Contrary to older views, with modern treatment some or many patients with schizophrenia may show intervals of recovery. The current 15-year prospectively designed follow-up research comparing schizophrenia patients with other types of psychotic and nonpsychotic patients studied how many schizophrenia patients ever show intervals of recovery. Two hundred seventy-four early young psychiatric patients from the Chicago Followup Study, including 64 schizophrenia patients, 12 schizophreniform patients, 81 other psychotic patients, and 117 nonpsychotic patients, were assessed as inpatients and then reassessed 5 times over 15 years. Patients were evaluated for recovery for 1 or more years using an operational definition of recovery. Cumulatively, over the 15-year period slightly over 40% of patients with schizophrenia showed 1 or more periods of recovery. However, schizophrenia is still a relatively poor outcome disorder, showing poorer courses than other types of psychotic and nonpsychotic disorders (p < .001). Most schizophrenia patients did not show the severe social isolation often described prior to the modern treatment era. Schizophreniform patients tended to show more favorable outcomes than schizophrenia patients. Over 50% of the schizophrenia patients did not have a disorder that was chronic and continuous. Rather, their disorder was episodic, although for many more vulnerable and less resilient schizophrenia patients the episodes were more frequent and severe, with slower recovery.

BackgroundThe prevailing standard of care in the field involves background assumptions about the importance of prolonged use of antipsychotic medications for all schizophrenia (SZ) patients. However, do all SZ patients need antipsychotics indefinitely? Are there factors that help to identify which SZ patients can enter into prolonged periods of recovery without antipsychotics? This 20-year longitudinal research studied these issues.MethodA total of 139 early young psychotic patients from the Chicago Follow-up Study, including 70 patients with SZ syndromes and 69 with mood disorders, were assessed, prospectively, at the acute phase and then followed up six times over the next 20 years. Patients were assessed with standardized instruments for major symptoms, psychosocial functioning, personality, attitudinal variables, neurocognition and treatment.ResultsAt each follow-up, 30–40% of SZ patients were no longer on antipsychotics. Starting at the 4.5-year follow-ups and continuing thereafter, SZ patients not on antipsychotics for prolonged periods were significantly less likely to be psychotic and experienced more periods of recovery; they also had more favorable risk and protective factors. SZ patients off antipsychotics for prolonged periods did not relapse more frequently.ConclusionsThe data indicate that not all SZ patients need treatment with antipsychotics continuously throughout their lives. SZ patients not on antipsychotics for prolonged periods are a self-selected group with better internal resources associated with greater resiliency. They have better prognostic factors, better pre-morbid developmental achievements, less vulnerability to anxiety, better neurocognitive skills, less vulnerability to psychosis and experience more periods of recovery.

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While documenting the heterogeneity in outcome and the generally poorer outcomes of patients with schizophrenia, the studies reviewed also alert us to the danger of suicide and early death in schizophrenia. In addition, they expose problems in clinical management and treatment and also help us anticipate the possibility of intervals or periods of recovery, some of which appear spontaneously and may be tied to individual patient factors such as resilience.

The 20-year data indicate that, longitudinally, after the first few years, antipsychotic medications do not eliminate or reduce the frequency of psychosis in schizophrenia, or reduce the severity of post-acute psychosis, although it is difficult to reach unambiguous conclusions about the efficacy of treatment in purely naturalistic or observational research. Longitudinally, on the basis of their psychotic activity and the disruption of functioning, the condition of the majority of SZ prescribed antipsychotics for multiple years would raise questions as to how many of them are truly in remission.

To determine how frequent chronic multiyear delusional activity is in modern-day schizophrenia, we studied 200 patients over a 20-year period. We also studied the relation of delusions to hallucinations and thought disorder-disorganization, to work disability, and to later periods of global recovery and assessed several protective factors against delusional activity. The sample was assessed 6 times over 20 years and includes 43 patients with schizophrenia. Participants were evaluated at each follow-up for delusions, hallucinations, thought disorder-disorganization, work disability, and global recovery. Possible protective factors were assessed prospectively at index hospitalization. Twenty-six percent of the patients with schizophrenia were delusional at all follow-ups over the 20 years. Overall, 57% had frequently recurring or persistent delusions. A subgroup of over 25% of the schizophrenia patients had no delusional activity at any of the 6 follow-ups over 20 years. Schizophrenia patients with posthospital delusional activity had increased work disability (P < .05). Delusions that persisted after the acute phase in schizophrenia patients predicted a lower likelihood of future global recovery (P < .01). In conclusion, slightly over half of modern-day schizophrenia patients are vulnerable to frequent or "chronic" delusional activity after the acute phase. Schizophreniform patients and other types of psychotic disorders are vulnerable to posthospital delusional activity, but less frequently, less severely, and more episodically. Delusional activity is associated with work disability. Internal factors such as good premorbid developmental achievements and favorable prognostic factors are protective factors that reduce the probability of chronic multiyear, delusional activity in schizophrenia (P < .01).

Antipsychotic medications are viewed as cornerstones for both the short-term and long-term treatment of schizophrenia. However, evidence on long-term (10 or more years) efficacy of antipsychotics is mixed. Double-blind discontinuation studies indicate significantly more relapses in unmedicated schizophrenia patients in the first 6-10 months, but also present some potentially paradoxical features. These issues are discussed.

Our 26-year longitudinal study and other longitudinal studies confirm older views that outcome for schizophrenia, while showing some variation for different schizophrenia patients, is still significantly poorer than that for other psychiatric disorders, with the exception of the dementias. Our research leads us to propose that risk factors, either stress related or those related to vulnerability to psychosis, account for the episodic course of periods of recovery followed by periods of recurrence that is experienced by most schizophrenia patients. These risk factors interact with personality, temperament, and cognitive traits that, while not causing psychosis, influence its course. It is these interactions that account for the heterogeneous outcome trajectories of different subgroups of people with this condition. Our research and that of others has focused on the contributions of these risk factors, such as vulnerability to trait anxiety, poor developmental achievements before the illness, personality traits such as locus of control, cognitive styles, neurocognitive impairments, length of untreated psychosis, and several others. Despite the proven efficacy of antipsychotic medications over the short term, there is a subgroup of schizophrenia patients who, a few years after the acute phase, function adequately or experience periods of recovery for a number of years, without treatment.