Evaluating the efficacy and mechanisms of a ketogenic diet as adjunctive treatment for people with treatment-resistant depression: A protocol for a randomised controlled trial.

BACKGROUND: One-third of people with depression do not respond to antidepressants, and, after two adequate courses of antidepressants, are classified as having treatment-resistant depression (TRD). Some case reports suggest that ketogenic diets (KDs) may improve some mental illnesses, and preclinical data indicate that KDs can influence brain reward signalling, anhedonia, cortisol, and gut microbiome which are associated with depression. To date, no trials have examined the clinical effect of a KD on TRD. METHODS: This is a proof-of-concept randomised controlled trial to investigate the efficacy of a six-week programme of weekly dietitian counselling plus provision of KD meals, compared with an intervention involving similar dietetic contact time and promoting a healthy diet with increased vegetable consumption and reduction in saturated fat, plus food vouchers to purchase healthier items. At 12 weeks we will assess whether participants have continued to follow the assigned diet. The primary outcome is the difference between groups in the change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to 6 weeks. PHQ-9 will be measured at weeks 2, 4, 6 and 12. The secondary outcomes are the differences between groups in the change in remission of depression, change in anxiety score, functioning ability, quality of life, cognitive performance, reward sensitivity, and anhedonia from baseline to 6 and 12 weeks. We will also assess whether changes in reward sensitivity, anhedonia, cortisol awakening response and gut microbiome may explain any changes in depression severity. DISCUSSION: This study will test whether a ketogenic diet is an effective intervention to reduce the severity of depression, anxiety and improve quality of life and functioning ability for people with treatment-resistant depression.

Effects of subcutaneous esketamine on blood pressure and heart rate in treatment-resistant depression.

INTRODUCTION AND OBJECTIVES: The impact of multiple subcutaneous (s.c.) esketamine injections on the blood pressure (BP) and heart rate (HR) of patients with unipolar and bipolar treatment-resistant depression (TRD) is poorly understood. This study aimed to assess the cardiovascular safety of multiple s.c. doses of esketamine in patients with TRD. METHODS: Seventy TRD patients received 394 weekly s.c. esketamine injections in conjunction with oral antidepressant therapy for up to six weeks. Weekly esketamine doses were 0.5, 0.75 or 1.0 mg/kg according to each patient's response to treatment. Participants were monitored before each treatment and every 15 minutes thereafter for 120 minutes. We assessed systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR measurements for the entire treatment course. RESULTS: BP increased after the first s.c. esketamine injection, reaching maximum mean SBP/DBP levels of 4.87/5.54 mmHg within 30-45 minutes. At the end of monitoring, 120 minutes post dose, vital signs returned to pretreatment levels. We did not detect significant differences in BP between doses of 0.5, 0.75, and 1 mg/kg esketamine. Mean HR did not differ significantly between doses or before and after s.c. esketamine injection. CONCLUSIONS: The BP changes observed with repeated s.c. esketamine injections were mild and well tolerated for doses up to 1 mg/kg. The s.c. route is a simple and safe method of esketamine administration, even for patients with clinical comorbidities, including obesity, hypertension, diabetes, and dyslipidemia. However, 14/70 patients experienced treatment-emergent transient hypertension (SBP >180 mmHg and/or a DBP >110 mmHg). Therefore, we strongly recommend monitoring BP for 90 minutes after esketamine dosing. Since s.c. esketamine is cheap, requires less frequent dosing (once a week), and is a simpler procedure compared to intravenous infusions, it might have an impact on public health.

Adjunctive low-dose docosahexaenoic acid (DHA) for major depression: An open-label pilot trial.

OVERVIEW: Whilst the majority of evidence supports the adjunctive use of eicosapentaenoic acid (EPA) in improving mood, to date no study exists using low-dose docosahexaenoic acid (DHA) alone as an adjunctive treatment in patients with mild to moderate major depressive disorder (MDD). METHODS: A naturalistic 8-week open-label pilot trial of low-dose DHA, (260 mg or 520 mg/day) in 28 patients with MDD who were non-responsive to medication or psychotherapy, with a Hamilton Depression Rating Scale (HAM-D) score of greater than 17, was conducted. Primary outcomes of depression, clinical severity, and daytime sleepiness were measured. RESULTS: After 8 weeks, 54% of patients had a ≥50% reduction on the HAM-D, and 45% were in remission (HAM-D ≤ 7). The eta-squared statistic (0.59) indicated a large effect size for the reduction of depression (equivalent to Cohen's d of 2.4). However confidence in this effect size is tempered due to the lack of a placebo. The mean score for the Clinical Global Impression Severity Scale was significantly improved by 1.28 points (P < 0.05). Despite a significant reduction in the HAM-D score for middle insomnia (P = 0.02), the reduction in excessive daytime somnolence on the total Epworth Sleepiness Scale (ESS) did not reach significance. No significant adverse reactions to DHA were found. CONCLUSION: Within the major limits of this open-label pilot study, the results suggest that DHA may provide additional adjunctive benefits in patients with mild- to -moderate depression.

Suplementos nutricionales en trastornos depresivos / Nutritional supplements in depressive disorders

Cada vez hay más evidencia que demuestra el papel de los nutrientes en la salud mental. Una adecuada alimentación contribuye a una mejor salud general y salud mental en particular. La depresión mayor es una enfermedad mental grave con una alta prevalencia para la que existen tratamientos eficaces pero no en todos los casos se consigue la remisión del paciente. Por ello, cada vez se apunta más hacia la optimización en la aportación de nutrientes necesarios para un adecuado funcionamiento cerebral como terapia coadyuvante al tratamiento antidepresivo. En este artículo revisamos aquellos nutrientes sobre los que se ha estudiado su implicación en dicha patología: ácidos grasos omega-3, vitaminas del grupo B, s-adenosilmetionina, triptófano, magnesio, zinc y probióticos (AU)

There is increasing evidence about the role of nutrients in mental health. An adequate intake of nutrients contributes to better overall health and mental health in particular. Major depression is a severe mental illness with a high prevalence for which effective treatments exist but not in all cases the patient’s remission is achieved. Therefore, it is increasingly aimed at optimizing the supply of nutrients necessary for adequate brain functioning as adjunctive therapy to antidepressant treatment in depressive disorders. In this article we review those nutrients that have been related to depression: Omega-3 fatty acids, B vitamins, s-adenosylmethionine, tryptophan, magnesium, zinc and probiotics (AU)

Electroconvulsivotherapy augmentation with folate in the treatment of a resistant depression.

Depression is a severe and heterogeneous disorder resulting from interacting genetic, environmental, and epigenetic factors. Nutrient deficiency resulting from bariatric bypass surgery has been involved in the pathophysiological mechanisms of depression and treatment response.We report the case of a patient who developed, after a bariatric bypass surgery, a severe depressive episode, refractory to both pharmacological treatment and electroconvulsivotherapy (ECT). Folate deficiency was evidenced. A dramatic response to ECT was observed after folate supplementation. We focused on the involvement of folate in the pathophysiological mechanisms of depression and response to both pharmacological treatment and ECT. We emphasize on the need for close monitoring of patients experiencing psychiatric disorder (in particular, depressive unipolar disorder) after bariatric surgery.