Our results showed that remission of both positive and negative symptoms predicted functioning after 2 years of treatment better than remission of positive symptoms alone according to all 3 types of analysis performed: a comparison of correlations between functional outcome and duration of remission, linear regressions predicting functional outcome based on remission status while controlling for confounding variables, and ROC analysis. In setting a time criterion for remission of positive and negative symptoms, linear regression analyses and sensitivity/specificity analysis showed that there was almost no difference between a criterion of 3 or 6 consecutive months of remission of positive and negative symptoms in predicting functional outcome.
It is not surprising that negative symptoms were found to be critical in the prediction of future functional status, given that there is considerable overlap between poor functioning and negative symptoms such as avolition and asociality, both being associated with impaired capacities in work and socialization, though it is worth noting from the regression analysis that they are not so important as to significantly predict functional outcome in the absence of positive symptom remission. Indeed, it is well established that negative symptoms are important in functional outcomes.24
While the results clearly stress the importance of considering negative symptoms in remission criteria in FEP, the general trend in early-episode schizophrenia has been to define remission solely on the basis of positive symptoms.26–29
Future studies should reinvestigate the clinical and neurobiological predictors and correlates of remission based instead on positive and negative symptoms.30
Monitoring the intensity of negative symptoms may be more challenging than tracking positive symptoms because a remission or relapse of positive symptoms is perhaps more easily noticed by clinicians. None of the studies assessing the utility of the consensus definition of remission performed regular assessment of negative symptoms.8–11
It may be erroneous to assume continuity of remission if positive and negative symptoms are below threshold level 6 months following initial remission, as done previously9,10
without additional symptom information during the intervening period. Applying this method in our data would have falsely categorized a full 25% (35/142) of all first remissions as continuous remissions by overlooking relapses of symptoms that had resolved by the 6-month time point. While most symptom ratings in our study were based on formal ratings using SAPS and SANS, some assessments were based on reevaluation of symptom ratings made by clinicians using the Life Chart Schedule.
The extent to which symptomatic remission must occur in order to achieve improved functioning and ultimately recovery is dependent on how stringent a definition of remission is used. As shown in , over the first 2 years following an FEP, patients who failed to achieve at least 3 consecutive months free of threshold-level positive and negative symptoms invariably did not have a good level of functioning at the end of a 2-year period, while 10% of subjects who failed to achieve 6 consecutive months free of positive and negative symptoms did go on to achieve good functioning nonetheless. This may constitute a key finding of the study, indicating that remission, defined by near absence of core symptoms sustained for a minimum of 3 months, may be necessary to achieve a good functional outcome during the early phase of psychotic disorders. However, remission of both positive and negative symptoms even for 6 months is obviously not sufficient for achieving functional outcome because many patients did not achieve such improvement in functional outcome despite being in remission.
In FEP, the 3-month consecutive remission of positive and negative symptoms may have further advantages over the 6-month definition. The ROC curve suggests that 3 months is a threshold before which prediction of good functional outcome is very low and after which further maintenance of remission does not contribute much more to prediction of good functional outcome. Also a 3-month remission can be affirmed sooner while the relatively high proportion of patients (70% of cases within 2 years of an FEP) being able to meet this status makes it a very realistic goal. It should, however, be emphasized that these patients had received ongoing treatment in a specialized early intervention service where intensive psychosocial interventions and close monitoring are likely to have achieved high rates of symptomatic remission, and future work will need to determine if it applies equally well to regular care environments. This definition is consistent with the results from a survey of experts suggesting that the best definition of remission in schizophrenia is 3-month remission of both positive and negative symptoms.7
On the other hand, the 6-month definition has the advantage of higher specificity and positive predictive value of good outcome. To ultimately determine the question of the ideal duration of sustained remission, it will be necessary to compare the results from studies in the early and later stages of illness. No study in long-term schizophrenia has yet examined a time criterion shorter than 6 months.8,10,11
Because the 6-month criterion performed as well under analysis as the 3-month criteria, we would not discourage its continued use especially in the interest of consistency across studies. Our findings may provide impetus for clinicians to work with patients to ensure they maintain at least 3-month remission of positive and negative symptoms with some confidence that this may be a threshold after which good clinical and functional status may be more likely to persist.
In conclusion, this study further supports the validity of the consensus definition of remission in schizophrenia. In FEP subjects, the consensus definition does not appear appreciably better than a definition of 3-month remission of positive and negative symptoms. There is clear evidence that negative symptoms are integral in defining remission as a step toward functional recovery in FEP and that at least 3-month sustained remission of both positive and negative symptoms over the first 2 years of treatment is necessary for a good functional outcome by the end of this period.