Antipsychotic Drugs: The Costs and Benefits

More disappointing news has emerged from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), a National Institute of Mental Health–funded project involving more than 1,400 patients with chronic schizophrenia. In its first phase, the study raised doubt whether the antipsychotic drugs that now dominate the market, called second-generation or atypical antipsychotics, are more effective or safer or have fewer side effects than older, less expensive drugs.

Further analysis, reported in the American Journal of Psychiatry, is confirming that the newer drugs may not offer enough benefits to justify their cost.

The CATIE researchers judged the real-world value of a medication by the length of time patients continued to use it before quitting or switching to another drug — an objective standard that takes account of both effectiveness and side effects and reflects the judgment of both patients and physicians. The original analysis showed that the first-generation drug perphenazine worked as well as the newer drugs quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon). Olanzapine (Zyprexa) was slightly more effective but also had more side effects.

An analysis indicates that taking all costs into account, including the need for psychiatric hospitalization, perphenazine treatment was about 40% to 50% less expensive than treatments with competing second-generation drugs — a difference amounting to several hundred dollars a month. The authors conclude that physicians treating schizophrenic patients should usually start with one of the older drugs, all of which closely resemble perphenazine in their effects.

In an accompanying review of eight previous comparative studies, most of which found the second-generation antipsychotics to be worth the expense, reviewers raise serious questions about the choice of patients, the quality of evidence, and the accuracy of the statistical analyses.

There's further disheartening news. Second-generation drugs, unlike the older ones, do not all act by exactly the same mechanism, so many physicians believe that patients who respond poorly to one of them might benefit by switching to another. But a second analysis of CATIE findings suggests that switching doesn't pay.

At the time they entered the study, most of the CATIE patients were already taking an antipsychotic drug, usually olanzapine or risperidone; some were randomly assigned to continue taking the same drug, others to a different drug. Patients did not enter the study unless they and their psychiatrists were at least somewhat dissatisfied with their current drug. But those who continued to take the same drug almost always stayed on it longer before switching or quitting.

The authors conclude that patients are not likely to find a more effective drug than the one they are already taking. If the treatment is not going well, they say, it is usually better to adjust the dose, add other medications such as mood stabilizers or anticonvulsants, or consider psychosocial therapy.

All these studies have some limitations, as the researchers acknowledge. CATIE lasted for 18 months — not enough time to compare drugs and assess the costs from diabetes, cardiovascular disease, and the often irreversible movement disorder called tardive dyskinesia. All of the CATIE patients had chronic schizophrenia and most were middle-aged. Results might differ for people in the early stages of the disorder, older patients with medical problems, and patients with other psychiatric disorders. Clozapine (Clozaril) and aripiprazole (Abilify), antipsychotic drugs not included in the first phase of the study, might have a better cost-benefit ratio than the drugs that were studied. But for now, it looks as though skepticism about the special virtues of second-generation drugs is warranted.