User login
COPENHAGEN – Recent studies emphasize the long-term merits of extending antipsychotic therapy beyond 1 year for patients in remission after a first psychotic episode, Mark Weiser, MD, observed at the annual congress of the European College of Neuropsychopharmacology.
Another emerging theme in the research literature, albeit a somewhat heretical one, is the value of antipsychotic polypharmacy, added Dr. Weiser, professor and chairman of the department of psychiatry at Sackler Faculty of Medicine, Tel Aviv University.
“Polypharmacy might not be so bad,” he declared in a keynote lecture in which he highlighted recent major publications addressing issues involving pharmacotherapy of schizophrenia.
“When we were residents, we were all taught that it’s not good to give two antipsychotics together, that all antipsychotics work only through dopamine D2 [receptor] blockade, hence there’s no point in giving more than one antipsychotic because all you’re doing is increasing side effects. But maybe it’s not as simple as that,” the psychiatrist said.
Exhibit 1: A recent Finnish national registry study of 62,250 patients with schizophrenia featuring up to 20-year follow-up showing that any antipsychotic polypharmacy was associated with a significantly lower risk of rehospitalization, compared with any antipsychotic monotherapy. The combination that stood out as having the lowest rehospitalization risk was clozapine plus aripiprazole, with a 14%-23% lower risk than for clozapine alone, which was the most effective monotherapy (JAMA Psychiatry. 2019 May; 76[5]:499-507).
Dr. Weiser pronounced himself a firm believer in the Finnish experience.
“The reason I think that this is true is that it’s exactly what I find in my own VA data,” he said.
Indeed, he and his coinvestigators are preparing to publish the results of their longitudinal study of 37,368 schizophrenia patients in the U.S. Veterans Affairs system. A key finding was that patients on antipsychotic polypharmacy had a longer time to treatment discontinuation than did those on monotherapy.
“Polypharmacy, at least in real-world study designs, seems to be good,” he noted.
Moreover, even in the world of highly selective randomized clinical trials, polypharmacy appears to fare pretty well as a treatment strategy, Dr. Weiser noted. A recent meta-analysis of six RCTs totaling 341 patients showed that switching patients from two antipsychotics to one was associated with a 2.2-fold increased risk of study discontinuation, although the investigators rated the quality of the trials as low to very low (Schizophr Res. 2019 Jul;209:50-7).
“I’m doing more polypharmacy now because of these data,” Dr. Weiser said. “My understanding of the polypharmacy data is that it’s not just blocking dopamine that’s important for treatment efficacy in schizophrenia.”
Getting a handle on first-episode psychosis
Dr. Weiser was a coinvestigator in the European Commission–funded OPTiMiSE study, in which 446 patients with first-episode schizophrenia or schizophreniform disorder in 14 European countries and Israel received 4 weeks of oral amisulpride. Then, if they were not in symptomatic remission, they were randomized double-blind to 6 weeks more of amisulpride or a switch to olanzapine. Those who weren’t in remission at 10 weeks were then placed on 12 weeks of open-label clozapine.
OPTiMiSE validated the clinical utility of a simple treatment algorithm, as 56% of patients achieved remission using stringent criteria by week 4 on amisulpride, and an additional 7% reached that endpoint by week 10, with the switch to olanzapine offering no added value over continued amisulpride. Switching week-10 nonresponders to clozapine enabled 28% of them to achieve remission (Lancet Psychiatry. 2018 Oct 1;5[10]:797-807).
A key take-home message of the trial, Dr. Weiser said, is that a switch to clozapine is justified after 10 weeks of unsuccessful treatment with a first-line antipsychotic; there’s no need to wait until patients have failed on two consecutive antipsychotics, as guidelines now recommend.
He observed that it can be a lot more challenging to keep patients in remission after a first psychotic episode than it is to get them to respond in the first place. For this reason, he found particularly instructive a recent study by psychiatrists at the University of Hong Kong that shined a light on the understudied long-term adverse consequences of stopping antipsychotic therapy after 1 year in patients successfully treated for a first-episode psychosis. At the 1-year point in this randomized trial, the successfully remitted patients were given maintenance therapy or their antipsychotic therapy was discontinued for 12 months. Ten years later, the investigators reported, the rate of a composite endpoint comprising persistent psychotic symptoms, requirement for clozapine, or completed suicide was 21% in the maintenance therapy group and significantly worse at 39% in those who had stopped treatment at 1 year (Lancet Psychiatry. 2018 May 1;5[5]:432-42).
“It’s probably a good idea to keep patients who are stable on maintenance therapy for longer than a year. A lot of first-episode patients don’t want to hear this. A lot of family members don’t want to hear this. And a lot of patients, of course, decide for themselves and stop treatment, although I tell them they should not.
Asked how low his low-dose long-term maintenance therapy is, he replied: “Negotiate with your patient about the lowest dose he or she is willing to take. In my opinion, 1 mg of risperidone is a lot better than 0 mg of risperidone, although that’s not an opinion supported by data.”
Dr. Weiser reported having no financial conflicts regarding his presentation.
COPENHAGEN – Recent studies emphasize the long-term merits of extending antipsychotic therapy beyond 1 year for patients in remission after a first psychotic episode, Mark Weiser, MD, observed at the annual congress of the European College of Neuropsychopharmacology.
Another emerging theme in the research literature, albeit a somewhat heretical one, is the value of antipsychotic polypharmacy, added Dr. Weiser, professor and chairman of the department of psychiatry at Sackler Faculty of Medicine, Tel Aviv University.
“Polypharmacy might not be so bad,” he declared in a keynote lecture in which he highlighted recent major publications addressing issues involving pharmacotherapy of schizophrenia.
“When we were residents, we were all taught that it’s not good to give two antipsychotics together, that all antipsychotics work only through dopamine D2 [receptor] blockade, hence there’s no point in giving more than one antipsychotic because all you’re doing is increasing side effects. But maybe it’s not as simple as that,” the psychiatrist said.
Exhibit 1: A recent Finnish national registry study of 62,250 patients with schizophrenia featuring up to 20-year follow-up showing that any antipsychotic polypharmacy was associated with a significantly lower risk of rehospitalization, compared with any antipsychotic monotherapy. The combination that stood out as having the lowest rehospitalization risk was clozapine plus aripiprazole, with a 14%-23% lower risk than for clozapine alone, which was the most effective monotherapy (JAMA Psychiatry. 2019 May; 76[5]:499-507).
Dr. Weiser pronounced himself a firm believer in the Finnish experience.
“The reason I think that this is true is that it’s exactly what I find in my own VA data,” he said.
Indeed, he and his coinvestigators are preparing to publish the results of their longitudinal study of 37,368 schizophrenia patients in the U.S. Veterans Affairs system. A key finding was that patients on antipsychotic polypharmacy had a longer time to treatment discontinuation than did those on monotherapy.
“Polypharmacy, at least in real-world study designs, seems to be good,” he noted.
Moreover, even in the world of highly selective randomized clinical trials, polypharmacy appears to fare pretty well as a treatment strategy, Dr. Weiser noted. A recent meta-analysis of six RCTs totaling 341 patients showed that switching patients from two antipsychotics to one was associated with a 2.2-fold increased risk of study discontinuation, although the investigators rated the quality of the trials as low to very low (Schizophr Res. 2019 Jul;209:50-7).
“I’m doing more polypharmacy now because of these data,” Dr. Weiser said. “My understanding of the polypharmacy data is that it’s not just blocking dopamine that’s important for treatment efficacy in schizophrenia.”
Getting a handle on first-episode psychosis
Dr. Weiser was a coinvestigator in the European Commission–funded OPTiMiSE study, in which 446 patients with first-episode schizophrenia or schizophreniform disorder in 14 European countries and Israel received 4 weeks of oral amisulpride. Then, if they were not in symptomatic remission, they were randomized double-blind to 6 weeks more of amisulpride or a switch to olanzapine. Those who weren’t in remission at 10 weeks were then placed on 12 weeks of open-label clozapine.
OPTiMiSE validated the clinical utility of a simple treatment algorithm, as 56% of patients achieved remission using stringent criteria by week 4 on amisulpride, and an additional 7% reached that endpoint by week 10, with the switch to olanzapine offering no added value over continued amisulpride. Switching week-10 nonresponders to clozapine enabled 28% of them to achieve remission (Lancet Psychiatry. 2018 Oct 1;5[10]:797-807).
A key take-home message of the trial, Dr. Weiser said, is that a switch to clozapine is justified after 10 weeks of unsuccessful treatment with a first-line antipsychotic; there’s no need to wait until patients have failed on two consecutive antipsychotics, as guidelines now recommend.
He observed that it can be a lot more challenging to keep patients in remission after a first psychotic episode than it is to get them to respond in the first place. For this reason, he found particularly instructive a recent study by psychiatrists at the University of Hong Kong that shined a light on the understudied long-term adverse consequences of stopping antipsychotic therapy after 1 year in patients successfully treated for a first-episode psychosis. At the 1-year point in this randomized trial, the successfully remitted patients were given maintenance therapy or their antipsychotic therapy was discontinued for 12 months. Ten years later, the investigators reported, the rate of a composite endpoint comprising persistent psychotic symptoms, requirement for clozapine, or completed suicide was 21% in the maintenance therapy group and significantly worse at 39% in those who had stopped treatment at 1 year (Lancet Psychiatry. 2018 May 1;5[5]:432-42).
“It’s probably a good idea to keep patients who are stable on maintenance therapy for longer than a year. A lot of first-episode patients don’t want to hear this. A lot of family members don’t want to hear this. And a lot of patients, of course, decide for themselves and stop treatment, although I tell them they should not.
Asked how low his low-dose long-term maintenance therapy is, he replied: “Negotiate with your patient about the lowest dose he or she is willing to take. In my opinion, 1 mg of risperidone is a lot better than 0 mg of risperidone, although that’s not an opinion supported by data.”
Dr. Weiser reported having no financial conflicts regarding his presentation.
COPENHAGEN – Recent studies emphasize the long-term merits of extending antipsychotic therapy beyond 1 year for patients in remission after a first psychotic episode, Mark Weiser, MD, observed at the annual congress of the European College of Neuropsychopharmacology.
Another emerging theme in the research literature, albeit a somewhat heretical one, is the value of antipsychotic polypharmacy, added Dr. Weiser, professor and chairman of the department of psychiatry at Sackler Faculty of Medicine, Tel Aviv University.
“Polypharmacy might not be so bad,” he declared in a keynote lecture in which he highlighted recent major publications addressing issues involving pharmacotherapy of schizophrenia.
“When we were residents, we were all taught that it’s not good to give two antipsychotics together, that all antipsychotics work only through dopamine D2 [receptor] blockade, hence there’s no point in giving more than one antipsychotic because all you’re doing is increasing side effects. But maybe it’s not as simple as that,” the psychiatrist said.
Exhibit 1: A recent Finnish national registry study of 62,250 patients with schizophrenia featuring up to 20-year follow-up showing that any antipsychotic polypharmacy was associated with a significantly lower risk of rehospitalization, compared with any antipsychotic monotherapy. The combination that stood out as having the lowest rehospitalization risk was clozapine plus aripiprazole, with a 14%-23% lower risk than for clozapine alone, which was the most effective monotherapy (JAMA Psychiatry. 2019 May; 76[5]:499-507).
Dr. Weiser pronounced himself a firm believer in the Finnish experience.
“The reason I think that this is true is that it’s exactly what I find in my own VA data,” he said.
Indeed, he and his coinvestigators are preparing to publish the results of their longitudinal study of 37,368 schizophrenia patients in the U.S. Veterans Affairs system. A key finding was that patients on antipsychotic polypharmacy had a longer time to treatment discontinuation than did those on monotherapy.
“Polypharmacy, at least in real-world study designs, seems to be good,” he noted.
Moreover, even in the world of highly selective randomized clinical trials, polypharmacy appears to fare pretty well as a treatment strategy, Dr. Weiser noted. A recent meta-analysis of six RCTs totaling 341 patients showed that switching patients from two antipsychotics to one was associated with a 2.2-fold increased risk of study discontinuation, although the investigators rated the quality of the trials as low to very low (Schizophr Res. 2019 Jul;209:50-7).
“I’m doing more polypharmacy now because of these data,” Dr. Weiser said. “My understanding of the polypharmacy data is that it’s not just blocking dopamine that’s important for treatment efficacy in schizophrenia.”
Getting a handle on first-episode psychosis
Dr. Weiser was a coinvestigator in the European Commission–funded OPTiMiSE study, in which 446 patients with first-episode schizophrenia or schizophreniform disorder in 14 European countries and Israel received 4 weeks of oral amisulpride. Then, if they were not in symptomatic remission, they were randomized double-blind to 6 weeks more of amisulpride or a switch to olanzapine. Those who weren’t in remission at 10 weeks were then placed on 12 weeks of open-label clozapine.
OPTiMiSE validated the clinical utility of a simple treatment algorithm, as 56% of patients achieved remission using stringent criteria by week 4 on amisulpride, and an additional 7% reached that endpoint by week 10, with the switch to olanzapine offering no added value over continued amisulpride. Switching week-10 nonresponders to clozapine enabled 28% of them to achieve remission (Lancet Psychiatry. 2018 Oct 1;5[10]:797-807).
A key take-home message of the trial, Dr. Weiser said, is that a switch to clozapine is justified after 10 weeks of unsuccessful treatment with a first-line antipsychotic; there’s no need to wait until patients have failed on two consecutive antipsychotics, as guidelines now recommend.
He observed that it can be a lot more challenging to keep patients in remission after a first psychotic episode than it is to get them to respond in the first place. For this reason, he found particularly instructive a recent study by psychiatrists at the University of Hong Kong that shined a light on the understudied long-term adverse consequences of stopping antipsychotic therapy after 1 year in patients successfully treated for a first-episode psychosis. At the 1-year point in this randomized trial, the successfully remitted patients were given maintenance therapy or their antipsychotic therapy was discontinued for 12 months. Ten years later, the investigators reported, the rate of a composite endpoint comprising persistent psychotic symptoms, requirement for clozapine, or completed suicide was 21% in the maintenance therapy group and significantly worse at 39% in those who had stopped treatment at 1 year (Lancet Psychiatry. 2018 May 1;5[5]:432-42).
“It’s probably a good idea to keep patients who are stable on maintenance therapy for longer than a year. A lot of first-episode patients don’t want to hear this. A lot of family members don’t want to hear this. And a lot of patients, of course, decide for themselves and stop treatment, although I tell them they should not.
Asked how low his low-dose long-term maintenance therapy is, he replied: “Negotiate with your patient about the lowest dose he or she is willing to take. In my opinion, 1 mg of risperidone is a lot better than 0 mg of risperidone, although that’s not an opinion supported by data.”
Dr. Weiser reported having no financial conflicts regarding his presentation.
REPORTING FROM ECNP 2019