Better safe than sorry? Knowns and unknowns in the maintenance treatment of remitted first-episode psychotic disorders

Psychotic disorders, including schizophrenia and related disorders, which affect up to 3% of the population, may have a pervasive negative impact on the lives of the patients, and constitute one of the highest burdens of disease globally. While the guidelines tend to focus on the treatment and stabilization of acute psychotic symptoms, clinical decisions regarding the long-term prevention of relapse, including the management of burdensome side effects with long-term use of antipsychotics, remain challenging. In this symposium, experts gave their views on current knowledge gaps and possible strategies for the maintenance treatment of remitted first-episode psychotic disorders.

Poorer outcomes following early discontinuation of maintenance treatment in patients in stable remission could still be observed at a 10-year follow-up

Use it or lose it: For how long should patients continue maintenance treatment after a first-episode psychotic disorder?

Although clinical guidelines recommend maintenance treatment for the first year after a first-episode psychotic disorder,1,2 Prof Eric Chen, Department of Psychiatry, University of Hong Kong, opened the symposium noting the lack of consensus regarding maintenance treatment beyond this time horizon, particularly for patients who have responded well to treatment and achieved stable remission.

Patients who respond well may be those profiting most from continuing maintenance treatment, not to lose the gain they initially achieved

Prof Chen threw light on this topic by presenting data from a 10-year prospective study,3 showing that patients in continued remission one year after successful treatment for a first-episode psychosis, had a substantially higher risk of relapse at a two-year follow-up if randomized to placebo, compared to patients who continued maintenance treatment. Poorer outcomes could still be observed at a 10-year follow-up.4 Although the total 10-year relapse rates were comparable for the groups, patients randomized to placebo relapsed faster, suggesting that the timing of relapse plays an important role for long-term clinical and functional outcomes.

According to Prof Chen, these data suggest that a single decision to discontinue medication too early could determine worse long-term outcomes, making patients lose the gain that they initially achieved, and giving rise to the paradox that patients who respond well may be those profiting most from continuing maintenance treatment.

 

Approximating zero: Guided dose reduction to support treatment adherence and shared decision making

Prof Chen-Chung Liu, Department of Psychiatry, National Taiwan University Hospital, continued the session by challenging the dichotomous view on continuation versus discontinuation maintenance treatment, suggesting a third approach aiming at determining the lowest effective dose for the individual patient. Using a guided dose reduction algorithm, dosage is reduced in fractions (no more than 25%) at a time, with a period of at least 6-month stabilization a prerequisite for reducing another 25% of the dose.5

Prof Liu highlighted the shared decision between patient and clinician as essential for this approach, as it relies on patients’ own wish to reduce medication, and the continuous evaluation if both patient and the physician feel ready for further dose tapering, or whether they should retreat to previous dosage if warning signs of relapse emerge.

According to Prof Liu, preliminary data from ongoing research suggest that guided dose reduction tailored for the individual patient may be a viable option to optimize the risk-benefit balance of maintenance treatment and support treatment satisfaction and adherence for patients with good response who wish to reduce their dose.

 

Left to their own devices: Clinicians’ perspectives on medication discontinuation in remitted first-episode patients

In a survey half of clinicians felt unsure whether continuation or discontinuation of treatment in remitted patients would be associated with better quality of life

Prof Swapna Verma, Institute of Mental Health, Hong Kong, concluded the symposium by highlighting the dilemma that clinicians often face, with patients expecting to stop medication when they are doing well, against the fact that clinical guidelines to not provide clear recommendations beyond 1 to 2 years.6,7

Illustrating the diversity in clinicians’ views, she presented data from a survey conducted among psychiatrists in four Asian countries,8 showing, for instance, that almost half of clinicians thought that 21 to 40 percent of patients could discontinue medication in the absence of psychotic symptoms, and further that approximately half of clinicians felt unsure whether discontinuation or discontinuation of treatment in remitted patients would be associated with better quality of life.

Prof Verma concluded the session noting the complexity of factors, including clinical, social, and situational patient factors that clinicians consider when deciding whether to discontinue maintenance treatment for remitted patients or not, urging more evidence and solid recommendations for discontinuation or dose reduction going forward.

 

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

References

1. American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia. 2nd ed. American Psychiatric Association, 2004

2. Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines Team for the Treatment of Schizophrenia and Related Disorders. Aust N Z J Psychiatry. 2005; 39(1-2): 1-30.

3. Chen et al. BMJ 2010; 341: c4024

4. Hui CLM et al. Lancet Psychiatry 2018; 5(5); 432-442

5. Liu C-C. Schizophr Bull 2018; 44(Suppl 1): S414

6. Buchanan RW et al, Schizophr Bulletin 2010; 36, 71-93

7. Crockford D. Can J Psych 2017; 62: 624-34

8. Hui et al. Early Interv Psychiatry 2018; Nov 28 [Epub ahead of print]

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