Hello, deprescribing world. Today we have Dr. Helene Speyer, MD, Ph.D. at Mental Health Center Copenhagen (Denmark), telling us about an ongoing project on deprescribing of antipsychotics. Take it away, Helene!
“When can I get off this medication?”
Most people taking an antipsychotic medication for psychosis will eventually ask the following question: When can I get off this medication?
The clinician’s answers are vague, clinical guidelines are vague, and reports from research are contradictory. Many patients feel obliged to lie about compliance and quit the medication without support from health professionals.
Deprescribing of antipsychotic medications should be no less evidence-based than the initiation of these medications. Further, when we identify a patient with a wish to discontinue their antipsychotic, we should be supportive and defend their personal right to try, even when we fear the consequences. Is it not a human right to try and (sometimes) fail? That being said, more evidence and guidance on this topic would hopefully make such attempts more successful.
It is perfectly understandable that most patients want to quit their antipsychotic medication. One-third of patients with psychotic symptoms do not need medication at long term follow up, and early dose reduction is associated with increased chance of recovery. There are also serious adverse effects from antipsychotics such as emotional blunting, weight gain, and sedation, while no one knows the long-term consequences of antipsychotic use. However, there may also be concerns about relapses or declining psychosocial functioning upon discontinuation.
Generating evidence on deprescribing of antipsychotics
In our small research group in Copenhagen, led by Professor Merete Nordentoft, we aim to improve the evidence base for deprescribing antipsychotic medications, hoping this knowledge can improve patient care in the future. Plan B is the working title of a new antipsychotic deprescribing project we are undertaking. This project is literally the plan B, as our plan A, the Tailor trial, was a true failure.
Tailor was a randomized clinical trial evaluating early tapering of antipsychotic medication compared to maintenance treatment in remitted first-episode psychosis patients diagnosed with schizophrenia. The trial was sadly terminated after two years due to substantial lack of recruitment. Eligible participants kept telling us that the choice to take medication or to discontinue was too important to be left to randomization and therefore refused to participate. Accepting the limitation of no randomization, we started the process of redesigning the project to create a new study, Plan B.
The aim of the Tailor trial was to inform guideline authors about the optimal duration of treatment after remission of psychotic symptoms. The outcome of interest was the difference in proportion of patients who were still in remission and without medication at follow-up. While this is in line with most current thinking in traditional group-level evidence-based medicine, it occurred to us that alternative methodology might provide more usable answers. A majority of these patients will discontinue medication no matter what, so the patient-relevant question will not be to continue or not continue, but rather how can I safely taper?
Realizing that individualized treatment plans are critical in this context, the aim of Plan B will be to inform the shared decision-making process and improve safety and quality of care during the tapering process. We have left the business of dichotomized risk ratios.
Moving forward with Plan B
Plan B is a clinical, naturalistic cohort study, closely following patients diagnosed with schizophrenia who choose to taper antipsychotic medication with the focus on long-term recovery. Over two years, we plan to recruit 200-250 individuals and follow them for 24 months after baseline. We will collect data from personal meetings, monthly phone calls, and a daily self-monitoring application, recAPP, where a personal relapse signature will be created.
In a qualitative analysis, we will explore if individuals who consider tapering medication feel they can be honest and open towards the psychiatrist, and if not, what it would take to develop a trusting relationship. Many patients feel obliged to lie about compliance as the psychiatrist has a different agenda.
In a descriptive analysis, we will report the most important consequences of tapering antipsychotic medication. How many can successfully stop medication without experiencing severe psychotic relapses? How many do relapse, must live with irreversible consequences like the loss of job, education and relationships, treatment resistance, or suicide?
In predictive analysis, we exploit that active and passive data gathered from mobile devices to develop a risk prediction model that can hopefully be used to take special care of those with an impending crisis.
Finally, in a “speculative” model, we will use daily self-monitoring of factors that we hypothesize could mediate an association between medication and personal recovery; psychotic symptoms, negative symptoms, cognitive dysfunction, sleep, anxiety, and emotional blunting. This mediation model is developed to serve two purposes. First, we hope that visualizations can qualify and support the conversation about how the tapering is going. Second, we hope that a deeper understanding of how medication can both facilitate and be a barrier of personal recovery can be extracted at the group level.
Moving towards patient-centred decisions
Accepting the discontinuation is the choice of many, it is our obligation to make the process safe and comfortable. To improve safety, we have developed a self-monitoring application, where a personal relapse signature, composed of individual early warning signs. It is our hope that we can identify an impending crisis, allowing for early interventions like stress reduction. To improve comfort, we will generate knowledge about withdrawal symptoms, as they can be ameliorated if identified.
The cornerstones of evidence-based practice are a triad of research data, expert knowledge, and the patients’ individual values and preferences. Rigid clinical recommendations regarding duration of maintenance treatment neglect the personal values and preferences, resulting in treatment that cannot be called evidence-based practice and moves away from personalized medicine. We hope that the knowledge generated from Plan B will inform the shared decision-process and allow for individual decisions that can be followed up with safe and respectful guidance.
If you have questions for Helene, you can reach via e-mail (Helene.Speyer@regionh.dk) or on Twitter (@helene_speyer).
The deprescribing blog is hosted by pharmacists and PhD students, Carina Lundby and Wade Thompson. We hope to be your new best deprescribing friends and supply you with deprescribing content and analysis on a biweekly basis. Please reach out to us if you have any questions or comments, or would like to contribute.
carina.lundby.olesen@rsyd.dk (Twitter: @CarinaLundby)
wthompson@health.sdu.dk (Twitter: @wadddee)
