N-acetyl cysteine for depressive symptoms in bipolar disorder - a double blind, randomized, placebo-controlled trial

Background: Treatment-resistant subthreshold depression is a major problem in bipolar disorder. Both depression and bipolar disorderare complicated by glutathione depletion. We hypothesized that treatment with N-acetyl cysteine (NAC), a safe, orally bioavailable precursor of glutathione, may improve the depressive component of bipolar disorder.

Methods: A randomized, double-blind, multicenter, placebo-controlled study of individuals (n 75) with bipolar disorder in the maintenance phase treated with NAC (1 g twice daily) adjunctive to usual medication over 24 weeks, with a 4-week washout. The two primary outcomes were the Montgomery Asberg Depression Rating Scale (MADRS) and time to a mood episode. Secondary outcomes included the Bipolar Depression Rating Scale and 11 other ratings of clinical status, quality of life, and functioning.

Results: NAC treatment caused a significant improvement on the MADRS (least squares mean difference [95% confidence interval]: 8.05 [13.16, 2.95], p .002) a n d most secondary scales at end point. Benefit was evident by 8 weeks on the Global Assessment of Functioning Scale and Social and Occupational Functioning Assessment Scale and at 20 weeks on the MADRS. Improvements were lost after washout. There was no effect of NAC on time to a mood episode (log-rank test: p .968) and no significant between-group differences inadverse events. Effect sizes at end point were medium to high for improvements in MADRS and 9 of the 12 secondary readouts.

Conclusions: NAC appears a safe and effective augmentation strategy for depressive symptoms in bipolar  disorder.

N-Acetyl cysteine as a glutathione precursor for schizophrenia : a double blind, randomized, placebo-controlled trial

Background: Brain glutathione levels are decreased in schizophrenia, a disorder that often is chronic and refractory to treatment. N-acetyl cysteine (NAC) increases brain glutathione in rodents. This study was conducted to evaluate the safety and effectiveness of oral NAC (1 g orally twice daily [b.i.d.]) as an add-on to maintenance medication for the treatment of chronic schizophrenia over a 24-week period.

Methods: A randomized, multicenter, double-blind, placebo-controlled study. The primary readout was change from baseline on the Positive and Negative Symptoms Scale (PANSS) and its components. Secondary readouts included the Clinical Global Impression (CGI) Severity and Improvement scales, as well as general functioning and extrapyramidal rating scales. Changes following a 4-week treatment discontinuation were evaluated. One hundred forty people with chronic schizophrenia on maintenance antipsychotic medication were randomized; 84 completed treatment.

Results: Intent-to-treat analysis revealed that subjects treated with NAC improved more than placebo-treated subjects over the study period in PANSS total [5.97 (10.44, 1.51), p .009], PANSS negative [mean difference 1.83 (95% confidence interval: 3.33, .32), p .018], and PANSS general [2.79 (5.38, .20), p .035], CGI-Severity (CGI-S) [.26 (.44,.08), p .004], and CGI-Improvement (CGI-I) [.22 (.41, .03), p .025] scores. No significant change on the PANSS positive subscale was seen. N-acetyl cysteine treatment also was associated with an improvement in akathisia (p .022). Effect sizes at end point were consistent with moderate benefits.

Conclusions: These data suggest that adjunctive NAC has potential as a safe and moderately effective augmentation strategy for chronic schizophrenia.

A pilot randomized, double-blind, placebo-controlled study of granisetron in the treatment of sexual dysfunction in women associated with antidepressant use

A pilot study was conducted to evaluate the usefulness of granisetron for the treatment of antidepressant induced sexual dysfunction in women. Twelve women with antidepressant induced sexual dysfunction (AISD) were assigned granisetron (n=5) or placebo (n=7) in a 14-day randomized, double-blind, placebo-controlled study. One participant in the granisetron group did not complete the study. Participants were assessed at baseline, day 7 and day 14 using the Feiger Sexual Function and Satisfaction Questionnaire and the Arizona Sexual Experience Scale. No statistical differences were measured at baseline or at endpoint between the granisetron or placebo group. This study did not produce evidence supporting the usefulness of granisetron in AISD.

Oral baclofen in children with cerebral palsy : a double-blind cross-over pilot study

Aim: To assess the effectiveness of oral baclofen in reducing spasticity and improving function in children with cerebral palsy. Methods: A double-blind, randomised cross-over pilot study of oral baclofen versus placebo. Assessment tools included the Goal Attainment Scale, Pediatric Evaluation of Disability Inventory, Modified Tardieu Scale and parent questionnaire. Results: Fifteen children with mean age 7.4 years (SD = 2.7 years) and spastic or spastic/dystonic quadriplegia (Gross Motor Function Classification System Level IV or V) were enrolled. Children scored significantly better on the Goal Attainment Scale with baclofen compared with placebo (F(1,13) = 4.5, P = 0.05). There was no significant difference between baclofen and placebo for the Pediatric Evaluation of Disability Inventory or Modified Tardieu Scale. Parent questionnaire results are described. Conclusion: This pilot study demonstrates that oral baclofen has an effect beyond placebo in improving goal-oriented tasks, such as transfers, in children with spastic quadriplegic cerebral palsy.

N-acetylcysteine versus placebo for treating nail biting, a double blind randomized placebo controlled clinical trial

Nail biting is a common behavioral problem. While there are established behavioral interventions for management, they are of modest efficacy, and there is minimal evidence for effective pharmacotherapy. This study investigated the role of N-acetylcysteine (NAC) a potent glutathione and glutamate modulator for the treatment of pathological nail biting in children and adolescents. This pilot randomized, double-blind, placebo-controlled clinical trial of NAC (800mg/day) or placebo enrolled 42 children and adolescents with chronic nail biting. Nail length was the objective outcome. Evaluations were carried out three times; before treatment, one month after enrollment in the study, and two months after enrollment. The duration (chronicity) of nail biting in the NAC and placebo groups was 3.63(2.45) and 5.09(3.74) years (P=0.14). The mean nail length gradually increased in both the NAC and placebo groups during this trial. There was a statistically significant difference between the two groups regarding increased nail length after the first month of trial [(5.21(5.75) and 1.18(3.02) millimeters], however no difference after two months was observed. Two patients in the NAC group discontinued medication due to adverse events. One patient experienced headache, agitation, and social withdrawal, and another patient expressed severe aggression after taking medication and was withdrawn from the study. This study supports the hypothesis that NAC decreases nail biting behavior in children and adolescents over the short term. NAC is relatively well tolerated and severe adverse effects are rare. However, there was a high rate of dropout. Further studies with longer durations that build on these preliminary data are recommended.

Lovastatin for the adjunctive treatment of schizophrenia: a preliminary randomized double-blind placebo-controlled trial.

While statins target many of the pathways to neuroprogression in schizophrenia, the safety and efficacy of statins for treating schizophrenia has never been examined. This is an 8-week randomized double blind controlled clinical trial examining the efficacy and safety of adjunctive lovastatin (20 mg/day) treatment or placebo for people with schizophrenia. The baseline characteristics of the two groups were not different. Endpoint changes in Positive and Negative Syndrome Scale (PANSS) total and subscale scores did not differ between the two groups. However there was a significant difference between the doses of risperidone used in the two groups. The mean dose in the lovastatin and placebo groups were 4.8(1.8) and 3.4(1.4) mg/day, respectively (P<.03). No serious adverse events were reported. Slowness of movements, muscle rigidity, increased appetite, and decreased energy were the most common adverse effects, and these rates did not differ between the two groups. This study failed to demonstrate a benefit of lovastatin on symptoms of schizophrenia. This combination was well tolerated. However, a higher dosage of risperidone was used for treating the disorder in those taking concomitant lovastatin compared to placebo.