-
1.
International Society for Nutritional Psychiatry Research Practice Guidelines for Omega-3 Fatty Acids in the Treatment of Major Depressive Disorder.
Guu, TW, Mischoulon, D, Sarris, J, Hibbeln, J, McNamara, RK, Hamazaki, K, Freeman, MP, Maes, M, Matsuoka, YJ, Belmaker, RH, et al
Psychotherapy and psychosomatics. 2019;(5):263-273
-
-
Free full text
-
Abstract
Major depressive disorder (MDD) is a complex mental illness with unmet therapeutic needs. The antidepressant effects of ω-3 polyunsaturated fatty acids (n-3 PUFAs) have been widely reported. The subcommittee of the International Society for Nutritional Psychiatry Research organized an expert panel and conducted a literature review and a Delphi process to develop a consensus-based practice guideline for clinical use of n-3 PUFAs in MDD. The guideline focuses on 5 thematic areas: general concepts, acute treatment strategy, depression recurrence monitoring and prevention, use in special populations, and potential safety issues. The key practice guidelines contend that: (1) clinicians and other practitioners are advised to conduct a clinical interview to validate clinical diagnoses, physical conditions, and measurement-based psychopathological assessments in the therapeutic settings when recommending n-3 PUFAs in depression treatment; (2) with respect to formulation and dosage, both pure eicosapentaenoic acid (EPA) or an EPA/docosahexaenoic acid (DHA) combination of a ratio higher than 2 (EPA/DHA >2) are considered effective, and the recommended dosages should be 1-2 g of net EPA daily, from either pure EPA or an EPA/DHA (>2:1) formula; (3) the quality of n-3 PUFAs may affect therapeutic activity; and (4) potential adverse effects, such as gastrointestinal and dermatological conditions, should be monitored, as well as obtaining comprehensive metabolic panels. The expert consensus panel has agreed on using n-3 PUFAs in MDD treatment for pregnant women, children, and the elderly, and prevention in high-risk populations. Personalizing the clinical application of n-3 PUFAs in subgroups of MDD with a low Omega-3 Index or high levels of inflammatory markers might be regarded as areas that deserve future research.
-
2.
L-theanine in the adjunctive treatment of generalized anxiety disorder: A double-blind, randomised, placebo-controlled trial.
Sarris, J, Byrne, GJ, Cribb, L, Oliver, G, Murphy, J, Macdonald, P, Nazareth, S, Karamacoska, D, Galea, S, Short, A, et al
Journal of psychiatric research. 2019;:31-37
Abstract
Partial or non-response to antidepressants in Generalized Anxiety Disorder (GAD) is common in clinical settings, and adjunctive biological interventions may be required. Adjunctive herbal and nutraceutical treatments are a novel and promising treatment option. L-theanine is a non-protein amino acid derived most-commonly from tea (Camellia sinensis) leaves, which may be beneficial in the treatment of anxiety and sleep disturbance as suggested by preliminary evidence. We conducted a 10-week study (consisting of an 8-week double-blind placebo-controlled period, and 1-week pre-study and 2-week post-study single-blinded observational periods) involving 46 participants with a DSM-5 diagnosis of GAD. Participants received adjunctive L-theanine (450-900 mg) or matching placebo with their current stable antidepressant treatment, and were assessed on anxiety, sleep quality, and cognition outcomes. Results revealed that adjunctive L-theanine did not outperform placebo for anxiety reduction on the HAMA (p = 0.73) nor insomnia severity on the Insomnia Severity Index (ISI; p = 0.35). However, LT treated participants reported greater self-reported sleep satisfaction than placebo (ISI item 4; p = 0.015). Further, a separation in favour of L-theanine was noted on the ISI in those with non-clinical levels of insomnia symptoms (ISI ≤ 14; p = 0.007). No significant cognitive effects (trail making time and the modified emotional Stroop) were revealed. While this preliminary study did not support the efficacy of L-theanine in the treatment of anxiety symptoms in GAD, further studies to explore the application of L-theanine in sleep disturbance are warranted.
-
3.
Effects of antidepressant and antipsychotic use on weight gain: A systematic review.
Alonso-Pedrero, L, Bes-Rastrollo, M, Marti, A
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2019;(12):1680-1690
Abstract
Weight gain is an adverse effect of antidepressants and antipsychotics. This side effect can lead to numerous comorbidities and reduces life expectancy. The use of these drugs is increasing worldwide, and the weight gain produced by them represents a common clinical challenge. The goal of this systematic review was to evaluate the potential association of antidepressant and antipsychotic therapy with body weight gain in cohort studies. A search of cohort studies investigating the association between weight gain and the use of antidepressants and antipsychotics in individuals was conducted through the PubMed database from 1 January 2008 to 31 January 2019 following the PRISMA statement. We found 27 independent eligible cohort studies that included children (2-18 years old) and adult (18-103 years old) subjects. Most of the included studies showed a 5% weight gain in individuals using antidepressant therapy. However, Quetiapine, Haloperidol, Trifluoperazine, Risperidone, Aripiprazole, Olanzapine, and Clozapine increased body weight ≥7% from baseline, which is considered a clinically significant result. Weight loss was found in individuals treated with Bupropion. Further cohort studies with higher sample sizes and longer durations of treatment are needed to confirm our observations.
-
4.
Longer-term open-label study of adjunctive riluzole in treatment-resistant depression.
Sakurai, H, Dording, C, Yeung, A, Foster, S, Jain, F, Chang, T, Trinh, NH, Bernard, R, Boyden, S, Iqbal, SZ, et al
Journal of affective disorders. 2019;:102-108
-
-
Free full text
-
Abstract
BACKGROUND While riluzole has been investigated for the treatment of depression, little is known about its longer-term efficacy and optimal treatment duration in treatment-resistant depression (TRD). The objective of this study is to characterize the longer-term outcome of adjunctive riluzole therapy for TRD in an open-label extension of an 8-week acute treatment trial. METHODS The data from 66 patients with TRD who received adjunctive riluzole in a 12-week open-label extension phase were analyzed. Response rates (⩾50% reduction in the Mongomery-Asberg Depression Rating Scale [MADRS] score), relapse rates (a MADRS score of ⩾22 in patients who had previously achieved response), and adverse events were examined in patients who had achieved response at the end of the acute phase and those who had not. RESULTS Among acute phase responders, the maintained response rate was 66.7% (8/12) and the relapse rate was 8.3% (1/12). In acute phase non-responders, the response rate was 24.1% (13/54). The most commonly reported adverse event was fatigue (9.1%). Three cases were considered serious adverse events; vomiting (n = 1), shortness of breath (n = 1), and aborted suicide attempt (n = 1). LIMITATIONS This longer-term study was open-label and uncontrolled. The sample size was relatively small. CONCLUSIONS Longer-term adjunctive riluzole appears relatively well tolerated and beneficial for maintaining previous response. Additionally, approximately one fourth of patients who did not respond to 8-week antidepressant treatment might respond if treated with riluzole for 12 weeks. Those findings warrant further investigation because adjunctive riluzole could represent an option for treatment of depression when standard antidepressants have failed.
-
5.
Nutraceuticals for major depressive disorder- more is not merrier: An 8-week double-blind, randomised, controlled trial.
Sarris, J, Byrne, GJ, Stough, C, Bousman, C, Mischoulon, D, Murphy, J, Macdonald, P, Adams, L, Nazareth, S, Oliver, G, et al
Journal of affective disorders. 2019;:1007-1015
Abstract
BACKGROUND One of the most pressing questions in "Nutritional Psychiatry" is whether using combinations of different nutraceuticals with putative antidepressant activity may provide an enhanced synergistic antidepressant effect. METHODS A phase II/III, Australian multi-site, 8-week, double-blind, RCT involving 158 outpatients with a DSM-5 diagnosis of MDD. The intervention consisted of a nutraceutical combination: S-adenosyl methionine; Folinic acid; Omega-3 fatty acids; 5-HTP, Zinc picolinate, and relevant co-factors versus placebo. The primary outcome was change in MADRS score. Hypothesis-driven analyses of potential moderators of response involving key SNPs, and BDNF were also conducted. RESULTS Placebo was superior to the nutraceutical combination in reducing MADRS score (differential reduction -1.75 points), however a mixed linear model revealed a non-significant Group X Time interaction (p = 0.33). Response rates were 40% for the active intervention and 51% for the placebo; remission rates were 34% and 43% for active and placebo groups, respectively. No significant differences were found between groups on any other secondary depression, anxiety, psychosocial, or sleep outcome measures. Key SNPs and BDNF did not significantly moderate response. No significant differences occurred between groups for total adverse effects, aside from more nausea in the active group. LIMITATIONS Very high placebo response rates suggest a placebo run-in design may have been valuable. INTERPRETATION The adoption of a nutraceutical 'shotgun' approach to treating MDD was not supported, and appeared to be less effective than adding placebo to treatment as usual.
-
6.
The efficacy of adjunctive N-acetylcysteine in acute bipolar depression: A randomized placebo-controlled study.
Ellegaard, PK, Licht, RW, Nielsen, RE, Dean, OM, Berk, M, Poulsen, HE, Mohebbi, M, Nielsen, CT
Journal of affective disorders. 2019;:1043-1051
Abstract
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.
-
7.
New Drug Discovery from Medicinal Plants and Phytoconstituents for Depressive Disorders.
Dereli, FTG, Ilhan, M, Akkol, EK
CNS & neurological disorders drug targets. 2019;(2):92-102
Abstract
BACKGROUND & OBJECTIVE Depression, a risk factor for several serious diseases, is a highly prevalent and life-threatening psychiatric disorder. It can affect the individual's position in life and reduce the living standards. The research on the use of medicinal plants in treating this disease has increased enormously because of the possible low rehabilitation rate and side effects of available synthetic drugs, such as sexual dysfunction, nausea, fatigue, insomnia, hypersomnia, and weight gain. CONCLUSION Therefore, this review aimed to draw attention to the antidepressant effects of culinary herbs and traditional medicinal plants and their active components, thereby promoting their use in the development of more potent antidepressants with improved side effect profile.
-
8.
Novel targets for parkinsonism-depression comorbidity.
Tizabi, Y, Getachew, B, Csoka, AB, Manaye, KF, Copeland, RL
Progress in molecular biology and translational science. 2019;:1-24
Abstract
With the aging population growing and the incidence of neurodegenerative diseases on the rise, the researchers in the field are yet more urgently challenged to slow and/or reverse the devastating consequences of such progression. The challenge is further enforced by psychiatric co-morbid conditions, particularly the feeling of despair in these population. Fortunately, as our understanding of the neurobiological substrates of maladies affecting the central nervous system increases, more therapeutic options are also presented. In this short review while providing evidence of shared biological substrates between Parkinson's disease and depression, novel therapeutic targets and drugs are suggested. The emphasis will be on neuroplasticity underscored by roles of neurotrophic and inflammatory factors. Examples of few therapeutic drugs as well as future directions are also touched upon.
-
9.
Drug treatment strategies for depression in Parkinson disease.
Ryan, M, Eatmon, CV, Slevin, JT
Expert opinion on pharmacotherapy. 2019;(11):1351-1363
Abstract
INTRODUCTION Depression is a common non-motor symptom in Parkinson disease (PD), occurring in approximately 20% of patients with PD. While depression can occur anytime in the disease process, it predates PD diagnosis in about 30% of patients. Between 20% and 60% of depressed patients with PD are either without recognition or treatment of their depression. AREAS COVERED The pathophysiology of depression in PD is unclear. There are several structural changes seen in depressed patients with PD that are also seen in patients with depression. In addition, the neurotransmitters dopamine, serotonin, and norepinephrine are all depleted in PD. This article covers the pharmacological treatment of depression in PD; this involves standard antidepressant treatment such as selective serotonin reuptake inhibitors, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, and monoamine oxidase inhibitors. As with depression not associated with PD, most treatment is partially successful. Non-pharmacological approaches are also touched upon. EXPERT OPINION Most antidepressant therapy shows partial efficacy in patients with PD. However, there is a need for better study design as well as more comparative studies for the treatment of depression in PD. Biomarkers will help identify patients with PD and depression earlier in the future.
-
10.
Monoaminergic system and depression.
Perez-Caballero, L, Torres-Sanchez, S, Romero-López-Alberca, C, González-Saiz, F, Mico, JA, Berrocoso, E
Cell and tissue research. 2019;(1):107-113
Abstract
Major depressive disorder is a severe, disabling disorder that affects around 4.7% of the population worldwide. Based on the monoaminergic hypothesis of depression, monoamine reuptake inhibitors have been developed as antidepressants and nowadays, they are used widely in clinical practice. However, these drugs have a limited efficacy and a slow onset of therapeutic action. Several strategies have been implemented to overcome these limitations, including switching to other drugs or introducing combined or augmentation therapies. In clinical practice, the most often used augmenting drugs are lithium, triiodothyronine, atypical antipsychotics, buspirone, and pindolol, although some others are in the pipeline. Moreover, multitarget antidepressants have been developed to improve efficacy. Despite the enormous effort exerted to improve these monoaminergic drugs, they still fail to produce a rapid and sustained antidepressant response in a substantial proportion of depressed patients. Recently, new compounds that target other neurotransmission system, such as the glutamatergic system, have become the focus of research into fast-acting antidepressant agents. These promising alternatives could represent a new pharmacological trend in the management of depression.