The efficacy of adjunctive N-acetylcysteine in acute bipolar depression: A randomized placebo-controlled study.

OBJECTIVE: To investigate the efficacy of adjunctive N-acetylcysteine (NAC) for the treatment of acute bipolar depression. METHOD: A randomized, double-blind, multicentre, placebo-controlled trial including adult subjects diagnosed with bipolar disorder, currently experiencing a depressive episode. Participants were treated with 3 g/day NAC or placebo as an adjunctive to standard treatment for 20 weeks, followed by a 4-week washout where the blinding was maintained. The primary outcome was the mean change in the Montgomery Asberg Depression Rating Scale (MADRS) score over the 20-week treatment phase. Linear Mixed Effects Repeated Measures (LMERM) was used for analysing the primary outcome. RESULTS: A total of 80 subjects were included. The mean MADRS score at baseline was 30.1 and 28.8 in participants randomized to NAC and placebo, respectively. Regarding the primary outcome measure, the between-group difference (NAC vs. placebo) was 0.5, which was statistically non-significant (95% CI: -7.0-5.9;p = 0.88). All findings regarding secondary outcomes were statistically or clinically insignificant. LIMITATIONS: The study had a placebo response rate of 55.6% - high placebo response rates are associated with failure to separate from placebo. CONCLUSIONS: Based on our primary outcome measure, we could not confirm previous studies showing a therapeutic effect of adjunctive NAC treatment on acute bipolar depression. Further studies with larger samples are needed to elucidate if specific subgroups could benefit from adjunctive NAC treatment.

Add-on treatment with N-acetylcysteine for bipolar depression: a 24-week randomized double-blind parallel group placebo-controlled multicentre trial (NACOS-study protocol).

BACKGROUND: Oxidative stress and inflammation may be involved in the development and progression of mood disorders, including bipolar disorder. Currently, there is a scarcity of useful treatment options for bipolar depressive episodes, especially compared with the efficacy of treatment for acute mania. N-Acetylcysteine (NAC) has been explored for psychiatric disorders for some time given its antioxidant and anti-inflammatory properties. The current trial aims at testing the clinical effects of adjunctive NAC treatment (compared to placebo) for bipolar depression. We will also explore the biological effects of NAC in this context. We hypothesize that adjunctive NAC treatment will reduce symptoms of depression, which will be reflected by changes in selected markers of oxidative stress. METHODS AND ANALYSIS: In the study, we will include adults diagnosed with bipolar disorder, in a currently depressive episode. Participants will undertake a 20-week, adjunctive, randomized, double-blinded, parallel group placebo-controlled trial comparing 3 grams of adjunctive NAC daily with placebo. The primary outcome is the mean change over time from baseline to end of study on the Montgomery-Asberg Depression Rating Scale (MADRS). Among the secondary outcomes are mean changes from baseline to end of study on the Bech-Rafaelsen Melancholia Scale (MES), the Young Mania Rating Scale (YMRS), the WHO-Five Well-being Index (WHO-5), the Global Assessment of Functioning scale (GAF-F), the Global Assessment of Symptoms scale (GAF-S) and the Clinical Global Impression-Severity scale (CGI-S). The potential effects on oxidative stress by NAC treatment will be measured through urine and blood samples. DNA will be examined for potential polymorphisms related to oxidative defences. TRIAL REGISTRATION: Registered at The European Clinical Trials Database, ClinicalTrials.gov: NCT02294591 and The Danish Data Protection Agency: 2008-58-0035.

Vitamin D supplementation for treatment of seasonal affective symptoms in healthcare professionals: a double-blind randomised placebo-controlled trial.

BACKGROUND: Low serum 25-hydroxyvitamin D levels (25(OH)D) have been associated with a higher likelihood of seasonal affective disorder (SAD) and poor mental well-being, yet firm evidence for either remains lacking. Thus, vitamin D supplementation may alleviate symptoms associated with SAD. METHODS: This study was a randomized, single-centre, double-blind, placebo-controlled trial including healthcare professionals employed in psychiatric and somatic hospitals. 3345 healthcare professionals were invited to participate, 50 participants were screened, and 34 were able to complete the study. The main inclusion criterion was 8 points or more on question no. 2 of the Seasonal Pattern Assessment Questionnaire (SPAQ-SAD). During a 3-month period, the participants received a daily dose of 70 µg vitamin D or placebo. The primary outcome was the sum of the self-reported questionnaire Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders (SIGH-SAD). The secondary outcome was World Health Organization-Five Well-Being Index (WHO-5) of the healthcare professionals during the winter period and the exploratory outcome measures were weight, waist circumference, blood pressure, absenteeism from work and 25(OH)D. RESULTS: There were no significant between-group differences in SIGH-SAD sums at 12 weeks (p = 0.7 (CI: - 3.27 to 4.81)). However, there was a significant improvement of primary SIGH-SAD over time from inclusion (autumn-winter) to the completion of the study (winter-spring) for all participants. The secondary and exploratory outcome measures were all insignificant between groups.The sums of the SIGH-SAD at 12 weeks were not significantly different [p = 0.701 (CI: 4.81-3.27)] between the groups. There was, however, a significant improvement in primary SIGH-SAD sums over time from inclusion (autumn-winter) to the completion of the study (winter-spring) in both groups. The secondary and explorative outcome measures were not significantly different between groups. CONCLUSIONS: There were no significant between-group differences in the primary (SIGH-SAD) and secondary (WH0-5) as well as the exploratory outcome measures (weight, waist circumference, blood pressure, absenteeism from work and 25(OH)D. Thus, the study failed to demonstrate an effect of vitamin D on SAD symptoms, but our findings may be limited by confounders. Furthermore, the study was underpowered and did not allow us to assess the ability of vitamin D to improve mood in those with low 25(OH)D. TRIAL REGISTRATION: ( http://www.clinicaltrials.gov registration number: NCT01462058).

A case of cola dependency in a woman with recurrent depression.

BACKGROUND: Cola is an extremely popular caffeinated soft drink. The media have recently cited a poll in which 16% of the respondents considered themselves to be addicted to cola soft drinks. We find the contrast between the apparent prevalence of cola addiction and the lack of scientific literature on the subject remarkable. To our knowledge, this is the first case of cola dependency described in the scientific literature. CASE PRESENTATION: The patient is a 40-year-old woman, who when feeling down used cola to give her an energy boost and feel better about herself. During the past seven years her symptoms increased, and she was prescribed antidepressant medication by her family doctor. Due to worsening of symptoms she was hospitalised and later referred to a specialised outpatient clinic for affective disorders. At entry to the clinic she suffered from constant tiredness, lack of energy, failing concentration, problems falling asleep as well as interrupted sleep. She drank about three litres of cola daily, and she had developed a metabolic syndrome.The patient fulfilled the ICD-10 criteria for dependency, and on the Yale Food Addiction Scale (YFAS) she scored 40 points. Her clinical mental status was at baseline assessed by the Major Depression Inventory (MDI) = 41, Hamilton Depression - 17 item Scale (HAMD-17) = 14, Young Mania Rating Scale (YMRS) = 2 and the Global Assessment of Functioning (GAF) Scale = 45.During cognitive therapy sessions she was guided to stop drinking cola and was able to moderate her use to an average daily consumption of 200 ml of cola. Her concentration improved and she felt mentally and physically better. At discharge one year after entry her YFAS was zero. She was mentally stable (MDI =1, HAMD-17 = 0, YMRS = 0 and GAF = 85) and without antidepressant medication. She had lost 7.2 kg, her waistline was reduced by 13 cm and the metabolic syndrome disappeared. CONCLUSION: This case serves as an example of how the overconsumption of a caffeinated soft drink likely was causing or accentuating the patient's symptoms of mental disorder. When diagnosing and treating depression, health professionals should pay attention to potential overuse of cola or other caffeinated beverages.