Managing first-episode psychosis: An early stage of schizophrenia with distinct treatment needs

Although there is evidence that, among multi-episode patients, early nonresponse to antipsychotic therapy could predict subsequent nonresponse,³⁶ the evidence is mixed for first-episode schizophrenia. Studies by Emsley et al³⁴ and Gallego et al³⁵ did not find that early nonresponse at weeks 1 or 2 predicted subsequent nonre­sponse at week 4 or later. However, other studies support the idea that early nonre­sponse predicts subsequent nonresponse and early antipsychotic response predicts future response in first-episode patients, with good specificity and sensitivity.^37,38

Overall, treatment response in first-episode schizophrenia is variable. An adequate antipsychotic trial may be lon­ger, 8 to 16 weeks, compared with 4 to 8 weeks in multi-episode patients. Because research suggests that failure to respond to treatment may lead to medication non­adherence,³⁹ it is reasonable to consider switching antipsychotics when a patient experiences minimal or no response to antipsychotic therapy at week 2; however, this should be a patient-specific decision.

How long should you continue therapy after symptom remission?
There is a lack of consensus on the dura­tion of therapy for a patient treated for first-episode schizophrenia because a small percentage (10% to 20%) do not relapse after the first psychotic episode.³ In general, treatment guidelines and expert consensus statements recommend at least 1 to 2 years of treatment before considering a discon­tinuation trial.^7,10-11 Discuss the benefits and risks of maintenance treatment with your patient and obtain informed consent. With patients with minimal insight, obtaining proper consent is not possible and the phy­sician must exercise judgment unilaterally, if necessary, after educating the family.

After at least 12 months of treatment, antipsychotic therapy could continue indefinitely, depending on patient-specific factors. There are no predictors for identi­fying patients who do not require mainte­nance therapy beyond the first psychotic episode. The absence of negative and cog­nitive deficits could provide clues that a patient might be a candidate for antipsy­chotic tapering.

Predicting the treatment course
Research investigating clinical predic­tors or biomarkers that forecast whether a patient will respond to treatment is pre­liminary. Many characteristics have been identified (Table 3^{1,3,4,23,25,40}) and include shorter DUP,¹ poorer premorbid function,³ antipsychotic discontinuation,³ a trusting patient-doctor relationship,⁴¹ and antipsychotic-related adverse effects,^23,25 which are predictive of response, nonre­sponse, relapse, adherence, and nonadher­ence, respectively.
 

Bottom Line
The goals of pharmacological treatment of first-episode schizophrenia are to minimize the duration of untreated psychosis and target full remission of positive symptoms using the lowest possible antipsychotic dosages. Pharmacotherapy should continued for 1 to 2 years, with longer duration considered if it is discussed with the patient and with vigilant monitoring for adverse effects and suboptimal medication nonadherence to prevent relapse.
 

Editor’s note: The second article in this series in the July 2015 issue reviews the rationale and evidence for non-standard, first-line therapies, including long-acting injectable antipsychotics and clozapine.

Related Resources
• Recovery After an Initial Schizophrenia Episode (RAISE) Project Early Treatment Program. National Institute of Mental Health. https://raiseetp.org.
• Martens L, Baker S. Promoting recovery from first epi­sode psychosis: a guide for families. Centre for Addiction and Mental Health. https://www.camh.ca/en/hospital/ Documents/www.camh.net/AboutCAMH/Guideto CAMH/MentalHealthPrograms/SchizophreniaProgram/ 3936PromotingRecoveryFirstEpisodePsychosisfinal.pdf.

Drug Brand Names
Aripiprazole • Abilify                Lurasidone • Latuda
Asenapine • Saphris                Olanzapine • Zyprexa
Clozapine • Clozaril                 Paliperidone • Invega
Fluphenazine • Prolixin            Quetiapine • Seroquel
Iloperidone • Fanapt               Risperidone • Risperdal
Haloperidol • Haldol                Ziprasidone • Geodon

Disclosures
Dr. Gardner reports no financial relationships with any companies whose products are mentioned in this article or with manufacturers of competing products.
Dr. Nasrallah is a consultant to Acadia, Alkermes, Lundbeck, Janssen, Merck, Otsuka, and Sunovion, and is a speaker for Alkermes, Lundbeck, Janssen, Otsuka, and Sunovion.