“Will I need to take these medications for the rest of my life?”
Authors: Stephen R. Marder, Michael F. Zito
Journal: World Psychiatry (2018)

Correll et al1 respond to a growing body of literature that calls into question the long-term use of antipsychotic medications in the treatment of schizophrenia. This recent literature has vexed clinicians who very commonly prescribe antipsychotics on a long-term basis, and who may have held a sense of certainty in the necessity of the therapy. To address this issue, Correll et al characterize the balance between risks and benefits of long-term antipsychotic treatment. They place past evidence of poor outcomes associated with long-term antipsychotic use in the context of many other benefits (such as that on mortality and relapse prevention), and stratify the literature according to possible bias in each research method. Ultimately, they give an analysis of the benefits and risks of long-term antipsychotic treatment that favors treatment. In this commentary we focus on applying these principles to working with individuals, particularly people who recently developed schizophrenia. We highlight challenges that will be faced by nearly every clinician who manages this disorder. First, many – perhaps most – recent onset patients will stop their medication at one time or another. First episode studies have reported up to a 37.1% non-adherence rate2 and other studies which include longer observation periods report even higher rates. One naturalistic study in Finland reported non-adherence in 58.4% of its sample, which was confirmed by measuring serum concentration3. Second, the relationship between clinicians and patients with schizophrenia is often skewed toward the patient feeling controlled by others, particularly prescribers or family members. For most other illnesses, patients accept treatment because it makes them feel better or because it protects them from something they wish to avoid. This is often not so in schizophrenia. For young patients with the illness, particularly those who enter a stable remission following a psychotic episode, the most impassioned psychoeducational approaches to improving adherence may not instill a belief that they need to continue their medication. In addition, nearly all patients will ask the question “Will I need to take these medications for the rest of my life?”. There is only one honest answer to this question, which is “Probably, but I can't be certain”. Many individuals believe that they will be the exceptional patient who will do well off medications. Correll et al cite that perhaps 4-30% of patients stabilized after an acute episode may discontinue antipsychotics without risk of relapse. They add that, currently, we do not have a clinically reliable means of predicting which patients will have this maverick response to antipsychotic discontinuation. A challenge then remains: how to help individuals with recent-onset schizophrenia to make decisions according to an optimal balance of clinical benefit and personal autonomy. We propose that a reasonable goal during these early years is to assist patients in taking some ownership of their illness and its management. In doing so, one might change the clinician-patient relationship from one in which the patient may feel controlled by the clinician to one in which the two work collaboratively. A poor relationship with a provider, and the experience of coercion, have been shown to be predictors of negative attitudes towards treatment in those receiving antipsychotics4. We emphasize the importance of changing this relationship. For many, a discussion of the benefits and risks described by Correll et al, combined with the memory of a painful psychotic experience, will suffice. Others may still be skeptical of their need for long-term medication. Prescribers should emphasize the importance of remaining on medications for the first one to two years as well as the potential risks of discontinuation, which includes high rates of relapse1, 5. However, if the patient is committed to stopping medication, we concur with the recommendation5 that a trial of dosage reduction with possible discontinuation may be carried out with medical supervision and concurrent psychosocial interventions, in a select population. Clinicians may choose to perform a longer and gentler dose-reduction schedule if they sense a higher risk of relapse. Dose reduction can be characterized as a learning opportunity for the benefit of both the patient and the prescriber. It may yield important data on the patient's ability to tolerate a period of time on a lower dose of antipsychotic medication, or off of it altogether. Although there are clearly risks associated with this approach, earlier studies6 found that careful monitoring of patients for prodromal symptoms can substantially reduce the risk of severe psychotic relapse. There are, of course, factors that may predict a more successful discontinuation trial. In a recent review5, several such factors were listed: lack of schizophrenia diagnosis, better premorbid social and occupational functioning, good social support, shorter duration of illness, and shorter duration of untreated psychosis. These factors may help identify the better candidates for discontinuation. Timing, as well, is an important component, as it appears that patients who achieve remission for three months in the first two years of illness have a better clinical prognosis7. This better prognosis is felt by some to indicate a higher likelihood of tolerating dose reduction and discontinuation5. We support the conclusions outlined in the paper by Correll et al, and we believe that the current literature undermines the clinical certainty of antipsychotic medications in the long-term treatment of schizophrenia. While not a certainty, long-term antipsychotic treatment is a very common outcome for people with schizophrenia. We encourage a sense of curiosity about the possibility of dose reduction and discontinuation in appropriate patients. This open-mindedness will strengthen the therapeutic bond between provider and patient, and might likely lead to better clinical outcomes. In her book The Center Cannot Hold8, E.R. Saks, a Professor in the Gould School of Law at the University of Southern California, describes how experiencing a different sense of reality on and off medications was a revelation which led her to accept that she had a mental illness. She observed that the more she accepted her illness, the less the illness defined her. Stephen R. Marder, Michael F. Zito Desert Pacific Mental Illness Research, Education, and Clinical Center, Semel Institute for Neuroscience at UCLA, Los Angeles, CA, USA