Quetiapine in the Anxiety Dimension of Mood Disorders: A Systematic Review of the Literature to Support Clinical Practice.

PURPOSE/BACKGROUND: Bipolar disorder and major depressive disorder are heterogeneous conditions characterized by marked variations in mood. High levels of anxiety are often present in these conditions and are associated with increased suicidal risk, increased disease duration, and treatment resistance. Mood stabilizers or antipsychotics are recommended for the treatment of bipolar disorder in comorbidity with anxiety disorders. This study examines current knowledge to evaluate the efficacy of quetiapine in the treatment of anxiety in mood disorders. METHODS/PROCEDURES: A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Cochrane guidelines, selecting randomized control trials that evaluated the efficacy of quetiapine on anxiety symptoms in patients diagnosed with bipolar disorder or major depressive disorder and included anxiety evaluation scales. FINDINGS/RESULTS: We collected 27 studies (19 with primary data analysis, 8 with secondary data analysis) regarding the use of quetiapine in mood disorders. Quetiapine was more effective than placebo and active comparators in reducing anxiety in unipolar and bipolar patients in 20 of these studies. In 7 studies, quetiapine was not superior to psychoactive comparators or placebo on the anxiety dimension. IMPLICATIONS/CONCLUSIONS: Statistical power might be limited by small sample size in 5 of the studies included in our review. Moreover, data on anxiety were a secondary outcome in most studies. Nevertheless, the reported studies show with good levels of concordance that quetiapine is effective in controlling anxiety symptoms in patients with mood disorders. This evidence supports current guidelines and recommendations concerning the use of quetiapine in clinical practice.

Special Issue "Saffron (Crocus sativus, L.): Omics and Other Techniques in Authenticity, Quality, and Bioactivity Studies".

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Neurobehavioral protective effects of Japanese sake yeast supplement against chronic stress-induced anxiety and depression-like symptoms in mice: Possible role of central adenosine receptors.

RATIONALE: Using routine synthetic drugs in the treatment of psychiatric disorders may have some restrictions due to serious side effects and pharmacoresistance. Some natural agents may be promising alternatives in this case. The neuroprotective activity of the neuromodulator adenosine and its receptor, A1 receptor (A1R) in the central nervous system has been mentioned in different studies. OBJECTIVE: We aimed to determine the anxiolytic, antidepressant and sedative effects of Japanese sake yeast as the first report. METHOD: Mice were subjected to a one-week stress protocol and concomitantly treated orally with sake yeast at the dose levels of 100, 200 and 300 mg kg-1 once daily for a week. The anxiolytic, antidepressant, and sedative actions of sake yeast were evaluated with the related tests. RESULTS: In all dose regiments, sake yeast significantly improved functions in the EPM and FST. 200 and 300 mg/kg of sake yeast significantly increased sleep duration and reduced sleep latency. Anxiolytic and antidepressant-like activities of sake yeast were maintained by the injection of ZM241385 (15 mg kg-1), a selective adenosine A2AR antagonist but completely counteracted by the injection of 8-cyclopentyltheophylline (10 mg kg-1), a selective adenosine A1R antagonist. 300 mg/kg of the yeast significantly increased the BDNF levels. Amygdala corticosterone levels did not show any significant changes at any dosage. Amygdala TNF-α, IL-6 and IL-1ß levels also decreased significantly with all the sake regiments compared to the control group. CONCLUSIONS: We conclude that oral sake yeast supplement exerts a neurobehavioral protective effect predominantly by activating central A1Rs.

Single treatments that have lasting effects: some thoughts on the antidepressant effects of ketamine and botulinum toxin and the anxiolytic effect of psilocybin.

Recent clinical trials suggest that 3 single biological treatments have effects that persist. Based on research showing that the muscles involved in facial expressions can feed back to influence mood, a single trial diminishing glabella frown lines with botulinum toxin demonstrated a significant antidepressant effect for 16 weeks. Based primarily on research with animal models of depression suggesting that glutamate may be involved in depression, the N-methyl-D-aspartate antagonist ketamine has been tested in several trials. A single dose decreased depression for up to a week. The reported effects of the use of mushrooms containing psilocybin by a number of cultures around the world has stimulated several trials showing beneficial effects of a single dose of psilocybin for over a year in healthy people, and for up to 3 months in patients with anxiety disorders who have advanced cancer. This article discusses these studies, their rationale, their possible mechanisms of action, the future clinical research required to establish these therapies and the basic research required to optimize single treatments that have lasting effects.

Lorazepam-diazepam protocol for catatonia in schizophrenia: a 21-case analysis.

OBJECTIVES: Catatonia is a unique clinical phenomenon characterized by concurrent motor, emotional, vegetative and behavioral signs. Benzodiazepines (BZD) and electroconvulsive therapy (ECT) can rapidly relieve catatonic signs. The lorazepam-diazepam protocol presented here has been proven to relieve catatonia in schizophrenia within a day. METHODS: From July 2002 to August 2011, schizophrenic patients requiring psychiatric intervention for catatonia in Kaohsiung Chang Gung Memorial Hospital were studied by medical chart review. The study used the Bush-Francis Catatonia Rating Scale (BFCRS). Patients receiving the lorazepam-diazepam protocol were identified. RESULTS: The survey included 21 patients (eight males and 13 females) with a mean age of 30.3 ± 12.6 years. Mean duration of schizophrenia was 4.7 ± 5.6 years. Thirteen (61.9%) patients responded within 2 h, 18 (85.7%) responded within one day, and all became catatonia-free within a week. Mean BFCRS score was 9.9 ± 3.0 before treatment. Patients that responded with a single intramuscular lorazepam injection had mean BFCRS score of 8.9 ± 2.8, significantly lower than the mean score (11.6 ± 2.5) of the rest of the patients (p = 0.034). CONCLUSIONS: The lorazepam-diazepam protocol can rapidly relieve retarded catatonia in schizophrenia. Most patients became catatonia-free within one day but some may require up to a week. ECT should be considered if the protocol fails.

Tolerance to benzodiazepines among long-term users in primary care.

BACKGROUND: Tolerance towards the effects of benzodiazepines is observed in various animal and human studies. Therefore, it is assumed that patients who use benzodiazepines for a longer period of time need to increase their dose over time to experience the same effect. OBJECTIVE: To observe whether long-term benzodiazepine users increase their dose over time. METHODS: From the Dutch National Information Network of Family Practices, a group of long-term benzodiazepine users was identified. This group was divided into an incident long-term benzodiazepine users group (N = 113) and a prevalent long-term benzodiazepine users group (N = 992). Long-term use of benzodiazepines was defined as usage for at least 6 months. The main outcome was a change in prescribed dose from baseline until 24 months after baseline. Linear regression analysis was performed to evaluate dose change. RESULTS: Neither incident long-term benzodiazepine users nor prevalent long-term benzodiazepine users were prescribed increasing dosages during follow-up. CONCLUSION: There is no increase in prescribed dose among long-term users, as might be expected due to the development of tolerance to the effects of benzodiazepines.

[Current treatment of depression and agitation in the elderly -- clinical use of trazodone]. / Az idoskori depresszió és agitáció korszeru kezelése - a trazodon alkalmazásának lehetoségei.

Due to their increasing frequency, mental disorders among the elderly have special importance in the clinical practice. In this article we summarize the characteristics, diagnostic problems and modern treatments of mental disorders (especially depression) in old age. As this period of life means special somatic and psychic features in people's condition, it may be difficult to find the most effective and well-tolerated treatment, especially in case of comorbid dementia or agitated behaviour. In this article we review the therapeutic experience with the SARI antidepressant trazodone. Clinical studies and everyday practice indicate that trazodone due to its special multifunctional receptorprofile can be particularly effective in the treatment of depression accompanied by severe insomnia and anxiety. Due to its special anxiolytic and sleep normalising effect and well-tolerated side effect profile trazodone is found to be clinically useful not only in the treatment of depression in the elderly, but also in the case of serious comorbidity with dementia or agitated behaviour. We also illustrate the possibilities of using trazodone in the everyday practice with the presentation of two case reports. Furthermore we review the viewpoints of complex therapy which facilitates the successful treatment of depression in the elderly and the restoration of quality of life.

[Efficacy of adaptol and the possibility of its differential use in patients with anxiety disorders after myocardial infarction].

AIM: To evaluate the efficacy and safety of adaptol in a dose of 1500-2000 mg/day in combination therapy for anxiety disorders (AD) in the early post-myocardial infarction period. SUBJECTS AND METHODS: The trial included 94 patients with AD who were divided into a study group of 60 patients and a control group of 34 patients. In addition to basic therapy, the study group took adaptol in a dose of 1500-200 mg/day for 30 +/- 2 days; the control group received basic therapy only. RESULTS: The drug given in a dose of 1500-2000 mg/day in the patients with AD in the early post-myocardial infarction period was found to have high anxiolytic, autonomically normalizing, stress-protective activities and a positive effect on heart rate variability just one month after treatment. The highest efficacy of Adaptol was observed in patients with baseline hypersympathicotonic and normal autonomic responsiveness. CONCLUSION: Adaptol proved to be more effective in patients with baseline hypersympathicotonic and normal autonomic responsiveness, which permits the drug to be differentially used in relation to the baseline type of autonomic responsiveness.

The Anxiolytic and Antidepressant Effects of Transcranial Magnetic Stimulation in Patients With Anxious Depression.

Objective: To determine the extent that treatment with transcranial magnetic stimulation (TMS) in diverse clinical settings has anxiolytic and antidepressant effects in patients with major depressive disorder (MDD) and moderate-to-severe anxiety symptoms and to contrast anxious and nonanxious depression subgroups in antidepressant effects.Methods: Within the NeuroStar Advanced Therapy System Clinical Outcomes Registry, 1,820 patients were identified with a diagnosis of MDD (using ICD-9, ICD-10, or DSM-IV) who completed the Patient Health Questionnaire-9 (PHQ-9) and Global Anxiety Disoder-7 scale (GAD-7) at baseline and following at least 1 TMS treatment between May 2016 and January 2021. Anxious depression was defined as a baseline GAD-7 score of 10 or greater (n = 1,514) and nonanxious depression by GAD-7 scores below this threshold (n = 306). Intent-to-treat and Completer samples were defined for patients treated with any TMS protocol and for the subgroup treated only with high-frequency left dorsolateral prefrontal cortex stimulation.Results: Patients with anxious depression showed clinically meaningful anxiolytic and antidepressant effects, averaging approximately 50% or greater reductions in both GAD-7 and PHQ-9 scores following TMS in all samples. The anxious and nonanxious depression groups had equivalent absolute improvement in PHQ-9 scores (P values ≥ .29). However, the anxious group had higher scores both at baseline and following TMS resulting in significantly lower categorical rates of response (P values < .02) and remission (P values < .001) in depressive symptoms. Among those with anxious depression, the change in anxiety and depression symptoms strongly covaried (r1512 = 0.75, P < .001).Conclusions: Routine TMS delivered in diverse clinical settings results in marked anxiolytic and antidepressant effects in patients with anxious depression. The extent of improvement in anxiety and depression symptoms strongly covaries.

Kava: a comprehensive review of efficacy, safety, and psychopharmacology.

OVERVIEW: Kava (Piper methysticum) is a South Pacific psychotropic plant medicine that has anxiolytic activity. This effect is achieved from modulation of GABA activity via alteration of lipid membrane structure and sodium channel function, monoamine oxidase B inhibition, and noradrenaline and dopamine re-uptake inhibition. Kava is available over the counter in jurisdictions such as the USA, Australia and New Zealand. Due to this, a review of efficacy, safety and clinical recommendations is advised. OBJECTIVE: To conduct a comprehensive review of kava, in respect to efficacy, psychopharmacology, and safety, and to provide clinical recommendations for use in psychiatry to treat generalized anxiety disorder (GAD). METHODS: A review was conducted using the electronic databases MEDLINE, CINAHL, PsycINFO and the Cochrane Library during mid 2010 of search terms relating to kava and GAD. A subsequent forward search was conducted of key papers using Web of Science cited reference search. RESULTS: The current weight of evidence supports the use of kava in treatment of anxiety with a significant result occurring in four out of six studies reviewed (mean Cohen's d = 1.1). Safety issues should however be considered. Use of traditional water soluble extracts of the rhizome (root) of appropriate kava cultivars is advised, in addition to avoidance of use with alcohol and caution with other psychotropic medications. Avoidance of high doses if driving or operating heavy machinery should be mandatory. For regular users routine liver function tests are advised. CONCLUSIONS: While current evidence supports kava for generalized anxiety, more studies are required to assess comparative efficacy and safety (on the liver, cognition, driving, and sexual effects) versus established pharmaceutical comparators.

The knowns and unknowns of SSRI treatment in young people with depression and anxiety: efficacy, predictors, and mechanisms of action.

The use of SSRIs for the treatment of depression and anxiety in young people is increasing. However, the effects of SSRIs in adolescence, a time when there are substantial changes in neural, cognitive, and social functioning, are not well understood. Here, we review evidence from clinical trials about the benefits and risks of SSRIs in young people and consider their mechanisms of action, as shown through human experimental work and animal models. We emphasise key outstanding questions about the effects of SSRIs in youth, identified through gaps in the literature and in consultation with young people with lived experience. It is crucial to characterise the mechanisms underpinning risks and benefits of SSRIs in this age group to progress the field, and to narrow the chasm between the widespread use of SSRIs in youth and the science on which this use is based.

Anxiolytic effect of midazolam premedication assessed by clinical and platelet aggregation profiles.

BACKGROUND: It is well documented that surgery is associated with increased anxiety, which has an adverse impact on patient's outcome. This study was designed to assess the anxiolytic effect of midazolam in pre-anaesthetic medication by using clinical and platelet aggregation profiles. METHODS: Sixty ASA I and II female patients aged between 35 and 60 years undergoing elective abdominal hysterectomy were randomly divided into two equal groups. Group I received placebo as pre-medication while group II received 0.15 mg/kg midazolam as pre-medication 1 hour preoperatively. They were monitored for visual analogue scale (VAS) for anxiety, observer's anxiety criteria, sedation score, blood pressure, heart rate and platelet aggregation profile immediately before and 1 hour after pre-medication. RESULTS: There was statistically significant difference with respect to VAS of anxiety, observer's anxiety criteria, sedation scores, systolic and diastolic blood pressure (p<0.05). Heart rate was higher in the midazolam group but this was not statistically significant. There was no statistical significant difference in platelet aggregation profile in the two groups. CONCLUSION: Findings of the study suggest midazolam is a good anxiolytic for pre-medication and its effect on platelet aggregation profile needs to be further evaluated.

Pharmacological challenge studies with acute psychosocial stress.

Chronic stress is known to affect many psychiatric disorders, and studies of responses to acute stress may reveal processes that ultimately lead to maladaptive responses to chronic stress. Many studies have used simulated public speaking tasks to induce stress in the laboratory and, of interest to this review, the tasks have been used to assess the effects of both therapeutic and nonmedical drugs on stress reactivity. Here we review 38 studies that examined effects of single doses of drugs on subjective, cardiovascular and hormonal responses to an acute social stressor in healthy volunteers. Most studies have used the Trier Social Stress Test (TSST), or variations on it involving public speaking or mental arithmetic. Pharmacological studies with the TSST (ph-TSST) have been conducted for three main reasons: i) to determine the clinical effectiveness of psychiatric medications to reduce stress responses, ii) to investigate the neurochemical mechanisms involved in the stress response, and iii) to determine whether drugs of abuse relieve, or occasionally worsen, responses to acute stress. The review indicates that standard anxiolytic medications consistently reduce subjective responses to the TSST, whereas single doses of antidepressants produce mixed effects. Mechanistic studies indicate that several neurotransmitter systems are involved in the stress response, including serotonin, norepinephrine, GABA, glutamate, opioids, and endocannabinoids. Among drugs of abuse, alcohol and cannabinoids exert some stress-dampening effects, whereas caffeine, nicotine, and amphetamines tend to increase stress responses. Comparing outcome measures of the responses to stress, subjective ratings of anxiety are among the most sensitive indices of the stress response, with cortisol levels second and cardiovascular responses least sensitive. We conclude that the TSST is a valuable tool to study the clinical effectiveness of medications for stress-related disorders, and that it is important to use standardized procedures to enable comparisons across studies.

GABA(A)-receptor subtypes: a new pharmacology.

The GABA(A) receptor is a pluripotent drug target mediating anxiolytic, sedative, anticonvulsant, muscle relaxant and amnesic activity. These drug actions have now been attributed to defined receptor subtypes. Thus, precise guidelines are available for the development of novel drugs with more selective action and less side effects than those currently in clinical use.

Fatigue in military aviation: an overview of US military-approved pharmacological countermeasures.

Uncomfortable working and sleeping environments, high operational tempos, sustained operations, and insufficient staffing make fatigue a growing concern. In aviation, where a single mistake can cost millions of dollars, it is essential to optimize operator alertness. Although behavioral and administrative fatigue countermeasures should comprise the "first line" approach for sustaining aircrew performance, pharmacological fatigue countermeasures are often required. Various components of the U.S. military have authorized the use of specific compounds for this purpose. Hypnotics such as temazepam, zolpidem, or zaleplon can mitigate the fatigue associated with insufficient or disturbed sleep. Alertness-enhancing compounds such as caffeine, modafinil, or dextroamphetamine can temporarily bridge the gap between widely spaced sleep periods. Each of these medications has a role in sustaining the safety and effectiveness of military aircrews. The present paper provides a short overview of these compounds as well as factors to be considered before choosing one or more to help manage fatigue.

Caffeine and psychiatric medication interactions: a review.

Caffeine can cause or worsen psychiatric symptoms but also has the potential to interact with many psychiatric medications. This article provides a literature review regarding interactions between caffeine and psychiatric medications. Caffeine is metabolized by the CYP1A2 enzyme and also acts as a competitive inhibitor of this enzyme. Thus, caffeine can interact with a wide range of psychiatric medications, including antidepressant agents, antipsychotic agents, antimanic agents, antianxiety agents, and sedative agents. These interactions may lead to caffeine-related or medication-related side effects that may complicate psychiatric treatment. By recognizing this potential, along with educating the patient, and utilizing a tapering approach, prevention of caffeine interactions is achievable.

Alterations of plasma lipid and lipoprotein levels associated with benzodiazepine use--the LRC Program Prevalence Study.

In a study of white adults from 10 North American Lipid Research Clinics populations, plasma lipid and lipoprotein levels in benzodiazepine (diazepam, chlordiazepoxide, flurazepam) users were compared to both the entire population of non-users and matched control non-users. Significantly higher plasma triglyceride and very low density lipoprotein cholesterol levels and by one method of analysis, lower high density lipoprotein cholesterol levels were noted in male benzodiazepine users. No significant differences were noted in total plasma cholesterol or low density lipoprotein cholesterol levels.

Cannabidiol: an overview of some pharmacological aspects.

Over the past few years, considerable attention has focused on cannabidiol (CBD), a major nonpsychotropic constituent of cannabis. The authors present a review on the chemistry of CBD and discuss the anticonvulsive, antianxiety, antipsychotic, antinausea, and antirheumatoid arthritic properties of CBD. CBD does not bind to the known cannabinoid receptors, and its mechanism of action is yet unknown. It is possible that, in part at least, its effects are due to its recently discovered inhibition of anandamide uptake and hydrolysis and to its antioxidative effect.

Clinical assessment of new I.V. sedation agents and techniques.

The purpose of this paper has been to describe the information that must be gathered before a new drug can be used effectively and safely for I.V. sedation. A new drug, midazolam, has been used as an illustrative example.

Cataleptic and anticataleptic effects of muscimol and gabaculine injected into globus pallidus and substantia nigra, and interactions with haloperidol or benzodiazepines.

Intranigral injection of muscimol induced hyperactivity in rats and antagonized haloperidol-induced catalepsy. Intranigral injection of gabaculine, an inhibitor of GABA transaminase, induced similar effects 5h after injection, when the nigral GABA content was increased 7-fold. On the other hand, injections of muscimol (30 ng) into the globus pallidus potentiated the cataleptic effect of haloperidol, and muscimol alone in high doses (100 and 200 ng) induced catalepsy. Gabaculine also induced catalepsy of medium intensity and potentiated the effect of haloperidol 24h after injection, when GABA was increased in the globus pallidus as well as in the substantia nigra. Injections of muscimol into either the globus pallidus or substantia nigra increased striatal HVA and enhanced haloperidol-induced elevation of HVA. Three benzodiazepines, nitrazepam, diazepam and chlordiazepoxide administered orally, potentiated the effect of muscimol (30 ng) injected into the globus pallidus and induced catalepsy. A similar effect was not obtained with phenobarbital. It is suggested that stimulation of GABA receptor or increase of GABA content in the sustantia nigra antagonize haloperidol-induced catalepsy by activation of nigral dopaminergic system, and that enhancement of pallidal GABA function induces catalepsy by non-dopaminergic mechanisms. Potentiation of haloperidol-induced catalepsy by benzodiazepines may be due to enhancement of GABA-ergic transmission within the globus pallidus.