Jonathan M. Meyer, MD Professore Clinico di Psichiatria presso l'Università della California, San Diego Consulente in Psicofarmacologia per il Dipartimento degli Ospedali Statali della California, Membro del Consiglio di CURESZ

Rimozione degli ostacoli all'uso della clozapina

Clozapine is the only effective medication for treatment resistant schizophrenia, with response rates ≥ 40% compared to < 5% for other antipsychotics.1 Despite this, clozapine is significantly underutilized with up to 8-fold variation in rates of clozapine use between states in the United States.2 The main barriers to clozapine use in the United States rest on two issues: the burdens of monitoring and prescriber fear.3

These two issues are intertwined and relate to the association between clozapine use and serious decreases in infection fighting cells (i.e. neutrophils) in 1% of patients. Clozapine’s U.S. approval (1989) came with mandatory monitoring to track neutrophil (white blood cell) counts: weekly for 6 months, every 2 weeks for the next 6 months, and monthly thereafter. While this monitoring has nearly eliminated infection-related fatalities from clozapine-induced neutropenia (a low white blood cell count), the fear which this and other unusual adverse effects created dissuades many clinicians from using clozapine or from learning how to use clozapine. Although data indicate that clozapine use lowers mortality,4 many clinicians overestimate the risks of treatment and, sadly, subject patients to multiple trials of other agents with little chance of therapeutic benefit. Mandatory monitoring has vastly improved safety, yet it poses a number of difficulties for patients: travel costs, time, possible need for assistance to travel, discomfort from the blood draw, concerns among some about uses of their specimen, and the impact of delays in receiving the next prescription. Clozapine dispensing is tightly tied to pharmacy notification of blood results, and the quantity dispensed matches the interval to the next blood draw. For those on weekly testing, a delay of 24 hours in going to the lab or transmitting lab results places the patient in jeopardy of running out of clozapine.

Yet, there is hope. In the state hospital system I consult with, a regular lecture series on clozapine increased prescribing more than two-fold. Moreover, healthcare systems in New York and the Netherlands showed that supporting prescribers facilitates greater clozapine use. Knowledge is indeed power, and clinicians in the United States have two new resources to facilitate clozapine prescribing. One is a handbook that I co-authored inspired by the lack of clinically oriented published resources on clozapine;1 l'altro è un sito educativo basato sul Web che (cosa importante) fornisce anche consulenze cliniche agli utenti registrati (https://smiadviser.org). Questa iniziativa è gratuita ed è sponsorizzata dall'American Psychiatric Association e dalla Substance Abuse and Mental Health Services Administration.

Per i pazienti, gli oneri di monitoraggio possono essere ridotti da un dispositivo point-of-care (POC) recentemente approvato che utilizza una piccola goccia di sangue prelevata da un polpastrello. Il primo di questi dispositivi (http://athelas.com) not only provides results within minutes, the results are automatically transmitted to the monitoring system, and the device is now FDA approved for home use. The discomfort is less, there is no risk of delay between obtaining the results and medication dispensing, and the patient sees exactly how their blood specimen is used. The lack of delay means that a patient can have the test done anytime, and in almost any setting with trained personnel.

La rinascita della clozapina è iniziata.

Riferimenti:
1. Meyer JM, Stahl SM. Il manuale della clozapina. New York, New York: Cambridge University Press; 2019.
2. Stroup TS, Gerhard T, Crystal S, Huang C, Olfson M. Variazione geografica e clinica nell'uso della clozapina negli Stati Uniti. Servizio psichiatrico 2014;65:186-92.
3. Cohen D. I prescrittori temono come uno dei principali effetti collaterali della clozapina. Acta Psychiatr Scand 2014;130:154-5.
4. Vermeulen JM, van Rooijen G, van de Kerkhof MPJ, Sutterland AL, Correll CU, de Haan L. Clozapina e rischio di mortalità a lungo termine nei pazienti con schizofrenia: una revisione sistematica e una meta-analisi di studi della durata di 1,1-12,5 anni . Bollettino sulla schizofrenia 2019; 45: 315-29.