Katherine Lowengrub

Topiramate versus fluvoxamine in the treatment of pathological gambling : A randomized, blind-rater comparison study

Pathologic gambling (PG) is a highly prevalent and disabling impulse control disorder. Recent studies have demonstrated that PG patients respond well to treatment with SSRIs, mood stabilizers, and opioid antagonists. These findings support the idea that PG and other disorders of impulse control may be conceptualized as part of the obsessive-compulsive spectrum disorders. Pilot studies have shown topiramate to be effective in the treatment of specific disorders of impulse control. The aim of the study is to compare the effectiveness of topiramate versus fluvoxamine in the treatment of PG. Thirty-one male PGs were assigned in a randomized fashion to receive either topiramate (15/31) or fluvoxamine (16/31) pharmacotherapy for 12 weeks. A comprehensive psychiatric diagnostic evaluation was performed on all patients, and all patients were evaluated for symptoms of gambling, depression, and anxiety using the South Oaks Gambling Screen, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Yale-Brown Obsessive Compulsive Symptoms Scale, and the Clinical Global Impression-Improvement Scale. The rating scales were administered at baseline and at the 12-week endpoint. In addition, the patients completed self-report questionnaires about their demographic status. Twelve of the 15 patients from the topiramate group completed the 12-week treatment. Nine of the 12 topiramate completers reported full remission of gambling behavior, and 3 completers had a partial remission. The CGI-improvement score was significantly better for the topiramate group at the 12-week visit as compared with baseline (F = 10.5, P < 0.01, df = 2,31). In the fluvoxamine treatment group 8/16 patients completed the study, and 6/8 fluvoxamine completers reported a full remission, and the remaining 2/8 fluvoxamine completers reported a partial remission. The fluvoxamine group showed improvement in the CGI-improvement score at week 12, although this difference was not significant (F = 3.7, P < 0.08, df = 2,31). Topiramate and fluvoxamine monotherapy may be effective in the treatment of pathologic gambling.

Sustained-release bupropion versus naltrexone in the treatment of pathological gambling : A preliminary blind-rater study

Background: Pathological gambling (PG) is a relatively common and highly disabling impulse control disorder. A range of psychotheraputic agents, including selective serotonin reuptake inhibitors, mood stabilizers, and opioid antagonists, has been shown to be effective in the treatment of PG. The use of selective serotonin reuptake inhibitors and opioid antagonists for PG is consistent with the observation that PG shares features of both the obsessive-compulsive spectrum disorders and addictive disorders. The aim of the study is to compare the effectiveness of sustained-release bupropion versus naltrexone in the treatment of PG. Methods: Thirty-six male pathological gamblers were enrolled in our study. A comprehensive psychiatric diagnostic evaluation was performed at baseline on all patients, and patients were screened for symptoms of gambling, depression, and anxiety using the South Oaks Gambling Screen, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression-Severity Scale. In addition, the patients completed self-report questionnaires about their demographic status. Patients were randomized in 2 groups and received either naltrexone (n = 19) or sustained-release bupropion (n = 17) for 12 weeks in a parallel fashion. Treatment response was monitored using the Clinical Global Impression-Improvement Scale which was performed at weeks 2, 4, 8, and 12. Patients were also assessed for the presence of gambling behavior via an unstructured interview, which was also performed at weeks 2, 4, 6, 8, and 12. Raters were blind to the study treatment. Results: The majority of patients responded well to the drug treatment. Twelve of 17 patients in the sustained-release bupropion group completed the 12-week study, and 13 of 19 naltrexone patients completed the study. Nine (75%) of the 12 completers were rated as full responders in the sustained-release bupropion group versus 10 (76%) of 12 in the naltrexone group. Three (25%) of 12 completers in the bupropion group were rated as partial responders. In the naltrexone group, 3 (23%) of 13 completers were rated as partial responders. Full response was defined as the absence of gambling for a 2-week duration together with improvement on the Clinical Global Impression-Improvement Scale. Partial response was defined as a decrease in the frequency of gambling behavior and a decrease in the amount of money spent on gambling. Conclusion: This preliminary study shows that sustained-release bupropion may be effective as naltrexone in the treatment of PG. Further studies are needed to confirm our findings.

Go–no-go performance in pathological gamblers

Previous neuropsychological studies demonstrated various deficits of impulse control in pathological gamblers (PGs). However, there are limited data available on response-inhibition impairment among PGs. The present study attempted to assess response inhibition in untreated PGs (N=83), in comparison with normal subjects (N=84). Go/no-go and target-detection conditions of a computerized task were used as a measure of response-inhibition ability. A repeated measures analysis of covariance (ANCOVA-RM) was used with response time, variability of response time, and number of false alarms and misses as dependent measures; group (PG and controls) as the between-subjects measure; condition (target detection or go/no-go) and time slice (first and second in each condition) as repeated measures within-subject factors; and educational level as a covariate. Our results showed that PGs were significantly more impaired in both target detection and go/no-go task performance than controls. The PGs had significantly more false alarms and misses than controls, and they were slower and less consistent in their responses.

Pathological gambling: an update on neuropathophysiology and pharmacotherapy.

Neurobiological research has shown the potential involvement of serotonergic, dopaminergic and opioid dysfunction in the pathophysiology of pathological gambling. In this review, we present current theories of the neuropathology of pathological gambling, paying particular attention to the role of the neural circuitry underlying motivation, reward, decision-making and impulsivity. This review also presents a literature review of current pharmacological treatment strategies for pathological gambling, such as SSRIs, opioid receptor antagonists, anti-addiction drugs and mood stabilizers, and also discusses the role of nonpharmacological interventions.A hypothetical model of the clinical subtypes of pathological gambling is presented, e.g. the impulsive subtype, the obsessive-compulsive subtype and the addictive subtype. This model attempts to integrate current knowledge in the field of pathological gambling regarding neuropathology, psychiatric co-morbidity, family history, genetics, course of illness, gender and response to pharmacological treatment. Finally, it is proposed that the existence of possible clinical subtypes of pathological gambling may provide a potential framework for matching the various subtypes with specific pharmacotherapies.

A naturalistic long-term comparison study of selective serotonin reuptake inhibitors in the treatment of panic disorder.

Objectives: Selective serotonin reuptake inhibitors (SSRIs) are currently considered as the first drug of choice in the treatment of panic disorder (PD). The aim of this long-term, naturalistic comparison study was to compare 4 SSRIs with respect to tolerability and treatment outcome of PD. Outcome measures included relapse rates and adverse effects. Methods: Two hundred patients with PD were enrolled in our study. All subjects met DSM-IV criteria for PD or PD with agoraphobia (PDA). All patients were assigned to receive SSRI monotherapy for 12 months with either citalopram (n = 50), fluoxetine (n = 50), fluvoxamine (n = 50), or paroxetine (n = 50) in a randomized, nonblinded fashion. Both the treating psychiatrist and the patients were not blind to the assigned treatment, but the clinician raters were blind to the study medication. The study design allowed for assignment of a particular SSRI as indicated according to the clinical judgment of the study psychiatrists. The Panic Self-Questionnaire, which is a self-report scale, was administered at baseline and then once per month during the duration of the 12-month study. The visual analog scale and the Clinical Global Impression Scale were administered at baseline and then once per month during the period of the study. Reports of sexual dysfunction were assessed using a nonstructured clinical interview at monthly visits. The body weight of study subjects was measured at baseline, and then at the 12th month visit end point. Results: Of 200 patients who entered the study, 127 patients (63.5%) completed the full 12-month protocol. Retention rates were highest for paroxetine (76% [38/50]), intermediate for citalopram (68% [34/50]) and fluvoxamine (60% [30/50]), and lowest for fluoxetine (50% [25/50]). Patients who completed the 12-month protocol responded favorably to the study treatment. The paroxetine and the citalopram groups had significantly lower rates of panic symptoms as measured at visits on weeks 4 and 8. At visits on months 3, 6, 9, and 12, however, there were no statistically significant differences between the 4 groups in relapse rates (defined as the occurrence of 1 or more panic attacks during the previous week of treatment) (F1,127 = 0.17; P = 0.13 [not statistically significant]). At the 12th month end point, patients in all 4 treatment groups had a statistically significant increase in body weight. Body weight among the study population increased by 6.1 + 4.9 kg from a mean weight of 72.4 + 7.3 kg at the onset of treatment. Reports of sexual adverse effects at the 12th month visit were similar in the citalopram, fluoxetine, and paroxetine groups, but the fluvoxamine patient group reported fewer sexual adverse effects at the 12th month visit. Conclusions: Most of our PD patients responded well to 12-month treatment with either citalopram, fluoxetine, fluvoxamine, or paroxetine, and the overall response rate was equal after the first 4 weeks of treatment. Although patients treated with paroxetine had the lowest dropout rates during the initiation phase, they had the highest rate of adverse effects as measured at the 12th month visit. Conversely, patients in the fluvoxamine group had the highest dropout rate (which was primarily caused by adverse effects in the initiation phase of treatment.); however, patients who were able to tolerate fluvoxamine throughout the full course of the study were observed to have lower rates of sexual dysfunction and weight gain compared with patients treated with the other agents. Overall, when measured at the 12th month visit, monotherapy with paroxetine and citalopram was associated with a higher rate of sexual adverse effects than was treatment with fluoxetine or fluvoxamine. In addition, monotherapy with paroxetine, citalopram, and fluoxetine seemed to cause more weight gain than did treatment with fluvoxamine.

Escitalopram in the treatment of negative symptoms in patients with chronic schizophrenia: A randomized double-blind placebo-controlled trial

Antidepressant medication treatment has been associated with improvement in negative symptoms in patients with schizophrenia. In this study, we evaluated the efficacy of escitalopram for the treatment of negative symptoms in patients with schizophrenia. Under double-blind conditions, 40 patients with chronic schizophrenia were randomized to add-on treatment with escitalopram (up to 20mg) or placebo for 10weeks. The primary outcome measures were the scores on the Positive and Negative Syndrome Scale (PANSS)-negative subscale and the Social Functioning Scale (SFS). Secondary outcome measures included the Positive and Negative Syndrome Scale (PANSS)-total and positive scales, the Scale for Assessment of Negative Symptoms (SANS), the Clinical Global Impression Scale (CGI), the Hamilton Depression Rating Scale (HDRS) and the Abnormal Involuntary Movement Scale (AIMS). Of 40 patients, 36 completed the study and another 2 were excluded after 8weeks due to side effects. Thus, 38 patients (19 on both treatment arms) were considered in the efficacy analysis. The reduction in the PANSS negative subscale score was 5% for escitalopram and 10% for placebo (NS). There were no significant inter-group differences in primary and secondary endpoints. Escitalopram was well tolerated, but was not more effective than placebo in the treatment of negative symptoms in patients with chronic schizophrenia. Further work in this field is needed to determine whether some subgroups of patients with negative symptoms may nevertheless respond to antidepressant medications.

Three year naturalistic outcome study of panic disorder patients treated with paroxetine

BackgroundThis naturalistic open label follow-up study had three objectives:1) To observe the course of illness in Panic Disorder patients receiving long-term versus intermediate-term paroxetine treatment2) To compare the relapse rates and side-effect profile after long-term paroxetine treatment between patients with Panic Disorder and Panic Disorder with Agoraphobia.3) To observe paroxetines tolerability over a 24 month period.Methods143 patients with panic disorder (PD), with or without agoraphobia, successfully finished a short-term (ie 12 week) trial of paroxetine treatment. All patients then continued to receive paroxetine maintenance therapy for a total of 12 months. At the end of this period, 72 of the patients chose to discontinue paroxetine pharmacotherapy and agreed to be monitored throughout a one year discontinuation follow-up phase. The remaining 71 patients continued on paroxetine for an additional 12 months and then were monitored, as in the first group, for another year while medication-free. The primary limitation of our study is that the subgroups of patients receiving 12 versus 24 months of maintenance paroxetine therapy were selected according to individual patient preference and therefore were not assigned in a randomized manner.ResultsOnly 21 of 143 patients (14%) relapsed during the one year medication discontinuation follow-up phase. There were no significant differences in relapse rates between the patients who received intermediate-term (up to 12 months) paroxetine and those who chose the long-term course (24 month paroxetine treatment). 43 patients (30.1%) reported sexual dysfunction. The patients exhibited an average weight gain of 5.06 kg. All patients who eventually relapsed demonstrated significantly greater weight increase (7.3 kg) during the treatment phase.ConclusionsThe extension of paroxetine maintenance treatment from 12 to 24 months did not seem to further decrease the risk of relapse after medication discontinuation. Twenty-four month paroxetine treatment is accompanied by sexual side effects and weight gain similar to those observed in twelve month treatment.

12-month follow-up study of drug treatment in pathological gamblers: a primary outcome study.

Background: Pathological gambling (PG) is a relatively common and highly disabling impulse control disorder. A range of psychotherapeutic agents including selective serotonin reuptake inhibitors, antiepileptic drugs, and opioid antagonists are shown to be effective in the short-term treatment of PG. The use of a wide range of pharmacological treatments for PG is consistent with the observation that PG shares features of obsessive-compulsive spectrum disorders, impulse control disorders, and addictive disorders. The aim of the study is to assess the rate of relapse in treatment-responder pathological gamblers after discontinuation of the active treatment. Methods: Our study sample was composed of 43 male pathological gamblers who had been full responders to 1 of 4 drug treatment regimens (fluvoxamine, topiramate, bupropion SR, or naltrexone) from several previous acute open-label (12-week) comparison studies. Full response was defined as the absence of gambling for a 1-month duration together with improvement on the Clinical Global Improvement scale. The 43 full responders were then followed prospectively for an additional 9 months, which included a 3-month open-label continuation phase and a 6-month medication-free follow-up phase. Follow-up visits were performed on a monthly basis throughout the duration of study. At every follow-up visit, a comprehensive psychiatric diagnostic evaluation was performed on all patients, and patients were assessed for symptoms of gambling using a self-report instrument and collateral family reports. The Clinical Global Impression Improvement scale was also administered at every follow-up visit. Raters were blind to the previous drug treatment. Results: Most patients did not relapse during the 6-month medication-free follow-up phase. Three of 6 patients with fluvoxamine, 3 of 9 with topiramate, 7 of 18 with bupropion SR, and 4 of 10 with naltrexone relapsed. Relapse was strictly defined as gambling behavior at any time during the 6-month medication-free follow-up period. Most of the patients did not gamble during the follow-up period, and the patients that did gamble reported a decrease in gambling losses. Conclusions: This naturalistic long-term follow-up outcome study demonstrates that among pathological gamblers who respond to a 6-month trial of medication, most patients seem to maintain full-response during a 6-month medication-free follow-up phase. Further studies are needed to confirm our findings.

Dual psychiatric diagnosis and substance abuse in pathological gamblers: a preliminary gender comparison study.

Abstract Background: Pathological Gambling (PG) is a highly prevalent and disabling impulse control disorder. Recent studies have consistently shown that PG patients have responded well to treatment with SSRIs, mood stabilizers, and opioid antagonists. These findings have supported the observation that PG is strongly associated with both mood and anxiety disorders as well as substance abuse. The aim of the study is to evaluate the comorbid psychiatric diagnoses in our sample of pathological gamblers. Methods: Thirty-six female, and forty-two male PGs were enrolled in our study. A comprehensive psychiatric diagnostic evaluation was performed on all patients, and patients were screened for symptoms of depression and anxiety using the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Yale-Brown Obsessive Compulsive Scale, and the Frost Multidimensional Perfectionism Scale. In addition, the patients completed self-report questionnaires about their demographic status and substance abuse. Results: The majority of patients were married with full or part-time employment. The study results demonstrated that PG in males is correlated with substance and alcohol abuse. Diagnoses which were prevalent among our cohort of female PGs included major depression, affective disorders, anxiety disorders, and eating disorders. Conclusion: In our sample of PGs, the men and women had different patterns of psychiatric comorbidity. The different patterns of psychiatric comorbidity seen in our male versus female PGs raises the question of whether the underlying etiopathology in PG may differ according to gender.

Cognitive Behavioral Group Therapy in Panic Disorder Patients: The Efficacy of CBGT versus Drug Treatment

The aim of our study was to evaluate the effectiveness of Cognitive Behavioral Group Therapy (CBGT) in the treatment of Panic Disorder (PD) and to compare the treatment outcome of CBGT versus Paroxetine pharmacotherapy. Fifty seven patients referred to our anxiety disorder clinic for the treatment of PD were randomly allocated to receive either CBGT or Paroxetine. Follow up was done by a masked rater after four and twelve weeks of treatment in order to compare the efficacy of CBGT versus Paroxetine. CBGT and Paroxetine were both effective in the short-term treatment of PD. Assessments at weeks four and twelve of treatment showed no statistically significant differences between the two groups in terms of treatment outcome. Treatment with CBGT alone for the acute phase of PD appears to be equally efficacious to treatment with Paroxetine alone. Our study shows that CBGT produced beneficial results, for it was associated with a reduction in the number and frequency of panic attacks and with an improved feeling of well-being.