis with onset prior to 35 were included.Patients with a substance dependence history within 1 month prior to entry were excluded.PANSS data were collected weekly from baseline to week 6, biweekly from week 6 to 12, and then every 4 weeks to year 2.


1.Compared with delayed-responders, early-responders maintain modest and infrequent periods of greater symptom response that last no more than 12 weeks.

2.Compared to non-responders: early- responders maintained significantly greater symptom change for up to 39 weeks, and delayed-responders for up to 15 weeks. After these times the initial response effects ceased, and non-responders had similar response levels to early- and delayed-responders.

The current findings uniquely show that compared to non-responders, early-responders maintain significantly greater total symptom change for approximately 39 weeks only.This suggests the utility of early-response as a marker for symptom change in recent-episode schizophrenia persists for a limited period compared to non-responders.


1.At baseline the non-responders had significantly greater PANSS severity than the other groups.2. sample has recent-onset schizophrenia and so may be limited in scope to generalise to other stages of illness.3.This is a post-hoc reanalysis.


As we follow up patients for longer periods, the difference between early responders  ( with in two weeks) and delayed responders ( in 2-4 weeks) thin out.Even non responders ( at 4 weeks) attain a comparable symptom change level to early-responders after approximately six months.

Summary of the article:

Early symptom response to antipsychotic medication as a marker of subsequent symptom change: An eighteen-month follow-up study of recent episode schizophrenia.Levine SZ, Leucht S.Schizophr Res. 2012 Nov;141(2-3):168-72

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