The effects of antipsychotic dose reduction/discontinuation on long-term outcome in FEP patients

Patients with FEP often ask whether they can discontinue their medication after a period of remission. This poses a difficult dilemma for psychiatrists. Short-term data show that reduced-dose maintenance treatment is effective for relapse prevention and that reduced rates of relapse are associated with improved outcome; however, long-term data are lacking. Recent studies suggest that dose reduction strategies are associated with better outcomes than maintenance treatment in the long-term but may lead to higher rates of relapse in the short-term. Studies suggest that treatment should be continued for at least 3 years.

Early dose reduction is associated with better long-term recovery in remitted FEP patients

A 7-year study in 103 remitted FEP patients found that recovery rates were significantly better in those receiving early dose reduction than in those receiving maintenance treatment (40.4% vs 17.6%).1 Functional remission rates were also higher in the dose reduction group (46.2% vs 19.6%), but were not related to symptomatic remission. This is great news for psychiatrists because it suggests dosages can be safely reduced, thereby avoiding unnecessary dopamine blockade and adverse effects on metabolic health and brain integrity. However, the study also found that relapse rates in patients receiving dose reduction were only reduced in the long-term and that rates actually increased in the first 3 years.

Recovery rates were significantly better in those receiving early dose reduction than in those receiving maintenance treatment (40.4% vs 17.6%)

Why is this important? The likelihood of recovery is closely related to the number of relapses in FEP patients.1 This suggests that relapse should be prevented at any cost. So how can psychiatrists achieve the 7-year benefits of dose reduction, whilst avoiding early relapses?

Dosages should be tailored to the individual patient to avoid relapse

Previous studies suggest that relapse risk and functional outcome might be predicted by baseline negative symptoms.1-4 If confirmed, relapse prevention strategies might have less impact on outcome than generally assumed.

To investigate this hypothesis, Dr Wunderlink et al from the University of Groningen carried out a post-hoc analysis of 7-year data to investigate whether differences in relapse rates were purely due to differences between maintenance treatment and dose reduction or whether certain patients are more likely to relapse than others. They found that the number and severity of negative symptoms at baseline significantly predicted relapse rates in all patients and also in patients treated with maintenance treatment. However, negative symptoms at baseline were not predictive of relapse in patients receiving dose reduction.

Further studies are required to investigate whether patients with high levels of negative symptoms at baseline should be treated differently, and whether results in people with maintenance treatment were because maintenance treatment dosages were too low to prevent relapse. In the meantime, maintenance strategies should be tailored to the individual patient in order to reduce the medication dosage without a resultant relapse.

Maintenance strategies should be tailored to the individual patient in order to reduce the medication dosage without a resultant relapse

Medication should be continued for at least 3 years

A study conducted in 178 patients with fully remitted FEP following antipsychotic treatment found that relapse rates after 1 year were significantly higher among patients that discontinued antipsychotics than in those receiving maintenance treatment (79% vs. 41%).2 To investigate the effects of treatment discontinuation on long-term outcomes, patients completing the 1-year study were assigned naturalistic care and were regularly assessed over a 10-year period.5 Overall, significantly more patients in the discontinuation group had poor clinical outcome compared to patients receiving maintenance treatment (39% vs 21%). Effects were largely due to relapse rates. Results suggest that medication continuation for at least the first 3 years after treatment initiation effectively prevents relapse and decreases the risk of poor long-term outcome.

To continue or not to continue?

Most clinical guidelines recommend continuing antipsychotic treatment for 1 to 2 years after FEP but provide no recommendations for long-term treatment.6 What do clinicians think?

Medication continuation for at least the first 3 years after treatment initiation effectively prevents relapse and decreases the risk of poor long-term outcome

According to a survey conducted in Singapore (N = 82), about 50% of clinicians feel treatment could be discontinued in 21-40% of asymptomatic patients and that patients should be monitored for 12-24 months after discontinuation. Overall, 50% felt that medications should be continued for 1-2 years after symptom remission and 28% felt that the period could be reduced to 6-12 months. Most clinicians agreed that the most important criteria for decision making are whether patients had good social support and whether they are able to cope with stressful situations. 

References
  1. Wunderlink L, et al. JAMA Psychiatry 2013;70(9):913-20
  2. Chen C, et al. Brit Med J 2010;341:c4024
  3. Hui CL, et al. Aust N Z J Psychiatry 2013;47(8):746-53
  4. Austin SF, et al. Schizophr Res 2015;168(1-2):84-91
  5. Hui CL, et al. Lancet Psychiatry 2018;5(5):432-42
  6. Takeuchi H, et al. Schizophr Res 2012;134(2-3):219-25
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