Is Dose Reduction the Ideal Strategy after First Episode of Psychosis?
What’s the optimal treatment for a first episode of psychosis? Few would argue against antipsychotic treatment, but what happens when the patient achieves remission? Is it best to continue medication indefinitely, or can the antipsychotic be reduced or discontinued altogether?
One hundred and twenty eight patients who had a first episode of psychosis (FEP) in 2001–2002 were successfully treated with antipsychotics. Of these, half were randomized to continue medications (MT), and the other half to reduce their doses (DR) after six months of remission, tapering off of medications if possible. Most (N=103) were identified seven years later for a follow-up evaluation. Of these, half (N=52) had been randomized to the symptom-guided dose reduction (DR) strategy.
At the seven-year mark, investigators evaluated the patients for both symptomatic and functional recovery. Symptoms were measured by the Positive and Negative Syndrome Scale (PANSS); function was measured by the Groningen Social Disability Scale (GSDS). Rates of symptomatic remission were essentially identical between the two groups (MT, 66.7%; DR, 69.2%) while functional remission was significantly higher in those randomly assigned to the dose-reduction group (MT, 19.6%; DR, 46.2%). “Recovery,” defined as both symptomatic and functional remission, was also higher in the DR group (MT, 17.6%; DR 40.2%).
Some patients in the MT group had discontinued antipsychotics or reduced their doses to amounts comparable to those in the DR group. When the investigators looked at all the patients who had either discontinued or reduced their doses to subtherapeutic levels (N=34), symptomatic remission was found in 85.3% (vs. 59.4% of those who had not, N=69) and functional remission in 55.9% (vs. 21.7%). These patients were also more likely to have recovered (52.9% vs. 17.4%).
When investigators looked at relapse rates over the seven-year trial, they found, perhaps not surprisingly, higher relapse rates in the DR group over the first three years. But they observed roughly equivalent rates thereafter. They argue that the key difference between the two groups after seven years is neither in relapse rate nor in level of symptoms, but in the degree of functional recovery, and that this measure requires further investigation, as it represents a better measure of patients’ overall status (Wunderlink L et al, JAMA Psychiatry 2013, online ahead of print).
TCPR’s TAKE: Few would argue that first-episode psychosis requires treatment, but this study suggests that maintenance of antipsychotics after remission may not be necessary. After the decrease or discontinuation of medications, symptoms do not become worse. In fact, function may actually improve over a seven-year period. The reasons are unclear, but they argue for a greater focus on functional improvement and psychosocial interventions than on maintenance antipsychotic medication.