Mental Health Matters

What is Clonazolam?

Published on 12/16/202112/16/2021 by Andrew Marshall4 Comments

Introduction

Clonazolam (also known as clonitrazolam) is a drug of the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring.

It has had very little research done about its effects and metabolism, and has been sold online as a designer drug. The synthesis of clonazolam was first reported in 1971 and the drug was described as the most active compound in the series tested.

Clonazolam is reported to be highly potent and concerns have been raised that it and flubromazolam in particular may pose comparatively higher risk than other designer benzodiazepines due to their ability to produce strong sedation and amnesia at as little as 0.5 mg.

Legality

United Kingdom

In the UK, clonazolam has been classified as a Class C drug by the May 2017 amendment to The Misuse of Drugs Act 1971 along with several other designer benzodiazepine drugs.

United States

It is an unscheduled medicine and not FDA approved. Virginia State Law has declared all of the following medications are now schedule I: clonazolam, etizolam, flualprazolam, flubromazolam, and flubromazepam. Minnesota declared clonazolam a Schedule I drug in August 2020.

Australia

In Australia, clonazolam is classified as a controlled substance in some states.

Sweden

Sweden’s public health agency suggested classifying clonazolam as a hazardous substance on 01 June 2015.

Effects

Clonazolam’s effects are similar to other benzodiazepines, such as anxiolysis, disinhibition, lethargy, muscle relaxation, and euphoria. While no dose of clonazolam is considered “safe” due to its lack of research and extreme potency, doses higher than 0.5 mg can cause benzodiazepine overdose in some individuals. The effects of a benzodiazepine overdose include sedation, confusion, insufficient breathing, loss of consciousness, and death. Because dependence can occur in a short period of time, or even with a large initial dose, withdrawal symptoms (including seizures and death) may occur acutely following the period of intoxication.

What is Flubromazolam?

Published on 12/16/202112/16/2021 by Andrew Marshall3 Comments

Introduction

Flubromazolam (JYI-73) is a triazolobenzodiazepine (TBZD), which are benzodiazepine (BZD) derivatives.

Flubromazolam is reputed to be highly potent, and concerns have been raised that clonazolam and flubromazolam in particular may pose comparatively higher risks than other designer benzodiazepines, due to their ability to produce strong sedation and amnesia at oral doses of as little as 0.5 mg. Life-threatening adverse reactions have been observed at doses of only 3 mg of flubromazolam.

Legal Status

Sweden

Flubromazolam has been classified as an illegal substance in Sweden after seizures by customs and police, as well as indications from the EMCDDA of wider use as a recreational drug.

Switzerland

Flubromazolam is illegal in Switzerland as of December 2015.

United Kingdom

In the UK, flubromazolam has been classified as a Class C drug by the May 2017 amendment to The Misuse of Drugs Act 1971 along with several other designer benzodiazepine drugs.

What is the Six-Factor Model of Psychological Well-Being?

Published on 12/15/2021 by Andrew Marshall1 Comment

Introduction

The Six-factor Model of Psychological Well-being is a theory developed by Carol Ryff which determines six factors which contribute to an individual’s psychological well-being, contentment, and happiness.

Psychological well-being consists of positive relationships with others, personal mastery, autonomy, a feeling of purpose and meaning in life, and personal growth and development. Psychological well-being is attained by achieving a state of balance affected by both challenging and rewarding life events.

Refer to Euthymia.

Measurement

The Ryff Scale of Measurement is a psychometric inventory consisting of two forms (either 54 or 84 items) in which respondents rate statements on a scale of 1 to 6, where 1 indicates strong disagreement and 6 indicates strong agreement. Ryff’s model is not based on merely feeling happy, but is based on Aristotle’s Nicomachean Ethics, “where the goal of life isn’t feeling good, but is instead about living virtuously”.

The Ryff Scale is based on six factors: autonomy, environmental mastery, personal growth, positive relations with others, purpose in life, and self-acceptance. Higher total scores indicate higher psychological well-being. Following are explanations of each criterion, and an example statement from the Ryff Inventory to measure each criterion.

Autonomy:
- High scores indicate that the respondent is independent and regulates their behaviour independent of social pressures.
- An example statement for this criterion is “I have confidence in my opinions, even if they are contrary to the general consensus”.
Environmental Mastery:
- High scores indicate that the respondent makes effective use of opportunities and has a sense of mastery in managing environmental factors and activities, including managing everyday affairs and creating situations to benefit personal needs.
- An example statement for this criterion is “In general, I feel I am in charge of the situation in which I live”.
Personal Growth:
- High scores indicate that the respondent continues to develop, is welcoming to new experiences, and recognises improvement in behaviour and self over time.
- An example statement for this criterion is “I think it is important to have new experiences that challenge how you think about yourself and the world”.
Positive Relations with Others:
- High scores reflect the respondent’s engagement in meaningful relationships with others that include reciprocal empathy, intimacy, and affection.
- An example statement for this criterion is “People would describe me as a giving person, willing to share my time with others”.
Purpose in Life:
- High scores reflect the respondent’s strong goal orientation and conviction that life holds meaning.
- An example statement for this criterion is “Some people wander aimlessly through life, but I am not one of them”.
Self-Acceptance:
- High scores reflect the respondent’s positive attitude about his or her self.
- An example statement for this criterion is “I like most aspects of my personality”

Applications and Research Findings

Contributing Factors

Positive Contributing Factors

Positive psychological well-being may emerge from numerous sources. A happy marriage is contributive, for example, as is a satisfying job or a meaningful relationship with another person. When marriages include forgiveness, optimistic expectations, positive thoughts about one’s spouse, and kindness, a marriage significantly improves psychological well-being. A propensity to unrealistic optimism and over-exaggerated self-evaluations can be useful. These positive illusions are especially important when an individual receives threatening negative feedback, as the illusions allow for adaptation in these circumstances to protect psychological well-being and self-confidence (Taylor & Brown, 1988). Optimism also can help an individual cope with stresses to their well-being.

Negative Contributing Factors

Psychological well-being can also be affected negatively, as is the case with a degrading and unrewarding work environment, unfulfilling obligations and unsatisfying relationships. Social interaction has a strong effect on well-being as negative social outcomes are more strongly related to well-being than are positive social outcomes. Childhood traumatic experiences diminish psychological well-being throughout adult life, and can damage psychological resilience in children, adolescents, and adults. Perceived stigma also diminished psychological well-being, particularly stigma in relation to obesity and other physical ailments or disabilities.

Extrinsic and Intrinsic Psychological Needs

A study conducted in the early 1990s exploring the relationship between well-being and those aspects of positive functioning that were put forth in Ryff’s model indicates that persons who aspired more for financial success relative to affiliation with others or their community scored lower on various measures of well-being.

Individuals that strive for a life defined by affiliation, intimacy, and contributing to one’s community can be described as aspiring to fulfil their intrinsic psychological needs. In contrast, those individuals who aspire for wealth and material, social recognition, fame, image, or attractiveness can be described as aiming to fulfil their extrinsic psychological needs. The strength of an individual’s intrinsic (relative to extrinsic) aspirations as indicated by rankings of importance correlates with an array of psychological outcomes. Positive correlations have been found with indications of psychological well-being: positive affect, vitality, and self-actualisation. Negative correlations have been found with indicators of psychological ill-being: negative affect, depression, and anxiety.

Relations with Others

A more recent study confirming Ryff’s notion of maintaining positive relations with others as a way of leading a meaningful life involved comparing levels of self-reported life satisfaction and subjective well-being (positive/negative affect). Results suggested that individuals whose actions had underlying eudaimonic tendencies as indicated by their self-reports (e.g. “I seek out situations that challenge my skills and abilities”) were found to possess higher subjective well-being and life satisfaction scores compared to participants who did not. Individuals were grouped according to their chosen paths/strategies to happiness as identified by their answers on an Orientation to Happiness Questionnaire. The questionnaire describes and differentiates individuals on the basis of three orientations to happiness which can be pursued, though some individuals do not pursue any. The “pleasure” orientation describes a path to happiness that is associated with adopting hedonistic life goals to satisfy only one’s extrinsic needs. Engagement and meaning orientations describe a pursuit of happiness that integrates two positive psychology constructs “flow/engagement” and “eudaimonia/meaning”. Both of the latter orientations are also associated with aspiring to meet intrinsic needs for affiliation and community and were amalgamated by Anić and Tončić into a single “eudaimonic” path to happiness that elicited high scores on all measures of well-being and life satisfaction. Importantly, she also produced scales for assessing mental health. This factor structure has been debated, but has generated much research in wellbeing, health, and successful ageing.

Heritability

Individual differences in both overall Eudaimonia, identified loosely with self-control and in the facets of eudaimonia are heritable. Evidence from one study supports 5 independent genetic mechanisms underlying the Ryff facets of this trait, leading to a genetic construct of eudaimonia in terms of general self-control, and four subsidiary biological mechanisms enabling the psychological capabilities of purpose, agency, growth, and positive social relations.

Well-Being Therapy

According to Seligman, positive interventions to attain positive human experience should not be at the expense of disregarding human suffering, weakness, and disorder. A therapy based on Ryff’s six elements was developed by Fava and others in this regards.

What is Euthymia?

Published on 12/15/202112/15/2021 by Andrew Marshall7 Comments

Introduction

In psychiatry and psychology, euthymia is a normal, tranquil mental state or mood.

In those with bipolar disorder, euthymia is a stable mental state or mood that is neither manic nor depressive, yet distinguishable from the state of healthy people. Euthymia is also the “baseline” of other cyclical mood disorders like major depressive disorder (MDD), borderline personality disorder (BPD) and narcissistic personality disorder (NPD). This state is the goal of psychiatric and psychological interventions.

Background

The term euthymia is derived from the Greek words “eu”, well, and “thymo”, soul or emotion. The word “thymos” also had four additional meanings: life energy; feelings and passions; desires and inclinations; and thought or intelligence. Euthymia is also derived from a verb, “euthymeo”, that means both “I am happy, in good spirits” and “I make others happy, I reassure and encourage”. This is the basis on which the first formal definition of euthymia was built.

Democritus, who coined the philosophical concept of euthymia, said that euthymia is achieved when “one is satisfied with what is present and available, taking little heed of people who are envied and admired and observing the lives of those who suffer and yet endure”. This was later amended in the translation given by the Roman philosopher Seneca the Younger in which euthymia means a state of internal calm and contentment. Seneca was also the first to link the state of euthymia to a learning process; in order to achieve it, one must be aware of psychological well-being. Seneca’s definition included a cache about detachment from current events. Later, the Greek biographer Plutarch removed this cache with his definition which focused more on learning from adverse events.

In 1958, Marie Jahoda gave a modern clinical definition of mental health in the terms of positive symptoms by outlining the criteria for mental health: “autonomy (regulation of behaviour from within), environmental mastery, satisfactory interactions with other people and the milieu, the individual’s style and degree of growth, development or self-actualization, the attitudes of an individual toward his/her own self”. In her definition she acknowledged the absence of disease as being necessary, but not enough, to constitute positive mental health, or euthymia.

Carol Ryff (1989) was the first to develop a comprehensive scale that could assess euthymia: the six-factor model of psychological well-being. The 84-item scale includes facets of self-acceptance, positive relations with others, autonomy, environmental mastery, purpose in life, and personal growth. It did not include a notion of resilience, which people in the field started working to add in the 2000s.

Parathymia, on the other hand, is related to pathological laughter (called “Witzelsucht”).

What is Eszopiclone?

Published on 12/15/2021 by Andrew MarshallLeave a comment

Introduction

Eszopiclone, sold under the brand-name Lunesta among others, is a medication used in the treatment of insomnia.

Evidence supports slight to moderate benefit up to six months. It is taken orally. Common side effects include headache, dry mouth, nausea, and dizziness. Severe side effects may include suicidal thoughts, unhealthy non-medical use, hallucinations, and angioedema. Greater care is recommended in those with liver problems and older people. Rapid decreasing of the dose may result in withdrawal. Eszopiclone is classified as a nonbenzodiazepine sedative hypnotic and as a cyclopyrrolone. It is the S-stereoisomer of zopiclone. It works by interacting with the GABA receptors.

Approved for medical use in the United States in 2004, eszopiclone is available as generic medication. In 2017, it was the 214th most commonly prescribed medication in the United States, with more than two million prescriptions. Eszopiclone is not sold in the European Union, as in 2009 the EMA ruled that it was too similar to zopiclone to be considered a new patentable product.

Brief History

In a controversial 2009 article in the New England Journal of Medicine, “Lost in Transmission — FDA Drug Information That Never Reaches Clinicians”, it was reported that the largest of three Lunesta trials found that compared to placebo Lunesta “was superior to placebo” while it only shortened initial time falling asleep by 15 minutes on average. “Clinicians who are interested in the drug’s efficacy cannot find efficacy information in the label: it states only that Lunesta is superior to placebo. The FDA’s medical review provides efficacy data, albeit not until page 306 of the 403-page document. In the longest, largest phase 3 trial, patients in the Lunesta group reported falling asleep an average of 15 minutes faster and sleeping an average of 37 minutes longer than those in the placebo group. However, on average, Lunesta patients still met criteria for insomnia and reported no clinically meaningful improvement in next-day alertness or functioning.”

Availability in Europe

On 11 September 2007, Sepracor signed a marketing deal with British pharmaceutical company GlaxoSmithKline for the rights to sell eszopiclone (under the name Lunivia rather than Lunesta) in Europe. Sepracor was expected to receive approximately $155 million if the deal went through. In 2008 Sepracor submitted an application to the EMA (the European Union’s equivalent to the US FDA) for authorisation to market the drug in the EU, and initially received a favourable response. However, Sepracor withdrew its authorization application in 2009 after the EMA stated it would not be granting eszopiclone ‘new active substance’ status, as it was essentially pharmacologically and therapeutically too similar to zopiclone to be considered a new patentable product. Since the patent on zopiclone has expired, this ruling would have allowed rival companies to also legally produce cheaper generic versions of eszopiclone for the European market. As of November 2012, Sepracor has not resubmitted its authorisation application and eszopiclone is not available in Europe. The deal with GSK fell through, and GSK instead launched a $3.3 billion deal to market Actelion’s almorexant sleeping tablet, which entered phase 3 medical trials before development was abandoned due to side effects.

Medical Uses

A 2018 Cochrane review found that it produced moderate improvement in sleep onset and maintenance. The authors suggest that where preferred non-pharmacological treatment strategies have been exhausted, eszopiclone provides an efficient treatment for insomnia. In 2014, the USFDA asked that the starting dose be lowered from 2 milligrams to 1 milligram after it was observed in a study that even 8 hours after taking the drug at night, some people were not able to cope with their next-day activities like driving and other activities that require full alertness.

Eszopiclone is slightly effective in the treatment of insomnia where difficulty in falling asleep is the primary complaint. Kirsch et al. found the benefit over placebo to be of questionable clinical significance. Although the drug effect and the placebo response were rather small and of questionable clinical importance, the two together produce a reasonably large clinical response. It is not recommended for chronic use in the elderly.

Elderly

Sedative hypnotic drugs including eszopiclone are more commonly prescribed to the elderly than to younger patients despite benefits of medication being generally unimpressive. Care should be taken in choosing an appropriate hypnotic drug and if drug therapy is initiated it should be initiated at the lowest possible dose to minimise side effects.

In 2015, the American Geriatrics Society reviewed the safety information about eszopiclone and similar drugs and concluded that the “nonbenzodiazepine, benzodiazepine receptor agonist hypnotics (eszopiclone, zaleplon, zolpidem) are to be avoided without consideration of duration of use because of their association with harms balanced with their minimal efficacy in treating insomnia.”

The review made this determination both because of the relatively large dangers to elderly individuals from zolpidem and other “z-drugs” together with the fact the drugs have “minimal efficacy in treating insomnia.” This was a change from the 2012 AGS recommendation, which suggested limiting use to 90 days or less. The review stated: “the 90‐day‐use caveat [was] removed from nonbenzodiazepine, benzodiazepine receptor agonist hypnotics, resulting in an unambiguous ‘avoid’ statement (without caveats) because of the increase in the evidence of harm in this area since the 2012 update.”

An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines, the nonbenzodiazepine sedative-hypnotics, including eszopiclone appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin receptor agonists, hold promise for the management of chronic insomnia in elderly people. Long-term use of sedative-hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. In addition, the effectiveness and safety of long-term use of these agents remain to be determined. It was concluded that more research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly persons with chronic insomnia.

A 2009 meta-analysis found a higher rate of infections.

Adverse Effects

Sleeping pills, including eszopiclone, have been associated with an increased risk of death.

Hypersensitivity to eszopiclone is a contra-indication to its use. Some side effects are more common than others. Recommendations around use of eszopiclone may be altered by other health conditions. These conditions or circumstances may occur in people that have lowered metabolism and other conditions. The presence of liver impairment, lactation and activities requiring mental alertness (e.g. driving) may be considered when determining frequency and dosage.

Unpleasant taste.
Headache.
Peripheral oedema.
Chest pain.
Abnormal thinking.
Behaviour changes.
Depression.
Hallucinations.
Sleep driving and sleepwalking.
Dry mouth.
Rash.
Altered sleep patterns.
Impaired coordination.
Dizziness.
Daytime drowsiness.
Itching.
Painful or frequent urination.
Back pain.
Aggressive behaviour.
Confusion.
Agitation.
Suicidal thoughts.
Depersonalisation.
Amnesia.

A 2009 meta-analysis found a 44% higher rate of mild infections, such as pharyngitis or sinusitis, in people taking eszopiclone or other hypnotic drugs compared to those taking a placebo.

Dependence

In the United States eszopiclone is a schedule IV controlled substance under the Controlled Substances Act. Use of eszopiclone may lead to physical and psychological dependence. The risk of non-medical use and dependence increases with the dose and duration of usage and concomitant use of other psychoactive substances. The risk is also greater in patients with a history of alcohol use disorder or other substance use disorder or history of psychiatric disorders. Tolerance may develop after repeated use of benzodiazepines and benzodiazepine-like drugs for a few weeks.

A study funded and carried out by Sepracor, the manufacturer of eszopiclone, found no signs of tolerance or dependence in a group of patients followed for up to six months.

Non-Medical Use

A study of non-medical use potential of eszopiclone found that in persons with a known history of non-medical benzodiazepine use, eszopiclone at doses of 6 and 12 mg produced effects similar to those of diazepam 20 mg. The study found that at these doses which are two or more times greater than the maximum recommended doses, a dose-related increase in reports of amnesia, sedation, sleepiness, and hallucinations was observed for both eszopiclone (Lunesta) as well as for diazepam (Valium).

Overdose

According to the US Prescribing Information, overdoses of eszopiclone up to 90 times the recommended dose have been reported in which the patient fully recovered. According to the May 2014 edition of the official US Prescribing Information, fatalities have been reported only in cases in which eszopiclone was combined with other drugs or alcohol.

Poison control centres reported that between 2005 and 2006 there were 525 total eszopiclone overdoses recorded in the state of Texas, the majority of which were intentional suicide attempts.

If consumed within the last hour, eszopiclone overdose can be treated with the administration of activated charcoal or via gastric lavage.

Interactions

There is an increased risk of central nervous system depression when eszopiclone is taken together with other CNS depressant agents, including antipsychotics, sedative hypnotics (like barbiturates or benzodiazepines), antihistamines, opioids, phenothiazines, and some antidepressants. There is also increased risk of central nervous system depression with other medications that inhibit the metabolic activities of the CYP3A4 enzyme system of the liver. Medications that inhibit this enzyme system include nelfinavir, ritonavir, ketoconazole, itraconazole and clarithromycin. Alcohol also has an additive effect when used concurrently with eszopiclone. Eszopiclone is most effective if it is not taken after a heavy meal with high fat content.

Pharmacology

Eszopiclone acts on benzodiazepine binding site situated on GABA_A neurons as a positive allosteric modulator. Eszopiclone is rapidly absorbed after oral administration, with serum levels peaking between .45 and 1.3 hours. The elimination half-life of eszopiclone is approximately 6 hours and it is extensively metabolized by oxidation and demethylation. Approximately 52% to 59% of a dose is weakly bound to plasma protein. Cytochrome P450 (CYP) isozymes CYP3A4 and CYP2E1 are involved in the biotransformation of eszopiclone; thus, drugs that induce or inhibit these CYP isozymes may affect the metabolism of eszopiclone. Less than 10% of the orally administered dose is excreted in the urine as racemic zopiclone. In terms of benzodiazepine receptor binding and relevant potency, 3 mg of eszopiclone is equivalent to 10 mg of diazepam.

What is Estazolam?

Published on 12/15/2021 by Andrew MarshallLeave a comment

Introduction

Estazolam, sold under the brand name Prosom among others, is a tranquiliser medication of the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring.

It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. Estazolam is an intermediate-acting oral benzodiazepine. It is used for short-term treatment of insomnia.

It was patented in 1968 and came into medical use in 1975.

Medical Uses

Estazolam is prescribed for the short-term treatment of certain sleep disorders. It is an effective hypnotic drug showing efficacy in increasing the time spent asleep as well as reducing awakenings during the night. Combination with non-pharmacological options for sleep management results in long-term improvements in sleep quality after discontinuation of short-term estazolam therapy. Estazolam is also sometimes used as a preoperative sleep aid. It was found to be superior to triazolam in side effect profile in preoperative patients in a trial. Estazolam also has anxiolytic properties and due to its long half life can be an effective short-term treatment for insomnia associated with anxiety.

Side Effects

A hang-over effect commonly occurs with next day impairments of mental and physical performance. Other side effects of estazolam include somnolence, dizziness, hypokinesia, and abnormal coordination.

In September 2020, the US Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.

Tolerance and Dependence

The main safety concern of benzodiazepines such as estazolam is a benzodiazepine dependence and the subsequent benzodiazepine withdrawal syndrome which can occur upon discontinuation of the estazolam. A review of the literature found that long-term use of benzodiazepines such as estazolam is associated with drug tolerance, drug dependence, rebound insomnia and CNS related adverse effects. Estazolam should only be used short term and at the lowest effective dose to avoid complications related to long-term use. Non-pharmacological treatment options however, were found to have sustained improvements in sleep quality. The short-term benefits of benzodiazepines on sleep begin to reduce after a few days due to tolerance to the hypnotic effects of benzodiazepines in the elderly.

Contraindications and Special Caution

Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol or drug-dependent individuals and individuals with comorbid psychiatric disorders.

Elderly

An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines including estazolam, the nonbenzodiazepine sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Long-term use of sedative-hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. In addition, the effectiveness and safety of long-term use of these agents remain to be determined. It was concluded that more research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly persons with chronic insomnia.

Pharmacology

Estazolam is classed as a “triazolo” benzodiazepine drug. Estazolam exerts its therapeutic effects via its benzodiazepines receptor agonist properties. Estazolam at high doses decreases histamine turnover via its action at the benzodiazepine-GABA receptor complex in mouse brains.

Pharmacokinetics

Peak plasma levels are achieved within 1-6 hours. Estazolam is an intermediate acting benzodiazepine. The elimination half life of estazolam is an average of 19 hours, with a range of 8-31 hours. The major metabolite of estazolam is 4-hydroxyestazolam. Other identified metabolites include 1-oxo-estazolam, 4′-hydroxy-estazolam, and benzophenone.

Interactions

Alcohol enhances the sedative hypnotic properties of estazolam. In package inserts, the manufacturer clearly warns about an interaction with Ritonavir, and although clinical interactions of Ritonavir with estazolam have not yet been described, the lack of clinical descriptions of the interactions does not negate the seriousness of the interaction.

EEG Effects in Rabbits

An animal study in rabbits demonstrated that estazolam induces a drowsy pattern of spontaneous EEG including high voltage slow waves and spindle bursts increase in the cortex and amygdala, while the hippocampal theta rhythm is desynchronised. Also low voltage fast waves occur particularly in the cortical EEG. The EEG arousal response to auditory stimulation and to electric stimulation of the mesencephalic reticular formation, posterior hypothalamus and centromedian thalamus is significantly suppressed. The photic driving response elicited by a flash light in the visual cortex is significantly suppressed by estazolam.

Abuse

Refer to Benzodiazepine Use Disorder.

A primate study found that estazolam has abuse potential. Estazolam is a drug with the potential for misuse. Two types of drug misuse can occur; recreational misuse, where the drug is taken to achieve a high or when the drug is continued long term against medical advice. Estazolam became notorious in 1998 when a large amount of an ‘herbal sleeping mix’ called Sleeping Buddha was recalled from the shelves after the FDA discovered that it contained estazolam. In 2007, a Canadian product called Sleepees was recalled after it was found to contain undeclared estazolam.

On This Day … 15 December

Published on 12/15/202112/10/2021 by Andrew MarshallLeave a comment

Events

1973 – The American Psychiatric Association votes 13-0 to remove homosexuality from its official list of psychiatric disorders, the Diagnostic and Statistical Manual of Mental Disorders.

People (Births)

1911 – Nicholas P. Dallis, American psychiatrist and illustrator (d. 1991).

Nicholas P. Dallis

Nicholas Peter Dallis (15 December 1911 to 06 July 1991), known as Nick Dallis, was an American psychiatrist turned comic strip writer, creator of the soap opera-style strips Rex Morgan, M.D., Judge Parker and Apartment 3-G. Separating his comics career from his medical practice, he wrote under pseudonyms, Dal Curtis for Rex Morgan, M.D. and Paul Nichols for Judge Parker.

Born in New York City, Nick Dallis grew up on Long Island. He graduated from Washington & Jefferson College in 1933 and from Temple University’s medical school in 1938 and married a nurse, Sarah Luddy. He decided to specialise in psychiatry, and after World War II, started a practice in Toledo, Ohio. Allen Saunders was chair at the time of the local mental hygiene centre that invited him there, and in his autobiography, he recalled that Dallis approached him, as a well-known comics writer (Steve Roper and Mike Nomad, Mary Worth), about “his desire to write a comic strip, one tracing the history of medicine. I told him that, commendable as his idea was, such a feature would not succeed. Readers want entertainment, not enlightenment. But a story about a handsome young doctor’s involvement with his patients might be a winner.”

An Overview of Digital Media Use & Mental Health

Published on 12/14/2021 by Andrew Marshall1 Comment

Introduction

The relationships between digital media use and mental health have been investigated by various researchers – predominantly psychologists, sociologists, anthropologists, and medical experts – especially since the mid-1990s, after the growth of the World Wide Web.

A significant body of research has explored “overuse” phenomena, commonly known as “digital addictions”, or “digital dependencies”. These phenomena manifest differently in many societies and cultures. Some experts have investigated the benefits of moderate digital media use in various domains, including in mental health, and the treatment of mental health problems with novel technological solutions.

The delineation between beneficial and pathological use of digital media has not been established. There are no widely accepted diagnostic criteria, although some experts consider overuse a manifestation of underlying psychiatric disorders. The prevention and treatment of pathological digital media use is also not standardised, although guidelines for safer media use for children and families have been developed. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the International Classification of Diseases (ICD-11) do not include diagnoses for problematic internet use and problematic social media use; the ICD-11 include diagnosis for gaming disorder (commonly known as video game addiction), whereas the DSM-5 does not. Experts are still debating how and when to diagnose these conditions. The use of the term addiction to refer to these phenomena and diagnoses has also been questioned.

Digital media and screen time have changed how children think, interact and develop in positive and negative ways, but researchers are unsure about the existence of hypothesised causal links between digital media use and mental health outcomes. Those links appear to depend on the individual and the platforms they use. Several large technology firms have made commitments or announced strategies to try to reduce the risks of digital media use.

Brief History and Terminology

The relationship between digital technology and mental health has been investigated from many perspectives. Benefits of digital media use in childhood and adolescent development have been found. Concerns have been expressed by researchers, clinicians and the public in regard to apparent compulsive behaviours of digital media users, as correlations between technology overuse and mental health problems become apparent.

Terminologies used to refer to compulsive digital-media-use behaviours are not standardised or universally recognised. They include “digital addiction”, “digital dependence”, “problematic use”, or “overuse”, often delineated by the digital media platform used or under study (such as problematic smartphone use or problematic internet use). Unrestrained use of technological devices may affect developmental, social, mental and physical well-being and may result in symptoms akin to other psychological dependence syndromes, or behavioural addictions. The focus on problematic technology use in research, particularly in relation to the behavioural addiction paradigm, is becoming more accepted, despite poor standardisation and conflicting research.

Internet addiction has been proposed as a diagnosis since the mid-1990s, and social media and its relation to addiction has been examined since 2009. A 2018 Organisation for Economic Co-operation and Development (OECD) report noted the benefits of structured and limited internet use in children and adolescents for developmental and educational purposes, but that excessive use can have a negative impact on mental well-being. It also noted an overall 40% increase in internet use in school-age children between 2010 and 2015, and that different OECD nations had marked variations in rates of childhood technology use, as well as differences in the platforms used.

The DSM has not formally codified problematic digital media use in diagnostic categories, but it deemed internet gaming disorder to be a condition for further study in 2013. Gaming disorder, commonly known as video game addiction, has been recognised in the ICD-11. Different recommendations in the DSM and the ICD are due partly to the lack of expert consensus, the differences in emphasis in the classification manuals, as well as difficulties utilising animal models for behavioural addictions.

The utility of the term addiction in relation to overuse of digital media has been questioned, in regard to its suitability to describe new, digitally mediated psychiatric categories, as opposed to overuse being a manifestation of other psychiatric disorders. Usage of the term has also been criticised for drawing parallels with substance use behaviours. Careless use of the term may cause more problems – both downplaying the risks of harm in seriously affected people, as well as overstating risks of excessive, non-pathological use of digital media. The evolution of terminology relating excessive digital media use to problematic use rather than addiction was encouraged by Panova and Carbonell, psychologists at Ramon Llull University, in a 2018 review.

Due to the lack of recognition and consensus on the concepts used, diagnoses and treatments are difficult to standardise or develop. Heightened levels of public anxiety around new media (including social media, smartphones and video games) further obfuscate population-based assessments, as well as posing management dilemmas. Radesky and Christakis, the 2019 editors of JAMA Paediatrics, published a review that investigated “concerns about health and developmental/behavioural risks of excessive media use for child cognitive, language, literacy, and social-emotional development.” Due to the ready availability of multiple technologies to children worldwide, the problem is bi-directional, as taking away digital devices may have a detrimental effect, in areas such as learning, family relationship dynamics, and overall development.

Problematic Use

Though associations have been observed between digital media use and mental health symptoms or diagnoses, causality has not been established; nuances and caveats published by researchers are often misunderstood by the general public, or misrepresented by the media. Females are more likely to overuse social media, and males video games. Following from this, problematic digital media use may not be singular constructs, may be delineated based on the digital platform used, or reappraised in terms of specific activities (rather than addiction to the digital medium).

Screen Time and Mental Health

In addition to noting with evolutionary biologist George C. Williams in the development of evolutionary medicine that most chronic medical conditions are the consequence of evolutionary mismatches between a stateless environment of nomadic hunter-gatherer life in bands and contemporary human life in sedentary technologically modern state societies (e.g. WEIRD societies), psychiatrist Randolph M. Nesse has argued that evolutionary mismatch is an important factor in the development of certain mental disorders. In 1948, 50% of US households owned at least one automobile. In 1955, a majority of US households had at least one television set, and by 1992, 60% of all US households received cable television subscriptions. In 2000, a majority of US households had at least one personal computer and internet access the following year.

In 2002, a majority of US survey respondents reported having a mobile phone. In September and December 2006 respectively, Luxembourg and the Netherlands became the first countries to completely transition from analogue to digital television, while the US commenced its transition in 2008. In September 2007, a majority of US survey respondents reported having broadband internet at home. In January 2013, a majority of US survey respondents reported owning a smartphone. According to estimates from Nielsen Media Research, approximately 45.7 million US households in 2006 (or approximately 40% of approximately 114.4 million) owned a dedicated home video game console, and by 2015, 51% of US households owned a dedicated home video game console according to an Entertainment Software Association annual industry report.

A 2019 systematic map of reviews suggested associations between some types of potentially problematic internet use and psychiatric or behavioural problems such as depression, anxiety, hostility, aggression and attention deficit hyperactivity disorder (ADHD). The studies could not determine if causal relationships exist, reviewers emphasising the importance of future prospective study designs. While overuse of digital media has been associated with depressive symptoms, digital media may also be utilised in some situations to improve mood. Symptoms of ADHD have been positively correlated with digital media use in a large prospective study. The ADHD symptom of hyperfocus may cause affected individuals to overuse video games, social media, or online chatting, however; the correlation between hyperfocus and problematic social media use is weak. Being exposed to high amounts of social media can also affect body image, which can lead to eating disorders, depression and anxiety. There has been research done showing that 84% of participants exposed to pro-ED social media developed symptoms of an eating disorder, along with depression and anxiety. This study also showed that only 14% of the individuals experiencing symptoms received treatment. The common treatment barriers were not believing their symptoms were serious enough to seek help, or thinking they could just help themselves. These results show that majority of people who are affected by eating disorders by social media will not get the help they need to recover. Additionally, diet-focused social media trends like “What I eat in a day” videos have been shown to have negative impacts on body image.

A 2016 technical report by Chassiakos, Radesky, and Christakis identified benefits and concerns in adolescent mental health regarding digital media use. It showed that the manner of social media use was the key factor, rather than the amount of time engaged. A decline in well-being and life-satisfaction was found in older adolescents who passively consumed social media, but these were not apparent in those who were more actively engaged. The report also found a U-shaped curvilinear relationship in the amount of time spent on digital media, with risk of depression increasing at both the low and high ends of internet use. A 2018 review into the Chinese social media platform WeChat found associations of self-reported mental health symptoms with excessive platform use. However, the motivations and usage patterns of WeChat users affected overall psychological health, rather than the amount of time spent using the platform. In the United Kingdom, a study of 1,479 individuals aged 14-24 compared psychological benefits and problems for five large social media platforms: Facebook, Instagram, Snapchat, Twitter and YouTube. It concluded that YouTube was the only platform with a net positive rating “based on the 14 health and wellbeing-related questions”, and the other platforms measured had net negative ratings, Instagram having the lowest rating. The study identified Instagram as having some positive effects including self-expression, self-identity, and community, but found that these were outweighed by the negative effects, specifically on sleep, body image, and “fear of missing out”.

A report published in Clinical Psychological Science in 2018 featured two cross-sectional surveys of 506,820 American high school students, and found that use of digital media was associated with higher rates of depressive symptoms and suicidality. They concluded that more time engaged with electronic devices, and less time on “non-screen activities” (such as in-person social interaction, sports/exercise, homework, and attending religious services) was correlated with depressive symptoms and suicide-related outcomes (suicidal ideation, plans, and attempts), especially among girls. A later report in the same publication questioned the survey’s research methodology, citing “inaccurate research measurements, negligible correlations between the main variables, [and] insufficient and inadequate statistical analyses”.

The relationship between bipolar disorder and technology use has been investigated in a singular survey of 84 participants for Computers in Human Behaviour. The survey found marked variations in technology use based on self-reported mood states. The authors of the report then postulated that for patients with bipolar disorder, technology may be a “double-edged sword”, with potential benefits and harms.

Fear of missing out (FoMO) is a disruptive behavioural phenomenon that causes emotional stress. Studies show that the more social media accounts an individual has, the higher chance they have FoMO. There is a direct correlation between the number of accounts an individual has and the individual’s levels of anxiety and depression.

There is no significant link between ethnicity and FoMO/overall loneliness meaning anxiety and depression caused by FoMO from social media is consistent across the board for all ethnicities.

A US study done in 2019 found an association between social media and depression in adolescence. Based on the upward social comparison, it may be that repeated exposure to idealized images lowers adolescents’ self-esteem, triggers depression, and enhances depression over time. Furthermore, heavier users of social media with depression appear to be more negatively affected by their time spent on social media, potentially by the nature of information that they select (e.g. blog posts about self-esteem issues), consequently potentially maintaining and enhancing depression over time.

In February 2019, experimental psychologists Amy Orben and Andrew K. Przybylski published a specification curve analysis of data from the Monitoring the Future survey, the Millennium Cohort Study, and the Youth Risk Behaviour Surveillance System that included a total of 355,358 subjects in Nature Human Behaviour to examine the correlational evidence for negative effects of digital technology on adolescent well-being and found that digital technology use accounted for only 0.4% of the variance and that such a small change did not require public policy changes and that the weight given to digital screen time in scientific and public discourse is outsized. In May 2019, Orben and Przybylski published a subsequent specification curve analysis in Psychological Science of three nationally representative samples from data sets including 17,247 subjects from the Republic of Ireland, the US, and the UK including time-use diary studies and found little evidence for substantial negative associations for digital screen engagement and adolescent well-being and noted that correlations between retrospective self-reports and time diaries are too low for retrospective self-reports to be useful.

In February 2020, Frontiers in Psychology published a commentary on Orben and Przybylski’s May 2019 study from psychologists Jean Twenge, Andrew B. Blake, Jonathan Haidt, and W. Keith Campbell that noted that the conclusion of Orben and Przybylski’s analysis that there is no meaningful link between screen time measured with time diaries and adolescent well-being made six analytical decisions (e.g. relying solely on linear correlations, primarily measuring participation in digital media activities rather than time spent, combining all types of screen time, not separating data by gender) that substantially reduced the size of the relationship and noted that the data sets Orben and Przybylski cite do demonstrate a clear and substantial relationship between depression and heavier usage of social media for girls (consistent with other research by Twenge and Haidt).

In April 2020, Nature Human Behaviour published a response to Orben and Przybylski’s February 2019 study from Twenge, Haidt, Thomas Joiner, and Campbell that noted that Orben and Przybylski likewise made six analytical decisions (e.g. only considering monotonic effects, combining all types of screen time and not separating data by gender, excluding hours-per-week items on non-television digital media such as social media, internet use, gaming, texting, and video chat) that lowered the effect sizes of their analysis, noting instead that all three of the datasets that they included in their analysis contained data that indicates that heavy use of social media is consistently associated with non-trivial negative mental health outcomes for girls, and considering the rising rates of depression, anxiety, self-harm, and suicide among girls in the United States and other countries that no other researchers have found a plausible alternative explanation for, Twenge et al. conclude instead that screen time research should not be dismissed in scientific and public discourse.

A systematic examination of reviews, published in 2019, concluded that evidence, although of mainly low to moderate quality, showed an association of screen time with a variety of health problems including: “adiposity, unhealthy diet, depressive symptoms and quality of life”. They also concluded that moderate use of digital media may have benefits for young people in terms of social integration, a curvilinear relationship found with both depressive symptoms and overall well-being.

A research study done on urban adolescents in China revealed that more than a quarter of adolescents in China were exposed to over 2 hours of screen time per day. They found that screen time and physical activity was independently associated with mental health. Specifically, an increase in screen time and decrease in physical activity contributed to an additional risk for mental health productivity by increasing depressive anxiety symptoms and life dissatisfaction.

A 2017 UK large-scale study of the “Goldilocks hypothesis” – of avoiding both too much and too little digital media use – was described as the “best quality” evidence to date by experts and non-government organisations (NGOs) reporting to a 2018 UK parliamentary committee. That study concluded that modest digital media use may have few adverse affects, and some positive associations in terms of well-being.

A study by The Lancet Child & Adolescent Health in 2019 showed a relationship between social media use by girls and an increase in their exposure to bullying, reduction in sleep and exercise.

ADHD

In September 2014, Developmental Psychology published a meta-analysis of 45 studies investigating the relationship between media use and ADHD-related behaviours in children and adolescents and found a small but significant relationship between media use and ADHD-related behaviours. In March 2016, Frontiers in Psychology published a survey of 457 post-secondary student Facebook users (following a face validity pilot of another 47 post-secondary student Facebook users) at a large university in North America showing that the severity of ADHD symptoms had a statistically significant positive correlation with Facebook usage while driving a motor vehicle and that impulses to use Facebook while driving were more potent among male users than female users. In June 2018, Children and Youth Services Review published a regression analysis of 283 adolescent Facebook users in the Piedmont and Lombardy regions of Northern Italy (that replicated previous findings among adult users) showing that adolescents reporting higher ADHD symptoms positively predicted Facebook addiction, persistent negative attitudes about the past and that the future is predetermined and not influenced by present actions, and orientation against achieving future goals, with ADHD symptoms additionally increasing the manifestation of the proposed category of psychological dependence known as “problematic social media use.”

In April 2015, the Pew Research Centre published a survey of 1,060 US teenagers ages 13 to 17 who reported that nearly three-quarters of them either owned or had access to a smartphone, 92% went online daily with 24% saying they went online “almost constantly.” Citing Centres for Disease Control data showing that nearly one-fourth of all deaths in the US in 2014 for people ages 15 to 24 were in motor vehicle accidents, psychiatrist Randolph M. Nesse has noted that fear of dangers in operating a motor vehicle cannot have a prewired learning module, and along with evolutionary biologist George C. Williams and psychiatrist Isaac Marks, Nesse has noted that people with systematically deficient fear responses to various adaptive phobias (e.g. basophobia, ophidiophobia, arachnophobia) are more temperamentally careless and more likely to end up in potentially fatal accidents, and Marks, Williams, and Nesse have proposed that such deficient phobia should be classified as “hypophobia” due to its selfish genetic consequences.

In July 2018, the Journal of the American Medical Association published a two-month longitudinal cohort survey of 3,051 US teenagers ages 15 and 16 (recruited at 10 different Los Angeles County, California secondary schools by convenience sampling) self-reporting engagement in 14 different modern digital media activities at high-frequency. 2,587 had no significant symptoms of ADHD at baseline with a mean number of 3.62 modern digital media activities used at high-frequency and each additional activity used frequently at baseline positively correlating with a significantly higher frequency of ADHD symptoms at follow-ups. Of the 495 who reported no high-frequency digital media activities at baseline had a 4.6% mean rate of having ADHD symptoms at follow-ups, while the 114 who reported 7 high-frequency activities had a 9.5% mean rate and the 51 with 14 high-frequency activities had a 10.5% mean rate (indicating a statistically significant but modest association between higher frequency of digital media use and subsequent symptoms of ADHD). In October 2018, PNAS USA published a systematic review of four decades of research on the relationship between children and adolescents’ screen media use and ADHD-related behaviours and concluded that a statistically small relationship between children’s media use and ADHD-related behaviours exists.

In April 2019, PLOS One published the results of a longitudinal birth cohort study of screen-time use reported by parents of 2,322 children in Canada at ages 3 and 5 and found that compared to children with less than 30 minutes per day of screen-time, children with more than 2 hours of screen-time per day had a 7.7-fold increased risk of meeting criteria for ADHD. In January 2020, the Italian Journal of Paediatrics published a cross-sectional study of 1,897 children from ages 3 through 6 attending 42 kindergartens in Wuxi, China that also found that children exposed to more than 1 hour of screen-time per day were at increased risk for the development of ADHD and noted its similarity to a finding relating screen-time and the development of autism (ASD). In November 2020, Infant Behaviour and Development published a study of 120 3-year-old children with or without family histories of ASD or ADHD (20 with ASD, 14 with ADHD, and 86 for comparison) examining the relationship between screen time, behavioural outcomes, and expressive/receptive language development that found that higher screen time was associated with lower expressive/receptive language scores across comparison groups and that screen time was associated with behavioural phenotype, not family history of ASD or ADHD.

In November 1999, Biological Psychiatry published a literature review by psychiatrists Joseph Biederman and Thomas Spencer on the pathophysiology of ADHD that found the average heritability estimate of ADHD from twin studies to be 0.8, while a subsequent family, twin, and adoption studies literature review published in Molecular Psychiatry in April 2019 by psychologists Stephen Faraone and Henrik Larsson that found an average heritability estimate of 0.74. Additionally, Randolph M. Nesse has argued that the 5:1 male-to-female sex ratio in the epidemiology of ADHD suggests that ADHD may be the end of a continuum where males are overrepresented at the tails, citing clinical psychologist Simon Baron-Cohen’s suggestion for the sex ratio in the epidemiology of autism as an analogue.

In the journal Globalization and Health Article number: Vol 17(48) (2021) Shauai et al. published a study titled Influences of digital media use on children and adolescents with ADHD during COVID-19 pandemic. They explored the influence of digital media on the core symptoms, emotional state, life events, learning motivation, executive function (EF), and family environment of children and adolescents diagnosed with ADHD. They included participants age 8 to 16 who met the criteria for ADHD and included a group who had problematic digital media use (PDMU) and a group who met the ADHD criteria who did not have PDMU. The study analysed the differences between the groups in ADHD symptoms, EF, anxiety, and depression, stress from life events, learning motivation, and family environment were compared respectively. The research concluded that the ADHD children with PDMU displayed more severe symptoms, negative emotions, impairments in executive functioning, difficulties in family functioning, pressure from life events, and a lower learning motivation than those who did not have PMDU. The research suggested that for children and adolescents who struggle with ADHD, it is essential to supervise digital media usage and increase physical exercise for better management of core symptoms and other associated difficulties associated with ADHD.

Researchers Siddharth Sagar, Dr. Navin Kumarhttp published a study in Psychology and Education Vol.58 No.4 (2021) titled Usages of Social Media and Symptoms of Attention Deficit Hyperactivity Disorder (ADHD): A Cross-Sectional Study. The study aimed to empirically test the association between social media usage and ADHD. They hypothesized that social media users will significantly differ in demographic variables such as age, gender, and education and that ADHD would be significantly associated with social media usage. The study did suggest that ADHD is significantly associated with addictive or excessive social media use and that addictive social media use was associated with being female, being a young individual, and with undergraduate-aged individuals. They further concluded that individuals with high social media usage have higher incidences of ADHD in comparison to average or low-frequency users. They suggest this may be due to social media being an ideal outlet for constant touching, fidgeting, and frequent shifts from one activity to another when bored or feeling inattentive. These are common ADHD behaviours (American Psychiatric Association, 2013).

Autism

In February 2017, PLOS One published a systematic review of 35 studies examining the prevalence of physical activity and sedentary behaviours and their potential correlates among children with autism spectrum disorder (ASD) and found that 15 reported physical activity prevalence, 10 reported physical activity correlates, 18 reported sedentary behaviour prevalence, and 10 reported sedentary behaviour correlates, and age was consistently inversely associated with physical activity, but noted that all but one of the studies were classified as having high risk of selection bias and that more research was needed to consistently identify the correlates of the behaviours. In September 2017, Scientific Reports published a meta-analysis of 15 epidemiological studies totalling 49,937,078 participants including 1,045,538 with ASD used a random effects model to examine associations between obesity, overweight, and ASD and found that while the prevalence of overweight participants with ASD was not significantly different from the control group, the prevalence of obesity was significantly higher among ASD participants than the control group.

In April 2018, Child and Adolescent Psychiatric Clinics of North America published a study of data from the American Academy of Child and Adolescent Psychiatry that found that children with ASD surveyed spent 4.5 hours more per day on screen time than typically developing peers, that children with ASD spent most of their free time on screen time as compared with 18% of typically developing peers, and that children with ASD played video games 1 hour more per day than typically developing peers and tended to prefer video games over television. Conversely, more than half of children with ASD surveyed had never played with a friend over electronic media, with only 15% engaging with friends in this way on a weekly basis and 64% using electronic media primarily non-socially (e.g. to play video games alone or with strangers, or surfing gaming web sites).

In October 2018, Evidence-Based Mental Health published a meta-analysis of 47 data sets using a random effects model to examine associations between sleep problems and ASD on 14 subjective and 14 objective sleep parameters and found that as compared with control groups, ASD participants differed significantly on 10 of the 14 subjective parameters and 7 of the 14 objective parameters. In November 2018, the Journal of Autism and Developmental Disorders published a study examining associations between environmental factors physical activity and screen time among 1,380 children with ASD and 1,411 children without ASD and found that the absence of a bedroom television and neighbourhood support for children without ASD were associated with physical activity, while a bedroom television and no parental limits on screen time was associated with screen time for children with ASD.

In May 2019, Behavioural Sciences published an online parental survey of 327 children with ASD that found that children with ASD mostly use television and after conducting 13 in-person interviews with parents the researchers concluded that screen media usage by children with ASD should be supervised. In November 2020, Infant Behaviour and Development published a study of 120 3-year-old children with or without family histories of ASD or ADHD (20 with ASD, 14 with ADHD, and 86 for comparison) examining the relationship between screen time, behavioural outcomes, and expressive/receptive language development that found that higher screen time was associated with lower expressive/receptive language scores across comparison groups and that screen time was associated with behavioural phenotype, not family history of ASD or ADHD.

In February 2021, Frontiers in Psychiatry published a study of 101 children with ASD and 57 children without ASD to examine the relationship between screen time of children with ASD and their development quotients and found that screen time for children with ASD was longer among children with ASD (3.34 ± 2.64 hours) than children without (0.91 ± 0.93 hours) and screen time for children with ASD was positively correlated with the Childhood Autism Rating Scale.

Insomnia

In August 2018, Sleep Medicine Reviews published a meta-analysis performed by psychiatrists Wai Sze Chan, Meredith P. Levsen, and Christina S. McCrae of 67 studies published since 2008 that found that multilevel random effects models showed that the odds of being obese among those who had an insomnia diagnosis was not significantly greater than the odds of being obese and not receiving an insomnia diagnosis, while a small but significant cross-sectional correlation was found between insomnia symptoms and body mass index, longitudinal data was limited to three studies that showed that developing insomnia symptoms in the future among the obese was not significantly greater than among the non-obese, finding the research to be inconclusive.

In May 2019, Sleep Medicine published a study of 2,865 US adolescents at the age 15 follow-up of the Fragile Families and Child Wellbeing Study who completed surveys quantifying personal sleep duration and insomnia symptoms, screen time use of social messaging, web surfing, television or movie watching, and gaming, and depressive systems and the researchers constructed a multiple mediation model while controlling for depressive symptoms at age 9 to identify associations between age 15 screen time, sleep, and depressive symptoms, and found through structural equation modelling that the association for social messaging, web surfing, and television and movie watching, the three sleep variables fully mediated the positive association between screen time and depressive symptoms while for gaming the sleep variables only accounted for 38.5% of the association between gaming and depressive symptoms.

In November 2019, Psychiatry Research published a study of a nationally representative sample of 14,603 US adolescents aged 14-18 years from the 2017 Youth Risk Behaviour Survey examining the association between excessive screen time and behaviours and insufficient sleep among adolescents using a logistic regression with insufficient sleep and the excessive screen time behaviours as the outcome and explanatory variables respectively and found that the odds for adolescents engaging in excessive screen time behaviours to be receiving insufficient sleep (controlling for all other predictors) was 1.34 times higher than adolescents not engaging in excessive screen time behaviours, with 74.8% of adolescents in the survey receiving less than 8 hours of sleep on an average school night and 43% engaging in excessive screen behaviours.

In December 2019, Eating and Weight Disorders – Studies on Anorexia, Bulimia and Obesity published a survey of a sample of 6,419 adults in Mexico from the 2016 National Health and Nutrition Survey in self-reported differences in sleep duration, insomnia symptoms, television screen time, total screen time, degree of physical activity with body mass index used to categorize participants and found that of the 39% and 37% of participants categorised as overweight and obese respectively, television screen time, total screen time, sleep duration, and physical activity were significantly correlated with being overweight or obese, with Obese II and Obese III participants spending 30 minutes on average more than normal weight participants in front of any screen and Obese II reporting 30 minutes less sleep on average and Obese III less likely to engage in physical activity.

In February 2020, Sleep Medicine Reviews published a systematic review of 31 studies examining associations between screen time or movement behaviours (sedentary vs. physical activity) and sleep outcomes in children younger than 5 years following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and that performed a Grading of Recommendations Assessment, Development and Evaluation with subjects stratified by age and found that screen time is associated with poorer sleep outcomes for children under the age of 5, with meta-analysis only confirming poor sleep outcomes among children under 2 years while for movement behaviours evidence was mixed but that physical activity and outdoor play among children 1-4 were favourably associated.

NPD

In July 2018, a meta-analysis published in Psychology of Popular Media found that grandiose narcissism positively correlated with time spent on social media, frequency of status updates, number of friends or followers, and frequency of posting self-portrait digital photographs,[90] while a meta-analysis published in the Journal of Personality in April 2018 found that the positive correlation between grandiose narcissism and social networking service usage was replicated across platforms (including Facebook and Twitter). In March 2020, the Journal of Adult Development published a regression discontinuity analysis of 254 Millennial Facebook users investigating differences in narcissism and Facebook usage between the age cohorts born from 1977 to 1990 and from 1991 to 2000 and found that the later born Millennials scored significantly higher on both. In June 2020, Addictive Behaviours published a systematic review finding a consistent, positive, and significant correlation between grandiose narcissism and problematic social media use. Also in 2018, social psychologist Jonathan Haidt and FIRE President Greg Lukianoff noted in The Coddling of the American Mind that former Facebook president Sean Parker stated in a 2017 interview that the Facebook like button was consciously designed to prime users receiving likes to feel a dopamine rush as part of a “social-validation feedback loop”.

“Conspicuous compassion” is the practice of publicly donating large sums of money to charity to enhance the social prestige of the donor, and is sometimes described as a type of conspicuous consumption. Jonathan Haidt and Greg Lukianoff argued that microaggression training on college campuses in the United States has led to a call-out culture and a climate of self-censorship due to fear of shaming by virtue signalling social media mobs with users who are often anonymous and tend to deindividuate as a consequence. Citing February 2017 Pew Research Centre survey data showing that critical Facebook postings expressing “indignant disagreement” were twice as likely to receive likes, comments, or shares (along with a similar finding for Twitter posts published in PNAS USA in July 2017), Haidt and Tobias Rose-Stockwell cited the phrase “moral grandstanding” in The Atlantic in December 2019 to describe how having an audience on social media forums converts much of its interpersonal communication into a public performance.

Following the murder of George Floyd in May 2020 and the subsequent protests in his name, Civiqs and YouGov/Economist polls showed that while net support for Black Lives Matter among White Americans increased from -4 points to +10 points in early June 2020 (with 43% in support) it fell to -6 points by early August 2020, and by April 2021, further Civiqs polls showed that support for Black Lives Matter among White Americans had reverted to roughly its level of support prior to George Floyd’s murder (37% in favour and 49% opposed). In a February 2021 interview on Firing Line, journalist Charles M. Blow criticised a minority of young white protestors in the George Floyd protests in the US whom he argued were using the protests for their own personal growth to substitute for social rites of passage (e.g. prom) and summertime social gatherings (e.g. attending movie theatres or concerts) that were precluded by COVID-19 lockdowns and social distancing measures, noting that as lockdowns began to be relaxed and removed, support for Black Lives Matter among whites began to decline.

In February 2021, Psychological Medicine published a survey reviewing 14,785 publicly reported murders in English language news worldwide between 1900 and 2019 compiled in a database by psychiatrists at the New York State Psychiatric Institute and the Columbia University Irving Medical Centre that found that of the 1,315 personal-cause mass murders (i.e. driven by personal motivations and not occurring within the context of war, state-sponsored or group-sponsored terrorism, gang activity, or organised crime) only 11% of mass murderers and only 8% of mass shooters had a “serious mental illness” (e.g. schizophrenia, bipolar disorder, major depressive disorder), that mass shootings have become more common than other forms of mass murder since 1970 (with 73% occurring in the US alone), and that mass shooters in the United States were more likely to have legal histories, to engage in recreational drug use or alcohol abuse, and to display non-psychotic psychiatric or neurologic symptoms.

Survey coauthor psychiatrist Paul S. Appelbaum argued that the data from the survey indicated that “difficulty coping with life events seem more useful foci for prevention [of mass shootings] and policy than an emphasis on serious mental illness”, while psychiatrist Ronald W. Pies has suggested that psychopathology should be understood as a three-gradation continuum of mental, behavioural and emotional disturbance with most mass shooters falling into a middle category of “persistent emotional disturbance”. In 2015, psychiatrists James L. Knoll and George D. Annas noted that the tendency of most media attention following mass shootings on mental health leads to sociocultural factors being comparatively overlooked. Instead, Knoll and Annas cite research by social psychologists Jean Twenge and W. Keith Campbell on narcissism and social rejection in the personal histories of mass shooters, as well as cognitive scientist Steven Pinker’s suggestion in The Better Angels of Our Nature (2011) that further reductions in human violence may be dependent upon reducing human narcissism.

Proposed Diagnostic Categories

Gaming disorder has been considered by the DSM-5 task force as warranting further study (as the subset internet gaming disorder), and was included in the ICD-11. Concerns have been raised by Aarseth and colleagues over this inclusion, particularly in regard to stigmatisation of heavy gamers.

Christakis has asserted that internet addiction may be “a 21st century epidemic”. In 2018, he commented that childhood Internet overuse may be a form of “uncontrolled experiment[s] on […] children”. International estimates of the prevalence of internet overuse have varied considerably, with marked variations by nation. A 2014 meta-analysis of 31 nations yielded an overall worldwide prevalence of 6%. A different perspective in 2018 by Musetti and colleagues reappraised the internet in terms of its necessity and ubiquity in modern society, as a social environment, rather than a tool, thereby calling for the reformulation of the internet addiction model.

Some medical and behavioural scientists recommend adding a diagnosis of “social media addiction” (or similar) to the next Diagnostic and Statistical Manual of Mental Disorders update. A 2015 review concluded there was a probable link between basic psychological needs and social media addiction. “Social network site users seek feedback, and they get it from hundreds of people – instantly. It could be argued that the platforms are designed to get users ‘hooked’.”

Internet sex addiction, also known as cybersex addiction, has been proposed as a sexual addiction characterised by virtual internet sexual activity that causes serious negative consequences to one’s physical, mental, social, and/or financial well-being. It may be considered a form of problematic internet use.

Online Problem Gambling

A 2015 review found evidence of higher rates of mental health comorbidities, as well as higher amounts of substance use, among internet gamblers, compared to non-internet gamblers. Causation, however, has not been established. The review postulates that there may be differences in the cohorts between internet and land-based problem gamblers.

Cyberbullying

Cyberbullying, bullying or harassment using social media or other electronic means, has been shown to have effects on mental health. Victims may have lower self-esteem, increased suicidal ideation, decreased motivation for usual hobbies, and a variety of emotional responses, including being scared, frustrated, angry, anxious or depressed. These victims may also begin to distance themselves from friends and family members.

According to the EU Kids Online project, the incidence of cyberbullying across seven European countries in children aged 8-16 increased from 8% to 12% between 2010 and 2014. Similar increases were shown in the United States and Brazil.

Media Multitasking

Concurrent use of multiple digital media streams, commonly known as media multitasking, has been shown to be associated with depressive symptoms, social anxiety, impulsivity, sensation seeking, lower perceived social success and neuroticism. A 2018 review found that while the literature is sparse and inconclusive, overall, heavy media multitaskers also have poorer performance in several cognitive domains. One of the authors commented that the data does not “unambiguously show that media multitasking causes a change in attention and memory”, therefore it is possible to argue that it is inefficient to multitask on digital media.

Assessment and Treatment

Rigorous, evidence-based assessment of problematic digital media use is yet to be comprehensively established. This is due partially to a lack of consensus around the various constructs and lack of standardization of treatments. The American Academy of Paediatrics (AAP) has developed a Family Media Plan, intending to help parents assess and structure their family’s use of electronic devices and media more safely. It recommends limiting entertainment screen time to two hours or less per day. The Canadian Paediatric Society produced a similar guideline. Ferguson, a psychologist, has criticised these and other national guidelines for not being evidence-based. Other experts, cited in a 2017 UNICEF Office of Research literature review, have recommended addressing potential underlying problems rather than arbitrarily enforcing screen time limits.

Different methodologies for assessing pathological internet use have been developed, mostly self-report questionnaires, but none have been universally recognised as a gold standard. For gaming disorder, both the American Psychiatric Association and the World Health Organisation (through the ICD-11) have released diagnostic criteria.

There is some limited evidence of the effectiveness of cognitive behavioural therapy and family-based interventions for treatment. In randomised controlled trials, medications have not been shown to be effective. A 2016 study of 901 adolescents suggested mindfulness may assist in preventing and treating problematic internet use. A 2019 UK parliamentary report deemed parental engagement, awareness and support to be essential in developing “digital resilience” for young people, and to identify and manage the risks of harm online. Treatment centres have proliferated in some countries, and China and South Korea have treated digital dependence as a public health crisis, opening 300 and 190 centres nationwide, respectively. Other countries have also opened treatment centres.

NGOs, support and advocacy groups provide resources to people overusing digital media, with or without codified diagnoses, including the American Academy of Child and Adolescent Psychiatry.

Mental Health Benefits

Individuals with mental illness can develop social connections over social media, that may foster a sense of social inclusion in online communities. Sufferers of mental illness may share personal stories in a perceived safer space, as well as gaining peer support for developing coping strategies.

People with mental illness are likely to report avoiding stigma and gaining further insight into their mental health condition by using social media. This comes with the risk of unhealthy influences, misinformation, and delayed access to traditional mental health outlets.

Other benefits include connections to supportive online communities, including illness or disability specific communities, as well as the LGBTQIA community. Young cancer patients have reported an improvement in their coping abilities due to their participation in an online community. The uses of social media for healthcare communication include providing reducing stigma and facilitating dialogue between patients and between patients and health professionals.

Furthermore, in children, the educational benefits of digital media use are well established.

According to the American Addiction Centres, apps like TikTok are also helpful for its users to share their stories of recovery, celebrating milestones, and cheering on others on the path to recovery. Hashtags such as, #sober, #mentalhealthawareness, and #soberlife are helping to destigmatize sobriety.

Other Disciplines

Digital Anthropology

Daniel Miller from University College London has contributed to the study of digital anthropology, especially ethnographic research on the use and consequences of social media and smartphones as part of the everyday life of ordinary people around the world. He notes the effects of social media are very specific to individual locations and cultures. He contends “a layperson might dismiss these stories as superficial. But the anthropologist takes them seriously, empathetically exploring each use of digital technologies in terms of the wider social and cultural context.”

Digital anthropology is a developing field which studies the relationship between humans and digital-era technology. It aims to consider arguments in terms of ethical and societal scopes, rather than simply observing technological changes. Brian Solis, a digital analyst and anthropologist, stated in 2018, “we’ve become digital addicts: it’s time to take control of technology and not let tech control us”.

Digital Sociology

Digital sociology explores how people utilise digital media using several research methodologies, including surveys, interviews, focus groups, and ethnographic research. It intersects with digital anthropology, and studies cultural geography. It also investigates longstanding concerns, and contexts around young people’s overuse of “these technologies, their access to online pornography, cyber bullying or online sexual predation”.

A 2012 cross-sectional sociological study in Turkey showed differences in patterns of internet use that related to levels of religiosity in 2,698 subjects. With increasing religiosity, negative attitudes towards internet use increased. Highly religious people showed different motivations for internet use, predominantly searching for information. A study of 1,296 Malaysian adolescent students found an inverse relationship between religiosity and internet addiction tendency in females, but not males.

A 2018 review published in Nature considered that young people may have different experiences online, depending on their socio-economic background, noting lower-income youths may spend up to three hours more per day using digital devices, compared to higher-income youths. They theorised that lower-income youths, who are already vulnerable to mental illness, may be more passive in their online engagements, being more susceptible to negative feedback online, with difficulty self-regulating their digital media use. It concluded that this may be a new form of digital divide between at-risk young people and other young people, pre-existing risks of mental illness becoming amplified among the already vulnerable population.

Neuroscience

Dar Meshi and colleagues noted in 2015 that “[n]euroscientists are beginning to capitalise on the ubiquity of social media use to gain novel insights about social cognitive processes”. A 2018 neuroscientific review published in Nature found the density of the amygdala, a brain region involved in emotional processing, is related to the size of both offline and online social networks in adolescents. They considered that this and other evidence “suggests an important interplay between actual social experiences, both offline and online, and brain development”. The authors postulated that social media may have benefits, namely social connections with other people, as well as managing impressions people have of other people such as “reputation building, impression management, and online self-presentation”. It identified “adolescence [as] a tipping point in development for how social media can influence their self-concept and expectations of self and others”, and called for further study into the neuroscience behind digital media use and brain development in adolescence. Although brain-imaging modalities are under study, neuroscientific findings in individual studies often fail to be replicated in future studies, similar to other behavioural addictions; as of 2017, the exact biological or neural processes that could lead to excessive digital media use are unknown.

Impact on Cognition

There is a debate about the cognitive impacts of smartphones and digital technology. A group reported that, contrary to widespread belief, scientific evidence does not show that these technologies harm biological cognitive abilities and that they instead only change predominant ways of cognition – such as a reduced need to remember facts or conduct mathematical calculations by pen and paper outside contemporary schools. However, some activities – like reading novels – that require long focused attention-spans and don’t feature ongoing rewarding stimulation may become more challenging in general. How extensive online media usage impacts cognitive development in youth is under investigation and impacts may substantially vary by the way and which technologies are being used – such as which and how digital media platforms are being used – and how these are designed. Impacts may vary to a degree such studies have not yet taken into account and may be modulated by the design, choice and use of technologies and platforms, including by the users themselves.

Worldwide adolescent loneliness in contemporary schools and depression increased substantially after 2012 and a study found this to be associated with smartphone access and Internet use. However, smartphone and Internet technologies also have potentials and implemented use-cases for positive impacts on social life which is inextricably linked to mental health.

Digital Mental Health Care

Although it has been a topic of sustained controversy, digital technologies have also provided opportunities for delivery of mental health care online; benefits have been found with computerised cognitive behavioural therapy for depression and anxiety. Research of digital health interventions in young people is preliminary, with a meta-review unable to draw firm conclusions because of problems in research methodology. Potential benefits according to one review include “the flexibility, interactivity, and spontaneous nature of mobile communications […] in encouraging persistent and continual access to care outside clinical settings”. Mindfulness based online intervention has been shown to have small to moderate benefits on mental health. The greatest effect size was found for the reduction of psychological stress. Benefits were also found regarding depression, anxiety, and well-being. Smartphone applications have proliferated in many mental health domains, with “demonstrably effective” recommendations listed in a 2016 review encouraging cognitive behavioural therapy, addressing both anxiety and mood. The review did however call for more randomised controlled trials to validate the effectiveness of their recommendations when delivered by digital apps.

The Lancet commission on global mental health and sustainability report from 2018 evaluated both benefits and harms of technology. It considered the roles of technologies in mental health, particularly in public education; patient screening; treatment; training and supervision; and system improvement. A study in 2019 published in Front Psychiatry in the National Centre for Biotechnology Information states that despite proliferation of many mental health apps there has been no “equivalent proliferation of scientific evidence for their effectiveness.”

Steve Blumenfield and Jeff Levin-Scherz, writing in the Harvard Business Review, claim that “most published studies show telephonic mental health care is as effective as in-person care in treating depression, anxiety and obsessive-compulsive disorder.” The also cite a 2020 study done with the Veterans Administration as evidence of this as well.

Industry and Government

Several technology firms have implemented changes intending to mitigate the adverse effects of excessive use of their platforms, and in Japan, China and South Korea legislative and/or regulatory governmental efforts have been enacted to address the interrelated issues.

In December 2017, Facebook admitted passive consumption of social media could be harmful to mental health, although they said active engagement can have a positive effect. In January 2018, the platform made major changes to increase user engagement. In January 2019, Facebook’s then head of global affairs, Nick Clegg, responding to criticisms of Facebook and mental health concerns, stated they would do “whatever it takes to make this environment safer online especially for youngsters”. Facebook admitted “heavy responsibilities” to the global community, and invited regulation by governments. In 2018 Facebook and Instagram announced new tools that they asserted may assist with overuse of their products. In 2019, Instagram, which has been investigated specifically in one study in terms of addiction, began testing a platform change in Canada to hide the number of “likes” and views that photos and videos received in an effort to create a “less pressurised” environment. It then continued this trial in Australia, Italy, Ireland, Japan, Brazil and New Zealand before extending the experiment globally in November of that year. The platform also developed artificial intelligence to counter cyberbullying.

China’s Ministry of Culture has enacted several public health efforts from as early as 2006 to address gaming and internet-related disorders. In 2007, an “Online Game Anti-Addiction System” was implemented for minors, restricting their use to 3 hours or less per day. The ministry also proposed a “Comprehensive Prevention Programme Plan for Minors’ Online Gaming Addiction” in 2013, to promulgate research, particularly on diagnostic methods and interventions. China’s Ministry of Education in 2018 announced that new regulations would be introduced to further limit the amount of time spent by minors in online games. In response, Tencent, the owner of WeChat and the world’s largest video game publisher, restricted the amount of time that children could spend playing one of its online games, to one hour per day for children 12 and under, and two hours per day for children aged 13-18.

In 2018, Alphabet Inc. released an update for Android smartphones, including a dashboard app enabling users to set timers on application use. Apple Inc. purchased a third-party application and then incorporated it in iOS 12 to measure “screen time”. Journalists have questioned the functionality of these products for users and parents, as well as the companies’ motivations for introducing them. Alphabet has also invested in a mental health specialist, Quartet, which uses machine learning to collaborate and coordinate digital delivery of mental health care.

South Korea has eight government ministries responsible for public health efforts in relation to internet and gaming disorders, a review article published in Prevention Science in 2018 stating that the “region is unique in that its government has been at the forefront of prevention efforts, particularly in contrast to the United States, Western Europe, and Oceania.” Efforts are coordinated by the Ministry of Science and ICT, and include awareness campaigns, educational interventions, youth counselling centres, and promoting healthy online culture.

Two institutional investors in Apple Inc., JANA Partners LLC and the California State Teachers’ Retirement System (CalSTRS), stated in 2018 that they “believe[d] both the content and the amount of time spent on phones need to be tailored to youths”. They called on Apple Inc. to act before regulators and consumers potentially force them to do so. Apple Inc. responded that they have, “always looked out for kids, and [they] work hard to create powerful products that inspire, entertain, and educate children while also helping parents protect them online”. The firm is planning new features that they asserted may allow them to play a pioneering role in regard to young people’s health.

Japan’s Ministry of Internal Affairs and Communications coordinates Japanese public health efforts in relation to problematic internet use and gaming disorder. Legislatively, the Act on Development of an Environment that Provides Safe and Secure Internet Use for Young People was enacted in 2008, to promote public awareness campaigns, and support NGOs to teach young people safe internet use skills.

What is Chlordiazepoxide?

Published on 12/13/2021 by Andrew Marshall2 Comments

Introduction

Chlordiazepoxide, trade name Librium among others, is a sedative and hypnotic medication of the benzodiazepine class; it is used to treat anxiety, insomnia and symptoms of withdrawal from alcohol and other drugs.

Chlordiazepoxide has a medium to long half-life but its active metabolite has a very long half-life. The drug has amnesic, anticonvulsant, anxiolytic, hypnotic, sedative and skeletal muscle relaxant properties.

Chlordiazepoxide was patented in 1958 and approved for medical use in 1960. It was the first benzodiazepine to be synthesized and the discovery of chlordiazepoxide was by pure chance. Chlordiazepoxide and other benzodiazepines were initially accepted with widespread public approval but were followed with widespread public disapproval and recommendations for more restrictive medical guidelines for its use.

Brief History

Chlordiazepoxide (initially called methaminodiazepoxide) was the first benzodiazepine to be synthesized in the mid-1950s. The synthesis was derived from work on a class of dyes, quinazolone-3-oxides. It was discovered by accident when in 1957 tests revealed that the compound had hypnotic, anxiolytic, and muscle relaxant effects. “The story of the chemical development of Librium and Valium was told by Sternbach. The serendipity involved in the invention of this class of compounds was matched by the trials and errors of the pharmacologists in the discovery of the tranquilising activity of the benzodiazepines. The discovery of Librium in 1957 was due largely to the dedicated work and observational ability of a gifted technician, Beryl Kappell. For some seven years she had been screening compounds by simple animal tests for muscle relaxant activity…” Three years later chlordiazepoxide was marketed as a therapeutic benzodiazepine medication under the brand name Librium. Following chlordiazepoxide, in 1963 diazepam hit the market under the brand name Valium – and was followed by many further benzodiazepine compounds over the subsequent years and decades.

In 1959 it was used by over 2,000 physicians and more than 20,000 patients. It was described as “chemically and clinically different from any of the tranquilisers, psychic energizers or other psychotherapeutic drugs now available.” During studies, chlordiazepoxide induced muscle relaxation and a quieting effect on laboratory animals like mice, rats, cats, and dogs. Fear and aggression were eliminated in much smaller doses than those necessary to produce hypnosis. Chlordiazepoxide is similar to phenobarbital in its anticonvulsant properties. However, it lacks the hypnotic effects of barbiturates. Animal tests were conducted in the Boston Zoo and the San Diego Zoo. Forty-two hospital patients admitted for acute and chronic alcoholism, and various psychoses and neuroses were treated with chlordiazepoxide. In a majority of the patients, anxiety, tension, and motor excitement were “effectively reduced.” The most positive results were observed among alcoholic patients. It was reported that ulcers and dermatologic problems, both of which involved emotional factors, were reduced by chlordiazepoxide.

In 1963, approval for use was given to diazepam (Valium), a “simplified” version of chlordiazepoxide, primarily to counteract anxiety symptoms. Sleep-related problems were treated with nitrazepam (Mogadon), which was introduced in 1972, temazepam (Restoril), which was introduced in 1979, and flurazepam (Dalmane), which was introduced in 1975.

Medical Uses

Chlordiazepoxide is indicated for the short-term (2-4 weeks) treatment of anxiety that is severe and disabling or subjecting the person to unacceptable distress. It is also indicated as a treatment for the management of acute alcohol withdrawal syndrome.

It can sometimes be prescribed to ease symptoms of irritable bowel syndrome combined with clidinium bromide as a fixed dose medication, Librax.

Contraindications

Use of chlordiazepoxide should be avoided in individuals with the following conditions:

Myasthenia gravis.
Acute intoxication with alcohol, narcotics, or other psychoactive substances.
Ataxia.
Severe hypoventilation.
Acute narrow-angle glaucoma.
Severe liver deficiencies (hepatitis and liver cirrhosis decrease elimination by a factor of 2).
Severe sleep apnoea.
Hypersensitivity or allergy to any drug in the benzodiazepine class.

Chlordiazepoxide is generally considered an inappropriate benzodiazepine for the elderly due to its long elimination half-life and the risks of accumulation. Benzodiazepines require special precaution if used in the elderly, pregnancy, children, alcohol- or drug-dependent individuals and individuals with comorbid psychiatric disorders.

Pregnancy

The research into the safety of benzodiazepines during pregnancy is limited and it is recommended that use of benzodiazepines during pregnancy should be based on whether the benefits outweigh the risks. If chlordiazepoxide is used during pregnancy the risks can be reduced via using the lowest effective dose and for the shortest time possible. Benzodiazepines should generally be avoided during the first trimester of pregnancy. Chlordiazepoxide and diazepam are considered to be among the safer benzodiazepines to use during pregnancy in comparison to other benzodiazepines. Possible adverse effects from benzodiazepine use during pregnancy include, abortion, malformation, intrauterine growth retardation, functional deficits, carcinogenesis and mutagenesis. Caution is also advised during breast feeding as chlordiazepoxide passes into breast milk.

Adverse Effects

Sedative drugs and sleeping pills, including chlordiazepoxide, have been associated with an increased risk of death. The studies had many limitations: possibly tending to overestimate risk, such as possible confounding by indication with other risk factors; confusing hypnotics with drugs having other indications. Common side-effects of chlordiazepoxide include:

Confusion.
Constipation.
Drowsiness.
Fainting.
Altered sex drive.
Liver problems.
Lack of muscle coordination.
Minor menstrual irregularities.
Nausea.
Skin rash or eruptions.
Swelling due to fluid retention.
Yellow eyes and skin.

Chlordiazepoxide in laboratory mice studies impairs latent learning. Benzodiazepines impair learning and memory via their action on benzodiazepine receptors, which causes a dysfunction in the cholinergic neuronal system in mice. It was later found that scopolamine impairment in learning was caused by an increase in benzodiazepine/GABA activity (and that benzodiazepines were not associated with the cholinergic system). In tests of various benzodiazepine compounds, chlordiazepoxide was found to cause the most profound reduction in the turnover of 5HT (serotonin) in rats. Serotonin is closely involved in regulating mood and may be one of the causes of feelings of depression in rats using chlordiazepoxide or other benzodiazepines.

Tolerance

Chronic use of benzodiazepines, such as chlordiazepoxide, leads to the development of tolerance, with a decrease in number of benzodiazepine binding sites in mouse forebrain. The Committee of Review of Medicines, who carried out an extensive review of benzodiazepines including chlordiazepoxide, found – and were in agreement with the Institute of Medicine (USA) and the conclusions of a study carried out by the White House Office of Drug Policy and the US National Institute on Drug Abuse – that there was little evidence that long-term use of benzodiazepines were beneficial in the treatment of insomnia due to the development of tolerance. Benzodiazepines tended to lose their sleep-promoting properties within 3-14 days of continuous use, and in the treatment of anxiety the committee found that there was little convincing evidence that benzodiazepines retained efficacy in the treatment of anxiety after 4 months’ continuous use due to the development of tolerance.

Dependence

Chlordiazepoxide can cause physical dependence and what is known as the benzodiazepine withdrawal syndrome. Withdrawal from chlordiazepoxide or other benzodiazepines often leads to withdrawal symptoms that are similar to those seen with alcohol and barbiturates. The higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can, however, occur at standard dosages and also after short-term use. Benzodiazepine treatment should be discontinued as soon as possible through a slow and gradual dose-reduction regime.

Chlordiazepoxide taken during pregnancy can cause a postnatal benzodiazepine withdrawal syndrome.

Overdose

Refer to Benzodiazepine Overdose.

An individual who has consumed excess chlordiazepoxide may display some of the following symptoms:

Somnolence (difficulty staying awake).
Mental confusion.
Hypotension.
Hypoventilation.
Impaired motor functions:
- Impaired reflexes.
- Impaired coordination.
- Impaired balance.
- Dizziness.
- Muscle weakness.
Coma.

Chlordiazepoxide is a drug that is very frequently involved in drug intoxication, including overdose. Chlordiazepoxide overdose is considered a medical emergency and, in general, requires the immediate attention of medical personnel. The antidote for an overdose of chlordiazepoxide (or any other benzodiazepine) is flumazenil. Flumazenil should be given with caution as it may precipitate severe withdrawal symptoms in benzodiazepine-dependent individuals.

Pharmacology

Chlordiazepoxide acts on benzodiazepine allosteric sites that are part of the GABA_A receptor/ion-channel complex and this results in an increased binding of the inhibitory neurotransmitter GABA to the GABA_A receptor thereby producing inhibitory effects on the central nervous system and body similar to the effects of other benzodiazepines. Chlordiazepoxide is anticonvulsant. There is preferential storage of chlordiazepoxide in some organs including the heart of the neonate. Absorption by any administered route and the risk of accumulation is significantly increased in the neonate. The withdrawal of chlordiazepoxide during pregnancy and breast feeding is recommended, as chlordiazepoxide rapidly crosses the placenta and also is excreted in breast milk. Chlordiazepoxide also decreases prolactin release in rats. Benzodiazepines act via micromolar benzodiazepine binding sites as Ca2+ channel blockers and significantly inhibit depolarization-sensitive Calcium uptake in animal nerve terminal preparations. Chlordiazepoxide inhibits acetylcholine release in mouse hippocampal synaptosomes in vivo. This has been found by measuring sodium-dependent high affinity choline uptake in vitro after pre-treatment of the mice in vivo with chlordiazepoxide. This may play a role in chlordiazepoxide’s anticonvulsant properties.

Pharmacokinetics

Chlordiazepoxide is a long-acting benzodiazepine drug. The half-life of Chlordiazepoxide is 5-30 hours but has an active benzodiazepine metabolite (desmethyldiazepam), which has a half-life of 36-200 hours. The half-life of chlordiazepoxide increases significantly in the elderly, which may result in prolonged action as well as accumulation of the drug during repeated administration. Delayed body clearance of the long half-life active metabolite also occurs in those over 60 years of age, which further prolongs the effects of the drugs with additional accumulation after repeated dosing.

Despite its name, chlordiazepoxide is not an epoxide; they are formed from different roots.

Recreational Use

Refer to Benzodiazepine Use Disorder.

In 1963, Carl F. Essig of the Addiction Research Centre of the National Institute of Mental Health stated that meprobamate, glutethimide, ethinamate, ethchlorvynol, methyprylon and chlordiazepoxide as drugs whose usefulness “can hardly be questioned.” However, Essig labelled these “newer products” as “drugs of addiction,” like barbiturates, whose habit-forming qualities were more widely known. He mentioned a 90-day study of chlordiazepoxide, which concluded that the automobile accident rate among 68 users was 10 times higher than normal. Participants’ daily dosage ranged from 5 to 100 milligrams.

Chlordiazepoxide is a drug of potential misuse and is frequently detected in urine samples of drug users who have not been prescribed the drug.

Legal Status

Internationally, chlordiazepoxide is a Schedule IV controlled drug under the Convention on Psychotropic Substances.

Toxicity

Animal

Laboratory tests assessing the toxicity of chlordiazepoxide, nitrazepam and diazepam on mice spermatozoa found that chlordiazepoxide produced toxicities in sperm including abnormalities involving both the shape and size of the sperm head. Nitrazepam, however, caused more profound abnormalities than chlordiazepoxide.

Availability

Chlordiazepoxide is available in various dosage forms, alone or in combination with other drugs, worldwide. In combination with Clidinium as NORMAXIN-CC and in combination with dicyclomine as NORMAXIN for IBS, and with the anti-depressant Amitriptyline as Limbitrol.

What is the Chinese Classification of Mental Disorders?

Published on 12/13/2021 by Andrew Marshall1 Comment

Introduction

The Chinese Classification of Mental Disorders (CCMD; Chinese: 中国精神疾病分类方案与诊断标准), published by the Chinese Society of Psychiatry (CSP), is a clinical guide used in China for the diagnosis of mental disorders.

It is currently on a third version, the CCMD-3, written in Chinese and English. It is intentionally similar in structure and categorisation to the International Classification of Diseases (ICD) and DSM, the two most well-known diagnostic manuals, though it includes some variations on their main diagnoses and around 40 culturally related diagnoses.

Brief History

The first published Chinese psychiatric classificatory scheme appeared in 1979. A revised classification system, the CCMD-1, was made available in 1981 and further modified in 1984 (CCMD-2-R). The CCMD-3 was published in 2001.

Many Chinese psychiatrists believed the CCMD had special advantages over other manuals, such as simplicity, stability, the inclusion of culture-distinctive categories, and the exclusion of certain Western diagnostic categories. The Chinese translation of the ICD-10 was seen as linguistically complicated, containing very long sentences and awkward terms and syntax (Lee, 2001).

Diagnostic Categories

The diagnosis of depression is included in the CCMD, with many similar criteria to the ICD or DSM, with the core having been translated as ‘low spirits’. However, Neurasthenia is a more central diagnosis. Although also found in the ICD, its diagnosis takes a particular form in China, called ‘shenjing shuairuo’, which emphasizes somatic (bodily) complaints as well as fatigue or depressed feelings. Neurasthenia is a less stigmatising diagnosis than depression in China, being conceptually distinct from psychiatric labels, and is said to fit well with a tendency to express emotional issues in somatic terms. The concept of neurasthenia as a nervous system disorder is also said to fit well with the traditional Chinese epistemology of disease causation on the basis of disharmony of vital organs and imbalance of qi.

The diagnosis of schizophrenia is included in the CCMD. It is applied quite readily and broadly in Chinese psychiatry.

Some of the wordings of the diagnosis are different, for example rather than borderline personality disorder as in the DSM, or emotionally unstable personality disorder (borderline type) as in the ICD, the CCMD has impulsive personality disorder.

Diagnoses that are more specific to Chinese or Asian culture, though they may also be outlined in the ICD (or DSM glossary section), includes:

Koro or Genital retraction syndrome: excessive fear of the genitals (and also breasts in women) shrinking or drawing back into the body.
Zou huo ru mo (走火入魔) or qigong deviation (氣功偏差): perception of uncontrolled flow of qi in the body.
Mental disorders due to superstition or witchcraft.
Travelling psychosis.

The CCMD-3 lists several “disorders of sexual preference” including ego-dystonic homosexuality, but does not recognise paedophilia.

Koro

Koro or Genital retraction syndrome is a culture-specific syndrome from Southeast Asia in which the patient has an overpowering belief that the genitalia (or nipples in females) are shrinking and will shortly disappear. In China, it is known as shuk yang, shook yong, and suo yang (simplified Chinese: 缩阳; traditional Chinese: 縮陽). This has been associated with cultures placing a heavy emphasis on balance, or on fertility and reproduction.

Zou Huo Ru Mo

Zou huo ru mo (走火入魔) or “qigong deviation” (氣功偏差) is a mental condition characterised by the perception that there is uncontrolled flow of qi in the body. Other complaints include localised pains, headache, insomnia, and uncontrolled spontaneous movements.

Introduction

Legality

United Kingdom

United States

Australia

Sweden

Effects

Introduction

Legal Status

Sweden

Switzerland

United Kingdom

Introduction

Measurement

Applications and Research Findings

Contributing Factors

Positive Contributing Factors

Negative Contributing Factors

Extrinsic and Intrinsic Psychological Needs

Relations with Others

Heritability

Well-Being Therapy

Introduction

Background

Introduction

Brief History

Availability in Europe

Medical Uses

Elderly

Adverse Effects

Dependence

Non-Medical Use

Overdose

Interactions

Pharmacology

Introduction

Medical Uses

Side Effects

Tolerance and Dependence

Contraindications and Special Caution

Elderly

Pharmacology

Pharmacokinetics

Interactions

EEG Effects in Rabbits

Abuse

Events

People (Births)

Nicholas P. Dallis

Introduction

Brief History and Terminology

Problematic Use

Screen Time and Mental Health

ADHD

Autism

Insomnia

NPD

Proposed Diagnostic Categories

Related Phenomena

Online Problem Gambling

Cyberbullying

Media Multitasking

Assessment and Treatment

Mental Health Benefits

Other Disciplines

Digital Anthropology

Digital Sociology

Neuroscience

Impact on Cognition

Impact on Social Life

Digital Mental Health Care

Industry and Government

Introduction

Brief History

Medical Uses

Contraindications

Pregnancy

Adverse Effects

Tolerance

Dependence