Decision-making deficits linked to real-life social dysfunction in crack cocaine-dependent individuals

Crack cocaine-dependent individuals (CCDI) present abnormalities in both social adjustment and decision making, but few studies have examined this association. This study investigated cognitive and social performance of 30 subjects (CCDI × controls); CCDI were abstinent for 2 weeks. We used the Social Adjustment Scale (SAS), Wisconsin Card Sorting Test (WCST), and Iowa Gambling Task (IGT). Disadvantageous choices on the IGT were associated with higher levels of social dysfunction in CCDI, suggesting the ecological validity of the IGT. Social dysfunction and decision making may be linked to the same underlying prefrontal dysfunction, but the nature of this association should be further investigated.     

Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders

BACKGROUND & AIMS: Studies of antidepressants and psychological treatments in functional bowel disorders (FBD) are methodologically limited. The aim of this study was to assess the clinical efficacy and safety of cognitive-behavioral therapy (CBT) against education (EDU) and desipramine (DES) against placebo (PLA) in female patients with moderate to severe FBD (irritable bowel syndrome, functional abdominal pain, painful constipation, and unspecified FBD). We also evaluated the amenability of clinically meaningful subgroups to these treatments. METHODS: This randomized, comparator-controlled, multicenter trial enrolled 431 adults from the University of North Carolina and the University of Toronto with moderate to severe symptoms of FBD. Participants received psychological (CBT vs. EDU) or antidepressant (DES vs. PLA) treatment for 12 weeks. Clinical, physiologic, and psychosocial assessments were performed before and at the end of treatment. RESULTS: The intention-to-treat analysis showed CBT as significantly more effective than EDU (P = 0.0001; responder rate, 70% CBT vs. 37% EDU; number needed to treat [NNT ], 3.1). DES did not show significant benefit over PLA in the intention-to-treat analysis (P = 0.16; responder rate, 60% DES vs. 47% PLA; NNT, 8.1) but did show a statistically significant benefit in the per-protocol analysis (P = 0.01; responder rate, 73% DES vs. 49% PLA; NNT, 5.2), especially when participants with nondetectable blood levels of DES were excluded (P = 0.002). Improvement was best gauged by satisfaction with treatment. Subgroup analyses showed that DES was beneficial over PLA for moderate more than severe symptoms, abuse history, no depression, and diarrhea-predominant symptoms; CBT was beneficial over EDU for all subgroups except for depression. CONCLUSIONS: For female patients with moderate to severe FBD, CBT is effective and DES may be effective when taken adequately. Certain clinical subgroups are more or less amenable to these treatments.     

Medical symptoms associated with tobacco smoking with and without marijuana abuse among crack cocaine-dependent patients

Despite the widespread use of tobacco and marijuana by cocaine abusers, it remains unclear whether combined tobacco and marijuana smoking is more harmful than tobacco smoking alone in cocaine abusers. We investigated the differences in medical symptoms reported among 34 crack cocaine abusers who did not smoke tobacco or marijuana (C), 86 crack cocaine abusers who also smoked tobacco (C + T), and 48 crack abusers who smoked both tobacco and marijuana (C + T + M). Medical symptoms were recorded using a 134-item self-report instrument (MILCOM), and drug use was assessed using the Addiction Severity Index (ASI). After controlling for clinical and demographic differences, the C + T + M group reported significantly more total symptoms on the MILCOM as well as on the respiratory, digestive, general, and nose/throat subscales than the C + T or C groups. The C + T group reported higher total and respiratory and nose/throat symptoms than the C group. HOwever, the C group had the highest number of mood symptoms among the three groups. The C + T and C + T + M groups were comparable in number of cigarettes smoked and ASI scores. Although tobacco smoking is associated with higher reports of medical problems in crack abusers, smoking both marijuana and tobacco seems to be associated with greater medical problems than smoking tobacco alone. Tobacco smoking was not related to changes in cocaine use. Also, marijuana smoking does not appear to be associated with a reduction in tobacco or cocaine use.     

Treatment of crack cocaine use with carbamazepine.

Crack is a rock crystalline alkaloid form of cocaine which can be smoked. At the University of Minnesota, we have developed an experimental pharmacologic treatment for cocaine abusers. Of 26 patients treated to date, 16 have been crack cocaine users. During the hundred days preceding treatment, the 16 crack subjects used cocaine by all routes an average of 71 days each. Improvement was based on a self-reported decrease in cocaine frequency of use. Using carbamazepine, seven highly successful and six partially successful patients reduced their use to 0.7 days and 26 days per 100 days, respectively. These results, though hopeful, must be viewed with caution and considered preliminary and tentative.     

Effects of desipramine on irritable bowel syndrome compared with atropine and placebo

Antidepressant treatment trials of irritable bowel syndrome (IBS) have suggested beneficial effects. Twenty-eight patients with the disorder (9 constipation-predominant, 19 diarrhea-predominant_ completed a double-blind crossover study using desipramine, atropine, and placebo in random sequence. A four-week observation period preceded three six-week test periods. Bowel habits, abdominal distress, and affect were reported daily and in biweekly evaluations. Psychological assessments and rectosigmoid contractile studies were done in each period. Stool frequency, diarrhea, abdominal pain, depression, and slow contractions decreased significantly more in diarrhea-predominant patients during desipramine compared with placebo and atropine treatments. Diarrheaprone patients' depression scores fell more in all periods than constipation-prone patients. Fifteen patients (13 diarrhea-predominant) improved globally during desipramine, five during placebo and six during atropine treatments. Desipramine may be helpful in treating IBS, perhaps through antidepressant and antimuscarinic effects.Supported in part by a grant from the National Institute of Mental Health (MH-34115).     

A three year follow up of patients allocated to placebo, or oral or injectable gold therapy for rheumatoid arthritis.

Ninety patients randomly allocated to receive auranofin, matching placebo, or sodium aurothiomalate have been followed up for three years. Inefficacy led to cessation of treatment in 14 patients receiving auranofin, 27 receiving placebo, and one receiving sodium aurothiomalate. Twenty seven of the patients receiving placebo were reallocated within the study and 16 continued therapy at three years. This group showed similar statistically significant improvement in clinical and laboratory parameters at one, two, and three years to those on an active drug from the outset. Patients who discontinued auranofin because of inefficacy were offered sodium aurothiomalate therapy--eight patients in this group completed three years of treatment on sodium aurothiomalate and showed significant improvement in some but not all parameters. A hand radiograph erosion score showed a deterioration in 80% of patients remaining on auranofin, 75% of those on sodium aurothiomalate, and 80% of the original placebo group who continued an active drug for three years. Although more patients discontinued auranofin over the study period because of inefficacy, no difference could be shown between the degree of improvement in the subgroup who remained on auranofin and those receiving sodium aurothiomalate. No disadvantage in outcome could be shown for patients originally assigned to placebo.     

A pilot randomized trial of adjuvant rituximab or placebo for nonsplenectomized patients with immune thrombocytopenia

The benefit of adding rituximab to standard treatment in nonsplenectomized patients with primary immune thrombocytopenia (ITP) is uncertain. We performed a pilot randomized trial to determine the feasibility of recruitment, protocol adherence, and blinding of a larger trial of rituximab versus placebo; and to evaluate the potential efficacy of adjuvant rituximab in ITP. Nonsplenectomized adults with newly diagnosed or relapsed ITP who were receiving standard ITP therapy for a platelet count below 30 × 10(9)/L were randomly allocated to receive 4 weekly infusions of 375 mg/m(2) rituximab or saline placebo. Sixty patients were recruited over 46 months, which was slower than anticipated. Protocol adherence and follow-up targets were achieved, and blinding was successful for research staff but not for patients. After 6 months, there was no difference between rituximab and placebo groups for the composite outcome of any platelet count below 50 × 10(9)/L, significant bleeding or rescue treatment once standard treatment was stopped (21/32 [65.6%] vs 21/26 [80.8%]; relative risk = 0.81, 95% confidence intervals, 0.59%-1.11%). Timely accrual poses a challenge to the conduct of a large randomized trial of rituximab for presplenectomy ITP. No difference in the frequency of the composite outcome was observed in this pilot trial (registered at www.clinicaltrials.gov NCT00372892).     

A pooled analysis of FEV1 decline in COPD patients randomized to inhaled corticosteroids or placebo

BACKGROUND: There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV(1). METHODS: The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting >/= 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV(1) decline in COPD patients, and whether this relationship is modified by gender and smoking. RESULTS: There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (+/- SE) relative increase in FEV(1) of 2.42 +/- 0.19% compared with placebo (p < 0.01), which is quantifiable in absolute terms as 42 mL in men and 29 mL in women over 6 months. From 6 to 36 months, there was no significant difference between placebo and ICS therapy in terms of FEV(1) decline (-0.01 +/- 0.09%; p = 0.86). The initial treatment effect was dependent on smoking status and gender. Smokers who continued to smoke had a smaller increase in FEV(1) during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV(1) with ICS therapy than did male ex-smokers. CONCLUSIONS: We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV(1) among those who completed these randomized clinical trials.     

Comparison of lisinopril versus placebo for congestive heart failure

A multicenter, randomized, double-blind assessment of 130 patients with congestive heart failure (New York Heart Association functional classes II to IV) was undertaken to assess the therapeutic efficacy of lisinopril, an angiotensin-converting enzyme inhibitor. All the subjects received concurrent therapy with digoxin and diuretics. Assessments performed periodically over 12 weeks revealed that the active treatment was associated with significant improvements in treadmill exercise time, cardiothoracic ratio, ejection fraction, functional status and clinical signs and symptoms of heart failure. Lisinopril exhibited a mild first-dose effect on blood pressure that was not significantly different from that observed with placebo. The incidence of adverse experiences was not markedly different in the 2 study groups, with only mild hypotension and dizziness occurring more frequently in association with the active medication.     

Comparison of 1 or 3 MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis

Ninety patients with histologically documented chronic non-A, non-B hepatitis were randomly allocated to receive SC injections of placebo or of 1 or 3 MU of recombinant interferon alfa-2b three times weekly for 24 weeks. Complete normalization of alanine aminotransferase levels occurred posttreatment in 43.3% of patients receiving 3 MU, in 20% of those receiving 1 MU, and in 6.7% of untreated patients (P less than 0.0005 vs. those treated with 3 MU). Alanine aminotransferase normalization was sustained for 6 months after therapy in 13.3% of the patients treated with 3 MU and in 3.3% of those given 1 MU or placebo. The decline of alanine aminotransferase levels following interferon therapy showed independent, positive correlations with female sex (P less than 0.03) and younger age (P less than 0.05). The Knodell's fibrosis score was strongly positively correlated with age (P less than 0.0001). It is concluded that 3 MU of interferon is a more effective dose than 1 MU for controlling disease activity in non-A, non-B chronic hepatitis patients. Women and younger and noncirrhotic patients are more likely to respond.     

Viral load response to a pneumococcal conjugate vaccine,polysaccharide vaccine or placebo among HIV-infected patients

We determined the HIV viral load in 66 adults randomly assigned to receive pneumococcal immunization with one or two doses of protein conjugate vaccine, one dose of polysaccharide vaccine, one dose of each, or placebo. Second doses were given 8 weeks after the first. Mean baseline viral load and CD4 cell count were 3.41 copies/ml (log10) and 457 cells/microl, respectively. We found no change in viral load during 24 weeks of follow-up for any vaccine or combination of vaccines or placebo.     

Using addiction severity profiles to differentiate cocaine-dependent patients with and without comorbid major depression

This study compared pretreatment addiction severity profiles of 339 abusers in three diagnostic groups: cocaine dependence only (CO), cocaine dependence with substance-induced major depression (SIMD), and cocaine dependence with independent major depression (IMD). Depressed subjects reported more severe problems than non-depressed subjects across numerous domains, regardless of diagnostic etiology. These findings support the need for specialized treatment approaches targeting depressive symptoms or life stress for cocaine-dependent patients with IMD or SIMD, though patients with IMD may require additional attention for chronic and comorbid psychiatric and medical problems.     

Risk of recurrent venous thromboembolism or bleeding in relation to thrombophilic risk factors in patients receiving ximelagatran or placebo for long-term secondary prevention of venous thromboembolism

The impact of prothrombotic abnormalities on the risk of recurrent venous thromboembolism (VTE) and bleeding in patients receiving long-term anticoagulation remains unclear. This analysis evaluated the influence of potential prothrombotic risk factors (antithrombin, protein C, protein S, factor V Leiden mutation, prothrombin gene G20210A mutation, cardiolipin antibodies, number of risk factors) on the risk of recurrent VTE or bleeding during treatment with oral ximelagatran (24 mg twice daily) or placebo for 18 months [THRombin Inhibitor in Venous thromboEmbolism (THRIVE) III trial]. Of the 1223 patients in the intention-to-treat population, prothrombotic state was analysed in 559 patients receiving ximelagatran and 540 patients receiving placebo. It is possible that patients at a high risk of recurrent VTE were poorly represented in this analysis because of selection bias. Prothrombotic risk factors were reported in 41% of patients (8% had > or = 2 factors). No significant interactions were found between ximelagatran treatment and potential prothrombotic risk factors for the risk of recurrent VTE or bleeding by Cox proportionate hazard modelling. There was no clear evidence for a higher risk of recurrent VTE or bleeding across subgroups according to the potential prothrombotic factors analysed in this study.     

Comparison of amantadine and desipramine combined with psychotherapy for treatment of cocaine dependence.

We conducted a single-blind, random assignment, placebo-controlled, 12-week comparison of desipramine hydrochloride and amantadine hydrochloride as adjunctive treatments to counseling for cocaine dependence. Subjects were 54 outpatients who met DSM III-R criteria for active cocaine dependence and who completed a minimum of 2 weeks of treatment. Subjects treated with fixed doses of 200 mg/day desipramine (N = 17), 400 mg/day amantadine-placebo (N = 16), and placebo (N = 21) did not differ for lifetime cocaine use, lifetime histories of psychopathology, admission scores on psychometric assessments, and sociodemographics. All treatment groups demonstrated dramatic and persistent decreases in cocaine use, craving for cocaine, and psychiatric symptoms consequent to treatment. Although there was a trend for more dropouts by subjects taking desipramine, there were no significant differences among treatment groups regarding retention in treatment, craving for cocaine, and decreased cocaine use confirmed by urine toxicology. There was a trend for subjects treated with desipramine to maintain longer periods of cocaine abstinence. Mean plasma concentration of desipramine in a subsample of our subjects was less than that recommended for treatment of depression, thus the dosage of desipramine may have been subtherapeutic.     

Evidence for altered desipramine disposition in methadone-maintained patients treated for cocaine abuse

Plasma concentrations of desipramine (DMI) and its 2-hydroxy metabolite (OHDMI) were compared among 72 patients being treated with desipramine for either depression (n = 39) or cocaine abuse (n = 33). Eleven cocaine abusers who were concurrently maintained on methadone had a significantly lower ratio of DMI dose to plasma concentration (0.9) than the depressives (2.2) or nonmethadone cocaine abusers (2.0). Their OHDMI/DMI ratios were significantly lower (0.19) than for either the other 22 cocaine abusers (0.39) or the depressed (0.50) patients. This difference was not due to DMI dosage. Although the underlying mechanism cannot be determined from these plasma studies, possible reduced hydroxylation of DMI in methadone patients suggests the need for DMI plasma monitoring.     

Fever after acute myocardial infarction in patients treated with intravenous timolol or placebo

Body temperature was studied in 65 patients admitted to hospital within four hours of the onset of symptoms of acute myocardial infarction. Thirty three patients had been randomly assigned to intravenous timolol treatment and 32 to placebo treatment. Infarct evolution was assessed by continuous vectorcardiography and creatine kinase release. Maximum and mean temperatures during the first eight days were significantly lower in the timolol group, who were discharged from hospital one day earlier. Eight patients in the placebo group had temperatures of greater than 39 degrees compared with one in the timolol group. Both the mean temperature and the maximum temperature correlated significantly with indices of infarct size and ischaemic area as estimated by cumulative creatine kinase release, QRS vector difference, and ST vector magnitude. The results were consistent with the view that reduction of infarct size may partly explain the reduced pyrexial response after timolol treatment. Other mechanisms are probably also involved in larger infarcts. Because high fever has detrimental haemodynamic effects in acute myocardial infarction, reduction of this response may be beneficial. The results support the early use of beta adrenoceptor blockade in acute myocardial infarction.     

QT time in patients treated with alprenolol or placebo after myocardial infarction.

Studies were made on the effects of long-term beta-blockade on the QT interval in patients discharged alive from hospital after myocardial infarction. The patients (n = 230) in this study constituted all those who participated in the alprenolol study on postmyocardial patients in G?teborg, Sweden. The study was double-blind (alprenolol 200 mg b.i.d. or placebo) and randomised. The patients were divided into 4 risk groups (1-4) with different predicted mortality. The electrocardiograms before and after 8 weeks of treatment were analysed with respect to heart rate and QT time. There was a decrease in heart rate of about 10% in the alprenolol treated patients. The QT time was not significantly influenced by alprenolol. The rate corrected QT time (QTc) decreased in the subgroup of the most severely diseased patients (subgroup 4) treated with alprenolol.     

QT time in patients treated with alprenolol or placebo after myocardial infarction.

Studies were made on the effects of long-term beta-blockade on the QT interval in patients discharged alive from hospital after myocardial infarction. The patients (n = 230) in this study constituted all those who participated in the alprenolol study on postmyocardial patients in Göteborg, Sweden. The study was double-blind (alprenolol 200 mg b.i.d. or placebo) and randomised. The patients were divided into 4 risk groups (1-4) with different predicted mortality. The electrocardiograms before and after 8 weeks of treatment were analysed with respect to heart rate and QT time. There was a decrease in heart rate of about 10% in the alprenolol treated patients. The QT time was not significantly influenced by alprenolol. The rate corrected QT time (QTc) decreased in the subgroup of the most severely diseased patients (subgroup 4) treated with alprenolol.