Duration Of Untreated Illness And Untreated Psychosis As Indicators Of An Unfavourable Further Illness Course

In current clinical practice, the first treatment contact of persons falling ill with schizophrenia is preceded by incipient psychosis with a mean duration of about a year or more (DUP) and a prepsychotic prodromal phase with a mean of several years (duration of untreated illness, DUI = duration of the prodrome+DUP) (see Table 1.1).

DUP and, in rare studies, also DUI have been described as prognostic indicators of unfavourable aspects of course and outcome in schizophrenia. The following short-term effects of a lengthy untreated first psychotic episode have been reported: delayed and incomplete remission of the first episode versus better therapy response and more rapid remission [14,16,4246], longer active illness or longer presence of psychotic and negative symptoms [47,48], reduced level of global functioning [49] and a longer duration of hospitalization and higher treatment costs [45,46,50].

The results on the association between DUP or DUI and medium- or long-term outcome are less clear-cut. McGorry et al. [16], in their investigation of 200 patients (about 50% with schizophrenia), demonstrated a positive association between DUP and positive and negative symptoms, global functioning and quality of life 12 months after first assessment. Johnstone et al. [42], Larsen et al. [51] and McGorry et al. [16] observed an increased frequency and severity of relapses. Helgason [52] found a higher risk of relapse and a longer duration of hospitalization and less compliance. A greater burden on the family and a higher expressed emotions level have also been reported [53,54]. Other effects observed are a less supportive social network [51], higher risk of depression and suicide [55-58], more stress in work- and education-related situations [59,60] and more substance abuse and delinquent behaviour [61]. In sum, almost all the characteristics that make up an unfavourable course of schizophrenia have been reported.

Analyses based on a representative follow-up sample of first illness episodes of schizophrenia in the ABC study [62] showed that DUP was a significant predictor only of psychotic and nonspecific symptoms at five-year follow-up. In contrast, DUI predicted negative and nonspecific symptoms and social outcome. Neither DUI nor DUP significantly predicted the frequency and duration of, and intervals between, psychotic relapses. This result sounds quite plausible because, apart from the nonspecific component, the powerful predictions were limited to the symptom categories prominent in these two phases. A prolonged DUI is characterized mainly by negative symptoms, a short DUP primarily by positive symptoms.

In contrast, three studies found no such association: Craig et al. [63] could not demonstrate any association between DUP, illness course and clinical outcome 24 months after first assessment, nor could Robinson et al. [64,65] or Ho et al. [66] in a well-designed and systematic study (Table 1.2).

The inconsistency of the results from the studies on the topic is very likely explained by great differences in the study samples. It is reasonable to presume that a prolonged prodromal stage - whatever its underlying cause may be - involving a great number and severity of negative symptoms and presumably also associated with a lengthy psychotic stage is an unfavourable prognostic indicator of the further illness course. Edwards and

Table 1.2 Selected studies on short- and long-term prediction of course and outcome by duration of untreated psychosis (DUP) or duration of untreated illness (DUI)

Shorter DUP or DUI redicts etter outcome or

Observation shorter first Longer-perspective course Study Subjects period episode and outcome

Altamura et al. [67]

67 DSM-III-R schizophrenia spectrum

4 years


Short DUP ? less psychotic relapses

Malla et al. [68]

106 non-affective psychoses

1 year


Short DUP ? positive outcome; long DUI ? higher negative and disorganization factor scores

Malla et al. [68]

53 non-affective psychoses

13 months


Little evidence of any association between DUP or DUI and course of schizophrenia; long DUI more likely unemployed, alone or homeless

Ho et al. [20]

156 DSM-IV schizophrenia spectrum disorder

First episode and retrospective until onset


No significant correlations between DUP and neurocognitive functioning

Joyce et al. [69]

136 schizophrenia, 81 controls

1 year


Long DUP ? neuro-psychological deficits and clinical deterioration

McGorry et al. [70]

203 schizophrenia

1 year


Long DUP ? strong and consistent prediction of severity of symptoms and functional outcome

Hoff et al. [71]

50 schizophrenia

1 year


Long DUP ? no association after recovery from first episode

Craig et al. [63]

155 schizophrenia, 115 bipolar disorder, 75 unipolar depression

2 years


No association

Barnes et al. [72]

53 schizophrenia (first episode)

First episode and retrospective until onset


No association

Harrigan et al. [73]

354 schizophrenia

1 year


Long DUP ? deterioration of functioning

Hafner et al. [62]

115 schizophrenia (first episode)

5 years


Long DUP ? more psychotic and unspecific symptoms; long DUI ? more negative symptoms and poorer social outcome

McGorry [74] have published a fairly comprehensive, but unsystematic list of the potential risks of delayed treatment:

1. slower and less complete recovery;

2. poorer prognosis (subsumed under this heading are numerous results or hypotheses on the further course of the disorder, measures of symptoms and impairment, relapse rates and duration of symptom-free intervals in particular);

3. increased risk of depression and suicide;

4. interference with psychological and social development;

5. strain on relationships;

6. loss of family and social support;

7. disruption of patient's parenting skills (for those with children);

8. distress and increased psychological problems within the patient's family;

9. disruption of study and employment;

10. substance misuse;

11. violence/criminal activity;

12. unnecessary hospitalization;

13. loss of self-esteem and self-confidence;

14. increased costs of management.

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