Antipsychotic Medication During the Critical Period Following Remission From First-Episode Psychosis

Abstract

Theperson recovering froma first episodeofpsychosis (FEP), the family, and the treating clinical teamhaveuntil now faced a real dilemma. Having reached the base camp of remission of psychotic symptoms, how long should antipsychoticmedication be continued? Most guidelines propose a trial of dose reduction anddiscontinuation, all beingwell, after 12months of treatment with careful monitoring subsequently. However, it is only recently that studies have been carried out to derive evidence regarding this decision. In theearly 21st century, thegoal of treatment inFEPmust be to pursue as full a functional recovery as possible. This means ameaningful lifewith vocational recovery, positive relationships, social inclusion, and good physical health. The worldwide development of specialized early psychosis care is based on these goals. Aswith cancer, and chronic disease generally, early detection and sophisticated use of the existing therapeutic armamentarium,evenwithoutdramaticbreakthroughs,cannotonlysave and extend lives but also facilitatemanymore recoveries. The “soft bigotry of low expectations” in psychosis is under seriouschallenge.Manywouldnowcontend thatmuchof thepoor outcome inpsychosis is anartifact of latedetection, crudeand reactive pharmacotherapy, sparse psychosocial care, and social neglect. Despite 60 years of use of antipsychotic medications, it is only now becoming clearer how best to use these medications to maximize recovery. A key issue in the management of FEP is relapse prevention in the early years after diagnosis when relapse rates are known to peak. Clinicians understandably want to safeguard a hard-won remission, influenced by the fact that the strongest predictor of relapse is medication nonadherence (relative risk, 4) (although there are several other environmental risk factors, notably, substance misuse and family climate1). Furthermore, discontinuation studies have shown increased relapse rates in patients who discontinue drug therapy, approaching 80% to 100%within 5 years inmainstreampsychiatric care (nonspecialized for FEP) if sensitive positive symptom–based definitions of relapse are used.2-4 Relapse has beenvariously defined fromsimply readmission to a hospital at one extreme to temporary exacerbation of positive symptoms with minimal functional impact at the other extreme. The former is too insensitive, but the latter might be too sensitive to serve as a basis for treatment decisions. Until now it has been assumed that relapse prevention is the top priority in treatment and a prerequisite for functional recovery, since genuine relapses are risky and distressing, setting back recovery in all domains. Although relapses were appropriately seenas agenuine threat to recovery, all too often, in research and clinical practice, prevention of relapse becameanend in itself rather thanan intermediate goal on the path to recovery. The data reported byWunderink et al5 highlight these issues and pose a challenge to linear thinking in relationship to relapse. They appear to put relapse in perspective. Although certainly not desirable, a contained relapse is rarely the end of the world. Modest exacerbations of symptoms, which are more common in the3 to5years afterdiagnosis,maybeaprice worth paying for better longer-term functional recovery. A trade-off may be available. Wunderink andcolleagues5 randomized 128patientswith remissionofpsychosis todose reduction/discontinuation (DR) ormaintenance treatment (MT) for 18months. At 18months, there had been twice the rate of relapse in the DR group (43% vs 21%)6 yet no more than a trend for better functional outcomes, consistent with both conventional wisdom and other recent data showing discontinuation to be an unwise course even in patients with remission.2 However, at 7 years’ follow-up byWunderink et al, the picture had changed dramatically. Patients assigned to DR manifested no increased relapse rates (the excess was confined to the first 3 years) yet achieved twice the level of functional recovery (40.4% vs 17.6%).Randomassignment toDRhad in fact resulted inminimal or very low-dose use of antipsychotic medications more frequently than didMT. That this was done randomlymeans that the 7-year results are very unlikely to be confounded. Ultimately, this studydemonstrates thatwithantipsychoticmedication in the critical period of FEP, “less is more.”