Double-blind, placebo-controlled evaluation of extended-release bupropion in elderly patients with major depressive disorder.

Major depressive disorder in the elderly is associated with increased morbidity and reduced quality of life. This 10 week, placebo-controlled study investigated the efficacy and tolerability of extended-release bupropion (150-300 mg once daily) in depressed patients aged 65 years or older. The statistical assumptions necessary for the validity of the protocol-specified analysis of covariance were not met for the analysis of the primary outcome variable (Montgomery-Asberg Depression Rating Scale total score at Week 10, last observation carried forward). Alternative statistical methods used for the analysis of this variable demonstrated statistical significance. Statistically significant improvements were observed on the majority of secondary end points when compared with placebo, including the health outcome measures for motivation and energy, and life satisfaction and contentment. Adverse events were generally mild to moderate and similar between treatment groups. This study demonstrated that the extended-release bupropion is an effective, well-tolerated treatment for major depression in the elderly.

Effect of bupropion-SR on orgasmic dysfunction in nondepressed subjects: a pilot study.

UNLABELLED: The objective of this study was to determine whether the aminoketone antidepressant bupropion has beneficial effects in orgasmic dysfunction. DESIGN: Single-blind, sequential treatment order of three weeks each: placebo, bupropion-SR 150 mg/day, bupropion-SR 300 mg/day. SUBJECTS: Nondepressed women (n = 20) and men (n = 10) having nonphysiologic orgasmic delay or inhibition. MAIN OUTCOME MEASURES: Reported difficulty or delay in achieving orgasm, satisfaction with orgasm and erectile function, and subjective impressions of drug effect. RESULTS: In the women, there were significant improvements relative to baseline (p < .01) on both doses of bupropion-SR in all measured aspects of sexual function, and significant improvements relative to placebo (p < .05) in overall sexual satisfaction on both doses and satisfaction with intensity of orgasm on 150 mg/day (300 mg/day, p = .10). In the men, significant improvements over baseline (p < .01) were observed with both doses in overall sexual satisfaction, ability to achieve an erection, and delay in reaching orgasm/ejaculation; significant improvements relative to placebo (p < .05) were observed in overall sexual satisfaction on both doses, ability to achieve erection on 150 mg/day, and delay in orgasm/ejaculation on 150 mg/day. Seventy percent of subjects reported improvement in libido, arousal, or orgasmic function during bupropion administration. CONCLUSIONS: Bupropion-SR may be a useful agent for treating orgasmic delay and inhibition, and possibly disorders of sexual arousal. The results argue against bupropion's apparent prosexual effect in depressed patients being simply a result of its antidepressant activity.

Unreliability of the infrared tympanic thermometer in clinical practice: a comparative study with oral mercury and oral electronic thermometers.

BACKGROUND: This study was designed to determine the magnitude and frequency of measurement errors with infrared tympanic thermometers in the clinical setting. METHODS: In a convenience sample of 137 adult inpatients, we compared body temperatures measured by a Diatek 9000 Infrared Aural Thermometer and an IVAC 2090 CoreCheck Tympanic Thermometer between themselves, in right versus left ears, and against concurrently measured oral temperatures using both an electronic thermoprobe and conventional glass mercury thermometer. RESULTS: There was a significant between-brand difference of 0.6 degrees C (IVAC

Comparative sexual side effects of bupropion, fluoxetine, paroxetine, and sertraline.

OBJECTIVE: To investigate patient reported prosexual side effects of the aminoketone antidepressant bupropion (INN, amfebutamone) and to compare directly the sexual side effects of bupropion and the selective serotonin reuptake inhibitor (SSRI) antidepressants fluoxetine, paroxetine, and sertraline. METHODS: One hundred seven psychiatric outpatient respondents receiving current treatment with one of the above antidepressants anonymously completed questionnaires that allowed reporting of both decreases and increases in sexual function. The main outcome measures were antidepressant-associated changes in libido, arousal, duration of time from arousal to orgasm, intensity of orgasm, and duration of orgasm relative to that experienced before the onset of the patients' psychiatric illnesses. RESULTS: Bupropion-treated patients reported significant increases in libido, level of arousal, intensity of orgasm, and duration of orgasm beyond levels experienced premorbidly. The three SSRIs to an equal degree significantly decreased libido, arousal, duration of orgasm, and intensity of orgasm below levels experienced premorbidly. Overall, 27% of the SSRI-treated patients had no adverse sexual side effects; in contrast, 86% of patients treated with bupropion had no adverse sexual effects, and 77% of bupropion-treated patients reported at least one aspect of heightened sexual functioning. CONCLUSIONS: SSRI-induced adverse sexual effects appear to be the rule rather than the exception and may be substantially underreported unless patients are specifically asked about the effects of these medications on various aspects of sexual function. In contrast, prosexual effects were reported by the majority of patients treated with bupropion. The findings are reviewed in light of the neurochemistry of these agents and the sexual response.

Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels.

OBJECTIVE: To determine if regional cerebral blood flow (rCBF) in the left and right hemithalami or the left and right heads of the caudate nucleus is abnormal in women with fibromyalgia (FM). METHODS: Resting-state rCBF in the hemithalami and left and right heads of the caudate nucleus of 10 untreated women with FM and 7 normal control women was measured by single-photon-emission computed tomography. Pain threshold levels at tender and control points also were assessed in both the women with FM and the controls. RESULTS: The rCBF in the left and right hemithalami and the left and right heads of the caudate nucleus was significantly lower in women with FM than in normal controls (P = 0.01, P = 0.003, P = 0.01, and P = 0.02, respectively). Compared with controls, the women with FM also were characterized by significantly lower cortical rCBF (P = 0.001) and lower pain threshold levels at both tender points (P = 0.0001) and control points (P = 0.0001). CONCLUSION: The findings of low rCBF and generalized low pain thresholds support the hypothesis that abnormal pain perception in women with FM may result from a functional abnormality within the central nervous system.

Focal cerebral blood flow change during craving for alcohol measured by SPECT.

To test the hypothesis that craving for alcohol in the alcohol-dependent individual is mediated by a limbic circuit involving the caudate nuclei, regional cerebral blood flow was measured with [99mTc]HMPAO SPECT during control and craving conditions in 9 alcohol-dependent subjects. In all subjects, blood flow in the head of the right caudate nucleus increased during the craving condition, and these blood flow increases were strongly correlated with the experimentally induced increases in craving for alcohol. These new findings suggest a functional role for the limbic striatum in the mediation of craving and impaired control over alcohol consumption.

Breath alcohol values following mouthwash use.

OBJECTIVE: To determine whether breath alcohol values (BrAV) attained following mouthwash use pose a realistic threat to the accuracy of blood alcohol determinations by breath analysis. DESIGN: Nonrandomized, open-label trial. SETTING: Outpatient research office. PARTICIPANTS: Ten normal subjects; convenience sample. INTERVENTIONS: Breath alcohol measurements were made 2, 4, 6, 10, and 15 minutes following rinsing of the mouth with Listerine (26.9% alcohol) [corrected], Scope (18.9% alcohol), and Lavoris (6.0% alcohol) using the Alco-Sensor III intoximeter. MAIN OUTCOME MEASURES: Breath alcohol values over time. RESULTS: Breath alcohol values following mouthwash use decayed exponentially (r2 > or = .98, P < .001) from mean values 2 minutes following mouthwash use of 52.8 mmol/L (240 mg/dL) for Listerine, 37.4 mmol/L (170 mg/dL) for Scope, and 7.9 mmol/L (36 mg/dL) for Lavoris to mean and maximum values after 10 minutes that were well below the usual driving-while-intoxicated range (> or = 17.6 mmol/L [80 mg/dL]) for all three brands. The nonalcoholic mouthwash ingredients did not significantly affect the BrAVs attained. CONCLUSION: The decay of BrAVs following mouthwash use is sufficiently rapid that mouthwash use would not pose a realistic threat to the accuracy of blood alcohol determinations by breath analysis under normal circumstances. Use of mouthwash immediately prior to breath testing, as might occur in the car or workplace in a mistaken attempt to hide the smell of alcohol or other substances, may, however, significantly increase the measured BrAV.

Effect of haloperidol on measures of craving and impaired control in alcoholic subjects.

We recently proposed that alcoholics suffer from a functional defect within the basal ganglia/limbic striatum or its modulation by dopaminergic projections from the ventral tegmentum, and that inhibition of striatal output caused by the prodopaminergic effects of alcohol ingestion induces or exacerbates craving and impaired control over alcohol consumption in alcoholic individuals. To test this hypothesis, 16 subjects with a diagnosis of alcohol dependence or abuse were studied in a double-blind, placebo-controlled experiment in which the effects of the D-2 antagonist haloperidol on measures of craving and impaired control were assessed before and after administration of a priming dose of alcohol. Subjects were pretreated with 0.015-0.025 mg/kg haloperidol (experimental condition) or 2 ml normal saline (control condition), and subsequently consumed 0.4-0.6 g/kg ethanol as their preferred alcohol-containing beverage. Significant increases in subjectively rated craving for alcohol and perceived difficulty resisting additional alcohol consumption occurred following the priming dose of alcohol when subjects were pretreated with saline. In contrast, no significant changes in reported ability to resist additional alcohol occurred when subjects were pretreated with haloperidol, and reported levels of craving decreased relative to baseline following haloperidol pretreatment. Subjects also consumed about 25% less optionally available alcohol when pretreated with haloperidol than when pretreated with saline. These findings support the hypothesis that craving and impaired control are induced or exacerbated by the prodopaminergic effects of alcohol consumption.

The ethics and safety of alcohol administration in the experimental setting to individuals who have chronic, severe alcohol problems.

There is a popular belief that the experimental administration of alcohol to individuals who have chronic, severe alcohol problems ('alcoholics') is inherently dangerous or unethical. This creates an environment in which researchers who desire to conduct a study involving the administration of alcohol to persons with severe alcohol problems must defend the relative safety and reasonableness of this practice when, in fact, scientific justification for not using this important methodologic technique in alcohol research is lacking. The primary purpose of this manuscript is to present and discuss the safety, ethical, and practical considerations of research involving administration of alcohol to subjects who have had difficulty refraining from harmful alcohol use in the natural setting. The authors also describe a study in which they monitored the short-term effects of administering 0.4-0.6 g/kg alcohol to 16 recently abstinent subjects who had chronic, severe alcohol problems. This study revealed no evidence that the administration of beverage alcohol in the experimental setting to such individuals causes an uncontrollable desire for more alcohol, precipitates immediate relapse, or creates any behavioral problems. The data also suggested that the knowledge gained from the effects of alcohol ingestion in the experimental setting might help many subjects to understand more completely their addiction or drinking behaviour. It is concluded that there is no overriding reason why alcohol cannot, with due precaution, be safely and ethically administered in the experimental setting to human subjects who suffer from alcohol problems.

Obsessive and compulsive characteristics of alcohol abuse and dependence: quantification by a newly developed questionnaire.

The purpose of the this study was to develop an instrument for measuring the obsessive and compulsive characteristics of drinking-related thought and behavior in subjects who abuse or are dependent on alcohol, and to quantify the extent to which drinking-related thought and behavior in these subjects resemble the obsessions and compulsions seen in obsessive-compulsive disorder (OCD). To achieve these goals, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was modified to reflect obsessionality and compulsivity specifically related to heavy drinking rather than to obsessions and compulsions generally. The modified Y-BOCS (Y-BOCS-hd) was administered to 62 subjects satisfying DSM-III-R criteria for alcohol abuse or alcohol dependence and 62 matched normal controls. The data showed that the Y-BOCS-hd is a sensitive and specific instrument for measuring the obsessive and compulsive characteristics of drinking-related thought and behavior in alcohol-abusing and alcohol-dependent populations, and that there are specific and quantifiable similarities between these characteristics and the obsessions and compulsions of OCD. The data also indicated that the Y-BOCS-hd may be a useful screening instrument for the presence of alcohol abuse and dependence.

Obsessive and compulsive characteristics of craving for alcohol in alcohol abuse and dependence.

The purpose of this study was to quantify the extent to which subjective ratings of craving for alcohol in the alcohol-abusing or dependent person (herein, alcoholic) correlate with measurable and specific characteristics of obsessions and compulsions. The Yale-Brown Obsessive Compulsive Scale modified to reflect obsessionality and compulsivity specifically related to heavy drinking (Y-BOCS-hd) was used for this purpose. Highly significant correlations were found in the alcoholic population (n = 62) between subjectively rated craving for alcoholic beverages and several of the Y-BOCS-hd questions regarding alcohol-related thoughts and drinking behavior. Additionally, mean craving scores were considerably greater in the alcoholic population than in the matched control population (n = 62). The data suggest that craving shares specific features in common with the obsessions of obsessive-compulsive disorder and that the existence of craving is dependent on the presence of obsessive thoughts about drinking. Positive correlations between craving and measures of compulsive drinking behavior also were found; compulsive drinking behavior, however, may reflect the consequences of craving rather than a fundamental characteristic of craving itself. The data show that despite difficulties in defining the term craving, it is clearly a phenomenon that is experienced or endorsed by most alcoholic subjects and is not by most persons who do not abuse alcohol.

Pathological lying associated with thalamic dysfunction demonstrated by [99mTc]HMPAO SPECT.

The authors report a case in which pathological lying is associated with right hemithalamic dysfunction as shown by [99mTc]HMPAO SPECT brain scanning. This association has not been demonstrated previously and is noteworthy because it supports the hypothesized roles of the thalamus and associated brain regions in the modulation of behavior and cognition.

Cerebellar and frontal hypometabolism in alcoholic cerebellar degeneration studied with positron emission tomography.

Local cerebral metabolic rate for glucose was studied utilizing 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 14 chronically alcohol-dependent patients and 8 normal control subjects of similar age and sex. Nine of the 14 patients (Group A) had clinical signs of alcoholic cerebellar degeneration, and the remaining 5 (Group B) did not have signs of alcoholic cerebellar degeneration. PET studies of Group A revealed significantly decreased local cerebral metabolic rates for glucose in the superior cerebellar vermis in comparison with the normal control subjects. Group B did not show decreased rates in the cerebellum. Both Groups A and B showed decreased local cerebral metabolic rates for glucose bilaterally in the medial frontal area of the cerebral cortex in comparison with the normal control subjects. The severity of the clinical neurological impairment was significantly correlated with the degree of hypometabolism in both the superior cerebellar vermis and the medial frontal region of the cerebral cortex. The degree of atrophy detected in computed tomography scans was significantly correlated with local cerebral metabolic rates in the medial frontal area of the cerebral cortex, but not in the cerebellum. The data indicate that hypometabolism in the superior cerebellar vermis closely follows clinical symptomatology in patients with alcoholic cerebellar degeneration, and does not occur in alcohol-dependent patients without clinical evidence of cerebellar dysfunction. Hypometabolism in the medial frontal region of the cerebral cortex is a prominent finding in alcohol-dependent patients with or without alcoholic cerebellar degeneration.

Anxiety and cerebral cortical metabolism in normal persons.

The State-Trait Anxiety Inventory (STAI) was administered to 43 normal volunteers immediately before and after a positron emission tomography (PET) procedure with [18F]-2-fluoro-2-deoxy-D-glucose (18F-FDG). High trait-anxious individuals had significantly higher state (situational) anxiety associated with the PET scan procedure than did low trait-anxious persons. State anxiety decreased significantly for all respondents following the PET scan procedure. No significant relationships between global or regional cortical metabolic rates and state anxiety were observed. The direct cortical metabolic effects of heightened anxiety in the scan setting, should they exist, are likely obscured in the normal variance of the 18F-FDG method.