long term antipsychotic useRecently, the blogosphere has been buzzing with controversy regarding the use of maintenance antipsychotic treatment. [1,2] On the one hand, most psychiatrists who have treated severely impaired patients with schizophrenia have little doubt that long-term antipsychotic (AP) treatment is both effective and necessary, in order to avoid relapse of psychotic illness.

On the other hand, a few recent studies seem to cast doubt on this belief and a number of psychiatry’s critics have seized upon these studies to argue against long-term AP use—even declaring that, in the long run, APs worsen psychosis and clinical outcome for those with schizophrenia. [1,2]

This article is by no means a comprehensive review of the voluminous, decades-old literature on AP maintenance; rather, it is a commentary on some recent studies and their sometimes controversial interpretation.

I would argue that interpreting these complex studies requires an in-depth understanding of medical research design, psychopharmacology and the numerous confounds that can affect treatment outcome.

Unfortunately, a lack of medical training has not stopped a few critics from confidently charging that psychiatrists are harming their patients by prescribing long-term AP treatment [1,2].

What Does the Recent Literature Say?

We need to make modest claims–not sweeping generalizations–about the literature on long-term use of antipsychotic medication. “Gold-standard,” randomized, placebo-controlled studies are fewer than we would like and existing studies are always subject to different interpretations.

Nonetheless–to prefigure my main arguments–I believe that most randomized, long-term studies of schizophrenia support the net benefit of antipsychotics in preventing relapse of the illness. Some data also show better “quality of life” with maintenance antipsychotic treatment, compared with drug discontinuation.

There is no convincing evidence that maintenance treatment causes worsening of schizophrenia or related psychotic illnesses or leads to poorer outcomes, when compared with discontinuation of the antipsychotic.

That said, recent data from Dr. Lex Wunderink [3] suggested to some that long-term AP treatment may do more harm than good. Essentially, Wunderink and colleagues compared rates of recovery in patients with remitted first-episode psychosis (FEP) after seven years of follow-up of a dose reduction/discontinuation (DR) vs. maintenance treatment (MT) trial.

After six months of remission, patients were randomly assigned to DR strategy or MT for 18 months. After the trial, treatment was at the discretion of the clinician. The primary outcome was rate of recovery, defined as meeting the criteria of symptomatic and functional remission.

At the 18-month mark, dose reduction/discontinuation resulted in significantly greater relapse rates compared to medication maintenance, as many psychiatrists would have expected. However, at seven years, the DR group showed unexpectedly higher recovery rates than the MT group–40.4% vs 17.6%. This finding seemed to suggest that long-term AP maintenance worsened outcome after first-episode psychosis.

But as schizophrenia specialist Dr. Joseph M. Pierre has pointed out [2], this conclusion is unwarranted. First of all, most of the subjects in the dose reduction/discontinuation arm of the study actually remained on antipsychotic medication, although at a reduced dose.

Secondly, as Dr. Pierre notes, “…while the initial treatment group allocation was randomized, the subsequent dose changes in both treatment groups were based on clinical response and occurred at the whim of the treating psychiatrists.” [2]

Thus, this study was not really a randomized study. And rather than AP treatment worsening outcome, it seems more likely that patients perceived by their doctors as doing relatively well were, understandably, given lower doses of medication; conversely, patients perceived as doing worse were likely maintained on higher doses.

As Dr. Pierre notes, “…the study was not so much a comparison of being on or off medications, [as] a comparison of being on higher versus lower antipsychotic doses.” [2] At most, the Wunderink study might suggest that for some people experiencing their first psychotic episode, “less is more;” that is, lower doses of antipsychotics may lead to better long-term recovery rates and social functioning than higher doses. The study does not support the claim that long-term AP maintenance is causally related to poorer outcome.

Furthermore, in a recent open-label, non-randomized, prospective study of antipsychotic discontinuation in patients who have fully recovered from their initial episode of psychosis, Spanish researchers found that discontinuation was associated with a high risk of symptom recurrence. [4]

Relapsed individuals had a greater severity of symptoms and lower functional status after three years. The rates of relapse over the three-year period were 67.4% (31 of 46) in the discontinuation group and 31.8% (7 of 22) in the maintenance group.

The resumption of antipsychotic medication after the relapse occurred was associated with clinical stability and lack of further relapses. To be sure, the lack of a randomized study design, the relatively small sample size and the fact that assessors were not blind to medication status are major limitations of this study–but the results provide no support for the claim that antipsychotic maintenance worsens outcome after a single episode of psychosis.

It’s important to understand that only a portion of people with a first psychotic episode have schizophrenia, which is usually a very chronic illness. Many have quite brief bouts of psychosis that never return, making long-term antipsychotic treatment unnecessary. So what does the recent literature tell us about AP treatment and relapse rates in patients with schizophrenia?


This article originally appeared in:

Psychiatric Times

It is reprinted here with permission.