Forcing pharmaceutical history into boxes.
Explore the source record for details and available documents.
Drug Industry↗
Biomedical subjects
Daniel Carpenter
Publications and source records attributed to Daniel Carpenter.
Treatment of epilepsy in adults: expert opinion, 2005.
RATIONALE: Over the past decade, there has been a proliferation of new therapies for the treatment of epilepsy. Faced with this growing list of options, clinicians must decide what therapy, or combination of therapies, is best for a given individual. Although controlled clinical trials exist for each treatment option, the answer to these questions may remain unclear. In 2000, a survey of expert opinion was done to address questions concerning which treatment options might be best in a number of clinical situations. We surveyed a group of US epileptologists again in 2004 and compared the results of the two surveys. METHODS: We sent a questionnaire on the treatment of adolescent and adult epilepsy syndromes to a group of opinion leaders in the field of epilepsy. The questions were formatted to simulate real-world clinical situations in the treatment of symptomatic localization related epilepsy (SLRE) and idiopathic generalized epilepsy (IGE). The experts were asked to rate treatment options based on a modified RAND 9-point scale (with "9" most appropriate and "1" least appropriate). Statistical analysis of data was performed as defined by the expert consensus method. The results were used to develop user-friendly recommendations concerning overall treatment strategies and choice of specific medications. RESULTS: Of the 48 experts to whom the survey was sent, 43 (90%) responded; 29 (67%) of the respondents had also participated in the first survey. For initial monotherapy for IGE (generalized tonic-clonic [GTC], absence, and myoclonic seizures), valproate was rated as treatment of choice. For IGE-GTC seizures, lamotrigine and topiramate were also identified as usually appropriate for initial monotherapy. For IGE-absence seizures, ethosuximide was also a treatment of choice, and lamotrigine was usually appropriate. For SLRE, the experts were again asked to rate treatment options based on seizure type: simple partial seizures (SPS), complex partial seizures (CPS), and secondarily generalized tonic-clonic seizures (SGTC). In SLRE-SPS and SLRE-SGTC, carbamazepine and oxcarbazepine were treatments of choice, with lamotrigine and levetiracetam also usually appropriate. In SLRE-CPS, carbamazepine, lamotrigine. and oxcarbazepine were treatments of choice, while levetiracetam was also usually appropriate. For women who are pregnant or trying to conceive, lamotrigine was treatment of choice for both syndrome types. In the elderly, whether medically stable or ill, the treatment of choice was lamotrigine, while levetiracetam was also usually appropriate (along with gabapentin for persons with comorbid medical illness). In persons with HIV and epilepsy, lamotrigine and levetiracetam were usually appropriate. In people with both epilepsy syndromes who have depression, lamotrigine was treatment of choice. In a person with seizures and renal disease, lamotrigine was usually appropriate for both syndromes, with valproate also usually appropriate for IGE. In patients with hepatic disease, levetiracetam and lamotrigine were usually appropriate for IGE; in SLRE, levetiracetam was treatment of choice, with gabapentin also usually appropriate. CONCLUSIONS: Although the panel of experts reached consensus on many treatment options, there are limitations to these types of data. Despite this, the expert consensus method concisely summarizes expert opinion, and this opinion may be helpful in situations in which the medical literature is scant or lacking. The information in this report should be evaluated in conjunction with evidence-based findings.
Adult↗
Essay: the political logic of regulatory error.
Regulatory error is an issue that has come to the fore following the withdrawal of rofecoxib (Vioxx; Merck) a year ago. Here, we provide a theoretical discussion of the factors that could influence regulatory error, drawing on the Vioxx episode in particular as a possible example of error, and consider the implications for future regulatory policy.
Drug Approval↗
The expert consensus guideline series. Treatment of behavioral emergencies 2005.
OBJECTIVES: Due to inherent dangers and barriers to research in emergency settings, few data are available to guide clinicians about how best to manage behavioral emergencies. Key constructs such as agitation are poorly defined. This lack of empirical data led us to undertake a survey of expert opinion, results of which were published in the 2001 Expert Consensus Guidelines on the Treatment of Behavioral Emergencies. Several second-generation (atypical) antipsychotics (SGAs) are now available in new formulations for treating behavioral emergencies (e.g., intramuscular [i.m.] olanzapine and ziprasidone; rapidly dissolving tablets of olanzapine and risperidone). Critical questions face the field. The SGAs are significantly different from the FGAs and from each other and have not been studied in unselected patients as were the FGAs. Can the SGAs can be thought of as a class, do all antipsychotics have similar anti-agitation effects in different conditions, and, if equally effective, what limits might their safety profiles impose? Should antipsychotics be used more specifically to treat psychotic conditions, while benzodiazepines (BNZs) alone are used nonspecifically? Few data are available concerning combinations of SGAs and BNZs, and findings concerning the traditional combination of haloperidol plus a BNZ may not be relevant to combinations with SGAs. The culture is also evolving with more emphasis on patient involvement in treatment decisions. An international consensus has been developing that calming rather than sedation is the appropriate endpoint of behavioral emergency interventions. We undertook a new survey of expert opinion to update recommendations from the earlier survey. METHOD: A written survey of 61 questions (1,020 options) was mailed to 50 experts in the field, 48 (96%) of whom completed it. The survey sought to define level of agitation at which emergency interventions are appropriate, scope of assessment depending on urgency and patients' ability to cooperate, guiding principles for selecting interventions, and appropriate physical and medication strategies at different levels of diagnostic confidence for a variety of provisional diagnoses and complicating conditions. A modified version of the RAND Corporation's 9-point scale for rating appropriateness of medical decisions was used to score most options. Consensus was defined as a non-random distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred, second line/alternate, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean. Ratings were used to develop guidelines for preferred strategies in key clinical situations. This study received financial support from multiple sponsors, with the panel kept blind to sponsorship to reduce possible bias. Medication ratings were based on responses of only those respondents with direct experience with each drug. In reporting practice patterns, the panel was asked to respond based on actual data rather than estimates. RESULTS: The expert panel reached consensus on 78% of the options rated on the 9-point scale. The responses suggest that physicians can make provisional diagnoses with some confidence and that pharmacological and nonpharmacological interventions are selected differentially based on diagnosis and other salient demographic and medical features. BNZs are recommended when no data are available, when there is no specific treatment (e.g., personality disorder), or when they may have specific benefits (e.g., intoxication). No single SGA emerges as a nonspecific replacement for haloperidol; instead, different SGAs are preferred in various circumstances consistent with current evidence. To the degree that haloperidol is recommended, it is almost always in combination with a BNZ; haloperidol alone is preferred only in the medically compromised. In contrast, the SGAs are more often recommended for use alone, and the panel would avoid combining BNZs with some SGAs. Oral risperidone alone or combined with a BNZ receives strong support in a variety of situations. Oral olanzapine was rated very similarly to risperidone, with slightly higher ratings than risperidone in situations where it has been studied (e.g., schizophrenia, mania) and slightly lower ratings where it has not been studied or safety may be a concern; there was less support for combining oral olanzapine with a BNZ. For oral treatment of agitation related to schizophrenia or mania, olanzapine alone, risperidone alone or combined with a BNZ, and haloperidol plus a BNZ are first line, with strong support also for combining divalproex with the antipsychotic for presumed mania. Oral ziprasidone and quetiapine generally received similar second-line ratings in most situations. If a parenteral agent is needed, i.m. olanzapine alone received somewhat more support than i.m. ziprasidone alone; however, there was more support for i.m. ziprasidone alone or combined with a BNZ than for i.m. olanzapine plus a BNZ, probably reflecting safety concerns. For example, for a provisional diagnosis of schizophrenia, first-line parenteral options are i.m. olanzapine or ziprasidone alone or i.m. haloperidol or ziprasidone combined with a BNZ. Neither of the new parenteral formulations received as much support as traditional agents (i.m. BNZs, i.m. haloperidol) when no data are available or the diagnosis involves medical comorbidity or intoxication. When initial intervention with risperidone, ziprasidone, or haloperidol is unsuccessful, the panel recommended adding a BZD to the antipsychotic. However, when initial treatment with olanzapine or quetiapine is unsuccessful, increasing the dosage is recommended. Perphenazine was consistently rated second line and droperidol and chlorpromazine received third-line ratings throughout. CONCLUSIONS: Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines suggest that the SGAs are now preferred for agitation in the setting of primary psychiatric illnesses but that BNZs are preferred in other situations.
Aggression↗
Treatment of pediatric epilepsy: expert opinion, 2005.
BACKGROUND: Childhood epilepsies are a heterogeneous group of conditions that differ in diagnostic criteria and management and have dramatically different outcomes. Despite increasing data on treatment of epilepsy, research findings on childhood epilepsy are more limited and many clinical questions remain unanswered, so that clinicians must often rely on clinical judgment. In such clinical situations, expert opinion can be especially helpful. METHODS: A survey on pediatric epilepsy and seizures (33 questions and 645 treatment options) was sent to 41 U.S. physicians specializing in pediatric epilepsy, 39 (95%) of whom completed it. In some questions, the experts were asked to recommend overall treatment approaches for specific syndromes (the order in which they would use certain strategies). Most of the questions asked the experts to rate options using a modified version of the RAND 9-point scale for medical appropriateness. Consensus was defined as a non-random distribution of scores by chi-square test, with ratings used to assign a categorical rank (first line/usually appropriate, second line/equivocal, and third line/usually not appropriate) to each option. RESULTS: Valproate was treatment of choice for symptomatic myoclonic and generalized tonic-clonic seizures except in the very young, with lamotrigine and topiramate also first line (usually appropriate). Zonisamide was first line only if the child also has myoclonic seizures. For initial monotherapy for complex partial seizures, oxcarbazepine and carbamazepine were treatments of choice, with lamotrigine and levetiracetam also first line. As initial therapy for infantile spasms caused by tuberous sclerosis, viagabatrin was treatment of choice, with adrenocorticotropic hormone (ACTH) also first line. As initial therapy for infantile spasms that are symptomatic in etiology, ACTH was treatment of choice, with topiramate also first line. As initial therapy for Lennox-Gastaut syndrome, valproate was treatment of choice, with topiramate and lamotrigine also first line. For acute treatment of a prolonged febrile seizure or cluster of seizures, rectal diazepam was treatment of choice. For benign childhood epilepsy with centro-temporal spikes, oxcarbazepine and carbamazepine were treatments of choice, with gabapentin, lamotrigine, and levetiracetam also first line. For childhood absence epilepsy, ethosuximide was treatment of choice, with valproate and lamotrigine also first line. For juvenile absence epilepsy, valproate and lamotrigine were treatments of choice. For juvenile myoclonic epilepsy in adolescent males, valproate and lamotrigine were treatments of choice, with topiramate also first line; for juvenile myoclonic epilepsy in adolescent females, lamotrigine was treatment of choice, with topiramate and valproate other first-line options. As initial therapy for neonatal status epilepticus, intravenous phenobarbital was treatment of choice, with intravenous lorazepam or fosphenytoin also first line. As initial therapy for all types of pediatric status epilepticus, lorazepam was treatment of choice, with intravenous diazepam also first line. For generalized tonic-clonic status epilepticus, rectal diazepam and fosphenytoin were also first line; for complex partial status epilepticus, fosphenytoin was also first line; and for absence status epilepticus, intravenous valproate was also first line. CONCLUSION: The expert panel reached consensus on many treatment options. Within the limits of expert opinion and with the understanding that new research data may take precedence, the experts' recommendations provide helpful guidance in situations where the medical literature is scant or lacking. The information in this report should be evaluated in conjunction with evidence-based findings.
Adolescent↗
The expert consensus guideline series. Treatment of dementia and its behavioral disturbances. Introduction: methods, commentary, and summary.
OBJECTIVES: New treatment options for dementia and its behavioral disturbances have become available since publication of The Expert Consensus Guidelines on the Treatment of Agitation in Older Persons with Dementia in 1998. While only 2 cholinesterase inhibitors, donepezil and tacrine, were available in 1998, 3 new cognitive-enhancing agents have been introduced since that time as well as several new atypical antipsychotics and antidepressants. However, there are still limited data from controlled studies to guide clinicians in choosing among these agents and sequencing and combining treatments. We therefore conducted a new survey study of expert opinion on the treatment of cognitive impairment and behavioral disturbances associated with dementia. METHODS: Based on a literature review, a 61-question survey was developed with 1,225 options. Most options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions. For other options, the experts were asked to write in answers. The survey was sent to 50 North American experts on dementia, 100% of whom completed it. In analyzing responses to items rated on the 9-point scale, consensus was defined as a nonrandom distribution of scores by chi-square "goodness-of-fit" test. Based on the 95% confidence interval around the mean, we assigned a categorical rank (first line/preferred, second line/alternate, third line/usually inappropriate) to each option. Guidelines indicating preferred treatment strategies were then developed for selected clinical situations. RESULTS: For patients at risk for dementia, the experts recommended control of hypertension and diabetes. They also recommended aspirin and would consider a lipid-lowering agent in patients at risk for vascular dementia. Cholinesterase inhibitors were an option for patients with mild cognitive impairment (i.e., at risk for Alzheimer's dementia [AD]). To slow cognitive impairment in mild/moderate AD, the experts recommended a cholinesterase inhibitor alone or combined with vitamin E. Donepezil and galantamine were the preferred cholinesterase inhibitors. The experts recommended combining a cholinesterase inhibitor with a N-methyl-D-aspartate (NMDA) antagonist (e.g., memantine) if a patient with mild/moderate dementia has an inadequate response to monotherapy. Control of hypertension and diabetes was the treatment of choice, in patients with mild/moderate vascular or mixed AD/vascular dementia, with aspirin another first-line option. Cholinesterase inhibitors were also a first-line option for mild/moderate mixed AD/vascular dementia. Among nonpharmacological interventions for mild/moderate dementia, the experts recommended caregiver education, supportive therapy for caregivers, referral to day treatment, exercise programs, and respite care. For moderate/severe AD or mixed AD/vascular dementia, the experts recommended combining an NMDA antagonist with a cholinesterase inhibitor. For moderate/severe vascular or mixed AD/vascular dementia, they recommended control of hypertension and diabetes. The experts' ratings underscore the importance of nonpharmacological strategies aimed at reducing caregiver burden in more severe dementia. Management of agitation and other behavioral disturbances was another focus of this study. The experts recommended using an atypical antipsychotic for agitation associated with delirium, psychosis, aggression, or anger. They would also consider divalproex to manage anger with a risk of physical aggression. Selective serotonin reuptake inhibitors were recommended for the treatment of depression or anxiety in patients with dementia. Benzodiazepines or atypical antipsychotics were viewed as short-term options for acute anxiety. Trazodone was recommended for insomnia. The experts also gave recommendations concerning dosage levels, duration of treatment, and choice of medications for patients with different complicating conditions. CONCLUSIONS: The experts reached high levels of consensus on key steps in treating dementia and associated behavioral disturbances. Within the limits of expert opinion and with the expectation that new research data will take precedence, these guidelines may provide direction for clinicians offering care to patients with dementia.
Alzheimer Disease↗
Staff resources speed FDA drug review: a critical analysis of the returns to resources in approval regulation.
Explore the source record for details and available documents.
Drug Approval↗
Using antipsychotic agents in older patients.
OBJECTIVES: Antipsychotics are widely used in geriatric psychiatric disorders. A growing number of atypical antipsychotics are available, expanding clinical options but complicating decision-making. Many questions about use of antipsychotics in older patients remain unanswered by available clinical literature. We therefore surveyed expert opinion on antipsychotic use in older patients (65 years of age or older) for recommendations concerning indications for antipsychotics, choice of antipsychotics for different conditions (e.g., delirium, dementia, schizophrenia, delusional disorder, psychotic mood disorders) and for patients with comorbid conditions or history of side effects, dosing strategies, duration of treatment, and medication combinations. METHOD: Based on a literature review, a 47-question survey with 1,411 options was developed. Approximately three quarters of the options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions. For other options, experts were asked to write in answers. The survey was sent to 52 American experts on treatment of older adults (38 geriatric psychiatrists, 14 geriatric internists/family physicians), 48 (92%) of whom completed it. In analyzing responses to items rated on the 9-point scale, consensus was defined as a nonrandom distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred, second line/alternate, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean. Guidelines indicating preferred treatment strategies were then developed for key clinical situations. RESULTS: The expert panel reached consensus on 78% of options rated on the 9-point scale. The experts did not recommend using antipsychotics in panic disorder, generalized anxiety disorder, nonpsychotic major depression, hypochondriasis, neuropathic pain, severe nausea, motion sickness, or irritability, hostility, and sleep disturbance in the absence of a major psychiatric syndrome. However, antipsychotics were favored in several other disorders. For agitated dementia with delusions, the experts' first-line recommendation is an antipsychotic drug alone; they would also consider adding a mood stabilizer. Risperidone (0.5-2.0 mg/day) was first line followed by quetiapine (50-150 mg/day) and olanzapine (5.0-7.5 mg/day) as high second-line options. There was no first-line recommendation for agitated dementia without delusions; an antipsychotic alone was high second line (rated first line by 60% of the experts). The experts'first-line recommendation for late-life schizophrenia was risperidone (1.25-3.5 mg/day). Quetiapine (100-300 mg/day), olanzapine (7.5-15 mg/day), and aripiprazole (15-30 mg/day) were high second line. For older patients with delusional disorder, an antipsychotic was the only treatment recommended. For agitated nonpsychotic major depression in an older patient, the experts' first-line recommendation was an antidepressant alone (77% first line); second-line options were an antidepressant plus an antipsychotic, electroconvulsive therapy (ECT), an antidepressant plus a benzodiazepine, and an antidepressant plus a mood stabilizer. For nonpsychotic major depression with severe anxiety, the experts recommended an antidepressant alone (79% first line) and would also consider adding a benzodiazepine or mood stabilizer to the antidepressant. If an older patient with adequate dosages for adequate duration, there was limited support for adding an atypical antipsychotic to the antidepressant (36% first line after two failed antidepressant trials). Treatment of choice for geriatric psychotic major depression was an antipsychotic plus an antidepressant (98% first line), with ECT another first-line option (71% first line). For mild geriatric nonpsychotic mania, the first-line recommendation is a mood stabilizer alone; the experts would also consider discontinuing an antidepressant if the patient is receiving one. For severe nonpsychotic mania, the experts recommend a mood stabilizer alone; the experts would also consider discontinuing an antidepressant if the patient is receiving one. For severe nonpsychotic mania, the experts recommend a mood stabilizer plus an antipsychotic (57%; first line) or a mood stabilizer alone (48%; first line) and would discontinue any antidepressant the patient is receiving. For psychotic mania, treatment of choice is a mood stabilizer plus an antipsychotic (98%; first line). Risperidone (1.25-3.0 mg/day) and olanzapine (5-15 mg/day) were first-line options in combination with a mood stabilizer for mania with psychosis, with quetiapine (50-250 mg/day) high second line. If a patient has responded well, the experts recommended the following duration of treatment before attempting to taper and discontinue the antipsychotic: delirium, 1 week; agitated dementia, taper within 3-6 months to determine the lowest effective maintenance dose; schizophrenia, indefinite treatment at the lowest effective dose; delusional disorder, 6 months-indefinitely at the lowest effective dose; psychotic major depression, 6 months; and mania with psychosis, 3 months. For patients with diabetes, dyslipidemia, or obesity, the experts would avoid clozapine, olanzapine, and conventional antipsychotics (especially low- and mid-potency). Quetiapine is first line for a patient with Parkinson's disease. Clozapine, ziprasidone, and conventional antipsychotics (especially low- and mid-potency) should be avoided in patients with QTc prolongation or congestive heart failure. For patients with cognitive impairment, constipation, diabetes, diabetic neuropathy, dyslipidemia, xerophthalmia, and xerostomia, the experts prefer risperidone, with quetiapine high second line. More than a quarter of the experts considered these combinations contraindicated: clozapine + carbamazepine, ziprasidone + tricyclic antidepressant (TCA), and a low-potency conventional antipsychotic + fluoxetine. In combining antidepressants and antipsychotics, the experts would be much more cautious with selective serotonin reuptake inhibitors that are more potent inhibitors of the CYP 450 enzymes (i.e., fluoxetine, fluvoxamine, paroxetine) and with nefazodone, TCAs, and monoamine oxidase inhibitors. The experts recommended extra monitoring when combining any antipsychotic with lithium, carbamazepine, lamotrigine, or valproate (except aripiprazole, risperidone, or a high-potency conventional plus valproate) or with codeine, phenytoin, or tramadol. CONCLUSIONS: The experts reached a high level of consensus on many of the key treatment questions. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide direction for common clinical dilemmas in the use of antipsychotics in elderly patients. Clinicians should keep in mind that no guidelines can address the complexities of an individual patient and that sound clinical judgment based on clinical experience should be used in applying these recommendations.
Aged↗
Expert consensus-based medication-use evaluation criteria for atypical antipsychotic drugs.
Medication-use criteria for the appropriate use of atypical antipsychotics were developed through a national consensus process utilizing an expert panel. A written survey was prepared which asked for opinions about options for psychopharmacologic interventions with seven antipsychotic drugs or categories (clozapine, olanzapine, quetiapine, risperidone, ziprasidone, long-acting intramuscular decanoate ester preparations of conventional antipsychotics, and oral conventional antipsychotics) in 19 specific clinical situations. The survey was sent to 50 psychiatrists and psychiatric pharmacist specialists, 42 (84%) of whom completed the survey. The survey was formatted as a grid with rows listing various clinical situations and columns itemizing the various antipsychotic medications relevant to the situations. Responses were scored using a 9-point scale for rating the level of medical review required for any given decision. Consensus on each option was defined as a nonrandom distribution of scores by a chi-square goodness-of-fit test. Consensus was reached for 1179 of the 1230 items reviewed. Use of clozapine as a first-line therapy warranted prospective or mandated review for all diagnoses. Use of nonclozapine atypical agents for schizophrenia and schizoaffective and delusional disorders was judged to be the standard of care. Oral conventional antipsychotic agents were not considered the standard of care for any indication. Combination antipsychotic treatment always warranted at least concurrent review. Continued concerns about the use of ziprasidone and its cardiac effects were apparent. This study demonstrated the utility of a consensus-based process in addressing issues and practices not adequately addressed in the scientific literature.
Antipsychotic Agents↗
The impact of a celebrity promotional campaign on the use of colon cancer screening: the Katie Couric effect.
BACKGROUND: Public participation in many preventive health programs is suboptimal. While various interventions to increase participation have been studied, the impact of a celebrity spokesperson on cancer screening has not been rigorously examined. The objective of this study was to assess the impact of Katie Couric's March 2000 Today Show colorectal cancer awareness campaign on colonoscopy rates. METHODS: A population-based observational study was conducted using 2 different data sources: (1) The Clinical Outcomes Research Initiative (CORI) database-a voluntary consortium of 400 endoscopists who performed 95 000 colonoscopies from July 1998 to December 2000; and (2) 44 000 adult members of a managed care organization. Using change point analyses and linear regression models, we compared colonoscopy utilization rates before and after Ms Couric's March 2000 television series. RESULTS: The number of colonoscopies performed per CORI physician per month after Ms Couric's campaign increased significantly (15.0 per month before campaign; 18.1 after campaign; P<.001). After adjusting for temporal trends, a significantly higher postcampaign colonoscopy rate was sustained for 9 months. Analysis also demonstrated a trend toward an increase in the percentage of colonoscopies performed on women (43.4% before campaign; 47.4% after campaign; P =.054). Colonoscopy rates also increased significantly in the managed care organization after Ms Couric's campaign (1.3 per 1000 members per month before; 1.8 after; P<.001). CONCLUSIONS: Katie Couric's televised colon cancer awareness campaign was temporally associated with an increase in colonoscopy use in 2 different data sets. These findings suggest that a celebrity spokesperson can have a substantial impact on public participation in preventive care programs.
Chi-Square Distribution↗
Treatment of behavioral emergencies: a summary of the expert consensus guidelines.
OBJECTIVES: Behavioral emergencies are a common and serious problem for consumers, their communities, and the healthcare settings on which they rely, but there is little research to guide provider responses to this challenge. Key constructs such as agitation have not been adequately operationalized so that the criteria defining a behavioral emergency are vague. A significant number of deaths of patients in restraint has focused government and regulators on these issues, but a consensus about key elements in the management of behavioral emergencies has not yet been articulated by the provider community. The authors assembled a panel of 50 experts to define the following elements: the threshold for emergency interventions, the scope of assessment for varying levels of urgency and cooperation, guiding principles in selecting interventions, and appropriate physical and medication strategies at different levels of diagnostic confidence and for a variety of etiologies and complicating conditions. METHOD: A written survey with 808 decision points was completed by 50 experts. A modified version of the RAND Corporation 9-point scale for rating appropriateness of medical decisions was used to score options. Consensus on each option was defined as a non-random distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred choice, second line/ alternate choice, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean rating. Guideline tables were constructed describing the preferred strategies in key clinical situations. RESULTS: The expert panel reached consensus on 83% of the options. The relative appropriateness of emergency interventions was ascertained for a continuum of behaviors. When asked about the frequency with which emergency interventions (parenteral medication, restraint, seclusion) were required in their services, 47% of the experts reported that such interventions were necessary for 1%-5% of patients seen in their services and 32% for 6%-20%. In general, the consensus of this panel lends support to many elements of recent regulations from the Health Care Financing Administration (now the Centers for Medicare and Medicaid Services), including the timing of clinician assessment and reassessment and the intensity of nursing care. However, the panel did not endorse the concept of "chemical restraint," instead favoring the idea that medications are treatments for target behaviors in behavioral emergencies even when the causes of these behaviors are not well understood. Control of aggressive behavior emerged as the highest priority during the emergency; however, preserving the physician-patient relationship was rated a close second and became the top priority in the long term. Oral medications, particularly concentrates, were clearly preferred if it is possible to use them. Benzodiazepines alone were top rated in 6 of 12 situations. High-potency conventional antipsychotics used alone never received higher ratings than benzodiazepines used alone. A combination of a benzodiazepine and an antipsychotic was preferred for patients with suspected schizophrenia, mania, or psychotic depression. There was equal support for high-potency conventional or atypical antipsychotics (particularly liquids) in oral combinations with benzodiazepines. Droperidol emerged in fourth place in some situations requiring an injection. CONCLUSIONS: To evaluate many of the treatment options in this survey, the experts had to extrapolate beyond controlled data. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide some direction for addressing common clinical dilemmas in the management of psychiatric emergencies and can be used to inform clinicians in acute care settings regarding the relative merits of various strategies.
Journal Article↗
What do consumers say they want and need during a psychiatric emergency?
Behavioral emergencies are a common and serious problem for consumers, their families and communities, and the healthcare providers on whom they rely for help. In recent years, serious concerns about the management of behavioral and psychiatric emergencies-in particular, the misapplication and overuse of physical and chemical restraints and seclusion-have become a focus of attention for mental health professionals and policy makers as well as for the lay public, the media, and patient advocacy organizations. Policy leaders and clinicians are searching for ways to balance the rights of consumers with considerations of safety and good care in an area in which it is difficult to conduct research. A survey of mental health professionals who are experts on the treatment of psychiatric and behavioral emergencies identified consumer input and collaboration between patient and clinician whenever possible as being extremely important in achieving the best short-term and particularly the best long-term outcomes for patients. The survey of consumer perspectives described in this article was undertaken in response to the need to better understand consumer experiences and preferences. The authors describe four emergency services forums conducted in 2002, which involved a total of 59 consumers. Each forum involved a written consumer survey as well as a workshop to develop and prioritize recommendations for improving psychiatric emergency care. The authors present the results of the consumer survey and summarize the top recommendations from the workshops. In both the survey and the workshops, the consumers repeatedly stressed the importance of having staff treat them with respect, talk to them, listen to them, and involve them in treatment decisions. There were a number of important areas of agreement between the recommendations of the consumer panel and those of the experts in emergency psychiatry surveyed for the Expert Consensus Guidelines on the Treatment of Behavioral Emergencies. These include the desirability of verbal interventions, the use of a collaborative approach, and the use of oral medications guided by the individual consumer's problems, medication experiences, and preferences. The majority of the consumer panel reported adverse experiences with general hospital emergency rooms and, in fact, called for the development of specialized psychiatric emergency services such as those recommended in the Expert Consensus Guidelines. One-fifth of the consumer panel attributed their emergency contact to lack of access to more routine mental health care. The consumers clearly do not reject medications categorically. Almost half indicated that they wanted medications and a similar number indicated benefit from medications, although many complained of forced administration and unwanted side effects. The consumer panel preferred benzodiazepines and ranked haloperidol as a least preferred option. Among their key recommendations for improving psychiatric emergency care, the consumer panel stressed the development of alternatives to traditional emergency room services, the increased use of advance directives, more comfortable physical environments for waiting and treatment, increased use of peer support services, improved training of emergency staff to foster a more humanistic and person-centered approach, increased collaboration between practitioners and patients, and improved discharge planning and post-discharge follow-up. The implications of these findings for improving psychiatric emergency care are considered.
Journal Article↗
The expert consensus guideline series. Optimizing pharmacologic treatment of psychotic disorders. Introduction: methods, commentary, and summary.
OBJECTIVES: A growing number of atypical antipsychotics are available for clinicians to choose from in the treatment of psychotic disorders. However, a number of important questions concerning medication selection, dosing and dose equivalence, and the management of inadequate response, compliance problems, and relapse have not been adequately addressed by clinical trials. To aid clinical decision-making, a consensus survey of expert opinion on the pharmacologic treatment of psychotic disorders was undertaken to address questions not definitively answered in the research literature. METHOD: Based on a literature review, a written survey was developed with 60 questions and 994 options. Approximately half of the options were scored using a modified version of the RAND 9-point scale for rating the appropriateness of medical decisions. For the other options, the experts were asked to write in answers (e.g., average doses) or check a box to indicate their preferred answer. The survey was sent to 50 national experts on the pharmacologic treatment of psychotic disorders, 47 (94%) of whom completed it. In analyzing the responses to items rated on the 9-point scale, consensus on each option was defined as a non random distribution of scores by chi-square "goodness-of-fit"test. We assigned a categorical rank (first line/preferred choice,second line/alternate choice, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean rating. Guideline tables indicating preferred treatment strategies were then developed for key clinical situations. RESULTS: The expert panel reached consensus on 88% of the options rated on the 9-point scale. The experts overwhelmingly endorsed the atypical antipsychotics for the treatment of psychotic disorders. Risperidone was the top choice for first-episode and multi-episode patients, with the other newer atypicals rated first line or high second line depending on the clinical situation. Clozapine and a long-acting injectable atypical (when available)were other high second line options for multi-episode patients. The expert's dosing recommendations agreed closely with the package inserts for the drugs, and their estimates of dose equivalence among the antipsychotics followed a linear pattern. The experts considered 3-6 weeks an adequate antipsychotic trial, but would wait a little longer (4-10 weeks) before making a major change in treatment regimen if there is a partial response. The experts recommended trying to improve response by increasing the dose of atypical and depot antipsychotics before switching to a different agent; there was less agreement about increasing the dose of conventional antipsychotics before switching, probably because of concern about side effects at higher doses. If it is decided to switch because of inadequate response, risperidone was the expert's first choice to switch to, no matter what drug was initially tried. Although there was some disparity in the expert's recommendations concerning how many agents to try before switching to clozapine, the expert's responses suggest that switching to clozapine should be Clozapine was also the antipsychotic of choice for patients with suicidal behavior. When switching oral antipsychotics,the experts considered cross-titration the preferred strategy. When switching to an injectable antipsychotic, the experts stressed the importance of continuing the oral antipsychotic until therapeutic levels of the injectable agent are achieved. The experts considered psychosocial interventions the first choice strategy for partially compliant patients, with pharmacologic interventions the first choice for patients with clear evidence of noncompliance. However, because it can be difficult to distinguish partially compliant from noncompliant patients, the editors recommended combining psychosocial and pharmacologic interventions to improve compliance whenever possible. When patients relapse because of compliance problems or if there is any doubt about compliance, the experts recommended the use of a long-acting injectable antipsychotic and would select an injectable atypical when this option becomes available. The experts would also consider using an injectable atypical antipsychotic (when available) in many clinical situations that do not involve compliance problems. The experts stressed the importance of monitoring for health problems-especially obesity, diabetes, cardiovascular problems,HIV risk behaviors, medical complications of substance abuse, heavy smoking and its effects, hypertension, and amenorrhea-in patients being treated with antipsychotics. Although many patients are prescribed adjunctive treatments,multiple antipsychotics, and combinations of different classes of drugs (e.g., antipsychotics plus mood stabilizers or antidepressants) in an effort to enhance response, the experts gave little support to any of these strategies, with the exception of antidepressants for patients with dysphoria/depression, antidepressants or ECT for patients with suicidal behavior, and mood stabilizers for patients with aggression/violence. When asked about indicators of remission and recovery, the experts considered acute improvement in psychotic symptoms the most important indicator of remission, whereas they considered more sustained improvement in multiple outcome domains (e.g., occupational/educational functioning, peer relationships,independent living) important in assessing recovery. CONCLUSIONS: The experts reached a high level of consensus on many of the key treatment questions in the survey. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide direction for addressing common clinical dilemmas that arise in the pharmacologic treatment of psychotic disorders. They can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions. Clinicians should keep in mind that no guidelines can address the complexities involved in the care of each individual patient and that sound clinical judgment based on clinical experience should be used in applying these recommendations.
Antipsychotic Agents↗
Approval times for new drugs: does the source of funding for FDA staff matter?
The Food and Drug Administration (FDA) has been criticized for injudicious and excessively rapid approval of new drugs as a result of pharmaceutical industry influence. Many critics focus on the Prescription Drug User Fee Act (PDUFA) of 1992, which augmented the FDA's budget through the charging of user fees. We assess the effect of FDA staffing patterns and attributes of submitting firms on approval times for 843 new drug applications (NDAs) submitted between 1977 and 2000. NDA review times shortened by 3.3 months for every 100 additional FDA staff. The amount of funding for FDA staff appears to be a much more important influence on NDA review time than the source of funding.
Drug Approval↗
A proposal for financing postmarketing drug safety studies by augmenting FDA user fees.
I propose to raise funds for postapproval studies of long-term drug safety by augmenting the existing "user-fee" system. Fees would be raised by an amount deemed optimal for revenue collection, and the U.S. Food and Drug Administration (FDA) would direct the incremental funds to a combination of randomized controlled trials, epidemiological studies, and postmarketing surveillance. User-fee augmentation is an achievable, incremental reform that would subsidize information that is now undersupplied in the U.S. health care system; spread the burden of funding postmarketing safety studies among pharmaceutical sponsors; and help restore public, scientific, and professional confidence in the FDA and its user-fee system.
Drug Industry↗