Peer reviewed Studies: Delaying Treatment leads to poorer recovery and prognosis

Edited by Dr. Fuller Torrey.

Prolonged recovery in first-episode psychosis.

Edwards J, Maude D, McGorry PD, Harrigan SM, and Cocks JT (1998). British Journal of Psychiatry (Supplement) 172 (Suppl 33): 107-116.


This study found that 6.6% of a sample of individuals experiencing their first episode of psychosis were treatment resistant, and that between 9 and 17% of individuals with schizophrenia, schizophreniform, and schizoaffective disorder were treatment resistant. These rates are much lower than the 30% reported in more chronic samples. In assessing differences between treatment resistant individuals and those who responded to treatment, it was found that the duration of psychotic symptoms before treatment approached significance, which suggests that untreated psychosis may lead to treatment resistance, and supports the argument for early intervention as soon as possible following the onset of positive symptoms. The lack of a difference between the groups on a scale assessing premorbid functioning further suggests that premorbid factors are less important than duration of untreated psychosis in preventing treatment refractoriness.


The aim of this study was to identify individuals experiencing treatment resistance early in the course of their psychotic disorder. It has been suggested that approximately 30% of individuals with schizophrenia have a less than adequate response to antipsychotic medications; however, it is not clear how many of these individuals are treatment refractory at the beginning of their illness and how many become so subsequently. Studies have suggested that the critical period for the development of chronic impairment is approximately one year.
The sample in this study consisted of 227 individuals experiencing their first psychotic episode, assessed at three time points (at admission, at stabilization of symptoms, at three or six months after stabilization, and at 12 months after stabilization) over a 12 month period. Thirty-six percent had schizophrenia, 22.5% had schizophreniform disorder, 11% had schizoaffective disorder, 2.2% had delusional disorder, 12.8% had bipolar disorder, 8.4% had depression with psychotic features, 0.4% had brief reactive psychosis, and 6.6% had psychotic disorder NOS. Individuals were identified as treatment resistant when they attained threshold on at least one positive symptom item of the Brief Psychiatric Rating Scale (BPRS) at stabilization, at the second time point (three or six months after stabilization), and at 12 months after stabilization.

The authors found that 6.6% of all the individuals with first-episode psychosis experienced psychotic symptoms at these three time points. When the analysis was restricted to people initially diagnosed with schizophrenia, schizophreniform, or schizoaffective disorder, the percentage of treatment-refractory individuals was 8.9%. When only schizophrenia and schizophreniform disorder were considered, the total rose to 11.4%. These numbers are much lower than the estimated 30% of treatment resistant schizophrenics in the larger schizophrenic population.
Treatment refractory individuals were found to have a significantly longer duration of psychotic symptoms during their first hospitalization, a greater severity of depressive symptoms 12 months after stabilization, and poor psychosocial functioning 12 months after stabilization. Interestingly, the treatment-refractory patients did not differ from the treatment responders on measures of premorbid functioning. However, the duration of psychotic symptoms before treatment also approached statistical significance, which suggests that untreated psychosis may lead to treatment resistance. The authors conclude that, in order to shorten the duration of active psychosis, there is a need to shorten not only the duration of untreated psychosis prior to entering treatment, but also to reduce the duration of psychosis after treatment has begun; the global aim can thus be seen as shortening the duration of active psychosis.

Course and outcome for schizophrenia versus other psychotic patients: a longitudinal study.

Harrow M, Sands JR, Silverstein ML, and Goldberg JF (1997). Schizophrenia Bulletin 23:287-303.


When looking at three groups of patients—those with schizophrenia, patients with other psychotic disorders, and patients with nonpsychotic disorders—the authors found that patients with schizophrenia show worse outcomes than other psychotic patients. In recent years, there has been speculation over whether patients with schizophrenia who respond to antipsychotic medications show relatively favorable or unfavorable outcomes over time. This study showed that, for individual patients with schizophrenia, the pattern of psychopathology and the level of functioning over time are related to previous psychopathology. It therefore suggests that preventing poor functioning at any given time for an individual with schizophrenia could be integral to preventing poor functioning in the future.


The authors studied 276 young, early-phase patients longitudinally, beginning at the acute phase and continuing through followups at roughly two years, four and a half years, and seven and a half years. Seventy-four of the patients were schizophrenic, 74 had other psychotic disorders, and 128 suffered from nonpsychotic mental illnesses. Patients were evaluated initially and at each successive followup for overall functioning; psychotic, anxiety, and affective symptoms; work and social functioning; potential rehospitalization; and medications.

The authors found that patients with schizophrenia functioned significantly more poorly than patients with other psychotic disorders at each of the three followups. The combined group of nonpsychotic and “other psychotic” patients tended to show improvement in overall outcome following the index hospitalization; in contrast, patients with schizophrenia showed more consistent psychopathology and evidence of psychotic symptoms, and had been rehospitalized significantly more frequently at each of the followups than the other patient groups. Although 32% of the schizophrenic sample showed a complete remission at one of the followups, less than 5% had a complete remission at all three of the followups. In contrast, at each followup after the first, more of the other psychotic patients had evidence of a complete remission than those who had uniformly poor outcomes.

Furthermore, schizophrenia patients deemed to be doing poorly at the initial evaluation showed significantly slower recovery at each followup than the other psychotic patients who had been doing poorly early on. There was a similar tendency for both schizophrenic and other psychotic patients with good functioning at one followup to show good functioning at the next followup. Schizophrenics also had the poorest outcome in terms of work functioning, although their social functioning was comparable to both the other patient groups. These results suggest that, during the early course of the illness, patients with schizophrenia still show relatively poor outcomes when compared with other mentally ill patients. Although a small number of them enter into complete remission, they tend to recover more slowly than other psychotic patients.