Aduvant therapy of depression with hopantenic acid

Adequate SSRI monotherapy does not produce a sufficient clinical effect in some patients, and about 30% of patients do not respond to therapy at all. Favorable experience of combined prescription of SSRIs with various nootropic (neuroprotective) agents has been described in the literature.The aim of the study was to investigate the efficacy and tolerability of hopantenic acid as an adjuvant therapy for depression. We obtained significant data that inclusion of hopantenic acid at a dose of 2000 mg per day in a 12-week complex antidepressant therapy with paroxetine (20 mg per day) statistically significantly reduces the severity of depression symptoms. The drug's effect is achieved by improving patients' cognitive functions, reducing anxiety symptoms and side effects of SSRIs. Improved efficacy and tolerability of antidepressant therapy with hopantenic acid in the long term will allow to achieve more significant improvement in the quality of life of patients.

Serotonin Transporter Genetic Variation and Antidepressant Response and Tolerability: A Systematic Review and Meta-Analysis

Antidepressants are used to treat several psychiatric disorders; however, a large proportion of patients do not respond to their first antidepressant therapy and often experience adverse drug reactions (ADR). A common insertion–deletion polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter (SLC6A4) gene has been frequently investigated for its association with antidepressant outcomes. Here, we performed a systematic review and meta-analysis to assess 5-HTTLPR associations with antidepressants: (1) response in psychiatric disorders other than major depressive disorder (MDD) and (2) tolerability across all psychiatric disorders. Literature searches were performed up to January 2021, yielding 82 studies that met inclusion criteria, and 16 of these studies were included in the meta-analyses. Carriers of the 5-HTTLPR LL or LS genotypes were more likely to respond to antidepressant therapy, compared to the SS carriers in the total and European ancestry-only study populations. Long (L) allele carriers taking selective serotonin reuptake inhibitors (SSRIs) reported fewer ADRs relative to short/short (SS) carriers. European L carriers taking SSRIs had lower ADR rates than S carriers. These results suggest the 5-HTTLPR polymorphism may serve as a marker for antidepressant outcomes in psychiatric disorders and may be particularly relevant to SSRI treatment among individuals of European descent.

Collateral Damage: A Mixed Methods Study to Investigate the Use and Withdrawal of Antidepressants Within a Naturalistic Population

<p>The use of modern antidepressants has flourished over the past few decades with the modern attribution of affective disorders such as depression to biomedical causation. However, recent re-examination of clinical trials has raised questions regarding antidepressant drug efficacy, and issues around side effects and dependency are prevalent. In spite of this, as many as 10% of us may be taking these medications (Szabo, 2009). This study examines responses to an anonymous online survey about antidepressant use and withdrawal. Participants included 176 current users, 181 currently withdrawing, 108 ex-users, and a control group of 44 participants who had never used antidepressants. Participant groups were compared quantitatively regarding attitude towards antidepressants use and perceived value, effect on well-being and mood, symptoms and side effects, and their perceived changes in themselves on and off the drugs. Participants were also given the opportunity to include spontaneous comments at the end of the survey which were analysed thematically. Key findings include: 1) Antidepressant users have a more positive estimation of the value of the drugs than those who have discontinued the drugs or who have never used them; 2) Scores on the WHO-5 well-being survey for all three groups with antidepressant experience (users, those withdrawing, and ex-users) showed poor levels of wellbeing, suggesting that neither antidepressant therapy nor cessation of antidepressant therapy were adequate interventions to create positive well-being; 3) Multivariate analysis of participant responses revealed a significant difference between the four groups on 35 of 37 physical and emotional symptoms associated with antidepressant use or withdrawal, with the never-used group scored the lowest in all cases except one, and the withdrawing group scoring the highest for 27 of the symptoms; 4) Concern over antidepressant dependency and withdrawal was the most prevalent topic reported by all user groups in spontaneous comments; other key themes included frustration with side effects and lack of information and support from the medical profession; 5) study results suggest that antidepressant withdrawal may take longer and be more challenging than the assumed "mild", "self-limiting" and "resolving spontaneously…three weeks after onset" (Haddad & Anderson, 2007); and 6) 30% of ex-users spontaneously reported what they believed were adverse drug reactions, or withdrawal reactions, months or years after antidepressant use had ceased, a long-term iatrogenic disablement that has yet to be addressed in the literature. Overall, the study reveals that antidepressants are not an adequate intervention to create positive well-being in patients and their use comes with a substantial risk of unpleasant side effects, dependency, and the potential for residual post-drug health complications.</p>

Collateral Damage: A Mixed Methods Study to Investigate the Use and Withdrawal of Antidepressants Within a Naturalistic Population

<p>The use of modern antidepressants has flourished over the past few decades with the modern attribution of affective disorders such as depression to biomedical causation. However, recent re-examination of clinical trials has raised questions regarding antidepressant drug efficacy, and issues around side effects and dependency are prevalent. In spite of this, as many as 10% of us may be taking these medications (Szabo, 2009). This study examines responses to an anonymous online survey about antidepressant use and withdrawal. Participants included 176 current users, 181 currently withdrawing, 108 ex-users, and a control group of 44 participants who had never used antidepressants. Participant groups were compared quantitatively regarding attitude towards antidepressants use and perceived value, effect on well-being and mood, symptoms and side effects, and their perceived changes in themselves on and off the drugs. Participants were also given the opportunity to include spontaneous comments at the end of the survey which were analysed thematically. Key findings include: 1) Antidepressant users have a more positive estimation of the value of the drugs than those who have discontinued the drugs or who have never used them; 2) Scores on the WHO-5 well-being survey for all three groups with antidepressant experience (users, those withdrawing, and ex-users) showed poor levels of wellbeing, suggesting that neither antidepressant therapy nor cessation of antidepressant therapy were adequate interventions to create positive well-being; 3) Multivariate analysis of participant responses revealed a significant difference between the four groups on 35 of 37 physical and emotional symptoms associated with antidepressant use or withdrawal, with the never-used group scored the lowest in all cases except one, and the withdrawing group scoring the highest for 27 of the symptoms; 4) Concern over antidepressant dependency and withdrawal was the most prevalent topic reported by all user groups in spontaneous comments; other key themes included frustration with side effects and lack of information and support from the medical profession; 5) study results suggest that antidepressant withdrawal may take longer and be more challenging than the assumed "mild", "self-limiting" and "resolving spontaneously…three weeks after onset" (Haddad & Anderson, 2007); and 6) 30% of ex-users spontaneously reported what they believed were adverse drug reactions, or withdrawal reactions, months or years after antidepressant use had ceased, a long-term iatrogenic disablement that has yet to be addressed in the literature. Overall, the study reveals that antidepressants are not an adequate intervention to create positive well-being in patients and their use comes with a substantial risk of unpleasant side effects, dependency, and the potential for residual post-drug health complications.</p>

Multi-omics driven predictions of response to acute phase combination antidepressant therapy: a machine learning approach with cross-trial replication

Combination antidepressant pharmacotherapies are frequently used to treat major depressive disorder (MDD). However, there is no evidence that machine learning approaches combining multi-omics measures (e.g., genomics and plasma metabolomics) can achieve clinically meaningful predictions of outcomes to combination pharmacotherapy. This study examined data from 264 MDD outpatients treated with citalopram or escitalopram in the Mayo Clinic Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) and 111 MDD outpatients treated with combination pharmacotherapies in the Combined Medications to Enhance Outcomes of Antidepressant Therapy (CO-MED) study to predict response to combination antidepressant therapies. To assess whether metabolomics with functionally validated single-nucleotide polymorphisms (SNPs) improves predictability over metabolomics alone, models were trained/tested with and without SNPs. Models trained with PGRN-AMPS’ and CO-MED’s escitalopram/citalopram patients predicted response in CO-MED’s combination pharmacotherapy patients with accuracies of 76.6% (p < 0.01; AUC: 0.85) without and 77.5% (p < 0.01; AUC: 0.86) with SNPs. Then, models trained solely with PGRN-AMPS’ escitalopram/citalopram patients predicted response in CO-MED’s combination pharmacotherapy patients with accuracies of 75.3% (p < 0.05; AUC: 0.84) without and 77.5% (p < 0.01; AUC: 0.86) with SNPs, demonstrating cross-trial replication of predictions. Plasma hydroxylated sphingomyelins were prominent predictors of treatment outcomes. To explore the relationship between SNPs and hydroxylated sphingomyelins, we conducted multi-omics integration network analysis. Sphingomyelins clustered with SNPs and metabolites related to monoamine neurotransmission, suggesting a potential functional relationship. These results suggest that integrating specific metabolites and SNPs achieves accurate predictions of treatment response across classes of antidepressants. Finally, these results motivate functional investigation into how sphingomyelins might influence MDD pathophysiology, antidepressant response, or both.

Brain Metabolic Profile after Intranasal vs. Intraperitoneal Clomipramine Treatment in Rats with Ultrasound Model of Depression

Background: Molecular mechanisms of depression remain unclear. The brain metabolome after antidepressant therapy is poorly understood and had not been performed for different routes of drug administration before the present study. Rats were exposed to chronic ultrasound stress and treated with intranasal and intraperitoneal clomipramine. We then analyzed 28 metabolites in the frontal cortex and hippocampus. Methods: Rats’ behavior was identified in such tests: social interaction, sucrose preference, forced swim, and Morris water maze. Metabolic analysis was performed with liquid chromatography. Results: After ultrasound stress pronounced depressive-like behavior, clomipramine had an equally antidepressant effect after intranasal and intraperitoneal administration on behavior. Ultrasound stress contributed to changes of the metabolomic pathways associated with pathophysiology of depression. Clomipramine affected global metabolome in frontal cortex and hippocampus in a different way that depended on the route of administration. Intranasal route was associated with more significant changes of metabolites composition in the frontal cortex compared to the control and ultrasound groups while the intraperitoneal route corresponded with more profound changes in hippocampal metabolome compared to other groups. Since far metabolic processes in the brain can change in many ways depending on different routes of administration, the antidepressant therapy should also be evaluated from this point of view.

Acupuncture Treatment for Social Defeat Stress

Depression is a mood disorder characterized by disordered affect, thoughts, cognition, and behavior. Antidepressant therapy is often the primary treatment for depression. However, antidepressant therapy may cause unwanted side effects, and its effects are slow. Therefore, some patients are seeking alternative treatments for depression, such as acupuncture. However, there are many unclear points regarding the mechanism of the effect of acupuncture on depression. In recent years, we have reported that acupuncture improves the symptoms of mild depression induced by water-immersion stress in a rat model and depression induced by forced swimming in a mouse model. In this study, we examined the effect of acupuncture on the symptoms of social defeat stress (SDS)-induced depression in mice that most closely resemble human symptoms. In this study, we investigated the preventive and therapeutic effects of acupuncture as part of GV20 “Bai-Hui” and Ex-HN3 “Yintang” on model mice with depression induced by SDS. To examine the mechanism of the preventive and therapeutic effects of acupuncture on depression model mice, we examined the expression of neurotrophic factors in the brains of SDS mice. Two weeks of simultaneous acupuncture stimulation as part of GV20 and Ex-HN3 restored SDS-reduced brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-3, and NT-4/5 expression, which was not observed with antidepressants. In contrast, acupuncture stimulation suppressed nerve growth factor (NGF) expression induced by SDS. These results suggest that acupuncture treatment could be effective in correcting the imbalance in the expression of neurotrophic factors. Furthermore, the effects of acupuncture on the expression of neurotrophic factors appear earlier than those of antidepressants, suggesting that it may be a useful treatment for depression.