American Journal of Health System Pharmacy Ajhp Official Journal of the American Society of Health System Pharmacists, Dec 15, 1995
The chemistry, pharmacology, pharmacokinetics, and clinical efficacy of nefazodone hydrochloride,... more The chemistry, pharmacology, pharmacokinetics, and clinical efficacy of nefazodone hydrochloride, a new antidepressant, are described. Nefazodone enhances serotonin (5-hydroxytryptamine [5-HT]) synaptic transmission by acting as an antagonist at 5-HT2 receptors and by inhibiting the reuptake of 5-HT. These two mechanisms combined may enhance 5-HT1A-mediated transmission. In addition, nefazodone weakly inhibits the reuptake of norepinephrine. Nefazodone is a structural analogue of trazodone but is pharmacologically distinct. In placebo-controlled trials, nefazodone was as effective as imipramine for the treatment of major depression and produced clinical benefits in patients with depression-related anxiety and sleep disturbances. More than 2000 patients have received nefazodone in clinical trials. The most commonly reported adverse drug reactions (ADRs) are asthenia, somnolence, dry mouth, nausea, constipation, dizziness, lightheadedness, confusion, abnormal vision, and blurred vision. The incidence of sexual-dysfunction ADRs may be less than that reported for other antidepressants. Nefazodone does not inhibit rapid-eye movement sleep. Nefazodone, an inhibitor of the hepatic P-450 isoenzyme CYP3A4, may increase concentrations of drugs metabolized by this isoenzyme, such as terfenadine, astemizole, triazolam, alprazolam, and midazolam. Caution should be exercised in administering nefazodone hydrochloride with triazolobenzodiazepines, and coadministration with terfenadine or astemizole is contra-indicated. The dosage should start at 100 mg twice daily and then be increased, depending on occurrence of ADRs and the patient's clinical response, to 300-600 mg daily. In elderly or debilitated patients, the initial dosage should be half the usual dosage. Nefazodone hydrochloride is as effective as other available antidepressants and may cause fewer ADRs.
Although community pharmacists have historically been paid primarily for drug distribution and di... more Although community pharmacists have historically been paid primarily for drug distribution and dispensing services, medication therapy management (MTM) services evolved in the 1990s as a means for pharmacists and other providers to assist physicians and patients in managing clinical, service, and cost outcomes of drug therapy. The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA 2003) and the subsequent implementation of Medicare Part D in January 2006 for the more than 20 million Medicare beneficiaries enrolled in the Part D benefit formalized MTM services for a subset of high-cost patients. Although Medicare Part D has provided a new opportunity for defining the value of pharmacist-provided MTM services in the health care system, few publications exist which quantify changes in the provision of pharmacist-provided MTM services over time. To (a) describe the changes over a 7-year period in the primary types of MTM services provided by community pharmacies...
Supraphysiologic doses of testosterone are associated with increased aggression that is hypothesi... more Supraphysiologic doses of testosterone are associated with increased aggression that is hypothesized to be a function of testosterone serum concentrations, mood, and personality. The study attempted to characterize this relationship among weightlifters who were users (n = 10) and nonusers (n = 18) of anabolic steroids. Participants were interviewed using the Modified Mania Rating Scale and Hamilton Rating Scale for Depression to assess mood, the Buss-Durkee Hostility Inventory (BDHI) and Point Subtraction Aggression Paradigm (PSAP) to assess aggression, and the Personality Disorder Questionnaire (PDQ-R) to assess personality. Blood samples were obtained for the determination of total, free, and weakly bound testosterone. Comparisons of continuous variables between testosterone users and non-users were performed with a parametric (unpaired t-test) or non-parametric (Mann-Whitney) test where appropriate. Correlations with testosterone were examined separately for testosterone users an...
The number of athletes self-administering ergogenic pharmacological agents to increase their comp... more The number of athletes self-administering ergogenic pharmacological agents to increase their competitive edge continues to be a problem. Most athletes using anabolic steroids (AS) have acquired a crude pharmacological database regarding these drugs. Their opinions regarding steroids have been derived from their subjective experiences and anecdotal information. For this reason, traditional warnings regarding the lack of efficacy and potential dangers of steroid misuse are disregarded. A common widely held opinion among bodybuilders is that the anabolic steroid experts are the athletic gurus who for years have utilised themselves as the experimental participants and then dispensed their empirical findings. This review will address the common anabolic steroid misconceptions held by many of today's athletes by providing an evaluation of the scientific literature related to AS in athletic performance.
Resveratrol is a cancer preventative agent that is found in red wine. Piceatannol is a closely re... more Resveratrol is a cancer preventative agent that is found in red wine. Piceatannol is a closely related stilbene that has antileukaemic activity and is also a tyrosine kinase inhibitor. Piceatannol differs from resveratrol by having an additional aromatic hydroxy group. The enzyme CYP1B1 is overexpressed in a wide variety of human tumours and catalyses aromatic hydroxylation reactions. We report here that the cancer preventative agent resveratrol undergoes metabolism by the cytochrome P450 enzyme CYP1B1 to give a metabolite which has been identified as the known antileukaemic agent piceatannol. The metabolite was identified by high performance liquid chromatography analysis using fluorescence detection and the identity of the metabolite was further confirmed by derivatisation followed by gas chromatography-mass spectrometry studies using authentic piceatannol for comparison. This observation provides a novel explanation for the cancer preventative properties of resveratrol. It demons...
modalities, and 2) to examine associations between clusters and key aspects of the Andersen healt... more modalities, and 2) to examine associations between clusters and key aspects of the Andersen health care utilization model. METHODS: Using the 2002 National Health Interview Survey (NHIS), the sample included 2949 AA adults who reported using at least 1 of 17 CAM modalities in the past 12 months. A cluster analysis was performed and a multivariate binary logistic regression tested which Andersen model variables (Predisposing, Enabling, Need) and disease conditions added unique explanation of the conditional probability of being in a particular cluster. RESULTS: Five clusters were identified: Spiritual-prayer only (64%); Mind/Body/Spirit-primarily prayer, herbal, and relaxation (7%); Mind Focus-primarily relaxation and prayer (10%); Spiritual/Biological-primarily prayer and herbal use (14%); and Mind/Body alternatives-relaxation, yoga/tai chi/ vitamins (5%). Overall, prayer, relaxation, and herbal use were the strongest influences on cluster makeup. The logistic regression results showed that compared to other clusters, the Spiritual cluster was less educated and less physically active. Additional predictors that were statistically significant for some clusters were: age; region of country; not having a usual source of medical care; retirement status; experiencing anxiety/depression; living with others; gender; currently smoking; experiencing limits in daily activities; suffering from insomnia, joint pain, high cholesterol, and diabetes; marital status; income; and over-thecounter drug use. CONCLUSION: The majority of AAs who use CAM can be grouped together based predominantly on prayer, relaxation, and herbal use. While predictors of usage vary by cluster, education and physical activity were important for all. Cluster analysis highlights differences within one racial group and these differences can be used by clinicians to engage AA CAM users and better understand how to treat their conditions.
A high-performance liquid chromatography assay for fluoxetine and its major metabolite, norfluoxe... more A high-performance liquid chromatography assay for fluoxetine and its major metabolite, norfluoxetine, was established. Serum concentrations of the two were measured in 13 depressed outpatients following a 6-week trial of the drug. No significant correlations were obvious between clinical improvement as measured by the Hamilton Rating Scale for Depression and the Clinical Global Impression scores and the serum concentrations of fluoxetine and its major metabolite, norfluoxetine, according to these initial pilot data.
Research in Social and Administrative Pharmacy, 2008
Antidepressant nonadherence is a significant threat to clinical outcomes and can be divided into ... more Antidepressant nonadherence is a significant threat to clinical outcomes and can be divided into 2 primary domains, persistence and consistency. Although antidepressant persistence has been well described, little is known about consistency patterns. The primary objective of this study was to characterize consistency among persistent antidepressant users. Patients with depression may also exhibit poor adherence to medications for chronic comorbid conditions. Thus, a second objective was to compare their consistency with chronic, nonpsychiatric medications with that of nonantidepressant users. Continuously eligible adult patients were selected from the Iowa Medicaid Pharmaceutical Case Management program based on receiving an antidepressant or a selected chronic nonpsychiatric medication for at least the first 4 months after program enrollment. Consistency over the first year of enrollment was determined from prescription refill patterns, using the MED-OUT index. The mean consistency rate was 86% among the 1122 persistent antidepressant users. Consistency was not significantly different among polyantidepressant users or across the antidepressant classes. Among antidepressant users, consistency with antidepressants was not significantly different from consistency with chronic nonpsychiatric medications. Antidepressant users were not significantly less consistent with chronic nonpsychiatric medications than nonantidepressant users, after controlling for the confounding factors of age, sex, and total number of medications. Consistency with medications in this population of persistent antidepressant users with medical illnesses was fairly good, and comparable to that of nonantidepressant users. The unique population may have influenced consistency rates. Focusing on persistent antidepressant users may have limited the expected impact of depression on medication consistency.
Received Ociober4, 1989: revised July 17, 1990: accepted July 17. 1990. From the Departments of P... more Received Ociober4, 1989: revised July 17, 1990: accepted July 17. 1990. From the Departments of Psychiatry, In-ternal Medicine, and Pharmacy. the Uni-versity of Iowa, Iowa City: the Department of Internal Medicine. Duke University. Durham. North Carolina: and the Department of ...
Although the introduction of antipsychotic drugs in 1954 was a breakthrough in the treatment of p... more Although the introduction of antipsychotic drugs in 1954 was a breakthrough in the treatment of patients with schizophrenia, these agents have a number of adverse effects that limit effectiveness and compliance. The atypical antipsychotic drugs provide an improved tolerability profile, particularly in minimizing extrapyramidal side effects; however, they are associated with significant weight gain, which may be related to growing evidence linking the atypical agents with diabetes and hyperlipidemia. Ziprasidone, a new atypical antipsychotic drug, was demonstrated in clinical trials to be more efficacious than placebo and similar in efficacy to haloperidol in the treatment of schizophrenia. Like the existing atypical agents, ziprasidone has a rate of extrapyramidal side effects similar to that of placebo and does not cause significant elevations in prolactin levels. In contrast, ziprasidone has a low propensity for causing weight gain. For patients requiring an antipsychotic drug, ziprasidone represents a new treatment option with a limited adverse effect profile.
Andropause, a syndrome in aging men, consists of physical, sexual, and psychologic symptoms that ... more Andropause, a syndrome in aging men, consists of physical, sexual, and psychologic symptoms that include weakness, fatigue, reduced muscle and bone mass, impaired hematopoiesis, oligospermia, sexual dysfunction, depression, anxiety, irritability, insomnia, memory impairment, and reduced cognitive function. Free testosterone levels begin to decline at a rate of 1% per year after age 40 years. It is estimated that 20% of men aged 60-80 years have levels below the lower limit of normal. Although the causal relationship between declining testosterone levels and development of andropause symptoms is not firmly established, administration of testosterone to this population resulted in improvements in many areas. Most studies to date focused on physical benefits of testosterone replacement and failed to assess psychologic symptoms rigorously. Preliminary data suggest that therapy may benefit elderly men with new-onset depression. Testosterone administration is not without problems, the most worrisome being the potential for increased prostate cancer risk. Despite this concern, a limited number of studies administered the hormone weekly for up to 2 years, with only mild increases in prostate-specific antigen over control values. Currently, insufficient evidence, primarily regarding psychologic safety and efficacy, exists to warrant general administration of testosterone to elderly hypogonadal men. Further clinical investigations of this therapy in men with low testosterone levels and andropause symptoms are justified and necessary. (Pharmacotherapy 1999;19(8):951-956)
We investigate and define the effects of exogenous testosterone on the normal prostate. A total o... more We investigate and define the effects of exogenous testosterone on the normal prostate. A total of 31 healthy volunteers 21 to 39 years old were randomized to receive either 100, 250 or 500 mg. testosterone via intramuscular injection once a week for 15 weeks. Baseline measurements of serum testosterone, free testosterone and prostate specific antigen (PSA) were taken at week 1. Semen samples were also collected for PSA content and prostate volumes were determined by transrectal ultrasound before testosterone injection. Blood was then drawn every other week before each testosterone injection for the 15 weeks, every other week thereafter until week 28 and again at week 40. After the first 15 weeks semen samples were again collected, and prostate volumes were determined by repeat transrectal ultrasound. Free and total serum testosterone levels increased significantly in the 250 and 500 mg. dose groups. No significant change occurred in the prostate volume or serum PSA levels at any dose of exogenous testosterone. Total semen PSA levels decreased following administration of testosterone but did not reach statistical significance. Despite significant elevations in serum total and free testosterone, healthy young men do not demonstrate increased serum or semen PSA levels, or increased prostate volume in response to exogenous testosterone injections.
Seizures were observed following the withdrawal of alprazolam administered in therapeutic dose fo... more Seizures were observed following the withdrawal of alprazolam administered in therapeutic dose for 10 weeks. A review of available case reports suggests that seizures, like other withdrawal phenomena, are more apt to occur with short-acting benzodiazepines. To prevent their occurrence these drugs should be discontinued gradually and consideration given to substituting long-acting drugs during the withdrawal period. Physicians should remain alert to the fact that seizures may occur as early as 24 hours after the abrupt withdrawal of short-acting benzodiazepines.
The primary aim of this study was to investigate the association between measured blood alcohol c... more The primary aim of this study was to investigate the association between measured blood alcohol concentration (BAC) and the presence and degree of amnesia (no amnesia, grayout, or blackout) in actively drinking subjects. A secondary aim was to determine potential factors other than BAC that contribute to the alcohol-induced memory loss. An interview questionnaire was administered to subjects regarding a recent alcohol associated arrest with a documented BAC greater than 0.08 g/dL for either public intoxication, driving under the influence, or under age drinking was administered. Demographic variables collected included drinking history, family history of alcoholism, presence of previous alcohol-related memory loss during a drinking episode, and drinking behavior during the episode. Memory of the drinking episode was evaluated to determine if either an alcohol-induced grayout (partial anterograde amnesia) or blackout (complete anterograde amnesia) occurred. Differences in (1) mean total number of drinks ingested before arrest, (2) gulping of drinks, and (3) BAC at arrest were found for those having blackouts compared with no amnesia; while differences in drinking more than planned were found between the no amnesia and grayout groups. A strong linear relationship between BAC and predicted probability of memory loss, particularly for blackouts was obvious. This finding clinically concludes that subjects with BAC of 310 g/dL or greater have a 0.50 or greater probability of having an alcoholic blackout.
The credibility of an increased risk of cerebrovascular events (CVEs) in elderly patients with de... more The credibility of an increased risk of cerebrovascular events (CVEs) in elderly patients with dementia being treated with second-generation antipsychotics (SGAs) is debatable. Although early published and unpublished data indicated a risk, much of the subsequent literature has not supported this initial finding. Previously published studies were flawed in part because they lacked a control group and did not stratify by dementia subtype. This study examined the risk of a CVE in patients diagnosed with Alzheimer or vascular dementia while being treated with SGA, first-generation antipsychotics, or no antipsychotic medication. Data from 14,029 patients aged 65 years and older were evaluated using patient information from Veterans Administration and Medicare databases. Patients who received care for dementia were categorized according to dementia subtype (vascular or Alzheimer) and antipsychotic use during an 18-month period. Patients were observed until they were admitted to a hospital for a CVE, stopped taking or switched antipsychotics, died, or until the 18-month observation period ended. Overall, CVE risk did not differ whether patients were receiving a first-generation antipsychotic, SGA, or no antipsychotic therapy. However, patients with vascular dementia had an increased risk in hospitalization for a CVE. There was no increase in risk of a CVE for patients treated with quetiapine, olanzapine, or risperidone relative to haloperidol, or for patients receiving olanzapine or risperidone relative to quetiapine. Stratified subgroup analyses demonstrated no difference in risk for CVE-related admission patients with Alzheimer dementia among individual agents. However, patients with vascular dementia receiving risperidone, but not olanzapine or quetiapine, were found to be at decreased risk for CVE admission relative to haloperidol. This study found no increase in overall risk for CVE-related hospital admission in patients treated with antipsychotic medications.
An analysis of the literature on tricyclic antidepressant level in blood using receiver operating... more An analysis of the literature on tricyclic antidepressant level in blood using receiver operating characteristics curves as the primary statistical tool was performed. For nortriptyline, a significant curvilinear relationship between therapeutic response and nortriptyline was observed that ranged from 58 to 148 ng/ml. The sensitivity and specificity for the nortriptyline therapeutic window were 78 and 61%, respectively. The response rate within the therapeutic range was 66% versus 26% outside the therapeutic range. For desipramine, a significant linear relationship between therapeutic response and desipramine concentration in plasma was observed. The threshold concentration in plasma for therapeutic response was 116 ng/ml. The sensitivity and specificity for the desipramine threshold level in blood were 81 and 59%, respectively. The response rate above the threshold level was 51% versus 15% below the therapeutic threshold concentration. For imipramine, a significant curvilinear relationship between therapeutic response and total imipramine (imipramine+desipramine) concentration in plasma was observed between 175 and 350 ng/ml. The sensitivity and specificity for the total imipramine concentrations in plasma were 52 and 74%, respectively. The response rate within the therapeutic range was 67% versus 39% outside the therapeutic range. For amitriptyline, a significant curvilinear relationship between therapeutic response and total amitriptyline (amitriptyline+nortriptyline) concentration in plasma was observed between 93 and 140 ng/ml. The sensitivity and specificity for the total imipramine concentrations in plasma were 37 and 80%, respectively. The response rate within the therapeutic range was 50% versus 30% outside the therapeutic range.
ABSTRACT Previous data suggest the possibility that haloperidol daily dosing requirements may be ... more ABSTRACT Previous data suggest the possibility that haloperidol daily dosing requirements may be confounded by smoking and, at higher doses, capacity-limited metabolism. Forty hospitalized patients suffering from an acute exacerbation of schizophrenia were treated for 2 weeks with fixed oral doses of haloperidol ranging from 10 to 70 mg/day (0.13 to 0.95 mg/kg/day) that produced mean steady-state concentrations between 4.5 and 55.4 ng/ml. No significant differences between the smoking and nonsmoking groups were obvious for the factors of weight, age, sex, daily doses, steady-state clearance, and steady-state haloperidol concentrations in plasma at week 1, week 2, and their mean. The hypothesis that the relationship between haloperidol dose and steady-state haloperidol concentration in plasma was affected by patients' smoking status and metabolic capacity was tested by multiple linear regression analysis and initially rejected. The relationship of dose to haloperidol concentration was fitted as a linear function. To improve the curve fit, the haloperidol concentrations and doses were transformed to their natural logs and then the regression line was refitted. The multiple regression analysis was repeated with the data in their transformed state. It was found that, although smoking status and dose of the drug did not independently affect the average haloperidol concentration, together they interacted in such a way that individual haloperidol concentrations were dependent on the smoking status at specific doses. Thus, two haloperidol dosing equations were generated, one for smokers and one for nonsmokers.
American Journal of Health System Pharmacy Ajhp Official Journal of the American Society of Health System Pharmacists, Dec 15, 1995
The chemistry, pharmacology, pharmacokinetics, and clinical efficacy of nefazodone hydrochloride,... more The chemistry, pharmacology, pharmacokinetics, and clinical efficacy of nefazodone hydrochloride, a new antidepressant, are described. Nefazodone enhances serotonin (5-hydroxytryptamine [5-HT]) synaptic transmission by acting as an antagonist at 5-HT2 receptors and by inhibiting the reuptake of 5-HT. These two mechanisms combined may enhance 5-HT1A-mediated transmission. In addition, nefazodone weakly inhibits the reuptake of norepinephrine. Nefazodone is a structural analogue of trazodone but is pharmacologically distinct. In placebo-controlled trials, nefazodone was as effective as imipramine for the treatment of major depression and produced clinical benefits in patients with depression-related anxiety and sleep disturbances. More than 2000 patients have received nefazodone in clinical trials. The most commonly reported adverse drug reactions (ADRs) are asthenia, somnolence, dry mouth, nausea, constipation, dizziness, lightheadedness, confusion, abnormal vision, and blurred vision. The incidence of sexual-dysfunction ADRs may be less than that reported for other antidepressants. Nefazodone does not inhibit rapid-eye movement sleep. Nefazodone, an inhibitor of the hepatic P-450 isoenzyme CYP3A4, may increase concentrations of drugs metabolized by this isoenzyme, such as terfenadine, astemizole, triazolam, alprazolam, and midazolam. Caution should be exercised in administering nefazodone hydrochloride with triazolobenzodiazepines, and coadministration with terfenadine or astemizole is contra-indicated. The dosage should start at 100 mg twice daily and then be increased, depending on occurrence of ADRs and the patient's clinical response, to 300-600 mg daily. In elderly or debilitated patients, the initial dosage should be half the usual dosage. Nefazodone hydrochloride is as effective as other available antidepressants and may cause fewer ADRs.
Although community pharmacists have historically been paid primarily for drug distribution and di... more Although community pharmacists have historically been paid primarily for drug distribution and dispensing services, medication therapy management (MTM) services evolved in the 1990s as a means for pharmacists and other providers to assist physicians and patients in managing clinical, service, and cost outcomes of drug therapy. The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA 2003) and the subsequent implementation of Medicare Part D in January 2006 for the more than 20 million Medicare beneficiaries enrolled in the Part D benefit formalized MTM services for a subset of high-cost patients. Although Medicare Part D has provided a new opportunity for defining the value of pharmacist-provided MTM services in the health care system, few publications exist which quantify changes in the provision of pharmacist-provided MTM services over time. To (a) describe the changes over a 7-year period in the primary types of MTM services provided by community pharmacies...
Supraphysiologic doses of testosterone are associated with increased aggression that is hypothesi... more Supraphysiologic doses of testosterone are associated with increased aggression that is hypothesized to be a function of testosterone serum concentrations, mood, and personality. The study attempted to characterize this relationship among weightlifters who were users (n = 10) and nonusers (n = 18) of anabolic steroids. Participants were interviewed using the Modified Mania Rating Scale and Hamilton Rating Scale for Depression to assess mood, the Buss-Durkee Hostility Inventory (BDHI) and Point Subtraction Aggression Paradigm (PSAP) to assess aggression, and the Personality Disorder Questionnaire (PDQ-R) to assess personality. Blood samples were obtained for the determination of total, free, and weakly bound testosterone. Comparisons of continuous variables between testosterone users and non-users were performed with a parametric (unpaired t-test) or non-parametric (Mann-Whitney) test where appropriate. Correlations with testosterone were examined separately for testosterone users an...
The number of athletes self-administering ergogenic pharmacological agents to increase their comp... more The number of athletes self-administering ergogenic pharmacological agents to increase their competitive edge continues to be a problem. Most athletes using anabolic steroids (AS) have acquired a crude pharmacological database regarding these drugs. Their opinions regarding steroids have been derived from their subjective experiences and anecdotal information. For this reason, traditional warnings regarding the lack of efficacy and potential dangers of steroid misuse are disregarded. A common widely held opinion among bodybuilders is that the anabolic steroid experts are the athletic gurus who for years have utilised themselves as the experimental participants and then dispensed their empirical findings. This review will address the common anabolic steroid misconceptions held by many of today's athletes by providing an evaluation of the scientific literature related to AS in athletic performance.
Resveratrol is a cancer preventative agent that is found in red wine. Piceatannol is a closely re... more Resveratrol is a cancer preventative agent that is found in red wine. Piceatannol is a closely related stilbene that has antileukaemic activity and is also a tyrosine kinase inhibitor. Piceatannol differs from resveratrol by having an additional aromatic hydroxy group. The enzyme CYP1B1 is overexpressed in a wide variety of human tumours and catalyses aromatic hydroxylation reactions. We report here that the cancer preventative agent resveratrol undergoes metabolism by the cytochrome P450 enzyme CYP1B1 to give a metabolite which has been identified as the known antileukaemic agent piceatannol. The metabolite was identified by high performance liquid chromatography analysis using fluorescence detection and the identity of the metabolite was further confirmed by derivatisation followed by gas chromatography-mass spectrometry studies using authentic piceatannol for comparison. This observation provides a novel explanation for the cancer preventative properties of resveratrol. It demons...
modalities, and 2) to examine associations between clusters and key aspects of the Andersen healt... more modalities, and 2) to examine associations between clusters and key aspects of the Andersen health care utilization model. METHODS: Using the 2002 National Health Interview Survey (NHIS), the sample included 2949 AA adults who reported using at least 1 of 17 CAM modalities in the past 12 months. A cluster analysis was performed and a multivariate binary logistic regression tested which Andersen model variables (Predisposing, Enabling, Need) and disease conditions added unique explanation of the conditional probability of being in a particular cluster. RESULTS: Five clusters were identified: Spiritual-prayer only (64%); Mind/Body/Spirit-primarily prayer, herbal, and relaxation (7%); Mind Focus-primarily relaxation and prayer (10%); Spiritual/Biological-primarily prayer and herbal use (14%); and Mind/Body alternatives-relaxation, yoga/tai chi/ vitamins (5%). Overall, prayer, relaxation, and herbal use were the strongest influences on cluster makeup. The logistic regression results showed that compared to other clusters, the Spiritual cluster was less educated and less physically active. Additional predictors that were statistically significant for some clusters were: age; region of country; not having a usual source of medical care; retirement status; experiencing anxiety/depression; living with others; gender; currently smoking; experiencing limits in daily activities; suffering from insomnia, joint pain, high cholesterol, and diabetes; marital status; income; and over-thecounter drug use. CONCLUSION: The majority of AAs who use CAM can be grouped together based predominantly on prayer, relaxation, and herbal use. While predictors of usage vary by cluster, education and physical activity were important for all. Cluster analysis highlights differences within one racial group and these differences can be used by clinicians to engage AA CAM users and better understand how to treat their conditions.
A high-performance liquid chromatography assay for fluoxetine and its major metabolite, norfluoxe... more A high-performance liquid chromatography assay for fluoxetine and its major metabolite, norfluoxetine, was established. Serum concentrations of the two were measured in 13 depressed outpatients following a 6-week trial of the drug. No significant correlations were obvious between clinical improvement as measured by the Hamilton Rating Scale for Depression and the Clinical Global Impression scores and the serum concentrations of fluoxetine and its major metabolite, norfluoxetine, according to these initial pilot data.
Research in Social and Administrative Pharmacy, 2008
Antidepressant nonadherence is a significant threat to clinical outcomes and can be divided into ... more Antidepressant nonadherence is a significant threat to clinical outcomes and can be divided into 2 primary domains, persistence and consistency. Although antidepressant persistence has been well described, little is known about consistency patterns. The primary objective of this study was to characterize consistency among persistent antidepressant users. Patients with depression may also exhibit poor adherence to medications for chronic comorbid conditions. Thus, a second objective was to compare their consistency with chronic, nonpsychiatric medications with that of nonantidepressant users. Continuously eligible adult patients were selected from the Iowa Medicaid Pharmaceutical Case Management program based on receiving an antidepressant or a selected chronic nonpsychiatric medication for at least the first 4 months after program enrollment. Consistency over the first year of enrollment was determined from prescription refill patterns, using the MED-OUT index. The mean consistency rate was 86% among the 1122 persistent antidepressant users. Consistency was not significantly different among polyantidepressant users or across the antidepressant classes. Among antidepressant users, consistency with antidepressants was not significantly different from consistency with chronic nonpsychiatric medications. Antidepressant users were not significantly less consistent with chronic nonpsychiatric medications than nonantidepressant users, after controlling for the confounding factors of age, sex, and total number of medications. Consistency with medications in this population of persistent antidepressant users with medical illnesses was fairly good, and comparable to that of nonantidepressant users. The unique population may have influenced consistency rates. Focusing on persistent antidepressant users may have limited the expected impact of depression on medication consistency.
Received Ociober4, 1989: revised July 17, 1990: accepted July 17. 1990. From the Departments of P... more Received Ociober4, 1989: revised July 17, 1990: accepted July 17. 1990. From the Departments of Psychiatry, In-ternal Medicine, and Pharmacy. the Uni-versity of Iowa, Iowa City: the Department of Internal Medicine. Duke University. Durham. North Carolina: and the Department of ...
Although the introduction of antipsychotic drugs in 1954 was a breakthrough in the treatment of p... more Although the introduction of antipsychotic drugs in 1954 was a breakthrough in the treatment of patients with schizophrenia, these agents have a number of adverse effects that limit effectiveness and compliance. The atypical antipsychotic drugs provide an improved tolerability profile, particularly in minimizing extrapyramidal side effects; however, they are associated with significant weight gain, which may be related to growing evidence linking the atypical agents with diabetes and hyperlipidemia. Ziprasidone, a new atypical antipsychotic drug, was demonstrated in clinical trials to be more efficacious than placebo and similar in efficacy to haloperidol in the treatment of schizophrenia. Like the existing atypical agents, ziprasidone has a rate of extrapyramidal side effects similar to that of placebo and does not cause significant elevations in prolactin levels. In contrast, ziprasidone has a low propensity for causing weight gain. For patients requiring an antipsychotic drug, ziprasidone represents a new treatment option with a limited adverse effect profile.
Andropause, a syndrome in aging men, consists of physical, sexual, and psychologic symptoms that ... more Andropause, a syndrome in aging men, consists of physical, sexual, and psychologic symptoms that include weakness, fatigue, reduced muscle and bone mass, impaired hematopoiesis, oligospermia, sexual dysfunction, depression, anxiety, irritability, insomnia, memory impairment, and reduced cognitive function. Free testosterone levels begin to decline at a rate of 1% per year after age 40 years. It is estimated that 20% of men aged 60-80 years have levels below the lower limit of normal. Although the causal relationship between declining testosterone levels and development of andropause symptoms is not firmly established, administration of testosterone to this population resulted in improvements in many areas. Most studies to date focused on physical benefits of testosterone replacement and failed to assess psychologic symptoms rigorously. Preliminary data suggest that therapy may benefit elderly men with new-onset depression. Testosterone administration is not without problems, the most worrisome being the potential for increased prostate cancer risk. Despite this concern, a limited number of studies administered the hormone weekly for up to 2 years, with only mild increases in prostate-specific antigen over control values. Currently, insufficient evidence, primarily regarding psychologic safety and efficacy, exists to warrant general administration of testosterone to elderly hypogonadal men. Further clinical investigations of this therapy in men with low testosterone levels and andropause symptoms are justified and necessary. (Pharmacotherapy 1999;19(8):951-956)
We investigate and define the effects of exogenous testosterone on the normal prostate. A total o... more We investigate and define the effects of exogenous testosterone on the normal prostate. A total of 31 healthy volunteers 21 to 39 years old were randomized to receive either 100, 250 or 500 mg. testosterone via intramuscular injection once a week for 15 weeks. Baseline measurements of serum testosterone, free testosterone and prostate specific antigen (PSA) were taken at week 1. Semen samples were also collected for PSA content and prostate volumes were determined by transrectal ultrasound before testosterone injection. Blood was then drawn every other week before each testosterone injection for the 15 weeks, every other week thereafter until week 28 and again at week 40. After the first 15 weeks semen samples were again collected, and prostate volumes were determined by repeat transrectal ultrasound. Free and total serum testosterone levels increased significantly in the 250 and 500 mg. dose groups. No significant change occurred in the prostate volume or serum PSA levels at any dose of exogenous testosterone. Total semen PSA levels decreased following administration of testosterone but did not reach statistical significance. Despite significant elevations in serum total and free testosterone, healthy young men do not demonstrate increased serum or semen PSA levels, or increased prostate volume in response to exogenous testosterone injections.
Seizures were observed following the withdrawal of alprazolam administered in therapeutic dose fo... more Seizures were observed following the withdrawal of alprazolam administered in therapeutic dose for 10 weeks. A review of available case reports suggests that seizures, like other withdrawal phenomena, are more apt to occur with short-acting benzodiazepines. To prevent their occurrence these drugs should be discontinued gradually and consideration given to substituting long-acting drugs during the withdrawal period. Physicians should remain alert to the fact that seizures may occur as early as 24 hours after the abrupt withdrawal of short-acting benzodiazepines.
The primary aim of this study was to investigate the association between measured blood alcohol c... more The primary aim of this study was to investigate the association between measured blood alcohol concentration (BAC) and the presence and degree of amnesia (no amnesia, grayout, or blackout) in actively drinking subjects. A secondary aim was to determine potential factors other than BAC that contribute to the alcohol-induced memory loss. An interview questionnaire was administered to subjects regarding a recent alcohol associated arrest with a documented BAC greater than 0.08 g/dL for either public intoxication, driving under the influence, or under age drinking was administered. Demographic variables collected included drinking history, family history of alcoholism, presence of previous alcohol-related memory loss during a drinking episode, and drinking behavior during the episode. Memory of the drinking episode was evaluated to determine if either an alcohol-induced grayout (partial anterograde amnesia) or blackout (complete anterograde amnesia) occurred. Differences in (1) mean total number of drinks ingested before arrest, (2) gulping of drinks, and (3) BAC at arrest were found for those having blackouts compared with no amnesia; while differences in drinking more than planned were found between the no amnesia and grayout groups. A strong linear relationship between BAC and predicted probability of memory loss, particularly for blackouts was obvious. This finding clinically concludes that subjects with BAC of 310 g/dL or greater have a 0.50 or greater probability of having an alcoholic blackout.
The credibility of an increased risk of cerebrovascular events (CVEs) in elderly patients with de... more The credibility of an increased risk of cerebrovascular events (CVEs) in elderly patients with dementia being treated with second-generation antipsychotics (SGAs) is debatable. Although early published and unpublished data indicated a risk, much of the subsequent literature has not supported this initial finding. Previously published studies were flawed in part because they lacked a control group and did not stratify by dementia subtype. This study examined the risk of a CVE in patients diagnosed with Alzheimer or vascular dementia while being treated with SGA, first-generation antipsychotics, or no antipsychotic medication. Data from 14,029 patients aged 65 years and older were evaluated using patient information from Veterans Administration and Medicare databases. Patients who received care for dementia were categorized according to dementia subtype (vascular or Alzheimer) and antipsychotic use during an 18-month period. Patients were observed until they were admitted to a hospital for a CVE, stopped taking or switched antipsychotics, died, or until the 18-month observation period ended. Overall, CVE risk did not differ whether patients were receiving a first-generation antipsychotic, SGA, or no antipsychotic therapy. However, patients with vascular dementia had an increased risk in hospitalization for a CVE. There was no increase in risk of a CVE for patients treated with quetiapine, olanzapine, or risperidone relative to haloperidol, or for patients receiving olanzapine or risperidone relative to quetiapine. Stratified subgroup analyses demonstrated no difference in risk for CVE-related admission patients with Alzheimer dementia among individual agents. However, patients with vascular dementia receiving risperidone, but not olanzapine or quetiapine, were found to be at decreased risk for CVE admission relative to haloperidol. This study found no increase in overall risk for CVE-related hospital admission in patients treated with antipsychotic medications.
An analysis of the literature on tricyclic antidepressant level in blood using receiver operating... more An analysis of the literature on tricyclic antidepressant level in blood using receiver operating characteristics curves as the primary statistical tool was performed. For nortriptyline, a significant curvilinear relationship between therapeutic response and nortriptyline was observed that ranged from 58 to 148 ng/ml. The sensitivity and specificity for the nortriptyline therapeutic window were 78 and 61%, respectively. The response rate within the therapeutic range was 66% versus 26% outside the therapeutic range. For desipramine, a significant linear relationship between therapeutic response and desipramine concentration in plasma was observed. The threshold concentration in plasma for therapeutic response was 116 ng/ml. The sensitivity and specificity for the desipramine threshold level in blood were 81 and 59%, respectively. The response rate above the threshold level was 51% versus 15% below the therapeutic threshold concentration. For imipramine, a significant curvilinear relationship between therapeutic response and total imipramine (imipramine+desipramine) concentration in plasma was observed between 175 and 350 ng/ml. The sensitivity and specificity for the total imipramine concentrations in plasma were 52 and 74%, respectively. The response rate within the therapeutic range was 67% versus 39% outside the therapeutic range. For amitriptyline, a significant curvilinear relationship between therapeutic response and total amitriptyline (amitriptyline+nortriptyline) concentration in plasma was observed between 93 and 140 ng/ml. The sensitivity and specificity for the total imipramine concentrations in plasma were 37 and 80%, respectively. The response rate within the therapeutic range was 50% versus 30% outside the therapeutic range.
ABSTRACT Previous data suggest the possibility that haloperidol daily dosing requirements may be ... more ABSTRACT Previous data suggest the possibility that haloperidol daily dosing requirements may be confounded by smoking and, at higher doses, capacity-limited metabolism. Forty hospitalized patients suffering from an acute exacerbation of schizophrenia were treated for 2 weeks with fixed oral doses of haloperidol ranging from 10 to 70 mg/day (0.13 to 0.95 mg/kg/day) that produced mean steady-state concentrations between 4.5 and 55.4 ng/ml. No significant differences between the smoking and nonsmoking groups were obvious for the factors of weight, age, sex, daily doses, steady-state clearance, and steady-state haloperidol concentrations in plasma at week 1, week 2, and their mean. The hypothesis that the relationship between haloperidol dose and steady-state haloperidol concentration in plasma was affected by patients' smoking status and metabolic capacity was tested by multiple linear regression analysis and initially rejected. The relationship of dose to haloperidol concentration was fitted as a linear function. To improve the curve fit, the haloperidol concentrations and doses were transformed to their natural logs and then the regression line was refitted. The multiple regression analysis was repeated with the data in their transformed state. It was found that, although smoking status and dose of the drug did not independently affect the average haloperidol concentration, together they interacted in such a way that individual haloperidol concentrations were dependent on the smoking status at specific doses. Thus, two haloperidol dosing equations were generated, one for smokers and one for nonsmokers.
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