Content uploaded by Robert H Belmaker
Author content
All content in this area was uploaded by Robert H Belmaker on Dec 16, 2015
Content may be subject to copyright.
Abstract
Earlier studies reported that inositol, a simple polyol second messenger precursor, was effective in controlled trials for patients with depression and panic. In this study its effectiveness in obsessive-compulsive disorder was investigated.
Thirteen patients with obsessive-compulsive disorder completed a double-blind, controlled crossover trial of 18 g/day of inositol or placebo for 6 weeks each.
The subjects had significantly lower scores on the Yale-Brown Obsessive Compulsive Scale when taking inositol than when taking placebo.
The authors conclude that inositol is effective in depression, panic, and obsessive-compulsive disorder, a spectrum of disorders responsive to selective serotonin reuptake inhibitors.
... Its novel mechanism of action-targeting intracellular signaling pathways-offers a new angle on serotonin-related psychiatric disorders (Concerto et al., 2023;Fux et al., 1996). In summary, inositol has significant potential to improve the functioning of the nervous system, particularly in serotonin-related disorders. ...
... Large dosages of inositol has been investigated as a potential therapy for depression; however, further research is required to confirm its therapeutic efficacy (Taylor et al. 2004). Research has suggested that inositol may assist in lowering the occurrence and intensity of panic episodes in those suffering from panic disorder through influencing the neurotransmission and serotonin receptors (Fux et al. 1996). ...
Inositols, regarded as a sugar-alcohol isomeric group, is a class of polyol compounds with six-carbon ring structure and each carbon being hydroxylated. Among different biologically active isomers of the group, myo-inositol (MI), is regarded one of the most widespread and versatile metabolite with occurrence in plants, animals, yeasts, and microorganisms. With respect to mammals, MI is particularly abundant in the brain and other organs such as kidneys, ovaries, heart, liver, and muscle tissues. Additionally, MI represents an important constituent of membrane phospholipids and mediating osmoregulation with its phosphorylated derivatives participating in several intracellular signalling pathways and other physiological processes. Of late, significance of MI has been also observed in medical research wherein altered levels of MI in the brains are associated with Alzheimer’s disease (AD), epilepsy, and psychiatric disorders. Moreover, MI supplements do help in preventing insulin resistance, decreasing hyperandrogenism, preventing polycystic ovarian syndrome, etc. Keeping in view the diverse roles of MI, the present chapter summarizes the current understanding on the role of MI as an osmolyte in response to hyperosmolarity, a cellular metabolite in the human brain and a biomarker for both healthy and disease conditions and an effective supplementation for treatment of wide variety of diseases such as polycystic ovary syndrome, cardiovascular diseases, respiratory distress syndrome, and neurological disorders. Future insights in this direction are also highlighted at the end of the chapter.
... A study by Jiang et al. [26] highlighted the efficacy of NAC in reducing OCD symptoms, particularly when used alongside conventional treatments. Other supplements, such as inositol, which influences serotonin pathways, have also been researched, with mixed results but promising potential for specific patient populations [27]. ...
Obsessive-Compulsive Disorder (OCD) is a chronic and debilitating mental health condition characterized by persistent, intrusive thoughts and repetitive behaviors. Traditional treatments, including cognitive-behavioral therapy (CBT) and pharmacotherapy, have shown efficacy but are often limited by partial response and high relapse rates. This literature review examines the emerging trends in the treatment of OCD, highlighting advancements in psychotherapy, novel pharmacological agents, neuromodulation techniques, digital interventions, genetic and biomarker research, and integrative therapies. Additionally, it explores tailored approaches for pediatric populations and discusses the future directions and challenges in the field. The review underscores the potential of these innovative treatments to enhance therapeutic outcomes and improve the quality of life for individuals with OCD.
This book is a detailed, evidence-based reference on the field of integrative geriatric medicine. It is intended for all healthcare providers and advocates who work with the geriatric population—in outpatient settings and nursing homes, assisted and independent living facilities, and senior community centers. In addition, it will provide valuable information for leaders and politicians who are involved with implementing policies and procedures for the care of elderly patients and who are looking for safer, less costly, and more patient-centered approaches. Integrative geriatrics is a new field of medicine that advocates for a whole-person, patient-centered, primarily non-pharmacological approach to medical care of the elderly. Most current geriatric practices overprescribe medications and procedures and underutilize non-pharmacological, low-cost, high-touch methods. Patients, however, often show reluctance toward these standard practices because they often involve invasive interventions. The practice of integrative geriatrics is rooted in lifestyle interventions, such as nutrition, movement therapies, and mind-body and spirituality approaches, that allow patients to take a different path to their health, one that utilizes pharmaceuticals and invasive procedures only when safer integrative approaches are not available or not effective.
OBJECTIVE:
CSF levels of inositol have been reported to be lower than normal in depressed subjects. The authors administered inositol to depressed patients in a double-blind, controlled trial.
METHOD:
Under double-blind conditions, 12 g/day of inositol (N = 13) or placebo (N = 15) was administered to depressed patients for 4 weeks.
RESULTS:
The overall improvement in scores on the Hamilton Depression Rating Scale was significantly greater for inositol than for placebo at week 4. No changes were noted in hematology or in kidney or liver function.
CONCLUSIONS:
This may be the first use of the precursor strategy for a second messenger rather than a neurotransmitter in treating depression. Although inositol had a significant antidepressant effect in this study, replication is crucial.
Because they found in an earlier study that inositol, an important intracellular second-messenger precursor, was effective against depression in open and double-blind trials, the authors studied its effectiveness against panic disorder.
Twenty-one patients with panic disorder with or without agoraphobia completed a double-blind, placebo-controlled, 4-week, random-assignment crossover treatment trial of 12 g/day of inositol.
The frequency and severity of panic attacks and the severity of agoraphobia declined significantly more after inositol than after placebo administration. Side effects were minimal.
The authors conclude that inositol's efficacy, the absence of significant side effects, and the fact that inositol is a natural component of the human diet make it a potentially attractive therapeutic for panic disorder.
The effect of myo-inositol was examined on 5-HT2 receptor mediated facilitation of NMDA depolarization of rat neocortical neurons in vitro. Myo-inositol (1-10 mM) potentiated the 5-HT facilitation, the potentiation increasing linearly with log 5-HT concentration. Myo-inositol also eliminated 5-HT induced heterologous desensitization of muscarinic and alpha 1-adrenergic receptor mediated facilitation. Our findings suggest that 5-HT induced homologous and heterologous desensitization results in part from depleting phosphoinositide substrate.
• The Yale-Brown Obsessive Compulsive Scale was designed to remedy the problems of existing rating scales by providing a specific measure of the severity of symptoms of obsessivecompulsive disorder that is not influenced by the type of obsessions or compulsions present. The scale is a clinician-rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms) (total range, 0 to 40), with separate subtotals for severity of obsessions and compulsions. In a study involving four raters and 40 patients with obsessive-compulsive disorder at various stages of treatment, interrater reliability for the total Yale-Brown Scale score and each of the 10 individual items was excellent, with a high degree of internal consistency among all item scores demonstrated with Cronbach's α coefficient. Based on pretreatment assessment of 42 patients with obsessive-compulsive disorder, each item was frequently endorsed and measured across a range of severity. These findings suggest that the Yale-Brown Scale is a reliable instrument for measuring the severity of illness in patients with obsessive-compulsive disorder with a range of severity and types of obsessive-compulsive symptoms.
Antidepressant drugs have been reported to improve ADDH symtomatology. Myoinositol is a simple isomer of glucose and is the precursor of the phosphatidylinositol second messenger system in brain. Both α1-adrenergic and 5HT2 receptors activate this second messenger system. Recently, we found inositol to be effective in depression. Therefore we decided to evaluate the effects of oral inositol in children with ADDH in a double-blind, cross-over, placebo-controlled manner. Eleven children, mean age 8.9 ± 3.6 years with a mean illness duration of 4.5 ± 2.8 years were enrolled in an 8-week trial. Inositol or dextrose (placebo) was dispensed in powder form at a dose of 200 mg/kg aggravation of the syndrome with myo-inositol as compared to placebo.
The coupling of muscarinic receptor-stimulated phosphatidylinositol 4,5-bisphosphate hydrolysis by phospholipase C to resynthesis of phosphatidylinositol (PtdIns) and the ability of Li+ to inhibit this after cellular inositol depletion were studied in 1321N1 astrocytoma cells cultured in medium +/- inositol (40 microM). In inositol-replete cells, 1 mM carbachol/10 mM LiCl evoked an initial (0-30 min) approximately > or = 20-fold activation of phospholipase C, whereas prolonged (> 60 min) stimulation turned over PtdIns equal to the cellular total mass, involving approximately 80% of the cellular PtdIns pool without reducing PtdIns concentrations significantly. PtdIns resynthesis was achieved by a similar, initial agonist activation of PtdIns synthase. The dose dependency for carbachol stimulation of PtdIns synthase and phospholipase C was similar (EC50 approximately 20 microM) as was the relative intrinsic activity of muscarinic receptor partial agonists. This demonstrates the tight coupling of phosphoinositide hydrolysis to resynthesis and suggests this is achieved by a direct mechanism. In inositol-replete or depleted cells basal concentrations of inositol and CMP-phosphatidate were respectively approximately 20 mM or < or = 100-500 microM and approximately 0.1 or approximately > or = 1-10 pmol/mg of protein. Comparison of the effects of agonist +/- Li+ on the concentrations of these cosubstrates for PtdIns synthase suggest that accelerated activity of this enzyme is differentially driven by stimulated increases in the amounts of CMP-phosphatidate or inositol in inositol-replete or depleted cells, respectively. Thus, the preferential capacity of Li+ to impair stimulated phosphoinositide turnover in systems expressing low cellular inositol can be attributed to its ability to attenuate the stimulated rise in inositol concentrations on which such systems selectively depend to trigger accelerated PtdIns resynthesis.
Inositol is a key metabolite in the phosphatidylinositol cycle, which is a second messenger system for serotonin-2 receptors that have been implicated in the pathophysiology of schizophrenia. Cerebrospinal fluid inositol levels were measured in 20 schizophrenic patients and 19 age- and sex-matched controls and no difference was found. However, the patients were all neuroleptic-treated. A controlled double-blind crossover trial of 12 g daily of inositol for a month in 12 anergic schizophrenic patients, twice the dose given before in schizophrenia, did not show any beneficial effects. However, the number of patients studied was small and the length of time of inositol administration may not have been sufficient.
Inositol is a key precursor for synthesis of phosphatidylinositol in a major second messenger signalling system. It is biologically active in syndromes such as respiratory distress syndrome but has been thought to be excluded from CNS by the blood-brain barrier. Oral inositol treatment of 8 patients is shown to significantly increase CSF inositol by almost 70%, suggesting possible CNS therapeutic applications of this compound and possible CNS side-effects of systemic therapy.
1. A double-blind controlled crossover trial of 6 gm of inositol daily vs glucose for one month each was carried out in 11 Alzheimer patients. 2. Overall CAMCOG scores showed a trend for greater improvement with inositol that was not significant. 3. Language and orientation improved significantly more on inositol than on placebo. There were no serious side effects. 4. Higher doses of inositol should be studied in Alzheimer's Disease for longer periods.
Keywords:PTSD;inositol;placebo;double-blind;crossover