The Early Stages of Schizophrenia

The editors of this well-written book, chock-full of information about schizophrenia, make a startling assertion:

The basis for this striking statement, which leaves me wondering what great improvement has occurred that has escaped my notice, is given:

Their second major claim is that “early recognition of psychosis and a fully coordinated approach to treatment have not been the norm” (p. xiii). In other words, we have ways of significantly improving the treatment of schizophrenia but we’re not using them. Does the volume support such dramatic claims?

Patrick McGorry, Alison Yung, and Lisa Phillips describe their work on the holy grail of schizophrenia research: can we detect future schizophrenia and prevent it? They describe their work in selecting a cohort of people with some symptoms resembling schizophrenia and following them carefully. In a sample of 45, they found that 41% became psychotic within 12 months. The best predictors were duration of symptoms, more psychopathology according to several of the usual rating scales, normal left hippocampal volume, cannabis dependence, and maternal age over 30 years.

I find the significance of these findings tantalizing. Will this area of research bear fruit in enabling us to detect true prodromal cases and then allow us to do treatment studies to see if we can prevent the full illness? Or are they merely elaborate demonstrations of the obvious: many people who develop the full symptom picture of schizophrenia start with milder symptoms, so we are not detecting future cases but current ones? It still remains unknown if earlier treatment will be of benefit. I fail to see how this research justifies the editors’ assertions about new optimism about course and treatment.

Evelyn J. Bromet, Ramin Majtobai, and Shmuel Fenning present the results of the Suffolk County Mental Health Project, which followed for 2 years a large sample of patients with first-episode psychosis. Many of their findings seem irrelevant to this book, such as the different outcomes for subjects with or without schizophrenia. Their chief relevant findings concern predicting poor outcome of schizophrenia. The predictors they found were insidious onset, longer hospital stay, negative symptoms, and lack of resolution of symptoms after 6 months. I don’t find these results too exciting. They seem to be less predictors than ways of describing poor outcome. Here, too, we see nothing that seems relevant to the editors’ claim that a new day has dawned in treating first-episode schizophrenia.

Jeffrey Lieberman describes the Hillside prospective study of first-episode schizophrenia, which used a large sample of patients admitted to Hillside Hospital in 1986 to 1996. The researchers carefully assessed outcome and used a standard algorithm for treatment. Of the 118 subjects, 87% remitted in the median time of 9 weeks, and most of these subjects had a full recovery without any symptoms and a return to premorbid functioning.

Here we seem to have the exciting findings the editors extolled. Most patients with first-episode schizophrenia made a complete recovery. After 1 year the subjects had the option of discontinuing medication. The risk of relapse was five times greater in those who stopped taking medication. The cumulative relapse rate for all subjects was 82% at 5 years. For those who recovered from the second episode, the cumulative relapse rate was 78%, and it was 86% after 4 years in those who recovered from the third episode.

What does this mean? Is this the great revolution: many recover from the first episode, but most relapse several times? Improved treatment? Compared with what? The researchers found schizophrenia to be a chronic, recurrent disorder. Not exactly news. This project was not designed to study treatment. It certainly suggests that continuing to take antipsychotic medication seems worthwhile, but this doesn’t tell us that we have entered a new treatment era with better results.

Dr. Zipursky provides a chapter on the drug treatment for first-episode patients. Initially he deals with the question of the optimal dose of a typical antipsychotic, mainly haloperidol, giving the impression that low doses might be effective and safer. A close reading shows that we lack adequate data from pivotal studies to support that claim, and the issue seems moot once we decide that atypical antipsychotics should be our first-line drugs. The author leaves the question open, saying that the reduced side effects of the atypical antipsychotics might not offer an advantage over low doses of typical agents, especially considering the side effect of weight gain with the atypical antipsychotics. Ziprasidone is too recent a drug to appear in this discussion, showing the problem of trying to get up-to-date information from books in such a fast-moving field.

Dr. Zipursky doesn’t assess the evidence as I do. We do not have clear evidence that low doses of typical antipsychotics are as beneficial as higher doses, so matching lower doses to atypical antipsychotics is speculative, not evidence-based. In the comparison of atypical antipsychotics with the usual doses of the typical antipsychotics, we face a difficult dilemma not emphasized in this book. Atypical antipsychotics have fewer extrapyramidal side effects and tardive dyskinesia compared with typical antipsychotics, but more weight gain, new onset of diabetes mellitus, and elevated blood lipids that may portend greater risk of heart disease. Ziprasidone avoids these risks, it seems, but has the possible risk of cardiac arrhythmias. Future research will have to provide the risk-benefit ratios of treating with the various antipsychotics, and we should avoid premature closure on the issue. One of the treatments to test should be low-dose typical antipsychotics.

We then hear about psychological approaches. One chapter discusses how to address “the emotional needs” of the patients. No studies have assessed psychotherapeutic approaches in first-episode schizophrenia, so the reader is left with not much to go on. Of course, we do not need scientific studies to determine that we should treat patients humanely and with sensitivity.

A chapter on family intervention summarizes data about expressed emotionality and psychosocial treatment, acknowledging that research has not addressed these modalities in first-episode schizophrenia. The author correctly points out that family intervention in chronic schizophrenia seems to reduce relapse and rehospitalization rates, but she does not mention the absence of evidence that such treatment improves pervasive positive and negative symptoms, overall social functioning, or occupational success (1).

The last part of the book has excellent chapters on childhood-onset schizophrenia, schizophrenia during adolescence, and cognitive impairment in early-stage schizophrenia. These chapters are full of interesting information, much of it new, but, once again, offering no justification for the optimism expressed by the editors that we have reached a new era of improved treatment, much less that this new knowledge has not been applied adequately.

All in all, this volume shows well the strengths and weaknesses of contemporary psychiatry. We feel justifiably proud of the advances in our understanding of the functioning of the normal brain, our ability to measure the anatomy and function of the brain, and the ever-increasing mass of knowledge about psychopharmacology. What we avoid facing, in our hubris over psychiatry entering the arena of a true neuroscience, is that this new knowledge has not done much to improve our ability to treat patients. We have not shown that the new antipsychotics improve symptoms to a significantly greater extent than chlorpromazine did in the 1950s, or that our psychosocial treatments and social policies have improved the lot of patients with chronic mental disorders, or, for that matter, that all the new drugs for mood and anxiety disorders work better than the few we had in the 1960s. There are some exceptions. Clozapine has added something new, but it hasn’t had the large effect we thought it would.

Nor, as I read the literature, has our vaunted scientific approach to psychotherapy hit the pay dirt of showing equality or superiority to the drug treatments we have for most of the axis I disorders. I say this not to be nihilistic, but to focus attention on the important work to be done. I recommend this book strongly for the information it provides about schizophrenia, even if it doesn’t bring us to the promised land.