Jane Salodof MacNeil

ALBUQUERQUE — Sexual trauma is the primary cause of posttraumatic stress disorder in female veterans, according to a psychologist who provides care at a trauma clinic for female veterans in New Mexico.

Diane T. Castillo, Ph.D., estimates that 80%–90% of female veterans who walk into the Women's Trauma Clinic with posttraumatic stress disorder (PTSD) had suffered sexual trauma before, during, and/or after their military service.

Most PTSD in male veterans is entirely combat related, but that is the case for only about 8% of cases in female veterans, she says. She calculates that about 70% of female PTSD patients have only sexual problems but adds that some women veterans have suffered sexual and combat traumas.

Dr. Castillo, coordinator of the Women's Stress Disorder Treatment Team in the Albuquerque-based New Mexico Veterans Affairs Health Care System, gave an overview of experiences from her clinic at a psychiatric symposium sponsored by the University of New Mexico.

Dr. Castillo said that the prevalence of sexual trauma in female PTSD patients varies among veterans' centers, but that it is higher overall than the prevalence that is found in the general population. PTSD prevalence among female veterans, she added, has inched up from about 8% during the Persian Gulf War to close to 9%.

Dr. Castillo presented a complex portrait of the traumas experienced by her patients, augmenting her talk with a videotape, “Women Who Served in Our Military: Insights for Interventions,” which was produced by the Veterans Affairs' National Center for PTSD and narrated by television journalist Jane Pauley.

The traumas discussed during the symposium ranged from a sexual assault by two male noncommissioned officers who were never prosecuted to the persistent sexual harassment of women while on duty in Iraq and in the Persian Gulf War. Many, but not all, women soldiers were in sexually threatening circumstances, Dr. Castillo said, telling of the exception: a reserve unit from Las Vegas, N.M., whose members, male and female, had served together for many years and looked out for one another like extended family in Iraq.

Preliminary data from an ongoing research project in her center suggest anger is a common manifestation of PTSD in women veterans, Dr. Castillo said. She has been administering the Buss-Durkee Hostility Inventory to males with PTSD and other psychiatric disorders and to female PTSD patients in her clinic.

Stressing that the sample of females screened is still small, she said her findings so far suggest that:

Males with PTSD have higher anger scores, in particular for assault and verbal hostility, than do females with PTSD.

Males and females with PTSD score comparably on cognitive measures such as resentment, suspicion, and guilt.

Females with PTSD score higher for resentment and suspicion than do males with other psychiatric disorders.

Dr. Castillo and her copresenter, Dr. Stephanie K. Fallon, described a treatment program built around therapy groups at the clinic. Victims of sexual trauma receive free care, they said. The first step, an assessment, includes an initial interview and computerized psychological testing.

Identifying suicidal patients is crucial at this stage, according to Dr. Castillo: “If a person is actively suicidal, this is not the time to do trauma work.”

Dr. Fallon, associate director of residency training at the NM VA Health Care System, said medications are used to ease symptoms such as insomnia and nightmares but are secondary to the group work at the clinic. “The cornerstone of treatment for PTSD is psychotherapy, not medication,” she said.

All groups are optional and female veterans who agree to psychotherapy start first with a support group designed to educate them about therapy and about PTSD.

Most PTSD in male veterans is combat related, but that is the case for only about 8% of female veterans. DR. CASTILLO

ALBUQUERQUE — Sexual trauma is the primary cause of posttraumatic stress disorder in female veterans, according to a psychologist who provides care at a trauma clinic for female veterans in New Mexico.

Diane T. Castillo, Ph.D., estimates that 80%–90% of female veterans who walk into the Women's Trauma Clinic with posttraumatic stress disorder (PTSD) had suffered sexual trauma before, during, and/or after their military service.

Most PTSD in male veterans is entirely combat related, but that is the case for only about 8% of cases in female veterans, she says. She calculates that about 70% of female PTSD patients have only sexual problems but adds that some women veterans have suffered sexual and combat traumas.

Dr. Castillo, coordinator of the Women's Stress Disorder Treatment Team in the Albuquerque-based New Mexico Veterans Affairs Health Care System, gave an overview of experiences from her clinic at a psychiatric symposium sponsored by the University of New Mexico.

Dr. Castillo said that the prevalence of sexual trauma in female PTSD patients varies among veterans' centers, but that it is higher overall than the prevalence that is found in the general population. PTSD prevalence among female veterans, she added, has inched up from about 8% during the Persian Gulf War to close to 9%.

Dr. Castillo presented a complex portrait of the traumas experienced by her patients, augmenting her talk with a videotape, “Women Who Served in Our Military: Insights for Interventions,” which was produced by the Veterans Affairs' National Center for PTSD and narrated by television journalist Jane Pauley.

The traumas discussed during the symposium ranged from a sexual assault by two male noncommissioned officers who were never prosecuted to the persistent sexual harassment of women while on duty in Iraq and in the Persian Gulf War. Many, but not all, women soldiers were in sexually threatening circumstances, Dr. Castillo said, telling of the exception: a reserve unit from Las Vegas, N.M., whose members, male and female, had served together for many years and looked out for one another like extended family in Iraq.

Preliminary data from an ongoing research project in her center suggest anger is a common manifestation of PTSD in women veterans, Dr. Castillo said. She has been administering the Buss-Durkee Hostility Inventory to males with PTSD and other psychiatric disorders and to female PTSD patients in her clinic.

Stressing that the sample of females screened is still small, she said her findings so far suggest that:

Males with PTSD have higher anger scores, in particular for assault and verbal hostility, than do females with PTSD.

Males and females with PTSD score comparably on cognitive measures such as resentment, suspicion, and guilt.

Females with PTSD score higher for resentment and suspicion than do males with other psychiatric disorders.

Dr. Castillo and her copresenter, Dr. Stephanie K. Fallon, described a treatment program built around therapy groups at the clinic. Victims of sexual trauma receive free care, they said. The first step, an assessment, includes an initial interview and computerized psychological testing.

Identifying suicidal patients is crucial at this stage, according to Dr. Castillo: “If a person is actively suicidal, this is not the time to do trauma work.”

Dr. Fallon, associate director of residency training at the NM VA Health Care System, said medications are used to ease symptoms such as insomnia and nightmares but are secondary to the group work at the clinic. “The cornerstone of treatment for PTSD is psychotherapy, not medication,” she said.

All groups are optional and female veterans who agree to psychotherapy start first with a support group designed to educate them about therapy and about PTSD.

Most PTSD in male veterans is combat related, but that is the case for only about 8% of female veterans. DR. CASTILLO

ALBUQUERQUE — Sexual trauma is the primary cause of posttraumatic stress disorder in female veterans, according to a psychologist who provides care at a trauma clinic for female veterans in New Mexico.

Diane T. Castillo, Ph.D., estimates that 80%–90% of female veterans who walk into the Women's Trauma Clinic with posttraumatic stress disorder (PTSD) had suffered sexual trauma before, during, and/or after their military service.

Most PTSD in male veterans is entirely combat related, but that is the case for only about 8% of cases in female veterans, she says. She calculates that about 70% of female PTSD patients have only sexual problems but adds that some women veterans have suffered sexual and combat traumas.

Dr. Castillo, coordinator of the Women's Stress Disorder Treatment Team in the Albuquerque-based New Mexico Veterans Affairs Health Care System, gave an overview of experiences from her clinic at a psychiatric symposium sponsored by the University of New Mexico.

Dr. Castillo said that the prevalence of sexual trauma in female PTSD patients varies among veterans' centers, but that it is higher overall than the prevalence that is found in the general population. PTSD prevalence among female veterans, she added, has inched up from about 8% during the Persian Gulf War to close to 9%.

Dr. Castillo presented a complex portrait of the traumas experienced by her patients, augmenting her talk with a videotape, “Women Who Served in Our Military: Insights for Interventions,” which was produced by the Veterans Affairs' National Center for PTSD and narrated by television journalist Jane Pauley.

The traumas discussed during the symposium ranged from a sexual assault by two male noncommissioned officers who were never prosecuted to the persistent sexual harassment of women while on duty in Iraq and in the Persian Gulf War. Many, but not all, women soldiers were in sexually threatening circumstances, Dr. Castillo said, telling of the exception: a reserve unit from Las Vegas, N.M., whose members, male and female, had served together for many years and looked out for one another like extended family in Iraq.

Preliminary data from an ongoing research project in her center suggest anger is a common manifestation of PTSD in women veterans, Dr. Castillo said. She has been administering the Buss-Durkee Hostility Inventory to males with PTSD and other psychiatric disorders and to female PTSD patients in her clinic.

Stressing that the sample of females screened is still small, she said her findings so far suggest that:

Males with PTSD have higher anger scores, in particular for assault and verbal hostility, than do females with PTSD.

Males and females with PTSD score comparably on cognitive measures such as resentment, suspicion, and guilt.

Females with PTSD score higher for resentment and suspicion than do males with other psychiatric disorders.

Dr. Castillo and her copresenter, Dr. Stephanie K. Fallon, described a treatment program built around therapy groups at the clinic. Victims of sexual trauma receive free care, they said. The first step, an assessment, includes an initial interview and computerized psychological testing.

Identifying suicidal patients is crucial at this stage, according to Dr. Castillo: “If a person is actively suicidal, this is not the time to do trauma work.”

Dr. Fallon, associate director of residency training at the NM VA Health Care System, said medications are used to ease symptoms such as insomnia and nightmares but are secondary to the group work at the clinic. “The cornerstone of treatment for PTSD is psychotherapy, not medication,” she said.

All groups are optional and female veterans who agree to psychotherapy start first with a support group designed to educate them about therapy and about PTSD.

Most PTSD in male veterans is combat related, but that is the case for only about 8% of female veterans. DR. CASTILLO

Clinicians should not rely on standard conversion tables when switching chronic pain patients to methadone from other opioid analgesics, according to three pain experts who have published guidance on methadone prescribing.

The widely available tables were designed mainly for acute single-dose pain control and not for long-term use. If a table calculates too high a dose, a patient could be at risk of overdose, they warned in separate interviews.

“Yet those tables have been utilized for chronic use, and that is a serious problem,” said Dr. Lynn Webster of Lifetree Pain Clinic in Salt Lake City. “They have to be abandoned. … It is particularly dangerous to go from other opioids to methadone.”

Dr. Webster recommended starting opioid-tolerant chronic patients on a ceiling dosage of 20 mg/day (10 mg if they are elderly or infirm) and slowly increasing the dosage (J. Opioid Mgmt. 2005;1:211–7). The previous opioid should not be stopped abruptly but titrated down while the methadone dosage increases. Dosage changes, he added, should be limited to once a week at most to allow side effects to become evident.

Dr. Howard Heit of Fairfax, Va., coauthor of a paper on universal precautions in pain medicine (Pain Med. 2005;6:107–12), said he uses the tables only “as a very, very rough guide.” When he switches a patient to methadone from another opioid, he multiplies whatever the conversion tables list by 20%–30% and titrates up slowly over time.

“I could always add medication, but I can't take out medication if the patient is on the floor, not breathing,” he said, describing methadone as a useful but unforgiving drug.

Lee A. Kral, Pharm.D., a faculty member at the University of Iowa Pain Center, Iowa City, tackled the conversion chart problem with a retrospective study to assess the efficacy and tolerability of methadone in chronic pain patients. She was scheduled to report on 107 patients at a November meeting of the American Society of Regional Anesthesia and Pain Medicine.

The average daily methadone dose was 20.5 mg, and the mean duration of therapy 21 months, according to Dr. Kral's abstract. About half the patients had adverse effects, the most common of which were sedation, gastrointestinal symptoms/constipation, cognitive difficulties, and headache. Although 29 patients stopped taking methadone, only 12 did so because of adverse effects.

Dr. Kral said she is not aware of sleep apnea in any of the Iowa patients, perhaps because they are kept on low doses. Methadone is not dangerous, she maintained. It is different, and it is misunderstood. “You can't put that kind of a label on a medication,” she said. “They are all dangerous in different ways.”

To help primary care physicians understand the pharmacokinetics and pharmacodynamics that distinguish methadone from other opioids, Dr. Kral collaborated with a family physician in writing a guide to methadone treatment for pain. They explained that methadone, a mu-opioid agonist, has a short-lasting analgesic effect but a long half-life, and that its metabolism varies among individuals. Pain relief, which may last as little as 3–6 hours at the start of methadone therapy, becomes longer with repeated dosing. Yet plasma levels can take 5–7 days to stabilize (Am. Fam. Physician 2005;71:1353–8).

In light of methadone's long half-life, Dr. Webster and Dr. Heit stressed that overdose risk may be highest at the outset of therapy. One pill does not relieve pain, so some at-risk patients pop another pill and maybe one more pill, not realizing that the drug is accumulating within them. “What they are trying to do is control their pain,” Dr. Webster said.

Education is vital, Dr. Webster said. Patients must understand that it could be fatal to deviate from the dosage or to mix methadone with alcohol, other prescriptions, or illicit substances.

Clinicians should not rely on standard conversion tables when switching chronic pain patients to methadone from other opioid analgesics, according to three pain experts who have published guidance on methadone prescribing.

The widely available tables were designed mainly for acute single-dose pain control and not for long-term use. If a table calculates too high a dose, a patient could be at risk of overdose, they warned in separate interviews.

“Yet those tables have been utilized for chronic use, and that is a serious problem,” said Dr. Lynn Webster of Lifetree Pain Clinic in Salt Lake City. “They have to be abandoned. … It is particularly dangerous to go from other opioids to methadone.”

Dr. Webster recommended starting opioid-tolerant chronic patients on a ceiling dosage of 20 mg/day (10 mg if they are elderly or infirm) and slowly increasing the dosage (J. Opioid Mgmt. 2005;1:211–7). The previous opioid should not be stopped abruptly but titrated down while the methadone dosage increases. Dosage changes, he added, should be limited to once a week at most to allow side effects to become evident.

Dr. Howard Heit of Fairfax, Va., coauthor of a paper on universal precautions in pain medicine (Pain Med. 2005;6:107–12), said he uses the tables only “as a very, very rough guide.” When he switches a patient to methadone from another opioid, he multiplies whatever the conversion tables list by 20%–30% and titrates up slowly over time.

“I could always add medication, but I can't take out medication if the patient is on the floor, not breathing,” he said, describing methadone as a useful but unforgiving drug.

Lee A. Kral, Pharm.D., a faculty member at the University of Iowa Pain Center, Iowa City, tackled the conversion chart problem with a retrospective study to assess the efficacy and tolerability of methadone in chronic pain patients. She was scheduled to report on 107 patients at a November meeting of the American Society of Regional Anesthesia and Pain Medicine.

The average daily methadone dose was 20.5 mg, and the mean duration of therapy 21 months, according to Dr. Kral's abstract. About half the patients had adverse effects, the most common of which were sedation, gastrointestinal symptoms/constipation, cognitive difficulties, and headache. Although 29 patients stopped taking methadone, only 12 did so because of adverse effects.

Dr. Kral said she is not aware of sleep apnea in any of the Iowa patients, perhaps because they are kept on low doses. Methadone is not dangerous, she maintained. It is different, and it is misunderstood. “You can't put that kind of a label on a medication,” she said. “They are all dangerous in different ways.”

To help primary care physicians understand the pharmacokinetics and pharmacodynamics that distinguish methadone from other opioids, Dr. Kral collaborated with a family physician in writing a guide to methadone treatment for pain. They explained that methadone, a mu-opioid agonist, has a short-lasting analgesic effect but a long half-life, and that its metabolism varies among individuals. Pain relief, which may last as little as 3–6 hours at the start of methadone therapy, becomes longer with repeated dosing. Yet plasma levels can take 5–7 days to stabilize (Am. Fam. Physician 2005;71:1353–8).

In light of methadone's long half-life, Dr. Webster and Dr. Heit stressed that overdose risk may be highest at the outset of therapy. One pill does not relieve pain, so some at-risk patients pop another pill and maybe one more pill, not realizing that the drug is accumulating within them. “What they are trying to do is control their pain,” Dr. Webster said.

Education is vital, Dr. Webster said. Patients must understand that it could be fatal to deviate from the dosage or to mix methadone with alcohol, other prescriptions, or illicit substances.

Clinicians should not rely on standard conversion tables when switching chronic pain patients to methadone from other opioid analgesics, according to three pain experts who have published guidance on methadone prescribing.

The widely available tables were designed mainly for acute single-dose pain control and not for long-term use. If a table calculates too high a dose, a patient could be at risk of overdose, they warned in separate interviews.

“Yet those tables have been utilized for chronic use, and that is a serious problem,” said Dr. Lynn Webster of Lifetree Pain Clinic in Salt Lake City. “They have to be abandoned. … It is particularly dangerous to go from other opioids to methadone.”

Dr. Webster recommended starting opioid-tolerant chronic patients on a ceiling dosage of 20 mg/day (10 mg if they are elderly or infirm) and slowly increasing the dosage (J. Opioid Mgmt. 2005;1:211–7). The previous opioid should not be stopped abruptly but titrated down while the methadone dosage increases. Dosage changes, he added, should be limited to once a week at most to allow side effects to become evident.

Dr. Howard Heit of Fairfax, Va., coauthor of a paper on universal precautions in pain medicine (Pain Med. 2005;6:107–12), said he uses the tables only “as a very, very rough guide.” When he switches a patient to methadone from another opioid, he multiplies whatever the conversion tables list by 20%–30% and titrates up slowly over time.

“I could always add medication, but I can't take out medication if the patient is on the floor, not breathing,” he said, describing methadone as a useful but unforgiving drug.

Lee A. Kral, Pharm.D., a faculty member at the University of Iowa Pain Center, Iowa City, tackled the conversion chart problem with a retrospective study to assess the efficacy and tolerability of methadone in chronic pain patients. She was scheduled to report on 107 patients at a November meeting of the American Society of Regional Anesthesia and Pain Medicine.

The average daily methadone dose was 20.5 mg, and the mean duration of therapy 21 months, according to Dr. Kral's abstract. About half the patients had adverse effects, the most common of which were sedation, gastrointestinal symptoms/constipation, cognitive difficulties, and headache. Although 29 patients stopped taking methadone, only 12 did so because of adverse effects.

Dr. Kral said she is not aware of sleep apnea in any of the Iowa patients, perhaps because they are kept on low doses. Methadone is not dangerous, she maintained. It is different, and it is misunderstood. “You can't put that kind of a label on a medication,” she said. “They are all dangerous in different ways.”

To help primary care physicians understand the pharmacokinetics and pharmacodynamics that distinguish methadone from other opioids, Dr. Kral collaborated with a family physician in writing a guide to methadone treatment for pain. They explained that methadone, a mu-opioid agonist, has a short-lasting analgesic effect but a long half-life, and that its metabolism varies among individuals. Pain relief, which may last as little as 3–6 hours at the start of methadone therapy, becomes longer with repeated dosing. Yet plasma levels can take 5–7 days to stabilize (Am. Fam. Physician 2005;71:1353–8).

In light of methadone's long half-life, Dr. Webster and Dr. Heit stressed that overdose risk may be highest at the outset of therapy. One pill does not relieve pain, so some at-risk patients pop another pill and maybe one more pill, not realizing that the drug is accumulating within them. “What they are trying to do is control their pain,” Dr. Webster said.

Education is vital, Dr. Webster said. Patients must understand that it could be fatal to deviate from the dosage or to mix methadone with alcohol, other prescriptions, or illicit substances.

PARIS – Generalized anxiety disorder occurs as a late-onset condition more often than is recognized, according to investigators who presented the first large treatment trial in elderly patients during the annual congress of the European College of Neuropsychopharmacology.

Dr. Francesca Baldinetti reported that the average age of onset was 56 years in 273 outpatients with generalized anxiety disorder (GAD) who were aged at least 65 years and who enrolled in the placebo-controlled trial. The study found pregabalin (Lyrica) to be at least as effective in the elderly as in previous trials with younger patients.

“In reality, there is a late onset of generalized anxiety disorder in the later stage of life,” said Dr. Baldinetti, medical director of worldwide neuroscience at Pfizer Inc., in a presentation of the new data at a session on psychiatric disorders in older people.

“That is not in the literature,” added the lead author, Dr. Stuart A. Montgomery, a professor emeritus of psychiatry at the Imperial College London.

Commenting from the audience at Dr. Montgomery's invitation, an investigator of pregabalin in adult patients described the characterization of GAD as an early-onset disorder as a misconception. Most patients develop the full syndrome after the age of 30, according to Dr. Hans-Ulrich Wittchen, professor of clinical psychology and epidemiology at the Technische Universität Dresden (Germany).

He urged careful questioning of newly diagnosed older GAD patients who report they first had symptoms as children. “It may be that there are anxiety disorders preceding that [new] development … But if you probe the GAD symptomatology, this is another disorder,” he said. “This is not an early anxiety disorder.”

In her presentation, Dr. Baldinetti said that at least half of all newly diagnosed cases of GAD occur after age 30 years and a third after age 40. Five different studies from the United States and Europe have shown prevalence rates ranging from 1.9% to 7.2% in the elderly, she said.

All patients in the pregabalin study had Hamilton Rating Scale for Anxiety (HAM-A) scores of 20 or more, with a baseline average of 26.6 for 177 patients randomized to pregabalin and 26.1 for 96 patients on placebo. Patients with major depression and other anxiety or substance abuse disorders were excluded. The participants had three to four prior episodes of GAD on average, with the current episode lasting about 15 months. The average age was 72 years, as about a third of the population was 75 years of age or older. About three-fourths of those enrolled were female.

A flexible-dose regimen started the active drug group on 150 mg per day of pregabalin, which clinicians could titrate up to 600 mg by week 6 of the 8-week trial. The average dose used was 270 mg.

Dr. Baldinetti suggested that the flexible dosing probably was responsible for the main difference in outcomes relative to the earlier adult trials. Whereas younger patients on pregabalin had a significantly better response than did those on placebo during week 1, elderly patients on pregabalin began to show significant improvement compared with the control group during week 2.

By the elderly trial's end, 64.2% of the pregabalin cohort had responded versus 50% of the control group. Total HAM-A scores fell by more than 12 points in the pregabalin group, versus more than 10 points with placebo in a last-observation-carried-forward (LOCF) analysis.

The effect was seen in HAM-A psychic and HAM-A somatic scores. HAM-A psychic scores fell by 7.8 points with pregabalin versus 6.3 points with placebo. HAM-A somatic scores fell by 6.6 points with pregabalin versus 5.4 points with placebo.

Dr. Baldinetti noted that the drug's benefits were significant in subgroups of patients with severe anxiety and with subsyndromal depression.

About a quarter of the patients–28% of those on placebo and 25% of the pregabalin group–dropped out of the study. Only 7% on placebo and 4% on pregabalin did so for lack of efficacy. Adverse events caused discontinuation by 11% of the pregabalin group and 9% on placebo. The most common adverse events with pregabalin were dizziness (20.3%), somnolence (13%), headache (10.2%) nausea (9%), and infection (5.6%).

An anticonvulsant with anxiolytic and analgesic properties, pregabalin is approved in the United States for treatment of neuropathic pain and seizures. It is also under study for fibromyalgia.

Elderly patients on pregabalin began to show significant improvement during week 2. DR. BALDINETTI

PARIS – Generalized anxiety disorder occurs as a late-onset condition more often than is recognized, according to investigators who presented the first large treatment trial in elderly patients during the annual congress of the European College of Neuropsychopharmacology.

Dr. Francesca Baldinetti reported that the average age of onset was 56 years in 273 outpatients with generalized anxiety disorder (GAD) who were aged at least 65 years and who enrolled in the placebo-controlled trial. The study found pregabalin (Lyrica) to be at least as effective in the elderly as in previous trials with younger patients.

“In reality, there is a late onset of generalized anxiety disorder in the later stage of life,” said Dr. Baldinetti, medical director of worldwide neuroscience at Pfizer Inc., in a presentation of the new data at a session on psychiatric disorders in older people.

“That is not in the literature,” added the lead author, Dr. Stuart A. Montgomery, a professor emeritus of psychiatry at the Imperial College London.

Commenting from the audience at Dr. Montgomery's invitation, an investigator of pregabalin in adult patients described the characterization of GAD as an early-onset disorder as a misconception. Most patients develop the full syndrome after the age of 30, according to Dr. Hans-Ulrich Wittchen, professor of clinical psychology and epidemiology at the Technische Universität Dresden (Germany).

He urged careful questioning of newly diagnosed older GAD patients who report they first had symptoms as children. “It may be that there are anxiety disorders preceding that [new] development … But if you probe the GAD symptomatology, this is another disorder,” he said. “This is not an early anxiety disorder.”

In her presentation, Dr. Baldinetti said that at least half of all newly diagnosed cases of GAD occur after age 30 years and a third after age 40. Five different studies from the United States and Europe have shown prevalence rates ranging from 1.9% to 7.2% in the elderly, she said.

All patients in the pregabalin study had Hamilton Rating Scale for Anxiety (HAM-A) scores of 20 or more, with a baseline average of 26.6 for 177 patients randomized to pregabalin and 26.1 for 96 patients on placebo. Patients with major depression and other anxiety or substance abuse disorders were excluded. The participants had three to four prior episodes of GAD on average, with the current episode lasting about 15 months. The average age was 72 years, as about a third of the population was 75 years of age or older. About three-fourths of those enrolled were female.

A flexible-dose regimen started the active drug group on 150 mg per day of pregabalin, which clinicians could titrate up to 600 mg by week 6 of the 8-week trial. The average dose used was 270 mg.

Dr. Baldinetti suggested that the flexible dosing probably was responsible for the main difference in outcomes relative to the earlier adult trials. Whereas younger patients on pregabalin had a significantly better response than did those on placebo during week 1, elderly patients on pregabalin began to show significant improvement compared with the control group during week 2.

By the elderly trial's end, 64.2% of the pregabalin cohort had responded versus 50% of the control group. Total HAM-A scores fell by more than 12 points in the pregabalin group, versus more than 10 points with placebo in a last-observation-carried-forward (LOCF) analysis.

The effect was seen in HAM-A psychic and HAM-A somatic scores. HAM-A psychic scores fell by 7.8 points with pregabalin versus 6.3 points with placebo. HAM-A somatic scores fell by 6.6 points with pregabalin versus 5.4 points with placebo.

Dr. Baldinetti noted that the drug's benefits were significant in subgroups of patients with severe anxiety and with subsyndromal depression.

About a quarter of the patients–28% of those on placebo and 25% of the pregabalin group–dropped out of the study. Only 7% on placebo and 4% on pregabalin did so for lack of efficacy. Adverse events caused discontinuation by 11% of the pregabalin group and 9% on placebo. The most common adverse events with pregabalin were dizziness (20.3%), somnolence (13%), headache (10.2%) nausea (9%), and infection (5.6%).

An anticonvulsant with anxiolytic and analgesic properties, pregabalin is approved in the United States for treatment of neuropathic pain and seizures. It is also under study for fibromyalgia.

Elderly patients on pregabalin began to show significant improvement during week 2. DR. BALDINETTI

PARIS – Generalized anxiety disorder occurs as a late-onset condition more often than is recognized, according to investigators who presented the first large treatment trial in elderly patients during the annual congress of the European College of Neuropsychopharmacology.

Dr. Francesca Baldinetti reported that the average age of onset was 56 years in 273 outpatients with generalized anxiety disorder (GAD) who were aged at least 65 years and who enrolled in the placebo-controlled trial. The study found pregabalin (Lyrica) to be at least as effective in the elderly as in previous trials with younger patients.

“In reality, there is a late onset of generalized anxiety disorder in the later stage of life,” said Dr. Baldinetti, medical director of worldwide neuroscience at Pfizer Inc., in a presentation of the new data at a session on psychiatric disorders in older people.

“That is not in the literature,” added the lead author, Dr. Stuart A. Montgomery, a professor emeritus of psychiatry at the Imperial College London.

Commenting from the audience at Dr. Montgomery's invitation, an investigator of pregabalin in adult patients described the characterization of GAD as an early-onset disorder as a misconception. Most patients develop the full syndrome after the age of 30, according to Dr. Hans-Ulrich Wittchen, professor of clinical psychology and epidemiology at the Technische Universität Dresden (Germany).

He urged careful questioning of newly diagnosed older GAD patients who report they first had symptoms as children. “It may be that there are anxiety disorders preceding that [new] development … But if you probe the GAD symptomatology, this is another disorder,” he said. “This is not an early anxiety disorder.”

In her presentation, Dr. Baldinetti said that at least half of all newly diagnosed cases of GAD occur after age 30 years and a third after age 40. Five different studies from the United States and Europe have shown prevalence rates ranging from 1.9% to 7.2% in the elderly, she said.

All patients in the pregabalin study had Hamilton Rating Scale for Anxiety (HAM-A) scores of 20 or more, with a baseline average of 26.6 for 177 patients randomized to pregabalin and 26.1 for 96 patients on placebo. Patients with major depression and other anxiety or substance abuse disorders were excluded. The participants had three to four prior episodes of GAD on average, with the current episode lasting about 15 months. The average age was 72 years, as about a third of the population was 75 years of age or older. About three-fourths of those enrolled were female.

A flexible-dose regimen started the active drug group on 150 mg per day of pregabalin, which clinicians could titrate up to 600 mg by week 6 of the 8-week trial. The average dose used was 270 mg.

Dr. Baldinetti suggested that the flexible dosing probably was responsible for the main difference in outcomes relative to the earlier adult trials. Whereas younger patients on pregabalin had a significantly better response than did those on placebo during week 1, elderly patients on pregabalin began to show significant improvement compared with the control group during week 2.

By the elderly trial's end, 64.2% of the pregabalin cohort had responded versus 50% of the control group. Total HAM-A scores fell by more than 12 points in the pregabalin group, versus more than 10 points with placebo in a last-observation-carried-forward (LOCF) analysis.

The effect was seen in HAM-A psychic and HAM-A somatic scores. HAM-A psychic scores fell by 7.8 points with pregabalin versus 6.3 points with placebo. HAM-A somatic scores fell by 6.6 points with pregabalin versus 5.4 points with placebo.

Dr. Baldinetti noted that the drug's benefits were significant in subgroups of patients with severe anxiety and with subsyndromal depression.

About a quarter of the patients–28% of those on placebo and 25% of the pregabalin group–dropped out of the study. Only 7% on placebo and 4% on pregabalin did so for lack of efficacy. Adverse events caused discontinuation by 11% of the pregabalin group and 9% on placebo. The most common adverse events with pregabalin were dizziness (20.3%), somnolence (13%), headache (10.2%) nausea (9%), and infection (5.6%).

An anticonvulsant with anxiolytic and analgesic properties, pregabalin is approved in the United States for treatment of neuropathic pain and seizures. It is also under study for fibromyalgia.

Elderly patients on pregabalin began to show significant improvement during week 2. DR. BALDINETTI

SANTA FE, N.M. — Anxiety disorders are a common comorbidity that lead to worse outcomes for patients with major depressive and bipolar disorders, speakers warned at a psychiatric symposium sponsored by the University of Arizona.

Dr. A. John Rush reported that more than half, 53%, of 2,876 depressed patients in the first phase of the STAR*D trial had anxious depression (Am. J. Psychiatry 2006;163:28–40).

Anxious patients were significantly less likely to achieve remission on their first medication for depression (odds ratio 0.77), according to Dr. Rush, principal investigator of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.

Each of the comorbid anxiety disorders was associated with a lower remission rate. Posttraumatic stress disorder (PTSD) had the most negative effect (OR 0.6). Only social phobia did not have a significant impact, though it also reduced the odds of remission (OR 0.87).

“A person coming in with anxiety disorder takes longer and is less likely to remit,” said Dr. Rush, a distinguished professor in mental health at the University of Texas Southwestern Medical Center in Dallas.

About half of bipolar depression patients also had an anxiety disorder, according to an analysis of the first 500 patients in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) trial, another large multicenter study supported by the National Institute of Mental Health. Lifetime prevalence was 51%, and 31% had a current anxiety disorder when they entered the study.

Bipolar patients with comorbid anxiety were significantly more likely to have a history of suicide attempts, said Dr. Gary Sachs, principal investigator of STEP-BD and director of the Bipolar Clinic and Research Program at Massachusetts General Hospital in Boston.

The rate of suicide attempts was 52% in patients with lifetime anxiety disorder, compared with 22% in patients who did not have a history of anxiety disorder. The highest rate, 65%, was in patients with a history of posttraumatic stress disorder (Am. J. Psychiatry 2004;161:2222–9).

Bipolar patients with lifetime anxiety disorders also had an earlier age of bipolar onset, 15.6 years vs. 19.4 years in patients who did not have a history of anxiety disorder, Dr. Sachs said at the meeting, which also was sponsored by the University of Texas Southwestern Medical Center at Dallas and the University of New Mexico.

Length of recovery was shorter as well in patients with a history of anxiety disorder. Their longest mean period of euthymia was 183 days, compared with 254 days for patients without lifetime anxiety.

Dr. Murray B. Stein called for greater efforts to treat comorbid anxiety in patients with mood disorders. About 50%–60% of people with mood disorders also have an anxiety disorder, according to Dr. Stein, director of the Anxiety and Traumatic Stress Disorders Program at the University of California, San Diego. Conversely, he estimated that 80%–90% of people with general anxiety disorder will also have major depression at some point, and most had the anxiety disorder first.

Though anxiety is an early-onset disorder, he noted that it is rarely studied in children. In one of the few studies that did so, he said, nearly two-thirds of children with social anxiety disorder responded to a selective serotonin reuptake inhibitor (SSRI), and nearly as many went into remission.

Most antidepressants relieve symptoms in adult patients with anxiety disorders, Dr. Stein said, possibly because they treat both syndromes. “You get some benefit, but you don't get a really robust response,” he said of SSRIs used in PTSD. Though SSRIs have been shown to be better than placebo for general anxiety disorder, he said the benefit likewise was not robust.

As benzodiazepines are effective for anxiety disorders, he suggested they might also treat depression. “We were taught it is important to separate anxiety and depression because benzodiazepines could make people worse. I don't think there are any data that benzodiazepines make people worse.”

Other classes of medication, including anticonvulsants, are sometimes used for resistant anxiety disorders, but Dr. Stein said more information is needed about their safety and effectiveness.

Cognitive-behavioral therapy should be considered as an adjunct or an alternative to medication for anxiety disorders, he added. “The best cognitive-behavioral therapy is as good as the best medication we can provide.”

SANTA FE, N.M. — Anxiety disorders are a common comorbidity that lead to worse outcomes for patients with major depressive and bipolar disorders, speakers warned at a psychiatric symposium sponsored by the University of Arizona.

Dr. A. John Rush reported that more than half, 53%, of 2,876 depressed patients in the first phase of the STAR*D trial had anxious depression (Am. J. Psychiatry 2006;163:28–40).

Anxious patients were significantly less likely to achieve remission on their first medication for depression (odds ratio 0.77), according to Dr. Rush, principal investigator of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.

Each of the comorbid anxiety disorders was associated with a lower remission rate. Posttraumatic stress disorder (PTSD) had the most negative effect (OR 0.6). Only social phobia did not have a significant impact, though it also reduced the odds of remission (OR 0.87).

“A person coming in with anxiety disorder takes longer and is less likely to remit,” said Dr. Rush, a distinguished professor in mental health at the University of Texas Southwestern Medical Center in Dallas.

About half of bipolar depression patients also had an anxiety disorder, according to an analysis of the first 500 patients in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) trial, another large multicenter study supported by the National Institute of Mental Health. Lifetime prevalence was 51%, and 31% had a current anxiety disorder when they entered the study.

Bipolar patients with comorbid anxiety were significantly more likely to have a history of suicide attempts, said Dr. Gary Sachs, principal investigator of STEP-BD and director of the Bipolar Clinic and Research Program at Massachusetts General Hospital in Boston.

The rate of suicide attempts was 52% in patients with lifetime anxiety disorder, compared with 22% in patients who did not have a history of anxiety disorder. The highest rate, 65%, was in patients with a history of posttraumatic stress disorder (Am. J. Psychiatry 2004;161:2222–9).

Bipolar patients with lifetime anxiety disorders also had an earlier age of bipolar onset, 15.6 years vs. 19.4 years in patients who did not have a history of anxiety disorder, Dr. Sachs said at the meeting, which also was sponsored by the University of Texas Southwestern Medical Center at Dallas and the University of New Mexico.

Length of recovery was shorter as well in patients with a history of anxiety disorder. Their longest mean period of euthymia was 183 days, compared with 254 days for patients without lifetime anxiety.

Dr. Murray B. Stein called for greater efforts to treat comorbid anxiety in patients with mood disorders. About 50%–60% of people with mood disorders also have an anxiety disorder, according to Dr. Stein, director of the Anxiety and Traumatic Stress Disorders Program at the University of California, San Diego. Conversely, he estimated that 80%–90% of people with general anxiety disorder will also have major depression at some point, and most had the anxiety disorder first.

Though anxiety is an early-onset disorder, he noted that it is rarely studied in children. In one of the few studies that did so, he said, nearly two-thirds of children with social anxiety disorder responded to a selective serotonin reuptake inhibitor (SSRI), and nearly as many went into remission.

Most antidepressants relieve symptoms in adult patients with anxiety disorders, Dr. Stein said, possibly because they treat both syndromes. “You get some benefit, but you don't get a really robust response,” he said of SSRIs used in PTSD. Though SSRIs have been shown to be better than placebo for general anxiety disorder, he said the benefit likewise was not robust.

As benzodiazepines are effective for anxiety disorders, he suggested they might also treat depression. “We were taught it is important to separate anxiety and depression because benzodiazepines could make people worse. I don't think there are any data that benzodiazepines make people worse.”

Other classes of medication, including anticonvulsants, are sometimes used for resistant anxiety disorders, but Dr. Stein said more information is needed about their safety and effectiveness.

Cognitive-behavioral therapy should be considered as an adjunct or an alternative to medication for anxiety disorders, he added. “The best cognitive-behavioral therapy is as good as the best medication we can provide.”

SANTA FE, N.M. — Anxiety disorders are a common comorbidity that lead to worse outcomes for patients with major depressive and bipolar disorders, speakers warned at a psychiatric symposium sponsored by the University of Arizona.

Dr. A. John Rush reported that more than half, 53%, of 2,876 depressed patients in the first phase of the STAR*D trial had anxious depression (Am. J. Psychiatry 2006;163:28–40).

Anxious patients were significantly less likely to achieve remission on their first medication for depression (odds ratio 0.77), according to Dr. Rush, principal investigator of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.

Each of the comorbid anxiety disorders was associated with a lower remission rate. Posttraumatic stress disorder (PTSD) had the most negative effect (OR 0.6). Only social phobia did not have a significant impact, though it also reduced the odds of remission (OR 0.87).

“A person coming in with anxiety disorder takes longer and is less likely to remit,” said Dr. Rush, a distinguished professor in mental health at the University of Texas Southwestern Medical Center in Dallas.

About half of bipolar depression patients also had an anxiety disorder, according to an analysis of the first 500 patients in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) trial, another large multicenter study supported by the National Institute of Mental Health. Lifetime prevalence was 51%, and 31% had a current anxiety disorder when they entered the study.

Bipolar patients with comorbid anxiety were significantly more likely to have a history of suicide attempts, said Dr. Gary Sachs, principal investigator of STEP-BD and director of the Bipolar Clinic and Research Program at Massachusetts General Hospital in Boston.

The rate of suicide attempts was 52% in patients with lifetime anxiety disorder, compared with 22% in patients who did not have a history of anxiety disorder. The highest rate, 65%, was in patients with a history of posttraumatic stress disorder (Am. J. Psychiatry 2004;161:2222–9).

Bipolar patients with lifetime anxiety disorders also had an earlier age of bipolar onset, 15.6 years vs. 19.4 years in patients who did not have a history of anxiety disorder, Dr. Sachs said at the meeting, which also was sponsored by the University of Texas Southwestern Medical Center at Dallas and the University of New Mexico.

Length of recovery was shorter as well in patients with a history of anxiety disorder. Their longest mean period of euthymia was 183 days, compared with 254 days for patients without lifetime anxiety.

Dr. Murray B. Stein called for greater efforts to treat comorbid anxiety in patients with mood disorders. About 50%–60% of people with mood disorders also have an anxiety disorder, according to Dr. Stein, director of the Anxiety and Traumatic Stress Disorders Program at the University of California, San Diego. Conversely, he estimated that 80%–90% of people with general anxiety disorder will also have major depression at some point, and most had the anxiety disorder first.

Though anxiety is an early-onset disorder, he noted that it is rarely studied in children. In one of the few studies that did so, he said, nearly two-thirds of children with social anxiety disorder responded to a selective serotonin reuptake inhibitor (SSRI), and nearly as many went into remission.

Most antidepressants relieve symptoms in adult patients with anxiety disorders, Dr. Stein said, possibly because they treat both syndromes. “You get some benefit, but you don't get a really robust response,” he said of SSRIs used in PTSD. Though SSRIs have been shown to be better than placebo for general anxiety disorder, he said the benefit likewise was not robust.

As benzodiazepines are effective for anxiety disorders, he suggested they might also treat depression. “We were taught it is important to separate anxiety and depression because benzodiazepines could make people worse. I don't think there are any data that benzodiazepines make people worse.”

Other classes of medication, including anticonvulsants, are sometimes used for resistant anxiety disorders, but Dr. Stein said more information is needed about their safety and effectiveness.

Cognitive-behavioral therapy should be considered as an adjunct or an alternative to medication for anxiety disorders, he added. “The best cognitive-behavioral therapy is as good as the best medication we can provide.”

PARIS — Tamoxifen, a drug that is widely used in the treatment of breast cancer, significantly reduced the manic symptoms of bipolar disorder in a randomized, placebo-controlled trial presented in a breaking news session at the annual congress of the European College of Neuropsychopharmacology.

Dr. Aysegul Yildiz-Yesiloglu reported that 14 of 29 acutely ill patients had at least a 50% reduction in their scores on standard measures of mania with tamoxifen treatment. Only 1 of 21 patients improved on placebo during the 3-week trial. Depressive symptoms were not affected.

Although tamoxifen use in breast cancer is based on its antiestrogen effects, the investigators were drawn to the drug's activity as a protein kinase C (PKC) inhibitor, according to Dr. Yildiz-Yesiloglu, of Dokuz Eylul University in Izmir, Turkey, where the study was conducted.

She said the researchers hypothesized that inhibiting the PKC pathway could be important in bipolar disorder because lithium and valproate interfere with PKC signaling. For reasons not well understood, both mood stabilizers can reduce mania despite being structurally different.

Tamoxifen was chosen for the trial because it is the only direct PKC inhibitor approved for use in humans. It had been well tolerated in a pilot study that reported amelioration of manic symptoms in five of seven bipolar patients in the neuropsychiatric research unit at the Detroit Medical Center (Arch. Gen. Psychiatry 2000;57:95–7).

Dr. Yildiz-Yesiloglu, currently at Harvard Medical School in Boston, and her colleagues randomized 67 manic patients in the double-blind study. All had provided written consent together with at least one first-degree relative.

Six patients in the tamoxifen group and 11 patients in the placebo group dropped out because of severity of symptoms. This left 29 patients randomized to tamoxifen and 21 to placebo who completed the trial. To counteract any potential bias, Dr. Yildiz-Yesiloglu said the researchers performed secondary linear mixed-model analyses, incorporating all patients and all observations up to the point a person who dropped out left the study.

Patients started on 20 mg of tamoxifen twice daily, and the dose was increased up to 40 mg twice daily. The only psychotropic agent they could use during the study was lorazepam as a rescue medication for anxiety. The number of tablets used declined significantly over the course of the study in patients treated with tamoxifen but not in those in the placebo group.

Mania scores began dropping within 2 weeks of the start of tamoxifen treatment on both the Young Mania Rating Scale and the Positive and Negative Syndrome Scale. The improvements observed over 3 weeks with both scales were highly significant statistically, compared with placebo.

Scores on the Hamilton Rating Scale for Depression showed no improvement with tamoxifen or placebo and no difference between the two groups.

Most adverse events were minor and did not include the hormonal effects common in breast cancer patients taking tamoxifen as an adjunct therapy. “For long-term use, there are some side effects that we would expect, but for 21 days' use we would expect only some flushing on the face and maybe some small acne reaction,” Dr. Yildiz-Yesiloglu said in an interview after her presentation.

The Stanley Medical Research Institute in Chevy Chase, Md., financed the study, which received no drug company funding. Dr. Yildiz-Yesiloglu said that the outcome supports further investigation of the PKC pathway as a target for drugs treating bipolar disorder.

Researchers focused on tamoxifen because of its activity as a protein kinase C inhibitor. DR. YILDIZ-YESILOGLU

PARIS — Tamoxifen, a drug that is widely used in the treatment of breast cancer, significantly reduced the manic symptoms of bipolar disorder in a randomized, placebo-controlled trial presented in a breaking news session at the annual congress of the European College of Neuropsychopharmacology.

Dr. Aysegul Yildiz-Yesiloglu reported that 14 of 29 acutely ill patients had at least a 50% reduction in their scores on standard measures of mania with tamoxifen treatment. Only 1 of 21 patients improved on placebo during the 3-week trial. Depressive symptoms were not affected.

Although tamoxifen use in breast cancer is based on its antiestrogen effects, the investigators were drawn to the drug's activity as a protein kinase C (PKC) inhibitor, according to Dr. Yildiz-Yesiloglu, of Dokuz Eylul University in Izmir, Turkey, where the study was conducted.

She said the researchers hypothesized that inhibiting the PKC pathway could be important in bipolar disorder because lithium and valproate interfere with PKC signaling. For reasons not well understood, both mood stabilizers can reduce mania despite being structurally different.

Tamoxifen was chosen for the trial because it is the only direct PKC inhibitor approved for use in humans. It had been well tolerated in a pilot study that reported amelioration of manic symptoms in five of seven bipolar patients in the neuropsychiatric research unit at the Detroit Medical Center (Arch. Gen. Psychiatry 2000;57:95–7).

Dr. Yildiz-Yesiloglu, currently at Harvard Medical School in Boston, and her colleagues randomized 67 manic patients in the double-blind study. All had provided written consent together with at least one first-degree relative.

Six patients in the tamoxifen group and 11 patients in the placebo group dropped out because of severity of symptoms. This left 29 patients randomized to tamoxifen and 21 to placebo who completed the trial. To counteract any potential bias, Dr. Yildiz-Yesiloglu said the researchers performed secondary linear mixed-model analyses, incorporating all patients and all observations up to the point a person who dropped out left the study.

Patients started on 20 mg of tamoxifen twice daily, and the dose was increased up to 40 mg twice daily. The only psychotropic agent they could use during the study was lorazepam as a rescue medication for anxiety. The number of tablets used declined significantly over the course of the study in patients treated with tamoxifen but not in those in the placebo group.

Mania scores began dropping within 2 weeks of the start of tamoxifen treatment on both the Young Mania Rating Scale and the Positive and Negative Syndrome Scale. The improvements observed over 3 weeks with both scales were highly significant statistically, compared with placebo.

Scores on the Hamilton Rating Scale for Depression showed no improvement with tamoxifen or placebo and no difference between the two groups.

Most adverse events were minor and did not include the hormonal effects common in breast cancer patients taking tamoxifen as an adjunct therapy. “For long-term use, there are some side effects that we would expect, but for 21 days' use we would expect only some flushing on the face and maybe some small acne reaction,” Dr. Yildiz-Yesiloglu said in an interview after her presentation.

The Stanley Medical Research Institute in Chevy Chase, Md., financed the study, which received no drug company funding. Dr. Yildiz-Yesiloglu said that the outcome supports further investigation of the PKC pathway as a target for drugs treating bipolar disorder.

Researchers focused on tamoxifen because of its activity as a protein kinase C inhibitor. DR. YILDIZ-YESILOGLU

PARIS — Tamoxifen, a drug that is widely used in the treatment of breast cancer, significantly reduced the manic symptoms of bipolar disorder in a randomized, placebo-controlled trial presented in a breaking news session at the annual congress of the European College of Neuropsychopharmacology.

Dr. Aysegul Yildiz-Yesiloglu reported that 14 of 29 acutely ill patients had at least a 50% reduction in their scores on standard measures of mania with tamoxifen treatment. Only 1 of 21 patients improved on placebo during the 3-week trial. Depressive symptoms were not affected.

Although tamoxifen use in breast cancer is based on its antiestrogen effects, the investigators were drawn to the drug's activity as a protein kinase C (PKC) inhibitor, according to Dr. Yildiz-Yesiloglu, of Dokuz Eylul University in Izmir, Turkey, where the study was conducted.

She said the researchers hypothesized that inhibiting the PKC pathway could be important in bipolar disorder because lithium and valproate interfere with PKC signaling. For reasons not well understood, both mood stabilizers can reduce mania despite being structurally different.

Tamoxifen was chosen for the trial because it is the only direct PKC inhibitor approved for use in humans. It had been well tolerated in a pilot study that reported amelioration of manic symptoms in five of seven bipolar patients in the neuropsychiatric research unit at the Detroit Medical Center (Arch. Gen. Psychiatry 2000;57:95–7).

Dr. Yildiz-Yesiloglu, currently at Harvard Medical School in Boston, and her colleagues randomized 67 manic patients in the double-blind study. All had provided written consent together with at least one first-degree relative.

Six patients in the tamoxifen group and 11 patients in the placebo group dropped out because of severity of symptoms. This left 29 patients randomized to tamoxifen and 21 to placebo who completed the trial. To counteract any potential bias, Dr. Yildiz-Yesiloglu said the researchers performed secondary linear mixed-model analyses, incorporating all patients and all observations up to the point a person who dropped out left the study.

Patients started on 20 mg of tamoxifen twice daily, and the dose was increased up to 40 mg twice daily. The only psychotropic agent they could use during the study was lorazepam as a rescue medication for anxiety. The number of tablets used declined significantly over the course of the study in patients treated with tamoxifen but not in those in the placebo group.

Mania scores began dropping within 2 weeks of the start of tamoxifen treatment on both the Young Mania Rating Scale and the Positive and Negative Syndrome Scale. The improvements observed over 3 weeks with both scales were highly significant statistically, compared with placebo.

Scores on the Hamilton Rating Scale for Depression showed no improvement with tamoxifen or placebo and no difference between the two groups.

Most adverse events were minor and did not include the hormonal effects common in breast cancer patients taking tamoxifen as an adjunct therapy. “For long-term use, there are some side effects that we would expect, but for 21 days' use we would expect only some flushing on the face and maybe some small acne reaction,” Dr. Yildiz-Yesiloglu said in an interview after her presentation.

The Stanley Medical Research Institute in Chevy Chase, Md., financed the study, which received no drug company funding. Dr. Yildiz-Yesiloglu said that the outcome supports further investigation of the PKC pathway as a target for drugs treating bipolar disorder.

Researchers focused on tamoxifen because of its activity as a protein kinase C inhibitor. DR. YILDIZ-YESILOGLU

PARIS — Two clinical trials have found agomelatine, an investigational drug targeting dysfunction in circadian rhythm, to be as effective as venlafaxine in treating major depressive disorder, but with fewer side effects.

In particular, sexual dysfunction occurred at significantly lower rates in patients who remitted on agomelatine, compared with those who remitted on venlafaxine (Effexor), Dr. Sidney H. Kennedy said at the annual congress of the European College of Neuropsychopharmacology.

He also presented a pooled analysis from three placebo-controlled trials that showed agomelatine's sexual side-effect profile to be similar to placebo and better than that of selective serotonin reuptake inhibitors (SSRIs).

Servier, a French pharmaceutical firm, sponsored the studies. It is seeking approval of agomelatine for major depressive disorder in Europe and has licensed the new agent to Novartis for development in the United States.

If approved, agomelatine could become the first melatonergic antidepressant. It is an agonist of the melatonin 1 and melatonin 2 receptors and also has antagonist properties against the serotonergic 5-HT_2C receptors. Other analyses have shown that it improves sleep quality.

“Its mechanisms appear to be normalizing a disruptive circadian rhythm,” said Dr. Kennedy, psychiatrist-in-chief at the University Health Network in Toronto and a professor of psychiatry at the University of Toronto.

Both agomelatine-venlafaxine trials were randomized, double-blind, and parallel-group studies conducted in multiple countries. Patients ranged in age from 18 to 60 years and met criteria for major depressive disorder in the studies, reported by Dr. Kennedy with Dr. Christian Guilleminault of Stanford (Calif.) University.

The first study randomized 165 patients to agomelatine and 167 to venlafaxine IR. Patients started on 25 mg/day of agomelatine or 75 mg/day of venlafaxine. If they did not improve over 2 weeks, the doses could be increased to 50 mg/day of agomelatine or 150 mg/day of venlafaxine.

After 6 weeks, 76.4% of the agomelatine group and 70.6% of the venlafaxine cohort had responded to treatment. In both groups, total Hamilton Rating Scale for Depression scores fell from about 26 points to about 9 points. Responders were allowed to stay on their study drug for 6 months, at which point the investigators found a statistically significant benefit for agomelatine in Clinical Global Impression-Improvement scores.

The second study randomized 137 patients to agomelatine and 140 to venlafaxine IR. Doses were fixed at 50 mg/day of agomelatine and 75 mg daily of venlafaxine IR, which increased after 2 weeks to 150 mg/day. Dr. Kennedy and Dr. Guilleminault reported the remission rates were similar at 12 weeks: 73% on agomelatine and 67% on venlafaxine. Total scores on the Montgomery-Asberg Depression Rating Scale fell from 27.9 points to about 10 points in both groups.

Combined data from both trials showed fewer patients on agomelatine withdrew because of adverse events, compared with those on venlafaxine: 4.3% vs. 13.2%, respectively, at 6 weeks and 2.2% vs. 8.6%, respectively, at 12 weeks. The most frequent adverse events at 6 weeks in 303 patients on agomelatine included psychiatric disorders (1.7%), nervous system disorders (1%), and gastrointestinal disorders (0.7%).

The sexual function data, reported by Dr. Kennedy with Beata S. Eisfeld of the University of Toronto, showed 80% of people who remitted on agomelatine had no dysfunction in drive-desire/arousal or orgasm, compared with 58.8% and 53%, respectively, on venlafaxine. In the pooled placebo-controlled data, 3.2% of 1,120 patients on agomelatine, 2.6% of 998 patients on placebo, and 10.8% of 567 patients on an SSRI had “at least one emergent sexual dysfunction event.”

In particular, sexual dysfunction occurred at significantly lower rates in patients who remitted on agomelatine. DR. KENNEDY

PARIS — Two clinical trials have found agomelatine, an investigational drug targeting dysfunction in circadian rhythm, to be as effective as venlafaxine in treating major depressive disorder, but with fewer side effects.

In particular, sexual dysfunction occurred at significantly lower rates in patients who remitted on agomelatine, compared with those who remitted on venlafaxine (Effexor), Dr. Sidney H. Kennedy said at the annual congress of the European College of Neuropsychopharmacology.

He also presented a pooled analysis from three placebo-controlled trials that showed agomelatine's sexual side-effect profile to be similar to placebo and better than that of selective serotonin reuptake inhibitors (SSRIs).

Servier, a French pharmaceutical firm, sponsored the studies. It is seeking approval of agomelatine for major depressive disorder in Europe and has licensed the new agent to Novartis for development in the United States.

If approved, agomelatine could become the first melatonergic antidepressant. It is an agonist of the melatonin 1 and melatonin 2 receptors and also has antagonist properties against the serotonergic 5-HT_2C receptors. Other analyses have shown that it improves sleep quality.

“Its mechanisms appear to be normalizing a disruptive circadian rhythm,” said Dr. Kennedy, psychiatrist-in-chief at the University Health Network in Toronto and a professor of psychiatry at the University of Toronto.

Both agomelatine-venlafaxine trials were randomized, double-blind, and parallel-group studies conducted in multiple countries. Patients ranged in age from 18 to 60 years and met criteria for major depressive disorder in the studies, reported by Dr. Kennedy with Dr. Christian Guilleminault of Stanford (Calif.) University.

The first study randomized 165 patients to agomelatine and 167 to venlafaxine IR. Patients started on 25 mg/day of agomelatine or 75 mg/day of venlafaxine. If they did not improve over 2 weeks, the doses could be increased to 50 mg/day of agomelatine or 150 mg/day of venlafaxine.

After 6 weeks, 76.4% of the agomelatine group and 70.6% of the venlafaxine cohort had responded to treatment. In both groups, total Hamilton Rating Scale for Depression scores fell from about 26 points to about 9 points. Responders were allowed to stay on their study drug for 6 months, at which point the investigators found a statistically significant benefit for agomelatine in Clinical Global Impression-Improvement scores.

The second study randomized 137 patients to agomelatine and 140 to venlafaxine IR. Doses were fixed at 50 mg/day of agomelatine and 75 mg daily of venlafaxine IR, which increased after 2 weeks to 150 mg/day. Dr. Kennedy and Dr. Guilleminault reported the remission rates were similar at 12 weeks: 73% on agomelatine and 67% on venlafaxine. Total scores on the Montgomery-Asberg Depression Rating Scale fell from 27.9 points to about 10 points in both groups.

Combined data from both trials showed fewer patients on agomelatine withdrew because of adverse events, compared with those on venlafaxine: 4.3% vs. 13.2%, respectively, at 6 weeks and 2.2% vs. 8.6%, respectively, at 12 weeks. The most frequent adverse events at 6 weeks in 303 patients on agomelatine included psychiatric disorders (1.7%), nervous system disorders (1%), and gastrointestinal disorders (0.7%).

The sexual function data, reported by Dr. Kennedy with Beata S. Eisfeld of the University of Toronto, showed 80% of people who remitted on agomelatine had no dysfunction in drive-desire/arousal or orgasm, compared with 58.8% and 53%, respectively, on venlafaxine. In the pooled placebo-controlled data, 3.2% of 1,120 patients on agomelatine, 2.6% of 998 patients on placebo, and 10.8% of 567 patients on an SSRI had “at least one emergent sexual dysfunction event.”

In particular, sexual dysfunction occurred at significantly lower rates in patients who remitted on agomelatine. DR. KENNEDY

PARIS — Two clinical trials have found agomelatine, an investigational drug targeting dysfunction in circadian rhythm, to be as effective as venlafaxine in treating major depressive disorder, but with fewer side effects.

In particular, sexual dysfunction occurred at significantly lower rates in patients who remitted on agomelatine, compared with those who remitted on venlafaxine (Effexor), Dr. Sidney H. Kennedy said at the annual congress of the European College of Neuropsychopharmacology.

He also presented a pooled analysis from three placebo-controlled trials that showed agomelatine's sexual side-effect profile to be similar to placebo and better than that of selective serotonin reuptake inhibitors (SSRIs).

Servier, a French pharmaceutical firm, sponsored the studies. It is seeking approval of agomelatine for major depressive disorder in Europe and has licensed the new agent to Novartis for development in the United States.

If approved, agomelatine could become the first melatonergic antidepressant. It is an agonist of the melatonin 1 and melatonin 2 receptors and also has antagonist properties against the serotonergic 5-HT_2C receptors. Other analyses have shown that it improves sleep quality.

“Its mechanisms appear to be normalizing a disruptive circadian rhythm,” said Dr. Kennedy, psychiatrist-in-chief at the University Health Network in Toronto and a professor of psychiatry at the University of Toronto.

Both agomelatine-venlafaxine trials were randomized, double-blind, and parallel-group studies conducted in multiple countries. Patients ranged in age from 18 to 60 years and met criteria for major depressive disorder in the studies, reported by Dr. Kennedy with Dr. Christian Guilleminault of Stanford (Calif.) University.

The first study randomized 165 patients to agomelatine and 167 to venlafaxine IR. Patients started on 25 mg/day of agomelatine or 75 mg/day of venlafaxine. If they did not improve over 2 weeks, the doses could be increased to 50 mg/day of agomelatine or 150 mg/day of venlafaxine.

After 6 weeks, 76.4% of the agomelatine group and 70.6% of the venlafaxine cohort had responded to treatment. In both groups, total Hamilton Rating Scale for Depression scores fell from about 26 points to about 9 points. Responders were allowed to stay on their study drug for 6 months, at which point the investigators found a statistically significant benefit for agomelatine in Clinical Global Impression-Improvement scores.

The second study randomized 137 patients to agomelatine and 140 to venlafaxine IR. Doses were fixed at 50 mg/day of agomelatine and 75 mg daily of venlafaxine IR, which increased after 2 weeks to 150 mg/day. Dr. Kennedy and Dr. Guilleminault reported the remission rates were similar at 12 weeks: 73% on agomelatine and 67% on venlafaxine. Total scores on the Montgomery-Asberg Depression Rating Scale fell from 27.9 points to about 10 points in both groups.

Combined data from both trials showed fewer patients on agomelatine withdrew because of adverse events, compared with those on venlafaxine: 4.3% vs. 13.2%, respectively, at 6 weeks and 2.2% vs. 8.6%, respectively, at 12 weeks. The most frequent adverse events at 6 weeks in 303 patients on agomelatine included psychiatric disorders (1.7%), nervous system disorders (1%), and gastrointestinal disorders (0.7%).

The sexual function data, reported by Dr. Kennedy with Beata S. Eisfeld of the University of Toronto, showed 80% of people who remitted on agomelatine had no dysfunction in drive-desire/arousal or orgasm, compared with 58.8% and 53%, respectively, on venlafaxine. In the pooled placebo-controlled data, 3.2% of 1,120 patients on agomelatine, 2.6% of 998 patients on placebo, and 10.8% of 567 patients on an SSRI had “at least one emergent sexual dysfunction event.”

In particular, sexual dysfunction occurred at significantly lower rates in patients who remitted on agomelatine. DR. KENNEDY

PARIS — A cohort study of 15,390 suicide-prone people in Finland found those who used antidepressants were much more likely to attempt suicide, but also much less likely to complete suicide or to die of any cause.

The use of antidepressants was associated with a 39% increase in suicide attempts, a 32% reduction in completed suicides, and a 49% drop in mortality, Dr. Jari Tiihonen reported at the annual congress of the European College of Neuropsychopharmacology.

Dr. Tiihonen, professor and chair of the department of forensic psychiatry at the University of Kuopio in Finland, said the results for patients aged 10–19 corresponded to those for the total study population with one exception. Adolescents were more than five times more likely to die while on paroxetine (relative risk 5.44).

By phrasing the central question addressed by the study as, “Is antidepressant use associated with increased risk of suicidal behavior?” Dr. Tiihonen said in conclusion that the answer is, “Yes, because of the increased risk of attempted suicide … but at the same time, no, because there is a decreased risk of completed suicide, and this is also very large.”

Dr. Tiihonen and his colleagues took advantage of Finland's nationwide computerized database of medical records to conduct the study. The investigators collected data on 15,390 people in a national hospital register who had been hospitalized during 1997–2003 because of suicide attempts. They also gathered data on these patients from a national prescription register and a national mortality register. The average follow-up period was 3.4 years.

“Since previous suicide attempts are the most important risk factor for suicide, a large cohort of suicidal patients would be an obvious choice to investigate the association between antidepressant treatment and the risk of suicide,” Dr. Tiihonen said.

The study recorded 602 suicides, 7,136 suicide attempts, and 1,583 deaths in the cohort. “The more prior suicide attempts, the more the risk of suicide goes up as well as the attempts,” Dr. Tiihonen said of the population, which ranged from 10 to 100 years of age.

Among patients who attempted suicide during this time, investigators determined that 3,224 took antidepressants and 3,912 did not. All classes of antidepressants were associated with increased risk of attempted suicide (adjusted relative risk 1.64), compared to no antidepressant use.

Completed suicides were significantly less common (adjusted relative risk 0.81) with antidepressants overall, but varied by the antidepressant used. Patients on fluoxetine had the lowest adjusted relative risk (0.52) of suicide while those on venlafaxine had the highest (1.61).

“Venlafaxine is generally considered to be one of the most efficacious, and it is used for patients who are the most severely depressed and the most severely suicidal,” Dr. Tiihonen said.

He attributed the significantly reduced risk of all-cause mortality to the impact of SSRIs. Patients on SSRIs had significantly lower mortality (relative risk 0.59), a benefit the investigators credited to significantly fewer cardiovascular and cerebrovascular deaths in this subgroup (relative risk 0.42).

In response to audience questions, Dr. Tiihonen said an analysis not presented at the meeting found that patients were at greatest risk of suicide immediately after starting their medications.

He also suggested that the disparity between attempted and completed suicides might occur because patients on antidepressants are more likely to overdose on pills, simply because they are available. According to Dr. Tiihonen, those not on antidepressants tended to use more violent methods, such as shooting or hanging themselves.

“Antidepressant use is not associated with increased risk of suicide,” Dr. Tiihonen said.

PARIS — A cohort study of 15,390 suicide-prone people in Finland found those who used antidepressants were much more likely to attempt suicide, but also much less likely to complete suicide or to die of any cause.

The use of antidepressants was associated with a 39% increase in suicide attempts, a 32% reduction in completed suicides, and a 49% drop in mortality, Dr. Jari Tiihonen reported at the annual congress of the European College of Neuropsychopharmacology.

Dr. Tiihonen, professor and chair of the department of forensic psychiatry at the University of Kuopio in Finland, said the results for patients aged 10–19 corresponded to those for the total study population with one exception. Adolescents were more than five times more likely to die while on paroxetine (relative risk 5.44).

By phrasing the central question addressed by the study as, “Is antidepressant use associated with increased risk of suicidal behavior?” Dr. Tiihonen said in conclusion that the answer is, “Yes, because of the increased risk of attempted suicide … but at the same time, no, because there is a decreased risk of completed suicide, and this is also very large.”

Dr. Tiihonen and his colleagues took advantage of Finland's nationwide computerized database of medical records to conduct the study. The investigators collected data on 15,390 people in a national hospital register who had been hospitalized during 1997–2003 because of suicide attempts. They also gathered data on these patients from a national prescription register and a national mortality register. The average follow-up period was 3.4 years.

“Since previous suicide attempts are the most important risk factor for suicide, a large cohort of suicidal patients would be an obvious choice to investigate the association between antidepressant treatment and the risk of suicide,” Dr. Tiihonen said.

The study recorded 602 suicides, 7,136 suicide attempts, and 1,583 deaths in the cohort. “The more prior suicide attempts, the more the risk of suicide goes up as well as the attempts,” Dr. Tiihonen said of the population, which ranged from 10 to 100 years of age.

Among patients who attempted suicide during this time, investigators determined that 3,224 took antidepressants and 3,912 did not. All classes of antidepressants were associated with increased risk of attempted suicide (adjusted relative risk 1.64), compared to no antidepressant use.

Completed suicides were significantly less common (adjusted relative risk 0.81) with antidepressants overall, but varied by the antidepressant used. Patients on fluoxetine had the lowest adjusted relative risk (0.52) of suicide while those on venlafaxine had the highest (1.61).

“Venlafaxine is generally considered to be one of the most efficacious, and it is used for patients who are the most severely depressed and the most severely suicidal,” Dr. Tiihonen said.

He attributed the significantly reduced risk of all-cause mortality to the impact of SSRIs. Patients on SSRIs had significantly lower mortality (relative risk 0.59), a benefit the investigators credited to significantly fewer cardiovascular and cerebrovascular deaths in this subgroup (relative risk 0.42).

In response to audience questions, Dr. Tiihonen said an analysis not presented at the meeting found that patients were at greatest risk of suicide immediately after starting their medications.

He also suggested that the disparity between attempted and completed suicides might occur because patients on antidepressants are more likely to overdose on pills, simply because they are available. According to Dr. Tiihonen, those not on antidepressants tended to use more violent methods, such as shooting or hanging themselves.

“Antidepressant use is not associated with increased risk of suicide,” Dr. Tiihonen said.

PARIS — A cohort study of 15,390 suicide-prone people in Finland found those who used antidepressants were much more likely to attempt suicide, but also much less likely to complete suicide or to die of any cause.

The use of antidepressants was associated with a 39% increase in suicide attempts, a 32% reduction in completed suicides, and a 49% drop in mortality, Dr. Jari Tiihonen reported at the annual congress of the European College of Neuropsychopharmacology.

Dr. Tiihonen, professor and chair of the department of forensic psychiatry at the University of Kuopio in Finland, said the results for patients aged 10–19 corresponded to those for the total study population with one exception. Adolescents were more than five times more likely to die while on paroxetine (relative risk 5.44).

By phrasing the central question addressed by the study as, “Is antidepressant use associated with increased risk of suicidal behavior?” Dr. Tiihonen said in conclusion that the answer is, “Yes, because of the increased risk of attempted suicide … but at the same time, no, because there is a decreased risk of completed suicide, and this is also very large.”

Dr. Tiihonen and his colleagues took advantage of Finland's nationwide computerized database of medical records to conduct the study. The investigators collected data on 15,390 people in a national hospital register who had been hospitalized during 1997–2003 because of suicide attempts. They also gathered data on these patients from a national prescription register and a national mortality register. The average follow-up period was 3.4 years.

“Since previous suicide attempts are the most important risk factor for suicide, a large cohort of suicidal patients would be an obvious choice to investigate the association between antidepressant treatment and the risk of suicide,” Dr. Tiihonen said.

The study recorded 602 suicides, 7,136 suicide attempts, and 1,583 deaths in the cohort. “The more prior suicide attempts, the more the risk of suicide goes up as well as the attempts,” Dr. Tiihonen said of the population, which ranged from 10 to 100 years of age.

Among patients who attempted suicide during this time, investigators determined that 3,224 took antidepressants and 3,912 did not. All classes of antidepressants were associated with increased risk of attempted suicide (adjusted relative risk 1.64), compared to no antidepressant use.

Completed suicides were significantly less common (adjusted relative risk 0.81) with antidepressants overall, but varied by the antidepressant used. Patients on fluoxetine had the lowest adjusted relative risk (0.52) of suicide while those on venlafaxine had the highest (1.61).

“Venlafaxine is generally considered to be one of the most efficacious, and it is used for patients who are the most severely depressed and the most severely suicidal,” Dr. Tiihonen said.

He attributed the significantly reduced risk of all-cause mortality to the impact of SSRIs. Patients on SSRIs had significantly lower mortality (relative risk 0.59), a benefit the investigators credited to significantly fewer cardiovascular and cerebrovascular deaths in this subgroup (relative risk 0.42).

In response to audience questions, Dr. Tiihonen said an analysis not presented at the meeting found that patients were at greatest risk of suicide immediately after starting their medications.

He also suggested that the disparity between attempted and completed suicides might occur because patients on antidepressants are more likely to overdose on pills, simply because they are available. According to Dr. Tiihonen, those not on antidepressants tended to use more violent methods, such as shooting or hanging themselves.

“Antidepressant use is not associated with increased risk of suicide,” Dr. Tiihonen said.

PARIS — Triiodothyronine supplementation significantly increased the antidepressant effects of sertraline in a randomized placebo-controlled clinical trial presented by Dr. Bernard Lerer in a breaking news session at the annual congress of the European College of Neuropsychopharmacology.

Israeli patients treated with sertraline (Zoloft) and triiodothyronine (T₃) were nearly three times more likely to respond (odds ratio 2.93), compared with a cohort given sertraline and a placebo. Some 69.8% (37/53 patients) had at least a 50% reduction in their Hamilton Rating Scale for Depression (HAM-D) scores on the active drug combination vs. 50% (25/50 patients) in the control group.

The sertraline-T₃ cohort also was much more likely (odds ratio 2.69) to go into remission by the sixth week of treatment. At that point, 58.5% (31/53) of the T₃-augmented patients but only 38% (19/50) of the placebo group was in remission.

“Results of the current controlled study support the efficacy of T₃ as an enhancer of antidepressant action,” said Dr. Lerer, director of the Hadassah Biological Psychiatry Laboratory and a professor of psychiatry at the Hadassah-Hebrew University Medical Center in Jerusalem.

Both groups of patients started on 50 mg per day of sertraline for 1 week, followed by 100 mg per day for 7 weeks. The T₃ dose also was titrated up from 20–25 mcg per day the first week to 40–50 mcg per day for the rest of the trial.

T₃'s effects in the trial appeared to be related to the hormone's effect on thyroid function, according to Dr. Lerer. He said patients who responded to the active-drug combination tended to have lower baseline levels of T₃ than those who did not. Patients who remitted on T₃ and sertraline also had greater reductions in thyroid-stimulating hormone (TSH) than those who did not go into remission. Neither effect was seen in the sertraline-placebo group.

“The precise clinical role of T₃ needs to be further defined, and predictors of response need to be identified,” Dr. Lerer said in his conclusion.

In September, an antidepressant trial in the United States reported that T₃ augmentation resulted in more remissions and fewer adverse events than lithium augmentation in treatment-resistant patients (Am. J. Psychiatry 2006;163:1519–30). Reviewing this and previous studies of T₃ and antidepressants, Dr. Lerer said researchers suspect patients with thyroid dysfunction are less able to respond to antidepressants. Prevalence of depression is higher in patients with hypothyroidism, he noted, whereas thyroid dysfunction is also more prevalent in patients with depression.

Though some studies have shown T₃ to elicit responses more often in women than in men and also to speed response to antidepressants, Dr. Lerer said neither effect was seen in the new trial. He also reported no difference in adverse events with T₃, compared with placebo.

Sertraline was chosen for the study because it is little used in Israel, Dr. Lerer said, and therefore, the trial was better able to enroll patients. Patients with clinical hyper- or hypothyroidism or other thyroid disorders, including subclinical hypothyroidism were excluded from the study.

Investigators randomized 124 patients (60 augmented with placebo and 64 with T₃). Only 103 patients (50 given placebo and 53 augmented with T₃) were included in the intent-to-treat analysis, as investigators did not count 21 patients who dropped out without completing one clinical visit.

Baseline characteristics were similar between both arms of the trial. Each had 29 female patients. The average age was 41–45 years.

Laboratory values also were comparable at baseline, but significantly different post treatment. Almost no change was seen in the placebo group. Both TSH and thyroxine fell during the trial and T₃ increased, however, in the group augmented with T₃.

Despite good results with T₃ augmentation, Dr. Lerer said no patients were kept on treatment for more than 3 months post study. He urged caution until long-term effects are better understood.

The study received support from the Stanley Medical Research Institute in Chevy Chase, Md. Investigators from Beer Yaakov Mental Health Center in Israel and Global Medical Institutes in Princeton, N.J., also participated in the trial, which was coordinated by Dr. Lerer's group.

PARIS — Triiodothyronine supplementation significantly increased the antidepressant effects of sertraline in a randomized placebo-controlled clinical trial presented by Dr. Bernard Lerer in a breaking news session at the annual congress of the European College of Neuropsychopharmacology.

Israeli patients treated with sertraline (Zoloft) and triiodothyronine (T₃) were nearly three times more likely to respond (odds ratio 2.93), compared with a cohort given sertraline and a placebo. Some 69.8% (37/53 patients) had at least a 50% reduction in their Hamilton Rating Scale for Depression (HAM-D) scores on the active drug combination vs. 50% (25/50 patients) in the control group.

The sertraline-T₃ cohort also was much more likely (odds ratio 2.69) to go into remission by the sixth week of treatment. At that point, 58.5% (31/53) of the T₃-augmented patients but only 38% (19/50) of the placebo group was in remission.

“Results of the current controlled study support the efficacy of T₃ as an enhancer of antidepressant action,” said Dr. Lerer, director of the Hadassah Biological Psychiatry Laboratory and a professor of psychiatry at the Hadassah-Hebrew University Medical Center in Jerusalem.

Both groups of patients started on 50 mg per day of sertraline for 1 week, followed by 100 mg per day for 7 weeks. The T₃ dose also was titrated up from 20–25 mcg per day the first week to 40–50 mcg per day for the rest of the trial.

T₃'s effects in the trial appeared to be related to the hormone's effect on thyroid function, according to Dr. Lerer. He said patients who responded to the active-drug combination tended to have lower baseline levels of T₃ than those who did not. Patients who remitted on T₃ and sertraline also had greater reductions in thyroid-stimulating hormone (TSH) than those who did not go into remission. Neither effect was seen in the sertraline-placebo group.

“The precise clinical role of T₃ needs to be further defined, and predictors of response need to be identified,” Dr. Lerer said in his conclusion.

In September, an antidepressant trial in the United States reported that T₃ augmentation resulted in more remissions and fewer adverse events than lithium augmentation in treatment-resistant patients (Am. J. Psychiatry 2006;163:1519–30). Reviewing this and previous studies of T₃ and antidepressants, Dr. Lerer said researchers suspect patients with thyroid dysfunction are less able to respond to antidepressants. Prevalence of depression is higher in patients with hypothyroidism, he noted, whereas thyroid dysfunction is also more prevalent in patients with depression.

Though some studies have shown T₃ to elicit responses more often in women than in men and also to speed response to antidepressants, Dr. Lerer said neither effect was seen in the new trial. He also reported no difference in adverse events with T₃, compared with placebo.

Sertraline was chosen for the study because it is little used in Israel, Dr. Lerer said, and therefore, the trial was better able to enroll patients. Patients with clinical hyper- or hypothyroidism or other thyroid disorders, including subclinical hypothyroidism were excluded from the study.

Investigators randomized 124 patients (60 augmented with placebo and 64 with T₃). Only 103 patients (50 given placebo and 53 augmented with T₃) were included in the intent-to-treat analysis, as investigators did not count 21 patients who dropped out without completing one clinical visit.

Baseline characteristics were similar between both arms of the trial. Each had 29 female patients. The average age was 41–45 years.

Laboratory values also were comparable at baseline, but significantly different post treatment. Almost no change was seen in the placebo group. Both TSH and thyroxine fell during the trial and T₃ increased, however, in the group augmented with T₃.

Despite good results with T₃ augmentation, Dr. Lerer said no patients were kept on treatment for more than 3 months post study. He urged caution until long-term effects are better understood.

The study received support from the Stanley Medical Research Institute in Chevy Chase, Md. Investigators from Beer Yaakov Mental Health Center in Israel and Global Medical Institutes in Princeton, N.J., also participated in the trial, which was coordinated by Dr. Lerer's group.

PARIS — Triiodothyronine supplementation significantly increased the antidepressant effects of sertraline in a randomized placebo-controlled clinical trial presented by Dr. Bernard Lerer in a breaking news session at the annual congress of the European College of Neuropsychopharmacology.

Israeli patients treated with sertraline (Zoloft) and triiodothyronine (T₃) were nearly three times more likely to respond (odds ratio 2.93), compared with a cohort given sertraline and a placebo. Some 69.8% (37/53 patients) had at least a 50% reduction in their Hamilton Rating Scale for Depression (HAM-D) scores on the active drug combination vs. 50% (25/50 patients) in the control group.

The sertraline-T₃ cohort also was much more likely (odds ratio 2.69) to go into remission by the sixth week of treatment. At that point, 58.5% (31/53) of the T₃-augmented patients but only 38% (19/50) of the placebo group was in remission.

“Results of the current controlled study support the efficacy of T₃ as an enhancer of antidepressant action,” said Dr. Lerer, director of the Hadassah Biological Psychiatry Laboratory and a professor of psychiatry at the Hadassah-Hebrew University Medical Center in Jerusalem.

Both groups of patients started on 50 mg per day of sertraline for 1 week, followed by 100 mg per day for 7 weeks. The T₃ dose also was titrated up from 20–25 mcg per day the first week to 40–50 mcg per day for the rest of the trial.

T₃'s effects in the trial appeared to be related to the hormone's effect on thyroid function, according to Dr. Lerer. He said patients who responded to the active-drug combination tended to have lower baseline levels of T₃ than those who did not. Patients who remitted on T₃ and sertraline also had greater reductions in thyroid-stimulating hormone (TSH) than those who did not go into remission. Neither effect was seen in the sertraline-placebo group.

“The precise clinical role of T₃ needs to be further defined, and predictors of response need to be identified,” Dr. Lerer said in his conclusion.

In September, an antidepressant trial in the United States reported that T₃ augmentation resulted in more remissions and fewer adverse events than lithium augmentation in treatment-resistant patients (Am. J. Psychiatry 2006;163:1519–30). Reviewing this and previous studies of T₃ and antidepressants, Dr. Lerer said researchers suspect patients with thyroid dysfunction are less able to respond to antidepressants. Prevalence of depression is higher in patients with hypothyroidism, he noted, whereas thyroid dysfunction is also more prevalent in patients with depression.

Though some studies have shown T₃ to elicit responses more often in women than in men and also to speed response to antidepressants, Dr. Lerer said neither effect was seen in the new trial. He also reported no difference in adverse events with T₃, compared with placebo.

Sertraline was chosen for the study because it is little used in Israel, Dr. Lerer said, and therefore, the trial was better able to enroll patients. Patients with clinical hyper- or hypothyroidism or other thyroid disorders, including subclinical hypothyroidism were excluded from the study.

Investigators randomized 124 patients (60 augmented with placebo and 64 with T₃). Only 103 patients (50 given placebo and 53 augmented with T₃) were included in the intent-to-treat analysis, as investigators did not count 21 patients who dropped out without completing one clinical visit.

Baseline characteristics were similar between both arms of the trial. Each had 29 female patients. The average age was 41–45 years.

Laboratory values also were comparable at baseline, but significantly different post treatment. Almost no change was seen in the placebo group. Both TSH and thyroxine fell during the trial and T₃ increased, however, in the group augmented with T₃.

Despite good results with T₃ augmentation, Dr. Lerer said no patients were kept on treatment for more than 3 months post study. He urged caution until long-term effects are better understood.

The study received support from the Stanley Medical Research Institute in Chevy Chase, Md. Investigators from Beer Yaakov Mental Health Center in Israel and Global Medical Institutes in Princeton, N.J., also participated in the trial, which was coordinated by Dr. Lerer's group.

PARIS — Generalized anxiety disorder occurs as a late-onset condition more often than is recognized, according to investigators who presented the first large treatment trial in elderly patients during the annual congress of the European College of Neuropsychopharmacology.

Dr. Francesca Baldinetti reported that the average age of onset was 56 years in 273 outpatients with generalized anxiety disorder (GAD) who were aged at least 65 years and who enrolled in the placebo-controlled trial. The study found pregabalin (Lyrica) to be at least as effective in the elderly as in previous trials with younger patients.

“In reality, there is a late onset of generalized anxiety disorder in the later stage of life,” said Dr. Baldinetti, medical director of worldwide neuroscience at Pfizer Inc., in a presentation of the new data at a session on psychiatric disorders in older people.

“That is not in the literature,” added the lead author, Dr. Stuart A. Montgomery, a professor emeritus of psychiatry at the Imperial College London.

Most patients develop the full syndrome after the age of 30, according to Dr. Hans-Ulrich Wittchen, professor of clinical psychology and epidemiology at the Technische Universität Dresden (Germany).

He urged careful questioning of newly diagnosed older GAD patients who report they first had symptoms as children. “It may be that there are anxiety disorders preceding that [new] development. … But if you probe the GAD symptomatology, this is another disorder,” he said. “This is not an early anxiety disorder.”

In her presentation, Dr. Baldinetti said that at least half of all newly diagnosed cases of GAD occur after age 30 years and a third after age 40. Five different studies from the United States and Europe have shown prevalence rates ranging from 1.9% to 7.2% in the elderly, she said.

All patients in the pregabalin study had Hamilton Rating Scale for Anxiety (HAM-A) scores of 20 or more, with a baseline average of 26.6 for 177 patients randomized to pregabalin and 26.1 for 96 patients on placebo. Patients with major depression and other anxiety or substance abuse disorders were excluded. The participants had three to four prior episodes of GAD on average, with the current episode lasting about 15 months. The average age was 72 years, as about a third of the population was 75 years of age or older. About three-fourths of those enrolled were female.

A flexible-dose regimen started the active drug group on 150 mg per day of pregabalin, which clinicians could titrate up to 600 mg by week 6 of the 8-week trial. The average dose used was 270 mg.

Dr. Baldinetti suggested that the flexible dosing probably was responsible for the difference in outcomes relative to the earlier adult trials. Whereas younger patients on pregabalin had a significantly better response than did those on placebo during week 1, elderly patients on pregabalin began to show significant improvement compared with the control group during week 2.

By the elderly trial's end, 64.2% of the pregabalin cohort had responded versus 50% of the control group. Total HAM-A scores fell by more than 12 points in the pregabalin group, versus more than 10 points with placebo in a last-observation-carried-forward (LOCF) analysis.

The effect was seen in HAM-A psychic and HAM-A somatic scores. HAM-A psychic scores fell by 7.8 points with pregabalin versus 6.3 points with placebo. HAM-A somatic scores fell by 6.6 points with pregabalin versus 5.4 points with placebo.

The drug's benefits were significant in subgroups of patients with severe anxiety and with subsyndromal depression.

Overall, 28% of those on placebo and 25% of the pregabalin group dropped out of the study. Only 7% on placebo and 4% on pregabalin did so for lack of efficacy. Adverse events caused discontinuation by 11% of the pregabalin group and 9% on placebo. The most common adverse events with pregabalin were dizziness (20.3%), somnolence (13%), headache (10.2%), nausea (9%), and infection (5.6%).

At least half of all newly diagnosed cases of GAD occur after age 30 years and a third after age 40. DR. BALDINETTI

PARIS — Generalized anxiety disorder occurs as a late-onset condition more often than is recognized, according to investigators who presented the first large treatment trial in elderly patients during the annual congress of the European College of Neuropsychopharmacology.

Dr. Francesca Baldinetti reported that the average age of onset was 56 years in 273 outpatients with generalized anxiety disorder (GAD) who were aged at least 65 years and who enrolled in the placebo-controlled trial. The study found pregabalin (Lyrica) to be at least as effective in the elderly as in previous trials with younger patients.

“In reality, there is a late onset of generalized anxiety disorder in the later stage of life,” said Dr. Baldinetti, medical director of worldwide neuroscience at Pfizer Inc., in a presentation of the new data at a session on psychiatric disorders in older people.

“That is not in the literature,” added the lead author, Dr. Stuart A. Montgomery, a professor emeritus of psychiatry at the Imperial College London.

Most patients develop the full syndrome after the age of 30, according to Dr. Hans-Ulrich Wittchen, professor of clinical psychology and epidemiology at the Technische Universität Dresden (Germany).

He urged careful questioning of newly diagnosed older GAD patients who report they first had symptoms as children. “It may be that there are anxiety disorders preceding that [new] development. … But if you probe the GAD symptomatology, this is another disorder,” he said. “This is not an early anxiety disorder.”

In her presentation, Dr. Baldinetti said that at least half of all newly diagnosed cases of GAD occur after age 30 years and a third after age 40. Five different studies from the United States and Europe have shown prevalence rates ranging from 1.9% to 7.2% in the elderly, she said.

All patients in the pregabalin study had Hamilton Rating Scale for Anxiety (HAM-A) scores of 20 or more, with a baseline average of 26.6 for 177 patients randomized to pregabalin and 26.1 for 96 patients on placebo. Patients with major depression and other anxiety or substance abuse disorders were excluded. The participants had three to four prior episodes of GAD on average, with the current episode lasting about 15 months. The average age was 72 years, as about a third of the population was 75 years of age or older. About three-fourths of those enrolled were female.

A flexible-dose regimen started the active drug group on 150 mg per day of pregabalin, which clinicians could titrate up to 600 mg by week 6 of the 8-week trial. The average dose used was 270 mg.

Dr. Baldinetti suggested that the flexible dosing probably was responsible for the difference in outcomes relative to the earlier adult trials. Whereas younger patients on pregabalin had a significantly better response than did those on placebo during week 1, elderly patients on pregabalin began to show significant improvement compared with the control group during week 2.

By the elderly trial's end, 64.2% of the pregabalin cohort had responded versus 50% of the control group. Total HAM-A scores fell by more than 12 points in the pregabalin group, versus more than 10 points with placebo in a last-observation-carried-forward (LOCF) analysis.

The effect was seen in HAM-A psychic and HAM-A somatic scores. HAM-A psychic scores fell by 7.8 points with pregabalin versus 6.3 points with placebo. HAM-A somatic scores fell by 6.6 points with pregabalin versus 5.4 points with placebo.

The drug's benefits were significant in subgroups of patients with severe anxiety and with subsyndromal depression.

Overall, 28% of those on placebo and 25% of the pregabalin group dropped out of the study. Only 7% on placebo and 4% on pregabalin did so for lack of efficacy. Adverse events caused discontinuation by 11% of the pregabalin group and 9% on placebo. The most common adverse events with pregabalin were dizziness (20.3%), somnolence (13%), headache (10.2%), nausea (9%), and infection (5.6%).

At least half of all newly diagnosed cases of GAD occur after age 30 years and a third after age 40. DR. BALDINETTI

PARIS — Generalized anxiety disorder occurs as a late-onset condition more often than is recognized, according to investigators who presented the first large treatment trial in elderly patients during the annual congress of the European College of Neuropsychopharmacology.

Dr. Francesca Baldinetti reported that the average age of onset was 56 years in 273 outpatients with generalized anxiety disorder (GAD) who were aged at least 65 years and who enrolled in the placebo-controlled trial. The study found pregabalin (Lyrica) to be at least as effective in the elderly as in previous trials with younger patients.

“In reality, there is a late onset of generalized anxiety disorder in the later stage of life,” said Dr. Baldinetti, medical director of worldwide neuroscience at Pfizer Inc., in a presentation of the new data at a session on psychiatric disorders in older people.

“That is not in the literature,” added the lead author, Dr. Stuart A. Montgomery, a professor emeritus of psychiatry at the Imperial College London.

Most patients develop the full syndrome after the age of 30, according to Dr. Hans-Ulrich Wittchen, professor of clinical psychology and epidemiology at the Technische Universität Dresden (Germany).

He urged careful questioning of newly diagnosed older GAD patients who report they first had symptoms as children. “It may be that there are anxiety disorders preceding that [new] development. … But if you probe the GAD symptomatology, this is another disorder,” he said. “This is not an early anxiety disorder.”

In her presentation, Dr. Baldinetti said that at least half of all newly diagnosed cases of GAD occur after age 30 years and a third after age 40. Five different studies from the United States and Europe have shown prevalence rates ranging from 1.9% to 7.2% in the elderly, she said.

All patients in the pregabalin study had Hamilton Rating Scale for Anxiety (HAM-A) scores of 20 or more, with a baseline average of 26.6 for 177 patients randomized to pregabalin and 26.1 for 96 patients on placebo. Patients with major depression and other anxiety or substance abuse disorders were excluded. The participants had three to four prior episodes of GAD on average, with the current episode lasting about 15 months. The average age was 72 years, as about a third of the population was 75 years of age or older. About three-fourths of those enrolled were female.

A flexible-dose regimen started the active drug group on 150 mg per day of pregabalin, which clinicians could titrate up to 600 mg by week 6 of the 8-week trial. The average dose used was 270 mg.

Dr. Baldinetti suggested that the flexible dosing probably was responsible for the difference in outcomes relative to the earlier adult trials. Whereas younger patients on pregabalin had a significantly better response than did those on placebo during week 1, elderly patients on pregabalin began to show significant improvement compared with the control group during week 2.

By the elderly trial's end, 64.2% of the pregabalin cohort had responded versus 50% of the control group. Total HAM-A scores fell by more than 12 points in the pregabalin group, versus more than 10 points with placebo in a last-observation-carried-forward (LOCF) analysis.

The effect was seen in HAM-A psychic and HAM-A somatic scores. HAM-A psychic scores fell by 7.8 points with pregabalin versus 6.3 points with placebo. HAM-A somatic scores fell by 6.6 points with pregabalin versus 5.4 points with placebo.

The drug's benefits were significant in subgroups of patients with severe anxiety and with subsyndromal depression.

Overall, 28% of those on placebo and 25% of the pregabalin group dropped out of the study. Only 7% on placebo and 4% on pregabalin did so for lack of efficacy. Adverse events caused discontinuation by 11% of the pregabalin group and 9% on placebo. The most common adverse events with pregabalin were dizziness (20.3%), somnolence (13%), headache (10.2%), nausea (9%), and infection (5.6%).

At least half of all newly diagnosed cases of GAD occur after age 30 years and a third after age 40. DR. BALDINETTI

PARIS – A consensus panel convened by the European College of Neuropsychopharmacology has drafted a report opposing separate clinical trials of central nervous system drugs in elderly patients.

The panel calls instead for dropping age cutoffs from clinical trials testing the efficacy of new CNS drugs. It favors inclusion of elderly patients in trial populations and use of the same placebo-controlled trial designs in studies across age ranges.

“We are of the opinion in the consensus meeting that specific studies in the elderly, while very interesting, are not worth doing,” said Dr. Stuart A. Montgomery, the panel's cochair, in a presentation of its preliminary findings at the annual congress of the college.

More than 200 experts participated when the panel on investigating CNS disorders in the elderly met in Nice, France, in March 2006, according to Dr. Montgomery, professor emeritus of psychiatry at the University of London. The written draft, currently under review, will be published in a journal when the process is completed.

He said a review of clinical trials in the elderly determined that elderly patients, whether 60 or 65 years of age or older, responded much the same as younger patients to CNS drugs. The widespread belief that older patients respond more slowly is a myth, Dr. Montgomery said; changes in physiologic function occur on a continuum throughout life rather than in response to an arbitrary age cutoff.

“There is such a paucity of data at the upper end–above 75 and above 80–it is really not possible to comment on what goes on at that point,” he said. “There is such substantial individual variation … that the effect of age becomes minimal by comparison.”

European regulatory agencies usually do ask drug companies to conduct separate studies in the elderly, said Dr. Montgomery. If these studies are not done, and often they are not, he said, a drug may not be approved for use in patients aged 65 and older. Therefore, the panel concluded that requiring separate studies in the elderly serves only to limit the availability of treatments in older patients.

“Excluding patients over 60 or 65 is inappropriate and unhelpful and in some ways regarded as counterproductive,” Dr. Montgomery said.

The panel focused on efficacy in its deliberations, but it agreed that safety can be an issue in older patients. Dr. Montgomery cited concerns about delays in elimination of CNS drugs in the elderly, who also tend to have more comorbidity and take more medications than younger patients.

Accordingly, the panel recommended that safety issues be addressed in subgroup analyses of older patients enrolled in placebo-controlled clinical trials with broad populations as well as in separate studies identified explicitly as safety studies.

“There are potentially more drug-drug interactions, more safety problems, and they should be the focus with increasing age, not efficacy,” Dr. Montgomery said.

He also summarized the panel's findings on age relative to the following disorders:

▸ Depression. Major depressive disorder is no different in the elderly; antidepressants that help younger people are just as effective in older people

▸ Bipolar disorder. Mania is an early-onset disorder affecting younger patients, but the elderly are more likely to present with depression. The efficacy of drugs for bipolar depression does not change with age.

▸ Anxiety. Generalized anxiety disorder is the most common late-onset anxiety disorder in the elderly. Response to treatment is not age related.

▸ Insomnia. Age has no effect on the efficacy of licensed treatments for insomnia, which is common in the elderly.

▸ Schizophrenia. Chronic schizophrenia patients who reach old age have more negative, cognitive, and depressive symptoms, possibly as a result of chronicity. The experts found no evidence of age-related changes in response to treatments for negative or positive symptoms.

The widespread belief that older patients respond more slowly to medication isa myth. DR. MONTGOMERY

PARIS – A consensus panel convened by the European College of Neuropsychopharmacology has drafted a report opposing separate clinical trials of central nervous system drugs in elderly patients.

The panel calls instead for dropping age cutoffs from clinical trials testing the efficacy of new CNS drugs. It favors inclusion of elderly patients in trial populations and use of the same placebo-controlled trial designs in studies across age ranges.

“We are of the opinion in the consensus meeting that specific studies in the elderly, while very interesting, are not worth doing,” said Dr. Stuart A. Montgomery, the panel's cochair, in a presentation of its preliminary findings at the annual congress of the college.

More than 200 experts participated when the panel on investigating CNS disorders in the elderly met in Nice, France, in March 2006, according to Dr. Montgomery, professor emeritus of psychiatry at the University of London. The written draft, currently under review, will be published in a journal when the process is completed.

He said a review of clinical trials in the elderly determined that elderly patients, whether 60 or 65 years of age or older, responded much the same as younger patients to CNS drugs. The widespread belief that older patients respond more slowly is a myth, Dr. Montgomery said; changes in physiologic function occur on a continuum throughout life rather than in response to an arbitrary age cutoff.

“There is such a paucity of data at the upper end–above 75 and above 80–it is really not possible to comment on what goes on at that point,” he said. “There is such substantial individual variation … that the effect of age becomes minimal by comparison.”

European regulatory agencies usually do ask drug companies to conduct separate studies in the elderly, said Dr. Montgomery. If these studies are not done, and often they are not, he said, a drug may not be approved for use in patients aged 65 and older. Therefore, the panel concluded that requiring separate studies in the elderly serves only to limit the availability of treatments in older patients.

“Excluding patients over 60 or 65 is inappropriate and unhelpful and in some ways regarded as counterproductive,” Dr. Montgomery said.

The panel focused on efficacy in its deliberations, but it agreed that safety can be an issue in older patients. Dr. Montgomery cited concerns about delays in elimination of CNS drugs in the elderly, who also tend to have more comorbidity and take more medications than younger patients.

Accordingly, the panel recommended that safety issues be addressed in subgroup analyses of older patients enrolled in placebo-controlled clinical trials with broad populations as well as in separate studies identified explicitly as safety studies.

“There are potentially more drug-drug interactions, more safety problems, and they should be the focus with increasing age, not efficacy,” Dr. Montgomery said.

He also summarized the panel's findings on age relative to the following disorders:

▸ Depression. Major depressive disorder is no different in the elderly; antidepressants that help younger people are just as effective in older people

▸ Bipolar disorder. Mania is an early-onset disorder affecting younger patients, but the elderly are more likely to present with depression. The efficacy of drugs for bipolar depression does not change with age.

▸ Anxiety. Generalized anxiety disorder is the most common late-onset anxiety disorder in the elderly. Response to treatment is not age related.

▸ Insomnia. Age has no effect on the efficacy of licensed treatments for insomnia, which is common in the elderly.

▸ Schizophrenia. Chronic schizophrenia patients who reach old age have more negative, cognitive, and depressive symptoms, possibly as a result of chronicity. The experts found no evidence of age-related changes in response to treatments for negative or positive symptoms.

The widespread belief that older patients respond more slowly to medication isa myth. DR. MONTGOMERY

PARIS – A consensus panel convened by the European College of Neuropsychopharmacology has drafted a report opposing separate clinical trials of central nervous system drugs in elderly patients.

The panel calls instead for dropping age cutoffs from clinical trials testing the efficacy of new CNS drugs. It favors inclusion of elderly patients in trial populations and use of the same placebo-controlled trial designs in studies across age ranges.

“We are of the opinion in the consensus meeting that specific studies in the elderly, while very interesting, are not worth doing,” said Dr. Stuart A. Montgomery, the panel's cochair, in a presentation of its preliminary findings at the annual congress of the college.

More than 200 experts participated when the panel on investigating CNS disorders in the elderly met in Nice, France, in March 2006, according to Dr. Montgomery, professor emeritus of psychiatry at the University of London. The written draft, currently under review, will be published in a journal when the process is completed.

He said a review of clinical trials in the elderly determined that elderly patients, whether 60 or 65 years of age or older, responded much the same as younger patients to CNS drugs. The widespread belief that older patients respond more slowly is a myth, Dr. Montgomery said; changes in physiologic function occur on a continuum throughout life rather than in response to an arbitrary age cutoff.

“There is such a paucity of data at the upper end–above 75 and above 80–it is really not possible to comment on what goes on at that point,” he said. “There is such substantial individual variation … that the effect of age becomes minimal by comparison.”

European regulatory agencies usually do ask drug companies to conduct separate studies in the elderly, said Dr. Montgomery. If these studies are not done, and often they are not, he said, a drug may not be approved for use in patients aged 65 and older. Therefore, the panel concluded that requiring separate studies in the elderly serves only to limit the availability of treatments in older patients.

“Excluding patients over 60 or 65 is inappropriate and unhelpful and in some ways regarded as counterproductive,” Dr. Montgomery said.

The panel focused on efficacy in its deliberations, but it agreed that safety can be an issue in older patients. Dr. Montgomery cited concerns about delays in elimination of CNS drugs in the elderly, who also tend to have more comorbidity and take more medications than younger patients.

Accordingly, the panel recommended that safety issues be addressed in subgroup analyses of older patients enrolled in placebo-controlled clinical trials with broad populations as well as in separate studies identified explicitly as safety studies.

“There are potentially more drug-drug interactions, more safety problems, and they should be the focus with increasing age, not efficacy,” Dr. Montgomery said.

He also summarized the panel's findings on age relative to the following disorders:

▸ Depression. Major depressive disorder is no different in the elderly; antidepressants that help younger people are just as effective in older people

▸ Bipolar disorder. Mania is an early-onset disorder affecting younger patients, but the elderly are more likely to present with depression. The efficacy of drugs for bipolar depression does not change with age.

▸ Anxiety. Generalized anxiety disorder is the most common late-onset anxiety disorder in the elderly. Response to treatment is not age related.

▸ Insomnia. Age has no effect on the efficacy of licensed treatments for insomnia, which is common in the elderly.

▸ Schizophrenia. Chronic schizophrenia patients who reach old age have more negative, cognitive, and depressive symptoms, possibly as a result of chronicity. The experts found no evidence of age-related changes in response to treatments for negative or positive symptoms.

The widespread belief that older patients respond more slowly to medication isa myth. DR. MONTGOMERY