Antipsychotic Maintenance Treatment: Time to Rethink? (2015)

Antipsychotic Maintenance Treatment: Time to Rethink?

Schizophrenia and psychotic disorders are estimated to affect 1% of the population and are one of the highest causes of global disability. They place a considerable burden on individuals, families, and society, with costs amounting to US$62.7 billion in the United States in 2002, for example. The highest costs are related to unemployment, and one long-term follow-up study found that more than 80% of people diagnosed with schizophrenia have some ongoing social disability.

Long-term antipsychotic treatment has been the norm for people diagnosed with schizophrenia and other recurrent psychotic disorders since the introduction of these drugs in the 1960s. Recent data from the United Kingdom indicate that 97.5% of mental health service patients diagnosed with schizophrenia are prescribed at least one antipsychotic. The practice is based on research believed to have established that continuous antipsychotic treatment reduces the risk of relapse. Interpreting the evidence is not straightforward, though, and other data are beginning to emerge that suggest that long-term treatment may have an adverse impact on levels of social functioning. Is it time, therefore, to review the practice of antipsychotic maintenance treatment and question whether it should continue to be the default treatment strategy in people diagnosed with schizophrenia or similar psychotic disorders?

  • Existing studies of long-term antipsychotic treatment for people with schizophrenia and related conditions are too short and have ignored the impact of discontinuation-related adverse effects: “antipsychotic discontinuation studies may partially, or even wholly, reflect the adverse effects of antipsychotic withdrawal, rather than the benefits of initiating maintenance treatment”
  • Recent evidence confirms that antipsychotics have a range of serious adverse effects, including reduction of brain volume.
  • The first really long-term follow-up of a randomised trial found that patients with first-episode psychosis who had been allocated to a gradual antipsychotic reduction and discontinuation programme had better functioning at seven-year follow-up than those allocated to maintenance treatment, with no increase in relapse.
  • Further studies with long-term follow-up and a range of outcomes should be conducted on alternatives to antipsychotic maintenance treatment for people with recurrent psychotic conditions.

“The majority of people who experience more than one episode of psychosis are currently recommended to remain on long-term antipsychotic treatment, with little guidance about whether the treatment should ever be stopped, and if so, how this should be done. Many patients find this approach unacceptable, and stop of their own accord without support, which likely leads to the complications of sudden medication withdrawal, including relapse.

The studies used to justify current clinical practice do not provide reliable data about the costs and benefits of long-term antipsychotic therapy. In particular, questions remain about how maintenance treatment affects people’s overall functioning over the long term, with some indications it may be detrimental for some people. There is abundant evidence that long-term antipsychotic treatment is associated with other serious and disabling adverse effects.

We need to do more research to establish the pros and cons of long-term antipsychotic treatment for people with one or more episodes of psychosis or schizophrenia. Further studies that evaluate a gradual and individualised approach to antipsychotic discontinuation are particularly important, both in people with first episode psychosis, and more challengingly, in people with recurrent conditions. Such studies need to include assessment of outcomes other than relapse and could assess what additional support might facilitate patients to successfully reduce their antipsychotic burden. Longer-term follow-up of five to ten years is required to reflect the duration of treatment in clinical practice. Research on treatments for other medical conditions demonstrates this can be achieved when it is prioritised.

Response to long-term antipsychotic treatment is likely to be heterogeneous, although so far there has been little success in identifying factors that might predict successful discontinuation. Existing research rarely distinguishes people who recover and are symptom-free between episodes from those who have ongoing positive psychotic symptoms. In the former situation, long-term antipsychotic treatment is aimed solely at preventing relapse, whereas in the latter, long-term treatment may be a form of symptom control, instead of, or in addition to, its desired prophylactic effect. The considerations involved in these situations may be different, and research needs to identify the varying pros and cons of long-term treatment for the two groups. For example, in people who recover completely, the adverse consequences of having reduced social or neuropsychological function may be more significant than for those people who are already somewhat disabled by ongoing symptoms.

While we await the results of further long-term discontinuation studies, I suggest we need to reconsider antipsychotic maintenance treatment as the default strategy for people with recurrent psychotic disorders. In 1976, two leading psychiatrists felt that the cost-benefit ratio of long-term antipsychotic medication was often not favourable for patients and recommended that “every chronic schizophrenic outpatient maintained on antipsychotic medication should have the benefit of an adequate trial without drugs”. Recent evidence suggests that, when risks allow, modern-day clinicians and patients could also consider this option.”

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