http://www.medscape.com/viewarticle/736461
Nicotine Replacement Therapy May Reduce Agitation in Schizophrenia
Kate Johnson
January 28, 2011 Schizophrenic smokers admitted to the hospital should be offered nicotine replacement as a treatment for agitation, regardless of whether they intend to quit smoking, new research suggests.
In a study published online January 18 in the American Journal of Psychiatry, Michael Allen, MD, and colleagues from the University of Colorado, Boulder, report that smokers admitted to a psychiatric emergency service with a diagnosis of schizophrenia showed significantly lower agitation scores at 4 and 24 hours when randomized to nicotine replacement patches compared with placebo.
"Hospitals have been willing to spend the money and put someone on a patch if they think the person wants to quit smoking, but they've not usually thought of it as a treatment for agitation," Dr. Allen told Medscape Medical News.
"That's really short-sighted because if the person gets agitated and violent that's much more of a problem. So I think it's worth giving people patches whether they want to quit or not. It shouldn't be tangled up with the issue of whether the person intends to quit smoking."
Significant Potential
Dr. Allen Michael The study included 40 nicotine-dependent schizophrenic patients aged 18 to 65 years who were hospitalized for a 24-hour period in the Psychiatric Emergency Department of the University of Geneva in Switzerland, where a smoke-free policy is in place.
To be included, subjects needed a significant baseline level of agitation as reflected in a minimum score of 14 on the excited component subscale of the Positive and Negative Syndrome Scale (PANSS).
Nicotine dependence was established with the Fagerström Test for Nicotine Dependence, and a score of 6 or more was required for study eligibility.
Patients were randomized to either a 21-mg transdermal nicotine patch (n = 20) or a placebo patch (n = 20), and all received usual care, including antipsychotics.
"Those who were receiving appropriate treatment continued the treatment unchanged. Those who were not already receiving treatment or were not receiving adequate treatment received 5 or 10 mg of olanzapine orally or intramuscularly or 5 mg of haloperidol intramuscularly," the study authors write.
Patients were confined to a secure area and regularly checked by nurses to ensure smoking abstinence. The study's main outcome was agitation at 4 and 24 hours as measured on the Agitated Behavior Scale.
Using this measure, scores in the intervention group compared with placebo approached statistical significance, with a 33% greater reduction at 4 hours (P = .028) and a 23% greater reduction at 24 hours (P = .050).
However, using the PANSS excited component subscale there was a significant reduction in agitation in the intervention compared with the control group at both time points (P = .006 and P = .014).
The study authors suggest that the baseline levels of agitation in the study population may not have been high enough to demonstrate pronounced differences between treatment and placebo and that treatment with antipsychotics might have blunted the results further.
"The effect size is small but the magnitude of the drug-placebo difference is similar to that observed in industry trials of parenteral antipsychotics," they note.
"Given the frequency and hazards of physical restraint and the limitations of available treatments, nicotine replacement therapy could have a significant effect on the care of agitated patients."
Quitting Not the Issue
"The problem people run into is that patients say they don't want to quit smoking," said Dr. Allen.
Don't fight with them about whether they can smoke or not, just try to convince them to use the patch and do that as part of their routine care don't wait until they start throwing the furniture and need a shot to have this conversation.
"What I'm recommending is that we say we're not asking them to quit smoking but that we think they'll be more comfortable if they use the patch. Don't fight with them about whether they can smoke or not, just try to convince them to use the patch and do that as part of their routine care don't wait until they start throwing the furniture and need a shot to have this conversation," he added.
The findings also revealed that patients with lower Fagerström scores, indicating a milder level of nicotine dependence, were more responsive to nicotine replacement.
For patients with Fagerström scores of 7 or 8 (low dependence), there was a significant reduction in agitation in the intervention group compared with placebo at 4 hours (P = .010) and 24 hours (P = .004). However, in patients with higher dependence the reduction was similar in both groups.
"It is possible that the 21-mg patch was inadequate for the more nicotine-dependent individuals in the study," the study authors write.
"We chose to study transdermal delivery of nicotine for its predictability, but nicotine gum should also be effective and has a rapid onset. It may be necessary to combine gum with the patch or otherwise obtain higher doses to better manage agitation in this patient population," they add.
Dr. Allen and colleagues discovered during the study that most patients did not want a patch at first.
"They want to smoke, and they don't think the patches will work. And there's a sense in which the patches don't work because they don't provide the kind of immediate rush that cigarettes do. But that's actually what's important about the study it demonstrates that even though the patient doesn't feel the rush, the nicotine is helping to calm them down."
Outcome Measure Accurate?
Reached for outside comment on the study, Tony George, MD, professor and head of the Division of Addiction Psychiatry at the University of Toronto, Ontario, Canada, said the study shows that "when you have psychiatric patients in the [emergency department], if you aggressively treat them with nicotine replacement you will have better outcomes."
Dr. George, who is also clinical director of the Schizophrenia Program at Toronto's Centre for Addiction and Mental Health, said his institution's emergency department has been smoke free for the past 4 years.
"We use nicotine patches, gum, bupropion, and varenicline, and we offer it to people immediately when they come into our emergency room," he told Medscape Medical News.
What you're really doing here is treating nicotine withdrawal and craving and the agitation related to that.
However, Dr. George took issue with the investigators' conclusion.
"I'm not sure the outcome that they were measuring was truly agitation. My worry is that because they didn't measure nicotine withdrawal or craving that this is likely the mediator of that.
"I think we should call a spade a spade because what you're really doing here is treating nicotine withdrawal and craving and the agitation related to that," said Dr. George.
Dr. Allen has received consulting fees from Alexza and research supported from AstraZeneca, Dainippon Sumitomo, Forest, 13 Research, NARSAD, National Institute of Mental Health, Novartis, Ortho-McNeil-Janssen, United Bio-Source Corporation, and Wyeth. The other study authors report no financial relationships with industry. Dr. George reports that he has received grant support from Pfizer Inc and has received consulting fees from Pfizer, Evotec, Eli Lilly, Janssen-Ortho, and Astra-Zeneca in the past 2 years. He receives grants from the Canadian Institute for Health Research, the Canadian Tobacco Control Research Initiative, the Canada Foundation for Innovation and the Ontario Mental Health Foundation, the National Institutes of Health, and the Chair in Addiction Psychiatry from the University of Toronto.
Am J Psychiatry. Published online January 18, 2011.
Authors and DisclosuresJournalist
Kate Johnson
Freelance writer, Montreal, Canada
Nicotine Replacement Therapy May Reduce Agitation in Schizophrenia
Kate Johnson
January 28, 2011 Schizophrenic smokers admitted to the hospital should be offered nicotine replacement as a treatment for agitation, regardless of whether they intend to quit smoking, new research suggests.
In a study published online January 18 in the American Journal of Psychiatry, Michael Allen, MD, and colleagues from the University of Colorado, Boulder, report that smokers admitted to a psychiatric emergency service with a diagnosis of schizophrenia showed significantly lower agitation scores at 4 and 24 hours when randomized to nicotine replacement patches compared with placebo.
"Hospitals have been willing to spend the money and put someone on a patch if they think the person wants to quit smoking, but they've not usually thought of it as a treatment for agitation," Dr. Allen told Medscape Medical News.
"That's really short-sighted because if the person gets agitated and violent that's much more of a problem. So I think it's worth giving people patches whether they want to quit or not. It shouldn't be tangled up with the issue of whether the person intends to quit smoking."
Significant Potential
Dr. Allen Michael The study included 40 nicotine-dependent schizophrenic patients aged 18 to 65 years who were hospitalized for a 24-hour period in the Psychiatric Emergency Department of the University of Geneva in Switzerland, where a smoke-free policy is in place.
To be included, subjects needed a significant baseline level of agitation as reflected in a minimum score of 14 on the excited component subscale of the Positive and Negative Syndrome Scale (PANSS).
Nicotine dependence was established with the Fagerström Test for Nicotine Dependence, and a score of 6 or more was required for study eligibility.
Patients were randomized to either a 21-mg transdermal nicotine patch (n = 20) or a placebo patch (n = 20), and all received usual care, including antipsychotics.
"Those who were receiving appropriate treatment continued the treatment unchanged. Those who were not already receiving treatment or were not receiving adequate treatment received 5 or 10 mg of olanzapine orally or intramuscularly or 5 mg of haloperidol intramuscularly," the study authors write.
Patients were confined to a secure area and regularly checked by nurses to ensure smoking abstinence. The study's main outcome was agitation at 4 and 24 hours as measured on the Agitated Behavior Scale.
Using this measure, scores in the intervention group compared with placebo approached statistical significance, with a 33% greater reduction at 4 hours (P = .028) and a 23% greater reduction at 24 hours (P = .050).
However, using the PANSS excited component subscale there was a significant reduction in agitation in the intervention compared with the control group at both time points (P = .006 and P = .014).
The study authors suggest that the baseline levels of agitation in the study population may not have been high enough to demonstrate pronounced differences between treatment and placebo and that treatment with antipsychotics might have blunted the results further.
"The effect size is small but the magnitude of the drug-placebo difference is similar to that observed in industry trials of parenteral antipsychotics," they note.
"Given the frequency and hazards of physical restraint and the limitations of available treatments, nicotine replacement therapy could have a significant effect on the care of agitated patients."
Quitting Not the Issue
"The problem people run into is that patients say they don't want to quit smoking," said Dr. Allen.
Don't fight with them about whether they can smoke or not, just try to convince them to use the patch and do that as part of their routine care don't wait until they start throwing the furniture and need a shot to have this conversation.
"What I'm recommending is that we say we're not asking them to quit smoking but that we think they'll be more comfortable if they use the patch. Don't fight with them about whether they can smoke or not, just try to convince them to use the patch and do that as part of their routine care don't wait until they start throwing the furniture and need a shot to have this conversation," he added.
The findings also revealed that patients with lower Fagerström scores, indicating a milder level of nicotine dependence, were more responsive to nicotine replacement.
For patients with Fagerström scores of 7 or 8 (low dependence), there was a significant reduction in agitation in the intervention group compared with placebo at 4 hours (P = .010) and 24 hours (P = .004). However, in patients with higher dependence the reduction was similar in both groups.
"It is possible that the 21-mg patch was inadequate for the more nicotine-dependent individuals in the study," the study authors write.
"We chose to study transdermal delivery of nicotine for its predictability, but nicotine gum should also be effective and has a rapid onset. It may be necessary to combine gum with the patch or otherwise obtain higher doses to better manage agitation in this patient population," they add.
Dr. Allen and colleagues discovered during the study that most patients did not want a patch at first.
"They want to smoke, and they don't think the patches will work. And there's a sense in which the patches don't work because they don't provide the kind of immediate rush that cigarettes do. But that's actually what's important about the study it demonstrates that even though the patient doesn't feel the rush, the nicotine is helping to calm them down."
Outcome Measure Accurate?
Reached for outside comment on the study, Tony George, MD, professor and head of the Division of Addiction Psychiatry at the University of Toronto, Ontario, Canada, said the study shows that "when you have psychiatric patients in the [emergency department], if you aggressively treat them with nicotine replacement you will have better outcomes."
Dr. George, who is also clinical director of the Schizophrenia Program at Toronto's Centre for Addiction and Mental Health, said his institution's emergency department has been smoke free for the past 4 years.
"We use nicotine patches, gum, bupropion, and varenicline, and we offer it to people immediately when they come into our emergency room," he told Medscape Medical News.
What you're really doing here is treating nicotine withdrawal and craving and the agitation related to that.
However, Dr. George took issue with the investigators' conclusion.
"I'm not sure the outcome that they were measuring was truly agitation. My worry is that because they didn't measure nicotine withdrawal or craving that this is likely the mediator of that.
"I think we should call a spade a spade because what you're really doing here is treating nicotine withdrawal and craving and the agitation related to that," said Dr. George.
Dr. Allen has received consulting fees from Alexza and research supported from AstraZeneca, Dainippon Sumitomo, Forest, 13 Research, NARSAD, National Institute of Mental Health, Novartis, Ortho-McNeil-Janssen, United Bio-Source Corporation, and Wyeth. The other study authors report no financial relationships with industry. Dr. George reports that he has received grant support from Pfizer Inc and has received consulting fees from Pfizer, Evotec, Eli Lilly, Janssen-Ortho, and Astra-Zeneca in the past 2 years. He receives grants from the Canadian Institute for Health Research, the Canadian Tobacco Control Research Initiative, the Canada Foundation for Innovation and the Ontario Mental Health Foundation, the National Institutes of Health, and the Chair in Addiction Psychiatry from the University of Toronto.
Am J Psychiatry. Published online January 18, 2011.
Authors and DisclosuresJournalist
Kate Johnson
Freelance writer, Montreal, Canada
