Is the Evidence Strong Enough to Warrant Long-Term Antipsychotic Use in Compulsory Outpatient Treatment?

Both within the psychiatric community and among the general public, there is a pervasive sense that psychotic illness, especially schizophrenia, requires lifelong medication. The idea of psychotic patients who are “off their meds” and prone to violence against society is likely what has driven the popularity of AOT in the public consciousness. The psychiatric literature often appears to confirm the importance of long-term antipsychotic medication. The American Psychiatric Association “strongly recommends” continued antipsychotic medications in the stable phase of schizophrenia (10). Medication nonadherence is reported to be the primary cause of schizophrenia relapse, with a fourfold increase in relapse compared with other factors (11). These recommendations and reports have led to the widely accepted notion that maintenance treatment with antipsychotic medications is necessary to minimize the chance of relapse. Some even argue that a placebo arm in schizophrenia relapse research may be unethical (12). Indeed, these reports appear to confirm the necessity of sustained, even lifelong antipsychotic medication treatment, despite the well-known cognitive, metabolic, and extrapyramidal effects (13) and the less-known neurotoxic effects (14,15) of these medications. However, a more in-depth review of the published data is worth considering in the light of the use of these medications in court-mandated treatment.

The vast majority of studies of long-term use of antipsychotics cover a period of six to 12 months, and, until recently, little data existed on antipsychotic maintenance use beyond one year. Most studies of the effectiveness of AOT also span this range of up to 12 months (4). A recent Cochrane review on antipsychotic maintenance treatment highlighted this lack of truly long-term data, reporting a clear benefit to maintenance antipsychotic treatment up to 12 months (16). However, when discussing the evidence for longer use, the authors of that review lamented that “nothing is known about the effects of antipsychotic drugs compared to placebo after three years.” One can sympathize with the practical difficulties of carrying out a controlled study of patients with schizophrenia and antipsychotic use over several years. This void of data has begun to be filled in recent years, with unexpected results.

Wunderink and colleagues (17) followed more than 100 participants for seven years after they were treated for a first episode of a psychotic disorder; half remained on antipsychotics continuously, and the rest followed a dose reduction–discontinuation approach when they were not acutely psychotic. This represents the first randomized controlled study of antipsychotic use over such a long period. Although those in the dose reduction–discontinuation group were more likely to have an initial relapse within the first year, the proportion of this group experiencing functional recovery after seven years (as measured by social relationships, self-care, employment, and so forth) was twice as high as in the group on continuous medications (40% compared with 18%). Both groups were found to have roughly equal rates of relapse when followed up to seven years.

Wunderink and colleagues’ data seem counterintuitive to the widely accepted belief in psychiatry that continuous antipsychotic maintenance is required to minimize relapse. However, other, less-controlled studies have suggested this pattern of an increase in relapse rates during the first year after antipsychotic discontinuation, followed by a relative evening out of relapse rates over the next few years (18,19). Reasons for this trend are unclear. They may include diminishing medication efficacy or receptor resistance over time, leading to the phenomenon of prolonged antipsychotic use actually increasing the risk of relapse after medication discontinuation. Another reason may be related to abrupt discontinuation—the usual case when patients go “off their meds”—as opposed to a directed and smooth medication taper over time (20). A lowered dopamine D₂ occupancy requirement in the maintenance phase versus the acute phase of treatment may also account for this pattern (21). These studies and similar recent reports prompted National Institute of Mental Health Director Thomas Insel, M.D., (22) to comment, “For some people, remaining on medication long-term might impede a full return to wellness. . . . For others, discontinuing medication can be disastrous.”

In defending AOT, Torrey and Stanley (23), who helped coin the term “assisted outpatient treatment,” point to the public health need to mandate compulsory treatment for a tuberculosis patient who poses a direct threat to the public if that patient denies the diagnosis and refuses treatment under the paranoid belief that the medications are poisoned. Few could argue with this logic. However, we would point out that the efficacy of antimycobacterial treatments for tuberculosis is well documented by clear and convincing evidence. In addition, both the pathophysiology of tuberculosis infection and the mechanism of antimycobacterial treatment are well established (24). This cannot be said for schizophrenia or for antipsychotic medication.

The current psychiatric tenet of long-term or lifetime use of antipsychotic medications to prevent psychotic relapse is based almost solely on studies lasting no more than one year. Although there can be little doubt that antipsychotic medications are effective in the acute phase of psychotic illness and among patients who are recently stabilized, recent data seem to cast at least a reasonable doubt on the efficacy of long-term (more than one to two years) use of antipsychotics. Far more work needs to be done to clarify this doubt, and it may well turn out that the recent data do not hold up. However, if a clinician is considering compulsory long-term use of these side effect–laden medications against a patient’s will, with the threat of involuntary psychiatric hold if the patient is noncompliant, then it is our opinion that the evidence for the long-term use of these medications should be far stronger than that provided in the current literature.

As clinicians who treat severe mental illness on a daily basis, we encourage continued academic and public discourse on how to best assist patients with severe mental illness. AOT offers mental health clinicians immense power to affect the lives and outcomes of people with severe mental illness. However with this power comes an immense responsibility to engage in the most ethical and evidence-based treatment, especially considering that noncompliance may have legal ramifications for patients. We argue that the involuntary use of long-term antipsychotic treatment for relapse prevention for an asymptomatic patient with severe mental illness is rarely justifiable.

The authors thank David Lehman, M.D., for his counsel, teaching, and inspiration. They also thank Sid Zisook, M.D., for his dedication to resident education and encouragement of critical thought.