Long-term Antipsychotic Treatment: Effective and Often Necessary, with Caveats

Schizophrenia and Long-term AP Treatment

Critics of long-term antipsychotic use often cite studies done by Dr. Martin Harrow and colleagues. Harrow et al [5] looked 139 patients with schizophrenia who were either on or off antipsychotic medications, over a 20-year study period.

Surprisingly, Harrow found that those not on antipsychotics had a lower severity of psychosis and significantly greater rates of recovery compared to those taking antipsychotics.

Specifically, more than 70% of schizophrenia patients continuously prescribed antipsychotics experienced psychotic activity, at four or more of six follow-up assessments over 20 years.

Longitudinally, schizophrenia patients not prescribed antipsychotics showed significantly less psychotic activity than those prescribed antipsychotics (p < 0.05). This finding led Harrow and others to suggest a “recovery paradox” in which antipsychotics help in the short-term, but lose effectiveness in the long-term.

More precisely, the study authors concluded, that “…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.”

This last point, however, is crucial. As Dr. Pierre has pointed out [2], patients in the Harrow study—like those in the Wunderink study– were not randomized. Patients themselves were allowed to decide whether or not to continue medication.

This approach means that those with milder symptoms may have “self-selected” to discontinue medication, whereas those with more severe illness—who would be expected to have a poorer outcome—elected to stay on medication.

So the Harrow studies did not prove that long-term antipsychotic treatment per se worsened outcome. It is more likely, as Dr. Pierre notes, that the type or severity of patients’ symptoms determined whether or not they and their doctors decided to continue medication.

Thus, in analyzing the Harrow studies, some critics of antipsychotic treatment may have misperceived the ‘arrow of causality.’

Another recent study cited by critics of long-term AP use was a 2015 review by Sohler et al [6]. The authors examined data from 18 English-language, published reports, based on studies conducted between 1947 and 2010.

The authors compared outcomes in patients who received antipsychotic medication during a follow-up period of at least two years with patients who did not receive antipsychotic medication. The study aimed at testing the hypothesis that “…people with schizophrenia who are exposed to long-term treatment with antipsychotic medications have worse outcomes than people with schizophrenia who are not exposed to these medications.”

Owing to “ubiquitous study design flaws” in the data examined, the authors concluded that the published data were “inadequate to test this hypothesis.” And, by extension, “…these data were also inadequate to conclusively evaluate whether long-term antipsychotic medication treatment results in better outcomes on average.”

This finding is certainly  disappointing for clinicians who prescribe long-term AP treatment; however, the Sohler et al study in no way demonstrated that long-term AP treatment worsens outcomes for patients with schizophrenia who receive long-term AP treatment.

The authors explicitly state: “Our study did not support the hypothesis that long-term treatment with antipsychotic medication causes harm.”

Indeed, data from other sources suggest that long-term AP treatment clearly improves outcome in schizophrenia. For example, Prof. Stefan Leucht and colleagues examined relapse rates in persons with schizophrenia or schizophrenia-like psychoses, either maintained on antipsychotic medication or given a placebo [7]. Leucht et al looked at 65 randomized controlled trials (RCTs) involving 6493 participants, covering studies from 1959 to 2011.

The authors concluded that “…the efficacy of antipsychotic drugs for maintenance treatment in schizophrenia was clear. Antipsychotic drugs were significantly more effective than placebo in preventing relapse at seven to 12 months.” [7]

On average, about 27% relapsed while taking medication, versus 64% taking placebo. Moreover, only 10% of patients in the treatment group were readmitted to the hospital, compared with 25% of those who were given placebo. Quality of life was also better in participants staying on medication.

Of course, the authors noted that: “This [benefit] must be weighed against the side effects of antipsychotic drugs”, which can include sedation, weight gain, and movement disorders.”

Long-term Antipsychotic Treatment: Effective and Often Necessary, with Caveats

This article originally appeared in:

Psychiatric Times

It is reprinted here with permission.


APA Reference
Pies, R. (2016). Long-term Antipsychotic Treatment: Effective and Often Necessary, with Caveats. Psych Central. Retrieved on July 21, 2019, from


Scientifically Reviewed
Last updated: 27 Feb 2016
Last reviewed: By John M. Grohol, Psy.D. on 27 Feb 2016
Published on All rights reserved.