Timothy W. Fong

Bupropion Reduces Methamphetamine-Induced Subjective Effects and Cue-Induced Craving

Bupropion is an antidepressant with stimulant properties, which inhibits the reuptake of dopamine (DA) and norepinepherine, and is purported to enhance DA neurotransmission. Bupropion is considered an appealing candidate medication for the treatment of methamphetamine dependence. The current laboratory study was set forth to assess the impact of bupropion treatment on the subjective effects produced by methamphetamine in the laboratory. We also assessed the effects of bupropion treatment on craving elicited by exposure to videotaped methamphetamine cues. A total of 26 participants were enrolled and 20 completed the entire study (n=10 placebo and n=10 bupropion, parallel groups design). Bupropion treatment was associated with reduced ratings of ‘any drug effect’ (p<0.02), and ‘high’ (p<0.02) following methamphetamine administration. There was also a significant bupropion-by-cue exposure interaction on General Craving Scale total score (p<0.002), and on the Behavioral Intention subscale (p<0.001). Overall, the data reveal that bupropion reduced acute methamphetamine-induced subjective effects and reduced cue-induced craving. Importantly, these data provide a rationale for the evaluation of bupropion in the treatment of methamphetamine dependence.

Report of Findings in a DSM‐5 Field Trial for Hypersexual Disorder

INTRODUCTION Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for hypersexual disorder (HD) have been proposed to capture symptoms reported by patients seeking help for out-of-control sexual behavior. The proposed criteria created by the DSM-5 Work Group on Sexual and Gender Identity Disorders require evaluation in a formal field trial. AIM This DSM-5 Field Trial was designed to assess the reliability and validity of the criteria for HD in a sample of patients seeking treatment for hypersexual behavior, a general psychiatric condition, or a substance-related disorder. METHOD Patients (N = 207) were assessed for psychopathology and HD by blinded raters to determine inter-rater reliability of the HD criteria and following a 2-week interval by a third rater to evaluate the stability of the HD criteria over time. Patients also completed a number of self-report measures to assess the validity of the HD criteria. MAIN OUTCOME MEASURES HD and psychopathology were measured by structured diagnostic interviews, the Hypersexual Behavior Inventory, Sexual Compulsivity Scale, and Hypersexual Behavior Consequences Scale. Emotional dysregulation and stress proneness were measured by facets on the NEO Personality Inventory-Revised. RESULTS Inter-rater reliability was high and the HD criteria showed good stability over time. Sensitivity and specificity indices showed that the criteria for HD accurately reflected the presenting problem among patients. The diagnostic criteria for HD showed good validity with theoretically related measures of hypersexuality, impulsivity, emotional dysregulation, and stress proneness, as well as good internal consistency. Patients assessed for HD also reported a vast array of consequences for hypersexual behavior that were significantly greater than those diagnosed with a general psychiatric condition or substance-related disorder. CONCLUSIONS The HD criteria proposed by the DSM-5 Work Group on Sexual and Gender Identity Disorders appear to demonstrate high reliability and validity when applied to patients in a clinical setting among a group of raters with modest training on assessing HD.

A double-blind, placebo-controlled trial of olanzapine for the treatment of video poker pathological gamblers.

Emerging evidence suggests that dopaminergic and serotonergic functioning are altered in pathological gamblers; yet, there are no FDA-approved medications for pathological gambling and there have only been a limited number of clinical trials that have been conducted. Olanzapine was identified as a candidate medication for pathological gamblers because it modifies both dopaminergic and serotonergic function. Moreover, preliminary studies have shown that olanzapine effectively reduces impulsivity in other psychiatric disorders, a pharmacological target of interest for pathological gamblers. In this study, 21 pathological gamblers, whose primary gambling activity was video poker, were enrolled in a seven-week, double-blind, placebo-controlled trial. Outcome measures included self-reported urges for gambling, frequency of gambling behavior, and self-reported mood and anxiety levels. The results revealed that all study participants reported reduced levels of gambling urges, gambling behavior, and mood and anxiety symptoms. Olanzapine administration was not associated with an incremental effect versus placebo. While these findings suggest that olanzapine is not an efficacious treatment for video poker pathological gamblers, olanzapine may still be an effective treatment for a specific subset of pathological gamblers, including those with a co-occurring psychiatric disorder.

Gender effects on mood and cigarette craving during early abstinence and resumption of smoking

Women are more likely than men to relapse after initiating abstinence from cigarette smoking. The reasons for this phenomenon are unclear but may relate to negative mood, cigarette craving, or other symptoms of nicotine withdrawal. We addressed this issue in a study of 26 female and 38 male smokers. The Profile of Mood States, Shiffman-Jarvik Withdrawal Scale, and Urge to Smoke Scale were administered twice in each of two test sessions on different days. One session began within 1 hr after smoking ad libitum and the other followed overnight abstinence (>13 hr). On each test day, the two assessment blocks were separated by a 5-10-min break, during which each participant smoked one cigarette. In the first test block, both men and women reported higher scores after >13 hr abstinence than after <1 hr abstinence on the tension-anxiety and anger-hostility subscales of the Profile of Mood States, and for the craving and psychological symptoms of the Shiffman-Jarvik Withdrawal Scale. Scores of female subjects showed significantly larger differences between sessions on the tension-anxiety subscale and a trend toward significance (p = .050) on the anger-hostility subscale of Profile of Mood States than those of males. Moreover, on the tension-anxiety subscale, women also reported a greater reduction than men from smoking one cigarette after overnight abstinence. The findings indicate that overnight abstinence produces more negative mood symptoms and cigarette craving in female smokers than in males, and that resumption of smoking produces greater relief from these symptoms in female smokers. These differences may contribute to the greater likelihood of relapse when women try to quit smoking.

Cocaine Dependence and Acute Cocaine Induce Decreases of Monocyte Proinflammatory Cytokine Expression across the Diurnal Period: Autonomic Mechanisms

Cocaine dependence is associated with an increased risk of infectious diseases. The innate immune system triggers effector pathways to combat microbial pathogens through expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). It is not known whether cocaine alters the capacity of monocytes to respond to a bacterial challenge in humans. In cocaine-dependent volunteers and control subjects, we analyzed monocyte TNF-α and IL-6 expression at rest and in response to the bacterial ligand, lipopolysaccharide (LPS), over a 24-h period. In addition, the in vivo effects of cocaine (40 mg) versus placebo on monocyte expression of TNF-α and IL-6 were profiled over 48 h. Cocaine-dependent volunteers showed a decrease in the capacity of monocytes to express TNF-α and IL-6 compared with control subjects. Moreover, acute infusion of cocaine induced a further decline in the responsiveness of monocytes to LPS, which persisted after cocaine had cleared from the blood. Heart rate variability analyses showed that increases of sympathetic activity along with vagal withdrawal were associated with decreases in monocyte expression of TNF-α. Cocaine alters autonomic activity and induces protracted decreases in innate immune mechanisms. Targeting sympathovagal balance might represent a novel strategy for partial amelioration of impairments of innate immunity in cocaine dependence.

Psychometric development of the hypersexual behavior consequences scale

Background and aims The past decade has seen an increased interest in understanding hypersexual behavior and its associated features. Beyond the obvious risks for sexually transmitted infections, there is a paucity of literature examining specific challenges encountered by hypersexual individuals. This study investigated and developed a new scale, the Hypersexual Behavior Consequences Scale (HBCS), to assess the various consequences reported among hypersexual patients. Methods Participants were drawn from a sample of patients recruited in a DSM-5 Field Trial for Hypersexual Disorder (HD). Participants completed the Hypersexual Behavior Inventory, a structured diagnostic interview to assess for psychopathology and HD, and self-report measures of personality, life satisfaction, and the initial item pool for the HBCS. Results Factor analysis reduced the HBCS items to a single factor solution which showed high internal consistency and stability over time. Higher HBCS scores were positively correlated with higher levels of emotional dysregulation, impulsivity, and stress proneness and lower levels of satisfaction with life and happiness. HBCS scores among the hypersexual patients were significantly higher than non-hypersexual patients. Conclusions The HBCS possesses good psychometric properties and appears to capture various consequences associated with the DSM-5 proposed criteria for HD. The HBCS can be used to aid clinicians and researchers in identifying consequences associated with hypersexual behavior. The HBCS may also prove a useful tool to guide treatment interventions aimed at reducing the negative impact of hypersexuality in patient populations.

Sexual desire, not hypersexuality, is related to neurophysiological responses elicited by sexual images

Background Modulation of sexual desires is, in some cases, necessary to avoid inappropriate or illegal sexual behavior (downregulation of sexual desire) or to engage with a romantic partner (upregulation of sexual desire). Some have suggested that those who have difficulty downregulating their sexual desires be diagnosed as having a sexual ‘addiction’. This diagnosis is thought to be associated with sexual urges that feel out of control, high-frequency sexual behavior, consequences due to those behaviors, and poor ability to reduce those behaviors. However, such symptoms also may be better understood as a non-pathological variation of high sexual desire. Hypersexuals are thought to be relatively sexual reward sensitized, but also to have high exposure to visual sexual stimuli. Thus, the direction of neural responsivity to sexual stimuli expected was unclear. If these individuals exhibit habituation, their P300 amplitude to sexual stimuli should be diminished; if they merely have high sexual desire, their P300 amplitude to sexual stimuli should be increased. Neural responsivity to sexual stimuli in a sample of hypersexuals could differentiate these two competing explanations of symptoms. Methods Fifty-two (13 female) individuals who self-identified as having problems regulating their viewing of visual sexual stimuli viewed emotional (pleasant sexual, pleasant-non-sexual, neutral, and unpleasant) photographs while electroencephalography was collected. Results Larger P300 amplitude differences to pleasant sexual stimuli, relative to neutral stimuli, was negatively related to measures of sexual desire, but not related to measures of hypersexuality. Conclusion Implications for understanding hypersexuality as high desire, rather than disordered, are discussed.

Psychometric properties of the Barratt Impulsiveness Scale in patients with gambling disorders, hypersexuality, and methamphetamine dependence.

Although the Barratt Impulsiveness Scale (BIS; Patton, Stanford, & Barratt, 1995) is a widely-used self-report measure of impulsivity, there have been numerous questions about the invariance of the factor structure across clinical populations (Haden & Shiva, 2008, 2009; Ireland & Archer, 2008). The goal of this article is to examine the factor structure of the BIS among a sample consisting of three populations exhibiting addictive behaviors and impulsivity: pathological gamblers, hypersexual patients, and individuals seeking treatment for methamphetamine dependence to determine if modification to the existing factors might improve the psychometric properties of the BIS. The current study found that the factor structure of the BIS does not replicate in this sample and instead produces a 12-item three-factor solution consisting of motor-impulsiveness (5 items), non-planning impulsiveness (3 items), and immediacy impulsiveness (4 items). The clinical utility of the BIS in this population is questionable. The authors suggest future studies to investigate comparisons with this modified version of the BIS and other impulsivity scales such as the UPPS-P Impulsive Behavior Scale in clinical populations when assessing disposition toward rash action.

Reliability, Validity, and Psychometric Development of the Pornography Consumption Inventory in a Sample of Hypersexual Men

This article reports the psychometric evaluation of the Pornography Consumption Inventory (PCI), which was developed to assess motivations for pornography use among hypersexual men. Initial factor structure and item analysis were conducted in a sample of men (N = 105) seeking to reduce their pornography consumption (Study 1), yielding a 4-factor solution. In a second sample of treatment-seeking hypersexual men (N = 107), the authors further investigated the properties of the PCI using confirmatory factor analytic procedures, reliability indices, and explored PCI associations with several other constructs to establish convergent and discriminant validity. These studies demonstrate psychometric evidence for the PCI items that measure tendencies of hypersexual men to use pornography (a) for sexual pleasure; (b) to escape, cope, or avoid uncomfortable emotional experiences or stress; (c) to satisfy sexual curiosity; and (d) to satisfy desires for excitement, novelty, and variety.

A double-blind, placebo-controlled trial of topiramate for pathological gambling

Abstract Objectives. Pathological gambling (PG) is an impulse control disorder characterized by recurrent gambling thoughts and behaviours that impair social functioning. Earlier studies suggested that topiramate may be effective in treating some impulse control disorders. We conducted the first randomized, controlled trial of topiramate in PG. Methods. PG patients were randomized to topiramate (N = 20) or placebo (N = 22) in this 14-week, double-blind, placebo-controlled, parallel-group trial. The primary outcome measure was change in the obsessions subscale of the Yale-Brown Obsessive-Compulsive Scale Modified for Pathological Gambling. Results. Mixed regression models (time [weeks] × treatment) revealed no significant treatment effect of topiramate on the primary or secondary outcome measures. The most statistically robust findings involved reducing the Barratt Impulsiveness Scale (BIS) total score and Motor and Non-Planning subscale scores, for which topiramate outperformed placebo at merely a trend level (P < 0.1). Conclusions. The observed trend in BIS score reductions may warrant further investigation to study whether topiramate reduces clinically important impulsivity in PG. Treatment studies with larger samples and less stringent exclusion criteria are needed to produce results that can be generalized to pathological gamblers in the community.