Angela Ibáñez

Efficacy of Functional Remediation in Bipolar Disorder: A Multicenter Randomized Controlled Study

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukeys post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.

A pilot placebo-controlled study of fluvoxamine for pathological gambling.

The objective of this study was to evaluate the efficacy of fluvoxamine in the treatment of pathological gambling. Thirty-two patients were treated for 6 months in a double-blind, placebo-controlled study of fluvoxamine 200 mg/day. Outcome measures included reduction in money and time spent gambling per week. Longitudinal mixed effects models and completers analyses were used for estimation and hypothesis testing. Fluvoxamine was not statistically significantly different from placebo in the overall sample. However, fluvoxamine was statistically significantly superior to placebo in males and in younger patients. The power of the study was limited by the high (59%) placebo-response rate. Fluvoxamine may be a useful treatment for certain subgroups of patients with pathological gambling. Several methodological recommendations are made for future pharmacological trials of pathological gambling.

Genetics of Pathological Gambling

Pathological gambling (PG) is an impulse control disorder and a model ‘behavioral’ addiction. Familial factors have been observed in clinical studies of pathological gamblers, and twin studies have demonstrated a genetic influence contributing to the development of PG. Serotonergic, noradrenergic, and dopaminergic dysfunction have been reported as biological factors contributing to the pathophysiology of PG. Molecular genetic techniques have been used to investigate the role of genetic factors in PG. Molecular genetic research has identified specific allele variants of candidate genes corresponding to these neurotransmitter systems to be associated with PG. Associations have been reported between pathological gamblers and allele variants of polymorphisms at dopamine receptor genes, the serotonin transporter gene, and the monoamine-oxidase A gene. Although preliminary data suggest that some of these differences are gender-specific, more research needs to be performed to substantiate gender-specific genetic contributions to the development of pathological gambling. The review of the current findings on genetics of PG suggests that liability to PG is in part mediated by genetic factors. Additional studies are needed to replicate and extend these findings, as well as to better understand the influence of specific allelic variants to differences in biological and behavioral functioning.

Paroxetine treatment of pathological gambling: a multi-centre randomized controlled trial.

&NA; Previous studies have suggested the efficacy of serotonergic agents in the treatment of pathological gambling. The aim of the present study was to determine whether treatment with paroxetine in a large sample of subjects with pathological gambling would effectively diminish the severity of gambling symptoms. A 16‐week, double‐blind, placebo‐controlled trial was conducted at five outpatient academic research centres in two countries (USA and Spain). Seventy‐six outpatients (mean age 45.4±10.6 years; 30 women, 46 men) with pathological gambling were randomized to acute treatment with paroxetine in flexible daily dosages of 10–60 mg/day (n=36) or placebo (n=40). The primary outcome measure was the Clinical Global Impressions scale. Both the paroxetine‐ and the placebo‐treated groups demonstrated comparable improvement at 16 weeks (59% response rate in the paroxetine group, 49% rate in the placebo group; chi squared=0.737; d.f.=1; P=0.390). Paroxetine consistently resulted in a greater percentage of responders at each study visit compared to placebo but failed to demonstrate statistical superiority to placebo on scores on the Clinical Global Impressions scale, the Yale–Brown Obsessive–Compulsive Scale Modified for Pathological Gambling, or the Gambling Symptom Assessment Scale. High rates of symptom improvement were observed in pathological gamblers receiving either paroxetine or placebo after 16 weeks. Paroxetine consistently demonstrated an advantage over placebo on the Clinical Global Impressions scale; however, a larger sample size may have registered significant differences.

A pilot study of impulsivity and compulsivity in pathological gambling

We examined the relationship between gambling severity, impulsivity and obsessionality/compulsivity in 38 pathological gamblers, representing the complete Minnesota sample of a randomized, placebo-controlled clinical trial of paroxetine for the treatment of pathological gambling (PG), using Pearson correlations and linear regression models at baseline and treatment endpoint. At baseline, Pathological Gambling Modification of the Yale-Brown Obsessive-Compulsive Scale (PG-YBOCS) scores correlated significantly with those of the Eysenck Impulsiveness Questionnaire (EIQ) Impulsiveness subscale and Padua Inventory (PI) factors I and IV (corresponding to impaired control over mental and motor activities, respectively). None of the associations between PI factors and the PG-YBOCS were significant after adjusting for Impulsiveness scores. There were no differences in changes in the PG-YBOCS between the paroxetine and placebo group. Changes in PG-YBOCS scores after treatment correlated with changes in Impulsiveness scores. These changes appeared independent of paroxetine treatment. The results suggest that, although PG exhibits features of both obsessionality/compulsivity and impulsivity and elements of both decrease with treatment, impulsivity predominates and changes in gambling severity are most associated with changes in impulsivity.

Pathological gambling and DNA polymorphic markers at MAO-A and MAO-B genes

This study was conducted to detect a possible association of MAOA and/or MAOB genes with pathological gambling (PG). DNA polymorphisms in MAOA and MAOB genes were screened by molecular analysis in 68 individuals (47 males and 21 females) meeting ICD-10 and DSM-IV criteria for pathological gambling and 68 healthy comparison controls matched for age and sex. There were no significant differences between pathological gamblers and healthy volunteers in overall allele distribution at the MAOA gene polymorphism. However there was a significant association between allele distribution and the subgroup of severe male gamblers (n = 31) compared to the males in the group of healthy volunteers (χ2 = 5246; df = 1; P < 0.05 [bonferroni corrected]). No association was found between the MAOB polymorphic marker and PG. Allele variants at the MAOA, but not the MAOB gene may be a genetic liability factor in PG, at least in severe male gamblers.

Epidemiology, Pathophysiology and Treatment of Pathological Gambling

Pathological gambling is a prevalent disorder that is gaining attention from patients, clinicians and policy makers. Aetiological factors that have been related to pathological gambling include: (i) abnormalities in the serotonergic, dopaminergic and noradrenergic systems; (ii) cognitive distortions; and (iii) a reinforcement of the gambling activity by either episodic gains or the excitement that accompanies gambling. Male gender, urban residence, lower income and the presence of a comorbid psychiatric disorder (particularly substance abuse) appear to constitute risk factors for the presence of the disorder.A number of treatments have been suggested as potentially effective: Gamblers Anonymous, behavioural therapy, manualised cognitive therapy and several medications. At present, only manualised cognitive therapy and the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor fluvoxamine have shown efficacy in systematic (albeit small) studies. However, much research remains to be done to better understand the psychophysiology of pathological gambling, to firmly demonstrate the efficacy of the different proposed treatment approaches, and to establish criteria for treatment selection for individual patients.

Plasma testosterone and pathological gambling

The authors studied plasma testosterone levels and psychological characteristics of male pathological gamblers. Twenty-nine male pathological gamblers and a group of healthy volunteers matched for age and gender were compared on levels of plasma testosterone and scores on the Eysenck Personality Questionnaire (EPQ) and the Psychopathic Deviance scale of the Minnesota Multiphasic Personality Inventory (MMPI). Plasma testosterone levels were similar in the pathological gambling and comparison group (476.06 ng/100 ml vs. 560.71 ng/100 ml). Patients had higher scores on the Neuroticism subscales of the EPQ (13.83 vs. 10.83) and the Psychopathic Deviance scale of the MMPI (27.03 vs. 21.03), but not on any of the other subscales of the EPQ. Testosterone levels did not correlate with the psychological ratings. Testosterone levels are probably not related to impulsivity in pathological gambling.

Functional remediation in bipolar disorder: 1-year follow-up of neurocognitive and functional outcome

BACKGROUND Few randomised clinical trials have examined the efficacy of an intervention aimed at improving psychosocial functioning in bipolar disorder. AIMS To examine changes in psychosocial functioning in a group that has been enrolled in a functional remediation programme 1 year after baseline. METHOD This was a multicentre, randomised, rater-masked clinical trial comparing three patient groups: functional remediation, psychoeducation and treatment as usual over 1-year follow-up. The primary outcome was change in psychosocial functioning measured by means of the Functioning Assessment Short Test (FAST). Group×time effects for overall psychosocial functioning were examined using repeated-measures ANOVA (trial registration NCT01370668). RESULTS There was a significant group×time interaction for overall psychosocial functioning, favouring patients in the functional remediation group (F = 3.071, d.f. = 2, P = 0.049). CONCLUSIONS Improvement in psychosocial functioning is maintained after 1-year follow-up in patients with bipolar disorder receiving functional remediation.

Functional remediation for patients with bipolar II disorder: Improvement of functioning and subsyndromal symptoms

Recently, Functional Remediation (FR) has proven to be effective in improving the functional outcome of euthymic bipolar patients. The aim of this study was to test the efficacy of the FR program in a subsample of euthymic bipolar II patients (BPII). A post-hoc analyses were undertaken using data of 53 BPII outpatients who had participated in a multicenter, rater-blind, randomized, controlled trial exploring the efficacy of FR (n=17) as compared with a Psychoeducation group (PSY) (n=19) and a treatment as usual control group (TAU n=17). The primary outcome variable was the functional improvement defined as the mean change in the Functioning Assessment Short Test (FAST) from baseline to endpoint after the intervention. Regarding the treatment effect, data reveal a significant functional improvement from baseline to endpoint, suggestive for an interaction between program pertinence and time (pre-post). Nevertheless, Tukey׳s post-hoc test only revealed a trend in favor of a better outcome for FR when compared to the other two groups. We also found an interaction between program pertinence and time when analysing the subdepressive symptoms, with BPII patients in FR showing a significant reduction when compared to the PSY group. Our results suggest that the FR appears to be effective in improving the overall functional outcome in BPII, as well as in reducing subdepressive symptoms.