APA 2014

NEW YORK – The safe, cheap, readily available medication N-acetylcysteine may be effective against difficult-to-treat compulsive grooming disorders, a trans-Atlantic study showed.

In a case series of six patients treated for trichotillomania (hair pulling) and/or skin excoriation (skin-picking disorder, or SPD) as comorbidities to an impulse control or affective disorder, treatment with N-acetylcysteine (NAC) 1,200-1,800 mg/day resulted in either complete abstinence or great improvement in self-damaging habits, said Dr. Gustavo Jesus of the Central Psychiatric Hospital of Lisbon.

Most cases show very good results of the use of NAC in difficult-to-treat grooming disorders, he said at the American Psychiatric Association annual meeting.

Although support for the use of NAC in grooming disorders comes largely from case reports, the available evidence supports his team’s findings, he added.

Neil Osterweil/Frontline Medical News

NAC is a precursor to cysteine, an amino acid that protects cells from oxidative stress, interacts with inflammatory mediators, and is a modulator of the glutaminergic system of neurotransmission.

The medication historically has been used to counteract acetaminophen overdose, as a mucolytic agent for the treatment of respiratory diseases, and in the treatment of contrast-induced nephropathy, polycystic ovary syndrome, and more recently, psychiatric disorders, because of its antioxidative and anti-inflammatory properties.

The agent has been studied most in schizophrenia, Dr. Jesus said, but has also been investigated in bipolar and depressive disorders, substance use problems, obsessive-compulsive disorders and impulse control disorders, including grooming disorders.

Few options

Dr. Jesus’s team, with colleagues in São Paulo, Brazil, reviewed the literature for drug treatment of trichotillomania, and found varying evidence for the use of clomipramine, desipramine, fluoxetine, olanzapine, naltrexone, and citalopram.

"Still, we are short of evidence for which medications can be used to treat grooming disorders," Dr. Jesus said.

He presented data on a case series of three Brazilian and three Portuguese patients, four of whom had SPD, one with trichotillomania, and one with both disorders secondary to conditions that included bipolar disorder, major depressive disorder, generalized anxiety disorder, and dysthymia.

Previous medications tried for their compulsive behaviors included lithium, quetiapine, fluoxetine, venlafaxine, oxcarbazepine, and gabapentin.

Two patients had complete abstinence from SPD for 10-12 months while taking NAC 1,200 mg daily. One of these patients had a relapse after 2 weeks off NAC and improved after restarting the drug. The second patient had a relapse 1 month after stopping the drug and also had improvement after restarting it, this time at a dose of 1,800 mg/day. This patient also had trichotillomania that was considered "greatly improved" with NAC 1,200 mg/day.

The remaining patients all had "great improvement" of SPD, and three had improvement of symptoms when they restarted the drug after hiatuses ranging from 2 weeks to 3 months.

Dr. Jesus emphasized that NAC treated the compulsive grooming symptoms only and not the underlying disorder. For example, one patient with SPD secondary to major depressive disorder also had pathologic jealousy and an addiction to the Internet; NAC did not diminish symptoms of either the jealousy or the addiction.

There has been only one small, randomized, double-blind placebo-controlled trial of NAC in trichotillomania to date, Dr. Jesus noted. The investigators of that study found that patients in the active treatment group had significant improvement of symptoms on both the Massachusetts General Hospital Hair Pulling Scale and the Psychiatric Institute Trichotillomania Scale (P = .001). They also found that more than half of the 50 patients were "much" or "very much" improved with NAC, compared with patients on placebo (P = .003).

Dr. Jesus did not disclose the funding source for the study but reported having no significant financial disclosures or relationships with the manufacturers of any products he discussed.

NEW YORK – The safe, cheap, readily available medication N-acetylcysteine may be effective against difficult-to-treat compulsive grooming disorders, a trans-Atlantic study showed.

In a case series of six patients treated for trichotillomania (hair pulling) and/or skin excoriation (skin-picking disorder, or SPD) as comorbidities to an impulse control or affective disorder, treatment with N-acetylcysteine (NAC) 1,200-1,800 mg/day resulted in either complete abstinence or great improvement in self-damaging habits, said Dr. Gustavo Jesus of the Central Psychiatric Hospital of Lisbon.

Most cases show very good results of the use of NAC in difficult-to-treat grooming disorders, he said at the American Psychiatric Association annual meeting.

Although support for the use of NAC in grooming disorders comes largely from case reports, the available evidence supports his team’s findings, he added.

Neil Osterweil/Frontline Medical News

NAC is a precursor to cysteine, an amino acid that protects cells from oxidative stress, interacts with inflammatory mediators, and is a modulator of the glutaminergic system of neurotransmission.

The medication historically has been used to counteract acetaminophen overdose, as a mucolytic agent for the treatment of respiratory diseases, and in the treatment of contrast-induced nephropathy, polycystic ovary syndrome, and more recently, psychiatric disorders, because of its antioxidative and anti-inflammatory properties.

The agent has been studied most in schizophrenia, Dr. Jesus said, but has also been investigated in bipolar and depressive disorders, substance use problems, obsessive-compulsive disorders and impulse control disorders, including grooming disorders.

Few options

Dr. Jesus’s team, with colleagues in São Paulo, Brazil, reviewed the literature for drug treatment of trichotillomania, and found varying evidence for the use of clomipramine, desipramine, fluoxetine, olanzapine, naltrexone, and citalopram.

"Still, we are short of evidence for which medications can be used to treat grooming disorders," Dr. Jesus said.

He presented data on a case series of three Brazilian and three Portuguese patients, four of whom had SPD, one with trichotillomania, and one with both disorders secondary to conditions that included bipolar disorder, major depressive disorder, generalized anxiety disorder, and dysthymia.

Previous medications tried for their compulsive behaviors included lithium, quetiapine, fluoxetine, venlafaxine, oxcarbazepine, and gabapentin.

Two patients had complete abstinence from SPD for 10-12 months while taking NAC 1,200 mg daily. One of these patients had a relapse after 2 weeks off NAC and improved after restarting the drug. The second patient had a relapse 1 month after stopping the drug and also had improvement after restarting it, this time at a dose of 1,800 mg/day. This patient also had trichotillomania that was considered "greatly improved" with NAC 1,200 mg/day.

The remaining patients all had "great improvement" of SPD, and three had improvement of symptoms when they restarted the drug after hiatuses ranging from 2 weeks to 3 months.

Dr. Jesus emphasized that NAC treated the compulsive grooming symptoms only and not the underlying disorder. For example, one patient with SPD secondary to major depressive disorder also had pathologic jealousy and an addiction to the Internet; NAC did not diminish symptoms of either the jealousy or the addiction.

There has been only one small, randomized, double-blind placebo-controlled trial of NAC in trichotillomania to date, Dr. Jesus noted. The investigators of that study found that patients in the active treatment group had significant improvement of symptoms on both the Massachusetts General Hospital Hair Pulling Scale and the Psychiatric Institute Trichotillomania Scale (P = .001). They also found that more than half of the 50 patients were "much" or "very much" improved with NAC, compared with patients on placebo (P = .003).

Dr. Jesus did not disclose the funding source for the study but reported having no significant financial disclosures or relationships with the manufacturers of any products he discussed.

NEW YORK – The safe, cheap, readily available medication N-acetylcysteine may be effective against difficult-to-treat compulsive grooming disorders, a trans-Atlantic study showed.

In a case series of six patients treated for trichotillomania (hair pulling) and/or skin excoriation (skin-picking disorder, or SPD) as comorbidities to an impulse control or affective disorder, treatment with N-acetylcysteine (NAC) 1,200-1,800 mg/day resulted in either complete abstinence or great improvement in self-damaging habits, said Dr. Gustavo Jesus of the Central Psychiatric Hospital of Lisbon.

Most cases show very good results of the use of NAC in difficult-to-treat grooming disorders, he said at the American Psychiatric Association annual meeting.

Although support for the use of NAC in grooming disorders comes largely from case reports, the available evidence supports his team’s findings, he added.

Neil Osterweil/Frontline Medical News

NAC is a precursor to cysteine, an amino acid that protects cells from oxidative stress, interacts with inflammatory mediators, and is a modulator of the glutaminergic system of neurotransmission.

The medication historically has been used to counteract acetaminophen overdose, as a mucolytic agent for the treatment of respiratory diseases, and in the treatment of contrast-induced nephropathy, polycystic ovary syndrome, and more recently, psychiatric disorders, because of its antioxidative and anti-inflammatory properties.

The agent has been studied most in schizophrenia, Dr. Jesus said, but has also been investigated in bipolar and depressive disorders, substance use problems, obsessive-compulsive disorders and impulse control disorders, including grooming disorders.

Few options

Dr. Jesus’s team, with colleagues in São Paulo, Brazil, reviewed the literature for drug treatment of trichotillomania, and found varying evidence for the use of clomipramine, desipramine, fluoxetine, olanzapine, naltrexone, and citalopram.

"Still, we are short of evidence for which medications can be used to treat grooming disorders," Dr. Jesus said.

He presented data on a case series of three Brazilian and three Portuguese patients, four of whom had SPD, one with trichotillomania, and one with both disorders secondary to conditions that included bipolar disorder, major depressive disorder, generalized anxiety disorder, and dysthymia.

Previous medications tried for their compulsive behaviors included lithium, quetiapine, fluoxetine, venlafaxine, oxcarbazepine, and gabapentin.

Two patients had complete abstinence from SPD for 10-12 months while taking NAC 1,200 mg daily. One of these patients had a relapse after 2 weeks off NAC and improved after restarting the drug. The second patient had a relapse 1 month after stopping the drug and also had improvement after restarting it, this time at a dose of 1,800 mg/day. This patient also had trichotillomania that was considered "greatly improved" with NAC 1,200 mg/day.

The remaining patients all had "great improvement" of SPD, and three had improvement of symptoms when they restarted the drug after hiatuses ranging from 2 weeks to 3 months.

Dr. Jesus emphasized that NAC treated the compulsive grooming symptoms only and not the underlying disorder. For example, one patient with SPD secondary to major depressive disorder also had pathologic jealousy and an addiction to the Internet; NAC did not diminish symptoms of either the jealousy or the addiction.

There has been only one small, randomized, double-blind placebo-controlled trial of NAC in trichotillomania to date, Dr. Jesus noted. The investigators of that study found that patients in the active treatment group had significant improvement of symptoms on both the Massachusetts General Hospital Hair Pulling Scale and the Psychiatric Institute Trichotillomania Scale (P = .001). They also found that more than half of the 50 patients were "much" or "very much" improved with NAC, compared with patients on placebo (P = .003).

Dr. Jesus did not disclose the funding source for the study but reported having no significant financial disclosures or relationships with the manufacturers of any products he discussed.

NEW YORK – Hoarding in adolescence is not characterized by accumulation of clutter, as it is in adults, but is no less burdensome a disorder both to patients and families, Volen Z. Ivanov reported at the annual meeting of the American Psychiatric Association.

Indeed, one of the most prominent features of the condition in adults, at least to observers – the presence of clutter – was not endorsed by any of 21 adolescents who met other hoarding criteria, he said.

However, "even if the clutter takes a while to build up, we know that other parts of the disorder are prominent early in life."

Mr. Ivanov, a PhD candidate at Karolinska Instituet, Solna, Sweden, looked at 8,455 adolescents born between 1994 and 1996 who were in the Swedish Twin Registry. The teens had been enrolled in a 2013 study, also by Mr. Ivanov, that assessed the prevalence of hoarding among adolescents.

In that study, Mr. Ivanov found that "clinically significant" hoarding symptoms were present in 2% of the adolescent Swedish population (95% confidence interval, 1.6%-2.5%), and exclusion of the diagnostic criterion stipulating the presence of clutter further increased the prevalence to 3.7% (95% CI 3.1%-4.3%) (PLoS ONE 2013;8:e69140 [doi:10.1371/journal.pone 0069140]).

The present study sought to validate that finding: namely, that clutter need not be present among adolescents to diagnose clinically significant hoarding.

To that end, the researchers targeted 21 of these previously identified hoarding adolescents who met at least criteria A and B according to the new DSM-5 diagnostic definition of hoarding: "persistent difficulty discarding or parting with possessions, regardless of their actual value" and "this difficulty is due to a perceived need to save items and to distress associated with discarding them."

None of the adolescents endorsed the third criteria, "the difficulty in discarding possessions results in the accumulation of possessions that congest and clutter active living areas and substantially compromise their intended use."

The hoarding adolescents were compared with 43 healthy controls, also from the registry.

The researchers found that hoarding adolescents scored a mean of 11.8 on the Hoarding Rating Scale–Self-Report, a 5-item scale with each item measured on a Likert scale from 0 to 8. Healthy controls, on the other hand, scored a mean of 4.1 (P less than .001). Similarly, hoarders tallied a mean 31.8 points on the Saving Inventory-Revised, compared with controls’ mean score of 12.8 (P less than .001).

The hoarders were more likely to have a higher psychiatric burden overall, in the form of comorbid diagnoses over their lifetime, compared with controls (mean 1.5 diagnoses among hoarders, versus 0.1 among controls, P less than .001).

On the other hand, looking at the Family Impact Scale for Hoarding (FISH), the researchers found no significant difference between family burden among hoarders (0.06) and nonhoarding teens (0.18) (P = .33).

According to Mr. Ivanov, while the present study is still ongoing with the goal of collecting data from at least 20 more hoarding adolescents in Sweden, the findings demonstrate that hoarding in young people need not manifest itself in the overwhelming clutter seen with adults and need not burden the child’s family.

Future studies should focus on how hoarding evolves from adolescence through adulthood, and how environment during adolescence might contribute to the development of the disorder, he added.

Mr. Ivanov disclosed no conflicts of interest.

NEW YORK – Hoarding in adolescence is not characterized by accumulation of clutter, as it is in adults, but is no less burdensome a disorder both to patients and families, Volen Z. Ivanov reported at the annual meeting of the American Psychiatric Association.

Indeed, one of the most prominent features of the condition in adults, at least to observers – the presence of clutter – was not endorsed by any of 21 adolescents who met other hoarding criteria, he said.

However, "even if the clutter takes a while to build up, we know that other parts of the disorder are prominent early in life."

Mr. Ivanov, a PhD candidate at Karolinska Instituet, Solna, Sweden, looked at 8,455 adolescents born between 1994 and 1996 who were in the Swedish Twin Registry. The teens had been enrolled in a 2013 study, also by Mr. Ivanov, that assessed the prevalence of hoarding among adolescents.

In that study, Mr. Ivanov found that "clinically significant" hoarding symptoms were present in 2% of the adolescent Swedish population (95% confidence interval, 1.6%-2.5%), and exclusion of the diagnostic criterion stipulating the presence of clutter further increased the prevalence to 3.7% (95% CI 3.1%-4.3%) (PLoS ONE 2013;8:e69140 [doi:10.1371/journal.pone 0069140]).

The present study sought to validate that finding: namely, that clutter need not be present among adolescents to diagnose clinically significant hoarding.

To that end, the researchers targeted 21 of these previously identified hoarding adolescents who met at least criteria A and B according to the new DSM-5 diagnostic definition of hoarding: "persistent difficulty discarding or parting with possessions, regardless of their actual value" and "this difficulty is due to a perceived need to save items and to distress associated with discarding them."

None of the adolescents endorsed the third criteria, "the difficulty in discarding possessions results in the accumulation of possessions that congest and clutter active living areas and substantially compromise their intended use."

The hoarding adolescents were compared with 43 healthy controls, also from the registry.

The researchers found that hoarding adolescents scored a mean of 11.8 on the Hoarding Rating Scale–Self-Report, a 5-item scale with each item measured on a Likert scale from 0 to 8. Healthy controls, on the other hand, scored a mean of 4.1 (P less than .001). Similarly, hoarders tallied a mean 31.8 points on the Saving Inventory-Revised, compared with controls’ mean score of 12.8 (P less than .001).

The hoarders were more likely to have a higher psychiatric burden overall, in the form of comorbid diagnoses over their lifetime, compared with controls (mean 1.5 diagnoses among hoarders, versus 0.1 among controls, P less than .001).

On the other hand, looking at the Family Impact Scale for Hoarding (FISH), the researchers found no significant difference between family burden among hoarders (0.06) and nonhoarding teens (0.18) (P = .33).

According to Mr. Ivanov, while the present study is still ongoing with the goal of collecting data from at least 20 more hoarding adolescents in Sweden, the findings demonstrate that hoarding in young people need not manifest itself in the overwhelming clutter seen with adults and need not burden the child’s family.

Future studies should focus on how hoarding evolves from adolescence through adulthood, and how environment during adolescence might contribute to the development of the disorder, he added.

Mr. Ivanov disclosed no conflicts of interest.

NEW YORK – Hoarding in adolescence is not characterized by accumulation of clutter, as it is in adults, but is no less burdensome a disorder both to patients and families, Volen Z. Ivanov reported at the annual meeting of the American Psychiatric Association.

Indeed, one of the most prominent features of the condition in adults, at least to observers – the presence of clutter – was not endorsed by any of 21 adolescents who met other hoarding criteria, he said.

However, "even if the clutter takes a while to build up, we know that other parts of the disorder are prominent early in life."

Mr. Ivanov, a PhD candidate at Karolinska Instituet, Solna, Sweden, looked at 8,455 adolescents born between 1994 and 1996 who were in the Swedish Twin Registry. The teens had been enrolled in a 2013 study, also by Mr. Ivanov, that assessed the prevalence of hoarding among adolescents.

In that study, Mr. Ivanov found that "clinically significant" hoarding symptoms were present in 2% of the adolescent Swedish population (95% confidence interval, 1.6%-2.5%), and exclusion of the diagnostic criterion stipulating the presence of clutter further increased the prevalence to 3.7% (95% CI 3.1%-4.3%) (PLoS ONE 2013;8:e69140 [doi:10.1371/journal.pone 0069140]).

The present study sought to validate that finding: namely, that clutter need not be present among adolescents to diagnose clinically significant hoarding.

To that end, the researchers targeted 21 of these previously identified hoarding adolescents who met at least criteria A and B according to the new DSM-5 diagnostic definition of hoarding: "persistent difficulty discarding or parting with possessions, regardless of their actual value" and "this difficulty is due to a perceived need to save items and to distress associated with discarding them."

None of the adolescents endorsed the third criteria, "the difficulty in discarding possessions results in the accumulation of possessions that congest and clutter active living areas and substantially compromise their intended use."

The hoarding adolescents were compared with 43 healthy controls, also from the registry.

The researchers found that hoarding adolescents scored a mean of 11.8 on the Hoarding Rating Scale–Self-Report, a 5-item scale with each item measured on a Likert scale from 0 to 8. Healthy controls, on the other hand, scored a mean of 4.1 (P less than .001). Similarly, hoarders tallied a mean 31.8 points on the Saving Inventory-Revised, compared with controls’ mean score of 12.8 (P less than .001).

The hoarders were more likely to have a higher psychiatric burden overall, in the form of comorbid diagnoses over their lifetime, compared with controls (mean 1.5 diagnoses among hoarders, versus 0.1 among controls, P less than .001).

On the other hand, looking at the Family Impact Scale for Hoarding (FISH), the researchers found no significant difference between family burden among hoarders (0.06) and nonhoarding teens (0.18) (P = .33).

According to Mr. Ivanov, while the present study is still ongoing with the goal of collecting data from at least 20 more hoarding adolescents in Sweden, the findings demonstrate that hoarding in young people need not manifest itself in the overwhelming clutter seen with adults and need not burden the child’s family.

Future studies should focus on how hoarding evolves from adolescence through adulthood, and how environment during adolescence might contribute to the development of the disorder, he added.

Mr. Ivanov disclosed no conflicts of interest.

NEW YORK – Patients with panic disorder can be effectively treated with either a benzodiazepine or a selective serotonin reuptake inhibitor, or both, but even long-term therapy might not prevent relapse in the majority of patients.

That’s the conclusion of a team of Brazilian researchers who compared clonazepam, paroxetine, and a combination of the two in patients with panic disorder in a randomized, open-label trial.

By the third year of follow-up, about 77% of patients had experienced a relapse despite being treated for 3 years, and after 6 years, 94% of patients had experienced at least one new panic attack, reported Dr. Antonio E. Nardi of the Federal University of Rio de Janeiro.

However, resumption of therapy with either drug or with a different medication was successful in preventing or reducing the incidence of additional attacks in nearly all patients.

"We propose to discontinue drug treatment as soon as patients are asymptomatic for 1 year and to restart treatment at the first sign of relapse," he said at the annual meeting of the American Psychiatric Association.

The good and the bad

The benzodiazepine clonazepam and the SSRI paroxetine each have their advantages and drawbacks, Dr. Nardi said.

Clonazepam has a rapid onset of action, decreases anticipatory anxiety, and has a good safety profile in terms of interactions and overdose risk. On the other hand, patients might experience withdrawal symptoms, develop memory problems, and become dependent on the agent.

Paroxetine has well documented antidepressive effects and little if any potential for abuse but can cause sexual dysfunction, hyperstimulation, anticholinergic effects, and weight gain.

With either agent, from 20% to 40% of patients remain symptomatic after short- or intermediate-term treatment, and relapse is frequent, even after 1 year of treatment, Dr. Nardi said.

The investigators designed an open-label clinical trial in which patients would be randomized to either clonazepam 2 mg/day or paroxetine 40 mg/day. Those who did not respond well to either drug were switched after 8 weeks to a combination of the drugs at or near the dose levels assigned for the individual drugs.

After the 8-week efficacy phase, patients were followed for safety and efficacy of both agents and the combination during 3 years of continuous treatment. Patients were tapered off drugs at 3 years and followed up through 6 years for the number of panic attacks per month, clinical global impression severity score (CGI-S), and Hamilton Anxiety Scale score (HAM-A).

Of the 120 patients enrolled, 94 completed the 3 years of treatment (45 on clonazepam, 33 on paroxetine, and 16 on the combination). In all, 66 of these patients had annual assessments out to 6 years; the remaining 28 had assessments at 5 or 6 years of follow-up. Among the 66 patients who were seen annually, relapse rates were 41% 1 year after therapy taper was completed, 77% at 4 years, and 94% at 6 years.

For most patients, restarting the original drug resulted in either a partial remission (54%) or full remission (36%). With treatment resumption, 73% of patients remained free of panic attacks, 91% had a CGI-S score of 1 (very much improved), and 39% had a HAM-A score from 5 to 10, indicating low anxiety.

Both drugs were generally well tolerated, although clonazepam was associated with significantly fewer adverse events, including drowsiness/fatigue, sexual dysfunction, nausea/vomiting, appetite/weight change, dry mouth, hyperhydrosis, and diarrhea/constipation, compared with paroxetine, in all but one category. No significant differences were found between the two drugs in their effects on memory and concentration, however.

The study was supported by the Brazilian Council for Scientific and Technological Development, and Brazil\'s National Institute for Translational Medicine. Dr. Nardi disclosed serving on advisory boards for Aché, CNPq, GlaxoSmithKline, Grupo A, and Lundbeck, and serving on the speakers bureaus for Solvay, Cristalia, GSK, Roche, and Aché.

NEW YORK – Patients with panic disorder can be effectively treated with either a benzodiazepine or a selective serotonin reuptake inhibitor, or both, but even long-term therapy might not prevent relapse in the majority of patients.

That’s the conclusion of a team of Brazilian researchers who compared clonazepam, paroxetine, and a combination of the two in patients with panic disorder in a randomized, open-label trial.

By the third year of follow-up, about 77% of patients had experienced a relapse despite being treated for 3 years, and after 6 years, 94% of patients had experienced at least one new panic attack, reported Dr. Antonio E. Nardi of the Federal University of Rio de Janeiro.

However, resumption of therapy with either drug or with a different medication was successful in preventing or reducing the incidence of additional attacks in nearly all patients.

"We propose to discontinue drug treatment as soon as patients are asymptomatic for 1 year and to restart treatment at the first sign of relapse," he said at the annual meeting of the American Psychiatric Association.

The good and the bad

The benzodiazepine clonazepam and the SSRI paroxetine each have their advantages and drawbacks, Dr. Nardi said.

Clonazepam has a rapid onset of action, decreases anticipatory anxiety, and has a good safety profile in terms of interactions and overdose risk. On the other hand, patients might experience withdrawal symptoms, develop memory problems, and become dependent on the agent.

Paroxetine has well documented antidepressive effects and little if any potential for abuse but can cause sexual dysfunction, hyperstimulation, anticholinergic effects, and weight gain.

With either agent, from 20% to 40% of patients remain symptomatic after short- or intermediate-term treatment, and relapse is frequent, even after 1 year of treatment, Dr. Nardi said.

The investigators designed an open-label clinical trial in which patients would be randomized to either clonazepam 2 mg/day or paroxetine 40 mg/day. Those who did not respond well to either drug were switched after 8 weeks to a combination of the drugs at or near the dose levels assigned for the individual drugs.

After the 8-week efficacy phase, patients were followed for safety and efficacy of both agents and the combination during 3 years of continuous treatment. Patients were tapered off drugs at 3 years and followed up through 6 years for the number of panic attacks per month, clinical global impression severity score (CGI-S), and Hamilton Anxiety Scale score (HAM-A).

Of the 120 patients enrolled, 94 completed the 3 years of treatment (45 on clonazepam, 33 on paroxetine, and 16 on the combination). In all, 66 of these patients had annual assessments out to 6 years; the remaining 28 had assessments at 5 or 6 years of follow-up. Among the 66 patients who were seen annually, relapse rates were 41% 1 year after therapy taper was completed, 77% at 4 years, and 94% at 6 years.

For most patients, restarting the original drug resulted in either a partial remission (54%) or full remission (36%). With treatment resumption, 73% of patients remained free of panic attacks, 91% had a CGI-S score of 1 (very much improved), and 39% had a HAM-A score from 5 to 10, indicating low anxiety.

Both drugs were generally well tolerated, although clonazepam was associated with significantly fewer adverse events, including drowsiness/fatigue, sexual dysfunction, nausea/vomiting, appetite/weight change, dry mouth, hyperhydrosis, and diarrhea/constipation, compared with paroxetine, in all but one category. No significant differences were found between the two drugs in their effects on memory and concentration, however.

The study was supported by the Brazilian Council for Scientific and Technological Development, and Brazil\'s National Institute for Translational Medicine. Dr. Nardi disclosed serving on advisory boards for Aché, CNPq, GlaxoSmithKline, Grupo A, and Lundbeck, and serving on the speakers bureaus for Solvay, Cristalia, GSK, Roche, and Aché.

NEW YORK – Patients with panic disorder can be effectively treated with either a benzodiazepine or a selective serotonin reuptake inhibitor, or both, but even long-term therapy might not prevent relapse in the majority of patients.

That’s the conclusion of a team of Brazilian researchers who compared clonazepam, paroxetine, and a combination of the two in patients with panic disorder in a randomized, open-label trial.

By the third year of follow-up, about 77% of patients had experienced a relapse despite being treated for 3 years, and after 6 years, 94% of patients had experienced at least one new panic attack, reported Dr. Antonio E. Nardi of the Federal University of Rio de Janeiro.

However, resumption of therapy with either drug or with a different medication was successful in preventing or reducing the incidence of additional attacks in nearly all patients.

"We propose to discontinue drug treatment as soon as patients are asymptomatic for 1 year and to restart treatment at the first sign of relapse," he said at the annual meeting of the American Psychiatric Association.

The good and the bad

The benzodiazepine clonazepam and the SSRI paroxetine each have their advantages and drawbacks, Dr. Nardi said.

Clonazepam has a rapid onset of action, decreases anticipatory anxiety, and has a good safety profile in terms of interactions and overdose risk. On the other hand, patients might experience withdrawal symptoms, develop memory problems, and become dependent on the agent.

Paroxetine has well documented antidepressive effects and little if any potential for abuse but can cause sexual dysfunction, hyperstimulation, anticholinergic effects, and weight gain.

With either agent, from 20% to 40% of patients remain symptomatic after short- or intermediate-term treatment, and relapse is frequent, even after 1 year of treatment, Dr. Nardi said.

The investigators designed an open-label clinical trial in which patients would be randomized to either clonazepam 2 mg/day or paroxetine 40 mg/day. Those who did not respond well to either drug were switched after 8 weeks to a combination of the drugs at or near the dose levels assigned for the individual drugs.

After the 8-week efficacy phase, patients were followed for safety and efficacy of both agents and the combination during 3 years of continuous treatment. Patients were tapered off drugs at 3 years and followed up through 6 years for the number of panic attacks per month, clinical global impression severity score (CGI-S), and Hamilton Anxiety Scale score (HAM-A).

Of the 120 patients enrolled, 94 completed the 3 years of treatment (45 on clonazepam, 33 on paroxetine, and 16 on the combination). In all, 66 of these patients had annual assessments out to 6 years; the remaining 28 had assessments at 5 or 6 years of follow-up. Among the 66 patients who were seen annually, relapse rates were 41% 1 year after therapy taper was completed, 77% at 4 years, and 94% at 6 years.

For most patients, restarting the original drug resulted in either a partial remission (54%) or full remission (36%). With treatment resumption, 73% of patients remained free of panic attacks, 91% had a CGI-S score of 1 (very much improved), and 39% had a HAM-A score from 5 to 10, indicating low anxiety.

Both drugs were generally well tolerated, although clonazepam was associated with significantly fewer adverse events, including drowsiness/fatigue, sexual dysfunction, nausea/vomiting, appetite/weight change, dry mouth, hyperhydrosis, and diarrhea/constipation, compared with paroxetine, in all but one category. No significant differences were found between the two drugs in their effects on memory and concentration, however.

The study was supported by the Brazilian Council for Scientific and Technological Development, and Brazil\'s National Institute for Translational Medicine. Dr. Nardi disclosed serving on advisory boards for Aché, CNPq, GlaxoSmithKline, Grupo A, and Lundbeck, and serving on the speakers bureaus for Solvay, Cristalia, GSK, Roche, and Aché.

Monthly intramuscular injections of paliperidone were significantly more effective than oral antipsychotics in maintaining patients with schizophrenia who were recently released from jail, according to a paper presented May 3 at the annual meeting of the American Psychiatric Association.

The PRIDE (Paliperidone Palmitate Research in Demonstrating Effectiveness) study "is the first prospective, randomized clinical trial to study schizophrenia treatments within the context of many ‘real world’ issues faced by patients in their daily lives, including some of the most challenging circumstances – recent incarceration or substance use," Dr. Mark Lerman, a PRIDE principal investigator, said in an interview. "Until now, no studies have been conducted comparing the effectiveness of psychopharmacologic treatments in individuals with schizophrenia following release from jail."

The PRIDE trial looked at time to treatment failure in 444 schizophrenia patients over 15 months – 226 were treated with IM paliperidone (Invega Sustenna) and 218 were treated with one of seven oral antipsychotics (aripiprazole, haloperidol, olanzapine, paliperidone, perphenazine, quetiapine, or risperidone). Time to treatment failure was defined as arrest/incarceration; psychiatric hospitalization; suicide; treatment discontinuation or supplementation due to inadequate efficacy, safety, or tolerability; or increased psychiatric services to prevent hospitalization.

All participants were adults diagnosed with schizophrenia who had been taken into custody by the criminal justice system at least twice in the previous 2 years, with at least one custody resulting in incarceration, said Dr. Lerman, medical director at the Center for Psychiatric Research at Alexian Brothers Behavioral Health Hospital in Hoffman Estates, Ill. All participants were released from their most recent custody within 90 days of screening for the trial.

IM paliperidone was associated with a significantly longer time to treatment failure than oral antipsychotics, with a median time of 416 days vs. 226 days (P = .011).

The most common treatment-emergent adverse events were injection-site pain (18.6% in patients on IM paliperidone vs. 0% on oral antipsychotics), insomnia (16.8% vs. 11.5%), weight gain (11.9% vs. 6.0%), akathisia (11.1% vs 6.9%), and anxiety (10.6% vs 7.3%).

Dr. Lerman stressed the importance of including "real world" adverse consequences in the study of schizophrenia, since mental illness patients represent a substantial proportion of the incarcerated population.

"When severely mentally ill individuals, including those with schizophrenia, are released from correctional facilities, many of them return to environments with limited support and without consistent medication or follow-up services," Dr. Lerman said. "This lack of continuous care when reentering the community can result in a ‘revolving door’ of relapse, rearrest, incarceration, and hospitalization.

"Lack of access to consistent community care may lead some individuals to cycle through jails dozens or even hundreds of times," Dr. Lerman said. "In addition to the impact on patients, these factors have created an increasingly large and costly problem for the U.S. health care system."

Dr. Lerman’s institution received funding from Janssen Pharmaceuticals. The study was sponsored by Janssen, which manufactures paliperidone.

[email protected]

On Twitter @mrajaraman

Monthly intramuscular injections of paliperidone were significantly more effective than oral antipsychotics in maintaining patients with schizophrenia who were recently released from jail, according to a paper presented May 3 at the annual meeting of the American Psychiatric Association.

The PRIDE (Paliperidone Palmitate Research in Demonstrating Effectiveness) study "is the first prospective, randomized clinical trial to study schizophrenia treatments within the context of many ‘real world’ issues faced by patients in their daily lives, including some of the most challenging circumstances – recent incarceration or substance use," Dr. Mark Lerman, a PRIDE principal investigator, said in an interview. "Until now, no studies have been conducted comparing the effectiveness of psychopharmacologic treatments in individuals with schizophrenia following release from jail."

The PRIDE trial looked at time to treatment failure in 444 schizophrenia patients over 15 months – 226 were treated with IM paliperidone (Invega Sustenna) and 218 were treated with one of seven oral antipsychotics (aripiprazole, haloperidol, olanzapine, paliperidone, perphenazine, quetiapine, or risperidone). Time to treatment failure was defined as arrest/incarceration; psychiatric hospitalization; suicide; treatment discontinuation or supplementation due to inadequate efficacy, safety, or tolerability; or increased psychiatric services to prevent hospitalization.

All participants were adults diagnosed with schizophrenia who had been taken into custody by the criminal justice system at least twice in the previous 2 years, with at least one custody resulting in incarceration, said Dr. Lerman, medical director at the Center for Psychiatric Research at Alexian Brothers Behavioral Health Hospital in Hoffman Estates, Ill. All participants were released from their most recent custody within 90 days of screening for the trial.

IM paliperidone was associated with a significantly longer time to treatment failure than oral antipsychotics, with a median time of 416 days vs. 226 days (P = .011).

The most common treatment-emergent adverse events were injection-site pain (18.6% in patients on IM paliperidone vs. 0% on oral antipsychotics), insomnia (16.8% vs. 11.5%), weight gain (11.9% vs. 6.0%), akathisia (11.1% vs 6.9%), and anxiety (10.6% vs 7.3%).

Dr. Lerman stressed the importance of including "real world" adverse consequences in the study of schizophrenia, since mental illness patients represent a substantial proportion of the incarcerated population.

"When severely mentally ill individuals, including those with schizophrenia, are released from correctional facilities, many of them return to environments with limited support and without consistent medication or follow-up services," Dr. Lerman said. "This lack of continuous care when reentering the community can result in a ‘revolving door’ of relapse, rearrest, incarceration, and hospitalization.

"Lack of access to consistent community care may lead some individuals to cycle through jails dozens or even hundreds of times," Dr. Lerman said. "In addition to the impact on patients, these factors have created an increasingly large and costly problem for the U.S. health care system."

Dr. Lerman’s institution received funding from Janssen Pharmaceuticals. The study was sponsored by Janssen, which manufactures paliperidone.

[email protected]

On Twitter @mrajaraman

Monthly intramuscular injections of paliperidone were significantly more effective than oral antipsychotics in maintaining patients with schizophrenia who were recently released from jail, according to a paper presented May 3 at the annual meeting of the American Psychiatric Association.

The PRIDE (Paliperidone Palmitate Research in Demonstrating Effectiveness) study "is the first prospective, randomized clinical trial to study schizophrenia treatments within the context of many ‘real world’ issues faced by patients in their daily lives, including some of the most challenging circumstances – recent incarceration or substance use," Dr. Mark Lerman, a PRIDE principal investigator, said in an interview. "Until now, no studies have been conducted comparing the effectiveness of psychopharmacologic treatments in individuals with schizophrenia following release from jail."

The PRIDE trial looked at time to treatment failure in 444 schizophrenia patients over 15 months – 226 were treated with IM paliperidone (Invega Sustenna) and 218 were treated with one of seven oral antipsychotics (aripiprazole, haloperidol, olanzapine, paliperidone, perphenazine, quetiapine, or risperidone). Time to treatment failure was defined as arrest/incarceration; psychiatric hospitalization; suicide; treatment discontinuation or supplementation due to inadequate efficacy, safety, or tolerability; or increased psychiatric services to prevent hospitalization.

All participants were adults diagnosed with schizophrenia who had been taken into custody by the criminal justice system at least twice in the previous 2 years, with at least one custody resulting in incarceration, said Dr. Lerman, medical director at the Center for Psychiatric Research at Alexian Brothers Behavioral Health Hospital in Hoffman Estates, Ill. All participants were released from their most recent custody within 90 days of screening for the trial.

IM paliperidone was associated with a significantly longer time to treatment failure than oral antipsychotics, with a median time of 416 days vs. 226 days (P = .011).

The most common treatment-emergent adverse events were injection-site pain (18.6% in patients on IM paliperidone vs. 0% on oral antipsychotics), insomnia (16.8% vs. 11.5%), weight gain (11.9% vs. 6.0%), akathisia (11.1% vs 6.9%), and anxiety (10.6% vs 7.3%).

Dr. Lerman stressed the importance of including "real world" adverse consequences in the study of schizophrenia, since mental illness patients represent a substantial proportion of the incarcerated population.

"When severely mentally ill individuals, including those with schizophrenia, are released from correctional facilities, many of them return to environments with limited support and without consistent medication or follow-up services," Dr. Lerman said. "This lack of continuous care when reentering the community can result in a ‘revolving door’ of relapse, rearrest, incarceration, and hospitalization.

"Lack of access to consistent community care may lead some individuals to cycle through jails dozens or even hundreds of times," Dr. Lerman said. "In addition to the impact on patients, these factors have created an increasingly large and costly problem for the U.S. health care system."

Dr. Lerman’s institution received funding from Janssen Pharmaceuticals. The study was sponsored by Janssen, which manufactures paliperidone.

[email protected]

On Twitter @mrajaraman