I thought it would be helpful to summarize the actual data on long-term follow-up studies in schizophrenia since there are still so many myths surrounding this area. I am still amazed to hear graduate students in various mental health disciplines speak of the “incurability” of severe mental illness. I derived the following information primarily from “Beyond dementia praecox: findings from long-term follow-up studies of schizophrenia” by Joseph Calabrese and Patrick Corrigan, published in Recovery in Mental Illness: Broadening Our Understanding of Wellness edited by Ruth O. Ralph and Patrick W. Corrigan in 2005 for the American Psychological Association.
The Burghölzli Hospital Study ( Switzerland)
Manfred Bleuler, son of Eugen Bleuler who was director of the Burghölzli clinic in Zurich and gave us the name schizophrenia, followed a cohort of 208 patients for an average of 23 years. This cohort included both first admissions and readmissions to the hospital during 1942 and 1943. The diagnostic criteria emphasized psychotic symptomatology. The results indicated that 53% of the group participants overall and 66% of the first admission participants were judged to have recovered or be significantly improved. Fully recovered participants comprised 23% of the first-admission group and 20% of all research participants.
The Iowa 500 Study ( United States)
In the Iowa 500 study, 186 persons with schizophrenia were followed for an average of 35 years. The researchers also included a group with affective disorder and a control group of 160 surgical patients. Compared to people from the other psychiatric groups (i.e., with a diagnosis of affective or schizoaffective disorder), 46% of those people with schizophrenia had improved or recovered.
The Bonn Hospital Study ( Germany)
This study followed 502 persons with schizophrenia for an average of 22.4 years. The results were that 22% of the research participants had complete remission of symptoms, 43% had non-characteristic types of remission (defined as involving non-psychotic symptomatology, such as cognitive disturbances, lack of energy, sleep disturbances, hypersensitivity; in regard to the latter, some patients have described this state as a type of “skinlessness”), and 35% experienced characteristic schizophrenia residual syndromes. Therefore, 65% had a more favorable outcome than would have been expected from clinical experience. In regard to social functioning, 56% of all participants were judged to be “fully recovered,” which was defined in this study as full-time employment. At the last follow-up, 13.3% were permanently hospitalized.
The Lausanne Study ( Switzerland)
This study reported the longest term follow-up of the major long-term studies. The researchers, who included Luc Ciompi, followed 289 participants for an average of 37 years and up to a total of 64 years. The results indicated that 27% reached a stabilized 5-year end state of recovery, 22% reached an end state described as “mild,” 24% were described as “moderately severe,” and 18% were judged to have a “severe” end state. There was a 14% rate of continuous hospitalization.
The Chestnut Lodge Hospital (United States)
In this study, 446 (72%) of the persons treated between 1950 and 1975 at Chestnut Lodge psychiatric hospital in Rockville, Maryland, were followed for an average of 15 years. This site specialized in psychoanalytically-oriented long-term residential treatment. The research population consisted of persons with chronic and treatment-resistant mental illness. The researchers used a highly restrictive definition of recovery: full time employment, absence of symptomatology and need for treatment, meaningful engagement in family and social activities. The results were that two thirds (64%) of the persons with schizophrenia were judged to be chronically ill or marginally functional. One third (36%) were recovered or functioning adequately. The investigators reported that there were recoveries that included persons who had been viewed as hopeless chronic cases.
The Japanese Long-Term Study ( Japan)
This study took place at Gumma University Hospital in Japan. One hundred and five persons with schizophrenia discharged between 1958 and 1962 were followed for a period of 21 to 27 years. Thirty one percent of the participants were judged to be recovered, 46% improved, and 23% unimproved. Results on social outcome indicated that 47% were fully or
partially self-supportive and 31% were hospitalized.
The Vermont Longitudinal Research Project ( United States)
This study, conducted by ISPS member Courtney Harding and colleagues, followed 269 persons for an average of 32 years. The participants had been ill for an average of 16 years and were hospitalized on the back wards of Vermont State Hospital for 6 years. This study is unique in that the participants were involved in an innovative rehabilitation program and were released with community supports already in place. DSM-III criteria were used. At follow-up, one half to two thirds of all participants were considered to have improved or recovered. Of the living participants with schizophrenia, 68% did not display further symptoms or signs of schizophrenia at follow-up. Almost half (45%) of the participants displayed no psychiatric symptoms at all. More than two thirds (68%) of the participants were assessed as having good functioning on the Global Assessment Scale, which provides a global measure of social and psychological functioning.
The Main-Vermont Comparison Study ( United States)
This study compared the outcomes of 269 persons with schizophrenia in Maine with the outcomes of the 269 persons in the Vermont Longitudinal Study. The average follow-up period for the Maine participants was 36 years and 32 years for the Vermont participants. The persons in the Vermont study were exposed to a model rehabilitative program organized around the goal of self-sufficiency, immediate residential and vocational placements in the community, and long-term continuity of care. The Maine participants received standard psychiatric care. Results of this study showed that the Vermont participants at follow-up were more productive, had fewer symptoms, better community adjustment, and global functioning than the Maine participants. Approximately one half (49%) of the Maine participants were rated as having good functioning on the Global Assessment Scale, the primary global measure used for both the Maine and Vermont participants. The authors suggested that it was the provision of the model rehabilitative program.
The Cologne Long-Term Study ( Germany)
This study followed 148 persons with a DSM-III diagnosis of schizophrenia and 101 persons with schizoaffective disorder for an average of 25 years. The results showed that 6.8% of persons with schizophrenia had full psychopathological remission and 51.4% had noncharacteristic residua. Therefore, 58.2% had a more favorable outcome than would have been expected with schizophrenia.
The World Health Organization International Study of Schizophrenia
The WHO Study of Schizophrenia is a long-term follow-up study of 14 culturally diverse, treated incidence cohorts and 4 prevalence cohorts comprising 1,633 persons diagnosed with schizophrenia and other psychotic illnesses. Global outcomes at 15 and 25 years were assessed to be favorable for greater than 50% of all participants. The researchers observed that 56% of the incidence cohort and 60% of the prevalence cohort were judged to be recovered. Those participants with a specific diagnosis of schizophrenia had a recovery rate which was close to 50%. Geographic factors were significant in terms of both symptoms and social disability. Certain research locations were associated with greater chance of recovery even in those participants with unfavorable early-onset illness courses. The course and outcome for persons diagnosed with schizophrenia were far better in the “developing countries” than for such persons in the “developed” world of Western Europe and America.
The first of the WHO studies, the International Pilot Study of Schizophrenia (IPSS), assessed 1,202 persons diagnosed with schizophrenia in nine countries. The results showed that persons with schizophrenia in the “developing” world (e.g., Columbia, India, Nigeria) had better outcomes than persons in the “developed” countries (e.g., Moscow, London, Washington, Prague, Aarhus, Denmark). Overall, 52% of persons in the developing countries were assessed to be in the “best” category of outcome (defined in this study as an initial episode only, followed by full or partial recovery) compared with 39% in the developed countries. This finding was also reported in a 5-year follow-up research study. In this study, 73% of those participants from the developing world were in the best outcome group compared with 52% in the developed world. A second study called the Determinants of Outcome of Severe Mental Disorder (DOSMD) used more rigorous criteria and followed more than 1,300 patients in 10 countries and, similar to the IPSS, discovered that the highest rates of recovery occurred in the developing world. At a 2-year follow-up, 56% of those in the developing world were in the best outcome group compared to 39% of the participants from the developed countries. The finding of better outcome for persons in the developing countries applied whether the illness was either acute or gradual in onset.
These findings by the WHO have been critiqued on the basis of differences in follow-up, arbitrary grouping of centers into developed or developing, diagnostic ambiguities (e.g., narrow versus broad definition of schizophrenia), selective outcome measures, gender-related factors, as well as age. However, a recent reanalysis of the data by Kim Hopper and Wanderling (2000) convincingly demonstrates that not a single one of these criticisms is sufficient to explain away the findings of differential course and outcome in schizophrenia favoring persons in the developing countries. These are surprisingly robust findings.
The findings of the WHO studies demonstrating better courses and outcomes for people in the developing world have been attributed to the following factors: family environment and expressed emotion; social role expectations; stigma and discrimination, etc.
Harding, Zubin and Strauss (1987) noted that the development of chronic illness in persons with schizophrenia “may be viewed as having less to do with any inherent natural outcome of the disorder and more to do with a myriad of environmental and other psychosocial factors interacting with the person and the illness” (p. 483).
In regard to all of the follow-up studies, Calabrese and Corrigan (2005)
“Each of these studies found that, rather than having a progressively deteriorating course, schizophrenia has a heterogeneous range of courses from severe cases requiring repeated or continuous hospitalization to cases in which a single illness episode is followed by complete remission of symptoms. The findings reported in these studies as a whole indicate that roughly half of the participants recovered or significantly improved over the long-term, suggesting that remission or recovery is much more common than originally thought” (p.71).
The Role of Medication
Most clinicians would agree that judicious use of medications, including antipsychotic agents, plays a significant role in the treatment of acute psychotic disturbance. However, the question of maintenance treatment, proves to be more difficult to ascertain valid guidelines for many patients. Manfred Bleuler (1974), son of Eugen Bleuler, the clinician who gave us the term “schizophrenia,” noted that of all his patients who maintained long-standing remissions or a stable recovery, not a single one had been on chronic neuroleptic medication. Instead, the patients were given medication during acute phases and never for longer than a few weeks after they had recovered from their acute episode. Harding and Zahniser (1994), in their assessment of the long-term follow-up literature, observed that at least 25% to 50% of participants were completely off medications, experienced no further symptoms of schizophrenia, and were functioning well.
We need to know a great deal more about the relationship between symptomatology, subjective suffering, cultural-environmental factors which are demonstrated to be neuroprotective or neurodisorganizing and gene expression/neurochemistry in general and within each individual patient before we can validly assert the need for continued long-term use of antipsychotic medications. Most patients are prescribed medications without corroborating studies of saturation levels in different receptor systems (such as can be done in research studies with PET, MRS-but is not practical for everyday clinical settings) in neural pathways of import-for we know that there is not always an isomorphic relationship between neurotransmitter/neuromodulator levels and clinical symptomatology, e.g., serotonin levels and levels of depression. Symptoms such as delusions and hallucinations, as clinicians are well aware, do not always, or perhaps even often, respond to changing neurochemistry in the theoretically desired direction. The human brain is so incredibly complex, in addition to the dozens of identified neurotransmitters, there are over 60 neuropeptides identified, many of which such as the neurokinins (substance P, neurokinin A and B) and neurotensin (coexistence with dopamine and modulates DA-induced behaviors) have been suggested to play a role in psychosis. We must all remain humble in regard to the big questions in regard to psychosis therapy and in understanding the biological etiology/correlates of this group of disorders. However, despite our ignorance, many patients are able to significantly recover (or get better than they had been prior to the index episode) on their own or with the support of significant others and the myriad of treatments we have at our disposal to assist persons in their recovery process.
In regard to the above data, I ask myself what kind of neurological illness or group of illnesses is schizophrenia? These disorders do not behave like traditional neurodegenerative disorders in which there is no significant degree of recovery or full remissions (some of which are seen in advanced age and cannot be fully attributed to a “burnout” process since the Maine-Vermont Comparison Study demonstrated the importance in this group of participants in Vermont of psychosocial interventions). The neuroscience research findings in schizophrenia are largely nonspecific and overlap with the neuroscience findings in profound and chronic stress/fear/anxiety and social isolation. I believe that what we call schizophrenia is a disorder of the self and the latter emerges biologically, intersubjectively and culturally within particular contexts. All of these levels are coactional, with significant feedforward and feedbackward processes operating in non-linear modes and interdigitated with random as well as subjective (agency, will, autonomy) processes.
Brian Koehler PhD
New York University
80 East 11th Street #339
New York NY 10003