What is Mindfulness-Based Stress Reduction?

Introduction

Mindfulness-based stress reduction (MBSR) is an eight-week evidence-based programme that offers secular, intensive mindfulness training to assist people with stress, anxiety, depression and pain.

Developed at the University of Massachusetts Medical Centre in the 1970s by Professor Jon Kabat-Zinn, MBSR uses a combination of mindfulness meditation, body awareness, yoga and exploration of patterns of behaviour, thinking, feeling and action. Mindfulness can be understood as the non-judgemental acceptance and investigation of present experience, including body sensations, internal mental states, thoughts, emotions, impulses and memories, in order to reduce suffering or distress and to increase well-being. Mindfulness meditation is a method by which attention skills are cultivated, emotional regulation is developed, and rumination and worry are significantly reduced. During the past decades, mindfulness meditation has been the subject of more controlled clinical research, which suggests its potential beneficial effects for mental health, as well as physical health. While MBSR has its roots in Buddhist wisdom teachings, the programme itself is secular. The MBSR programme is described in detail in Kabat-Zinn’s 1990 book Full Catastrophe Living.

Brief History

In 1979, Jon Kabat-Zinn founded the Mindfulness Based Stress Reduction Clinic at the University of Massachusetts Medical Centre, and nearly twenty years later the Centre for Mindfulness in Medicine, Health Care and Society at the University of Massachusetts Medical School. Both these institutions supported the growth and implementation of MBSR into hospitals worldwide. Kabat-Zinn described the MBSR program in detail in his bestselling 1990 book Full Catastrophe Living, which was reissued in a revised edition in 2013. In 1993, the MBSR course taught by Jon Kabat-Zinn was featured in Bill Moyer’s Healing from Within. In the year 2015, close to 80% of medical schools are reported to offer some element of mindfulness training, and research and education centres dedicated to mindfulness have proliferated.

Programme

A meta-analysis described MBSR as “a group programme that focuses upon the progressive acquisition of mindful awareness, of mindfulness”. The MBSR programme is an eight-week workshop taught by certified trainers that entails weekly group meetings (2.5 hour classes) and a one-day retreat (seven-hour mindfulness practice) between sessions six and seven, homework (45 minutes daily), and instruction in three formal techniques: mindfulness meditation, body scanning and simple yoga postures. Group discussions and exploration – of experience of the meditation practice and its application to life – is a central part of the program. Body scanning is the first prolonged formal mindfulness technique taught during the first four weeks of the course, and entails quietly sitting or lying and systematically focusing one’s attention on various regions of the body, starting with the toes and moving up slowly to the top of the head. MBSR is based on non-judging, non-striving, acceptance, letting go, beginners mind, patience, trust, and non-centring.

According to Kabat-Zinn, the basis of MBSR is mindfulness, which he defined as “moment-to-moment, non-judgmental awareness.” During the programme, participants are asked to focus on informal practice as well by incorporating mindfulness into their daily routines. Focusing on the present is thought to heighten sensitivity to the environment and one’s own reactions to it, consequently enhancing self-management and coping. It also provides an outlet from ruminating on the past or worrying about the future, breaking the cycle of these maladaptive cognitive processes. The validity and reliability of a weekly single-item practice quality assessment have been confirmed by research. Increases in practice quality predicted improvements in self-report mindfulness and psychological symptoms but not behavioural mindfulness, and longer practice sessions were linked to better practice quality.

Scientific evidence of the debilitating effects of stress on human body and its evolutionary origins were pinpointed by the work of Robert Sapolsky, and explored for lay readers in the book Why Zebras Don’t Get Ulcers. Engaging in mindfulness meditation brings about significant reductions in psychological stress, and appears to prevent the associated physiological changes and biological clinical manifestations that happen as a result of psychological stress. According to early neuroimaging studies, MBSR training has an influence on the areas of the brain responsible for attention, introspection, and emotional processing.

Extent of Practice

According to a 2014 article in Time magazine, mindfulness meditation is becoming popular among people who would not normally consider meditation. The curriculum started by Kabat-Zinn at University of Massachusetts Medical Centre has produced nearly 1,000 certified MBSR instructors who are in nearly every state in the US and more than 30 countries. Corporations such as General Mills have made MBSR instruction available to their employees or set aside rooms for meditation. Democratic Congressman Tim Ryan published a book in 2012 titled A Mindful Nation and he has helped organise regular group meditation periods on Capitol Hill.

Methods of Practice

Mindfulness-based stress reduction classes and programs are offered by various facilities including hospitals, retreat centres, and various yoga facilities. Typically the programs focus on teaching

  • mind and body awareness to reduce the physiological effects of stress, pain or illness
  • experiential exploration of experiences of stress and distress to develop less emotional reactivity
  • equanimity in the face of change and loss that is natural to any human life
  • non-judgemental awareness in daily life
  • promote serenity and clarity in each moment
  • to experience more joyful life and access inner resources for healing and stress management
  • mindfulness meditation

Evaluation of Effectiveness

Mindfulness-based approaches have been found to be beneficial for healthy adults for adolescents and children, healthcare professionals, as well as for different health-related outcomes including eating disorders, psychiatric conditions, pain management, sleep disorders, cancer care, psychological distress, and for coping with health-related conditions. As a major subject of increasing research interest, 52 papers were published in 2003, rising to 477 by 2012. Nearly 100 randomised controlled trials had been published by early 2014.

The development of therapies to improve individuals’ flexibility in switching between using and not using emotion regulation (ER) methods is necessary because it is linked to better mental health, wellbeing, and resilience. According to research, those who attended MBSR training exhibited greater regulatory decision flexibility. In post-secondary students, research on mindfulness-based stress reduction has demonstrated that it can reduce psychological distress, which is common in this age range. In one study, the long-term impact of an 8-week Mindfulness-Based Stress Reduction (MBSR) treatment extended to two months after the intervention was completed.

Individuals with eating disorders have benefited from the mindfulness-based approach. MBSR therapy has been found to assist individuals improve the way they view their bodies. Interventions, such as mindfulness-based approaches, which focus on effective coping skills and improving one’s relationship with themselves through increased self-compassion can positively impact a person’s body image and contribute to overall well-being.

Research suggests mindfulness training improves focus, attention, and ability to work under stress. Mindfulness may also have potential benefits for cardiovascular health. Evidence suggests efficacy of mindfulness meditation in the treatment of substance use disorders. Mindfulness training may also be beneficial for people with fibromyalgia.

In addition, recent research has explored the ability of mindfulness-based stress reduction to increase self-compassion and enhance the well-being of those who are caregivers, specifically mothers, for youth struggling with substance use disorders. Mindfulness-based interventions allowed for the mothers to experience a decrease in stress as well as a better relationship with themselves which resulted in improved interpersonal relationships.

It has been demonstrated that mindfulness-based stress reduction has beneficial impacts on healthy individuals as well as suffering individuals and those close to suffering individuals. Roca et al. (2019) conducted an 8-week mindfulness-based stress reduction programme for healthy participants. Five pillars of MBSR, including mindfulness, compassion, psychological well-being, psychological distress, and emotional-cognitive control were identified. Participants psychological functioning were examined and assessed using questionnaires. Mindfulness and overall well-being was significant between the five pillars observed.

Mindfulness-based interventions and their impact have become prevalent in every-day life, especially when rooted in an academic setting. After interviewing children, of the average age of 11, it was apparent that mindfulness had contributed to their ability to regulate their emotions. In addition to these findings, these children expressed that the more mindfulness was incorporated by their school and teachers, the easier it was to apply its principles.

Mindfulness-based stress approaches have been shown to increase self-compassion. Higher levels of self-compassion have been found to greatly reduce stress. In addition, as self-compassion increases it seems as though self-awareness increases as well. This finding has been observed to occur during treatment as well as a result at the conclusion, and even after, treatment. Self-compassion is both a result and an informative factor of the effectiveness of mindfulness-based approaches.

MBIs (mindfulness-based intervations) showed a positive effect on mental and somatic health in social when compared to other active treatments in adults. This effects may be gender dependent. However, the effects seemed independent of duration and compliance with these kind of intervention.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Mindfulness-based_stress_reduction >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

What is Clonazepam?

Introduction

Clonazepam, sold under the brand name Klonopin among others, is a medication used to prevent and treat seizures, panic disorder, anxiety, and the movement disorder known as akathisia. It is a tranquiliser of the benzodiazepine class. It is typically taken by mouth. Effects begin within one hour and last between six and twelve hours.

Common side effects include sleepiness, poor coordination, and agitation. Long-term use may result in tolerance, dependence, and withdrawal symptoms if stopped abruptly. Dependence occurs in one-third of people who take clonazepam for longer than four weeks. There is an increased risk of suicide, particularly in people who are already depressed. If used during pregnancy it may result in harm to the foetus. Clonazepam binds to GABAA receptors, thus increasing the effect of the chief inhibitory neurotransmitter γ-aminobutyric acid (GABA).

Clonazepam was patented in 1960 and went on sale in 1975 in the United States from Roche. It is available as a generic medication. In 2019, it was the 46th most commonly prescribed medication in the United States, with more than 15 million prescriptions. In many areas of the world it is commonly used as a recreational drug.

Medical Uses

Clonazepam is prescribed for short term management of epilepsy, anxiety, and panic disorder with or without agoraphobia.

Seizures

Clonazepam, like other benzodiazepines, while being a first-line treatment for acute seizures, is not suitable for the long-term treatment of seizures due to the development of tolerance to the anticonvulsant effects.

Clonazepam has been found effective in treating epilepsy in children, and the inhibition of seizure activity seemed to be achieved at low plasma levels of clonazepam. As a result, clonazepam is sometimes used for certain rare childhood epilepsies; however, it has been found to be ineffective in the control of infantile spasms. Clonazepam is mainly prescribed for the acute management of epilepsies. Clonazepam has been found to be effective in the acute control of non-convulsive status epilepticus; however, the benefits tended to be transient in many people, and the addition of phenytoin for lasting control was required in these patients.

It is also approved for treatment of typical and atypical absences (seizures), infantile myoclonic, myoclonic, and akinetic seizures. A subgroup of people with treatment resistant epilepsy may benefit from long-term use of clonazepam; the benzodiazepine clorazepate may be an alternative due to its slow onset of tolerance.

Anxiety Disorders

  • Panic disorder with or without agoraphobia.
  • Clonazepam has also been found effective in treating other anxiety disorders, such as social phobia, but this is an off-label use.

The effectiveness of clonazepam in the short-term treatment of panic disorder has been demonstrated in controlled clinical trials. Some long-term trials have suggested a benefit of clonazepam for up to three years without the development of tolerance but these trials were not placebo-controlled. Clonazepam is also effective in the management of acute mania.

Muscle Disorders

Restless legs syndrome can be treated using clonazepam as a third-line treatment option as the use of clonazepam is still investigational. Bruxism also responds to clonazepam in the short-term. Rapid eye movement sleep behaviour disorder responds well to low doses of clonazepam.

  • The treatment of acute and chronic akathisia induced by neuroleptics, also called antipsychotics.
  • Spasticity related to amyotrophic lateral sclerosis.
  • Alcohol withdrawal syndrome

Other

  • Benzodiazepines, such as clonazepam, are sometimes used for the treatment of mania or acute psychosis-induced aggression. In this context, benzodiazepines are given either alone, or in combination with other first-line drugs such as lithium, haloperidol, or risperidone. The effectiveness of taking benzodiazepines along with antipsychotic medication is unknown, and more research is needed to determine if benzodiazepines are more effective than antipsychotics when urgent sedation is required.
  • Hyperekplexia: A very rare neurologic disorder classically characterised by pronounced startle responses to tactile or acoustic stimuli and hypertonia.
  • Many forms of parasomnia and other sleep disorders are treated with clonazepam..
  • It is not effective for preventing migraines.

Contraindications

  • Coma.
  • Current alcohol use disorder.
  • Current substance use disorder.
  • Respiratory depression.

Adverse Effects

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.

Common

  • Sedation.
  • Motor impairment.

Less Common

  • Confusion.
  • Irritability and aggression.
  • Psychomotor agitation.
  • Lack of motivation.
  • Loss of libido.
  • Impaired motor function.
  • Impaired coordination.
  • Impaired balance.
  • Dizziness.
  • Cognitive impairments.
  • Hallucinations.
  • Short-term memory loss.
  • Anterograde amnesia (common with higher doses).
  • Some users report hangover-like symptoms of drowsiness, headaches, sluggishness, and irritability upon waking up if the medication was taken before sleep.
    • This is likely the result of the medication’s long half-life, which continues to affect the user after waking up.
    • While benzodiazepines induce sleep, they tend to reduce the quality of sleep by suppressing or disrupting REM sleep.
    • After regular use, rebound insomnia may occur when discontinuing clonazepam.
  • Benzodiazepines may cause or worsen depression.

Occasional

  • Dysphoria.
  • Induction of seizures or increased frequency of seizures.
  • Personality changes.
  • Behavioural disturbances.
  • Ataxia.

Rare

  • Cognitive Euphoria.
  • Suicide through disinhibition.
  • Psychosis.
  • Incontinence.
  • Liver damage.
  • Paradoxical behavioural disinhibition (most frequently in children, the elderly, and in persons with developmental disabilities).
  • Rage.
  • Excitement.
  • Impulsivity.
  • The long-term effects of clonazepam can include depression, disinhibition, and sexual dysfunction.

Drowsiness

Clonazepam, like other benzodiazepines, may impair a person’s ability to drive or operate machinery. The central nervous system depressing effects of the drug can be intensified by alcohol consumption, and therefore alcohol should be avoided while taking this medication. Benzodiazepines have been shown to cause dependence. Patients dependent on clonazepam should be slowly titrated off under the supervision of a qualified healthcare professional to reduce the intensity of withdrawal or rebound symptoms.

Withdrawal-Related

  • Anxiety.
  • Irritability.
  • Insomnia.
  • Tremors.
  • Headaches.
  • Stomach pain.
  • Hallucinations.
  • Suicidal thoughts or urges.
  • Depression.
  • Fatigue.
  • Dizziness.
  • Sweating.
  • Confusion.
  • Potential to exacerbate existing panic disorder upon discontinuation.
  • Seizures similar to delirium tremens (with long-term use of excessive doses).

Benzodiazepines such as clonazepam can be very effective in controlling status epilepticus, but, when used for longer periods of time, some potentially serious side-effects may develop, such as interference with cognitive functions and behaviour. Many individuals treated on a long-term basis develop a dependence. Physiological dependence was demonstrated by flumazenil-precipitated withdrawal. Use of alcohol or other central nervous system (CNS)-depressants while taking clonazepam greatly intensifies the effects (and side effects) of the drug.

A recurrence of symptoms of the underlying disease should be separated from withdrawal symptoms.

Tolerance and Withdrawal

Refer to Benzodiazepine Withdrawal Syndrome.

Like all benzodiazepines, clonazepam is a GABA-positive allosteric modulator. One-third of individuals treated with benzodiazepines for longer than four weeks develop a dependence on the drug and experience a withdrawal syndrome upon dose reduction. High dosage and long-term use increase the risk and severity of dependence and withdrawal symptoms. Withdrawal seizures and psychosis can occur in severe cases of withdrawal, and anxiety and insomnia can occur in less severe cases of withdrawal. A gradual reduction in dosage reduces the severity of the benzodiazepine withdrawal syndrome. Due to the risks of tolerance and withdrawal seizures, clonazepam is generally not recommended for the long-term management of epilepsies. Increasing the dose can overcome the effects of tolerance, but tolerance to the higher dose may occur and adverse effects may intensify. The mechanism of tolerance includes receptor desensitisation, down regulation, receptor decoupling, and alterations in subunit composition and in gene transcription coding.

Tolerance to the anticonvulsant effects of clonazepam occurs in both animals and humans. In humans, tolerance to the anticonvulsant effects of clonazepam occurs frequently. Chronic use of benzodiazepines can lead to the development of tolerance with a decrease of benzodiazepine binding sites. The degree of tolerance is more pronounced with clonazepam than with chlordiazepoxide. In general, short-term therapy is more effective than long-term therapy with clonazepam for the treatment of epilepsy. Many studies have found that tolerance develops to the anticonvulsant properties of clonazepam with chronic use, which limits its long-term effectiveness as an anticonvulsant.

Abrupt or over-rapid withdrawal from clonazepam may result in the development of the benzodiazepine withdrawal syndrome, causing psychosis characterised by dysphoric manifestations, irritability, aggressiveness, anxiety, and hallucinations. Sudden withdrawal may also induce the potentially life-threatening condition, status epilepticus. Anti-epileptic drugs, benzodiazepines such as clonazepam in particular, should be reduced in dose slowly and gradually when discontinuing the drug to mitigate withdrawal effects. Carbamazepine has been tested in the treatment of clonazepam withdrawal but was found to be ineffective in preventing clonazepam withdrawal-induced status epilepticus from occurring.

Overdose

Refer to Benzodiazepine Overdose.

Excess doses may result in:

  • Difficulty staying awake.
  • Mental confusion.
  • Impaired motor functions.
  • Impaired reflexes.
  • Impaired coordination.
  • Impaired balance.
  • Dizziness.
  • Respiratory depression.
  • Low blood pressure.
  • Coma.

Coma can be cyclic, with the individual alternating from a comatose state to a hyper-alert state of consciousness, which occurred in a four-year-old boy who overdosed on clonazepam. The combination of clonazepam and certain barbiturates (for example, amobarbital), at prescribed doses has resulted in a synergistic potentiation of the effects of each drug, leading to serious respiratory depression.

Overdose symptoms may include extreme drowsiness, confusion, muscle weakness, and fainting.

Detection in Biological Fluids

Clonazepam and 7-aminoclonazepam may be quantified in plasma, serum, or whole blood in order to monitor compliance in those receiving the drug therapeutically. Results from such tests can be used to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage. Both the parent drug and 7-aminoclonazepam are unstable in biofluids, and therefore specimens should be preserved with sodium fluoride, stored at the lowest possible temperature and analysed quickly to minimise losses.

Special Precautions

The elderly metabolise benzodiazepines more slowly than younger people and are also more sensitive to the effects of benzodiazepines, even at similar blood plasma levels. Doses for the elderly are recommended to be about half of that given to younger adults and are to be administered for no longer than two weeks. Long-acting benzodiazepines such as clonazepam are not generally recommended for the elderly due to the risk of drug accumulation.

The elderly are especially susceptible to increased risk of harm from motor impairments and drug accumulation side effects. Benzodiazepines also require special precaution if used by individuals that may be pregnant, alcohol- or drug-dependent, or may have comorbid psychiatric disorders. Clonazepam is generally not recommended for use in elderly people for insomnia due to its high potency relative to other benzodiazepines.

Clonazepam is not recommended for use in those under 18. Use in very young children may be especially hazardous. Of anticonvulsant drugs, behavioural disturbances occur most frequently with clonazepam and phenobarbital.

Doses higher than 0.5-1 mg per day are associated with significant sedation.

Clonazepam may aggravate hepatic porphyria.

Clonazepam is not recommended for patients with chronic schizophrenia. A 1982 double-blinded, placebo-controlled study found clonazepam increases violent behaviour in individuals with chronic schizophrenia.

Clonazepam has similar effectiveness to other benzodiazepines at often a lower dose.

Interactions

Clonazepam decreases the levels of carbamazepine, and, likewise, clonazepam’s level is reduced by carbamazepine. Azole antifungals, such as ketoconazole, may inhibit the metabolism of clonazepam. Clonazepam may affect levels of phenytoin (diphenylhydantoin). In turn, Phenytoin may lower clonazepam plasma levels by increasing the speed of clonazepam clearance by approximately 50% and decreasing its half-life by 31%. Clonazepam increases the levels of primidone and phenobarbital.

Combined use of clonazepam with certain antidepressants, anticonvulsants (such as phenobarbital, phenytoin, and carbamazepine), sedative antihistamines, opiates, and antipsychotics, nonbenzodiazepines (such as zolpidem), and alcohol may result in enhanced sedative effects.

Pregnancy

There is some medical evidence of various malformations (for example, cardiac or facial deformations when used in early pregnancy); however, the data is not conclusive. The data are also inconclusive on whether benzodiazepines such as clonazepam cause developmental deficits or decreases in IQ in the developing foetus when taken by the mother during pregnancy. Clonazepam, when used late in pregnancy, may result in the development of a severe benzodiazepine withdrawal syndrome in the neonate. Withdrawal symptoms from benzodiazepines in the neonate may include hypotonia, apnoeic spells, cyanosis, and impaired metabolic responses to cold stress.

The safety profile of clonazepam during pregnancy is less clear than that of other benzodiazepines, and if benzodiazepines are indicated during pregnancy, chlordiazepoxide and diazepam may be a safer choice. The use of clonazepam during pregnancy should only occur if the clinical benefits are believed to outweigh the clinical risks to the foetus. Caution is also required if clonazepam is used during breastfeeding. Possible adverse effects of use of benzodiazepines such as clonazepam during pregnancy include: miscarriage, malformation, intrauterine growth retardation, functional deficits, carcinogenesis, and mutagenesis. Neonatal withdrawal syndrome associated with benzodiazepines include hypertonia, hyperreflexia, restlessness, irritability, abnormal sleep patterns, inconsolable crying, tremors, or jerking of the extremities, bradycardia, cyanosis, suckling difficulties, apnoea, risk of aspiration of feeds, diarrhoea and vomiting, and growth retardation. This syndrome can develop between three days to three weeks after birth and can have a duration of up to several months. The pathway by which clonazepam is metabolised is usually impaired in newborns. If clonazepam is used during pregnancy or breastfeeding, it is recommended that serum levels of clonazepam are monitored and that signs of central nervous system depression and apnoea are also checked for. In many cases, non-pharmacological treatments, such as relaxation therapy, psychotherapy, and avoidance of caffeine, can be an effective and safer alternative to the use of benzodiazepines for anxiety in pregnant women.

Pharmacology

Mechanism of Action

Clonazepam enhances the activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system to give its anticonvulsant, skeletal muscle relaxant, and anxiolytic effects. It acts by binding to the benzodiazepine site of the GABA receptors, which enhances the electric effect of GABA binding on neurons, resulting in an increased influx of chloride ions into the neurons. This further results in an inhibition of synaptic transmission across the central nervous system.

Benzodiazepines do not have any effect on the levels of GABA in the brain. Clonazepam has no effect on GABA levels and has no effect on gamma-aminobutyric acid transaminase. Clonazepam does, however, affect glutamate decarboxylase activity. It differs from other anticonvulsant drugs it was compared to in a study.

Clonazepam’s primary mechanism of action is the modulation of GABA function in the brain, by the benzodiazepine receptor, located on GABAA receptors, which, in turn, leads to enhanced GABAergic inhibition of neuronal firing. Benzodiazepines do not replace GABA, but instead enhance the effect of GABA at the GABAA receptor by increasing the opening frequency of chloride ion channels, which leads to an increase in GABA’s inhibitory effects and resultant central nervous system depression. In addition, clonazepam decreases the utilisation of 5-HT (serotonin) by neurons and has been shown to bind tightly to central-type benzodiazepine receptors. Because clonazepam is effective in low milligram doses (0.5 mg clonazepam = 10 mg diazepam), it is said to be among the class of “highly potent” benzodiazepines. The anticonvulsant properties of benzodiazepines are due to the enhancement of synaptic GABA responses, and the inhibition of sustained, high-frequency repetitive firing.

Benzodiazepines, including clonazepam, bind to mouse glial cell membranes with high affinity. Clonazepam decreases release of acetylcholine in the feline brain and decreases prolactin release in rats. Benzodiazepines inhibit cold-induced thyroid-stimulating hormone (also known as TSH or thyrotropin) release. Benzodiazepines act via micromolar benzodiazepine binding sites as Ca2+ channel blockers and significantly inhibit depolarisation-sensitive calcium uptake in experimentation on rat brain cell components. This has been conjectured as a mechanism for high-dose effects on seizures in the study.

Clonazepam is a 2′-chlorinated derivative of nitrazepam, which increases its potency due to electron-attracting effect of the halogen in the ortho-position.

Pharmacokinetics

Clonazepam is lipid-soluble, rapidly crosses the blood-brain barrier, and penetrates the placenta. It is extensively metabolised into pharmacologically inactive metabolites, with only 2% of the unchanged drug excreted in the urine. Clonazepam is metabolised extensively via nitroreduction by cytochrome P450 enzymes, including CYP3A4. Erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, cimetidine, and grapefruit juice are inhibitors of CYP3A4 and can affect the metabolism of benzodiazepines. It has an elimination half-life of 19-60 hours. Peak blood concentrations of 6.5-13.5 ng/mL were usually reached within 1-2 hours following a single 2 mg oral dose of micronized clonazepam in healthy adults. In some individuals, however, peak blood concentrations were reached at 4-8 hours.

Clonazepam passes rapidly into the central nervous system, with levels in the brain corresponding with levels of unbound clonazepam in the blood serum. Clonazepam plasma levels are very unreliable amongst patients. Plasma levels of clonazepam can vary as much as tenfold between different patients.

Clonazepam has plasma protein binding of 85%. Clonazepam passes through the blood-brain barrier easily, with blood and brain levels corresponding equally with each other. The metabolites of clonazepam include 7-aminoclonazepam, 7-acetaminoclonazepam and 3-hydroxy clonazepam. These metabolites are excreted by the kidney.

It is effective for 6-8 hours in children, and 6-12 in adults.

Society and Culture

Recreational Use

Refer to Benzodiazepine Misuse.

A 2006 US government study of hospital emergency department (ED) visits found that sedative-hypnotics were the most frequently implicated pharmaceutical drug in visits, with benzodiazepines accounting for the majority of these. Clonazepam was the second most frequently implicated benzodiazepine in ED visits. Alcohol alone was responsible for over twice as many ED visits as clonazepam in the same study. The study examined the number of times the non-medical use of certain drugs was implicated in an ED visit. The criteria for non-medical use in this study were purposefully broad, and include, for example, drug abuse, accidental or intentional overdose, or adverse reactions resulting from legitimate use of the medication.

Formulations

Clonazepam was approved in the United States as a generic drug in 1997 and is now manufactured and marketed by several companies.

Clonazepam is available as tablets and orally disintegrating tablets (wafers) an oral solution (drops), and as a solution for injection or intravenous infusion.

Brand Names

It is marketed under the trade name Rivotril by Roche in Argentina, Australia, Austria, Bangladesh, Belgium, Brazil, Bulgaria, Canada, Colombia, Costa Rica, Croatia, the Czech Republic, Denmark, Estonia,[136] Germany, Hungary, Iceland, Ireland, Italy, China, Mexico, the Netherlands, Norway, Portugal, Peru, Pakistan, Romania, Serbia, South Africa, South Korea, Spain, Turkey, and the United States; Emcloz, Linotril and Clonotril in India and other parts of Europe; under the name Riklona in Indonesia and Malaysia; and under the trade name Klonopin by Roche in the United States. Other names, such as Clonoten, Ravotril, Rivotril, Iktorivil, Clonex (Israel), Paxam, Petril, Naze, Zilepam and Kriadex, are known throughout the world.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Clonazepam >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

What is Bromazepam?

Introduction

Bromazepam, sold under many brand names, is a benzodiazepine. It is mainly an anti-anxiety agent with similar side effects to diazepam (Valium). In addition to being used to treat anxiety or panic states, bromazepam may be used as a premedicant prior to minor surgery. Bromazepam typically comes in doses of 3 mg and 6 mg tablets.

It was patented in 1961 by Roche and approved for medical use in 1974.

Medical Uses

Treatment of severe anxiety. Despite certain side effects and the emergence of alternative products (e.g. pregabalin), benzodiazepine medication remains an effective way of reducing problematic symptoms, and is typically deemed effective by patients and medical professionals. Similarly to other intermediate-acting depressants, it may be used as hypnotic medication or in order to mitigate withdrawal effects of alcohol consumption.

Pharmacology

Bromazepam is a “classical” benzodiazepine; other classical benzodiazepines include: diazepam, clonazepam, oxazepam, lorazepam, nitrazepam, flurazepam, and clorazepate. Its molecular structure is composed of a diazepine connected to a benzene ring and a pyridine ring, the benzene ring having a single nitrogen atom that replaces one of the carbon atoms in the ring structure. It is a 1,4-benzodiazepine, which means that the nitrogens on the seven-sided diazepine ring are in the 1 and 4 positions.

Bromazepam binds to the GABA receptor GABAA, causing a conformational change and increasing the inhibitory effects of GABA. It acts as a positive modulator, increasing the receptors’ response when activated by GABA itself or an agonist (such as alcohol). As opposed to barbital, BZDs are not GABA-receptor activators and rely on increasing the neurotransmitter’s natural activity. Bromazepam is an intermediate-acting benzodiazepine, is moderately lipophilic compared to other substances of its class and metabolised hepatically via oxidative pathways. It does not possess any antidepressant or antipsychotic qualities.

After night time administration of bromazepam a highly significant reduction of gastric acid secretion occurs during sleep followed by a highly significant rebound in gastric acid production the following day.

Bromazepam alters the electrical status of the brain causing an increase in beta activity and a decrease in alpha activity in EEG recordings

Pharmacokinetics

Bromazepam is reported to be metabolised by a hepatic enzyme belonging to the Cytochrome P450 family of enzymes. In 2003, a team led by Oda Manami at Oita Medical University reported that CYP3A4, a member of the Cytochrome P450 family, was not the responsible enzyme since itraconazole, a known inhibitor of CYP3A4, did not affect its metabolism. In 1995, J. van Harten at the Solvay Pharmaceutical Department of Clinical Pharmacology in Weesp reported that fluvoxamine, which is a potent inhibitor of CYP1A2, a less potent CYP3A4 inhibitor, and a negligible inhibitor of CYP2D6, does inhibit its metabolism.

The major metabolite of bromazepam is hydroxybromazepam, which is an active agent too and has a half-life approximately equal to that of bromazepam.

Side-Effects

Bromazepam is similar in side effects to other benzodiazepines. The most common side effects reported are drowsiness, sedation, ataxia, memory impairment, and dizziness. Impairments to memory functions are common with bromazepam and include a reduced working memory and reduced ability to process environmental information. A 1975 experiment on healthy, male college students exploring the effects of four different drugs on learning capacity observed that taking bromazepam alone at 6 mg 3 times daily for 2 weeks impaired learning capacities significantly. In combination with alcohol, impairments in learning capacity became even more pronounced. Various studies report impaired memory, visual information processing and sensory data and impaired psychomotor performance; deterioration of cognition including attention capacity and impaired co-ordinative skills; impaired reactive and attention performance, which can impair driving skills; drowsiness and decrease in libido. Unsteadiness after taking bromazepam is, however, less pronounced than other benzodiazepines such as lorazepam.

On occasion, benzodiazepines can induce extreme alterations in memory such as anterograde amnesia and amnesic automatism, which may have medico-legal consequences. Such reactions occur usually only at the higher dose end of the prescribing spectrum.

Very rarely, dystonia can develop.

Up to 30% treated on a long-term basis develop a form of dependence, i.e. these patients cannot stop the medication without experiencing physical and/or psychological benzodiazepine withdrawal symptoms.

Leukopenia and liver-damage of the cholestatic type with or without jaundice (icterus) have additionally been seen; the original manufacturer Roche recommends regular laboratory examinations to be performed routinely.

Ambulatory patients should be warned that bromazepam may impair the ability to drive vehicles and to operate machinery. The impairment is worsened by consumption of alcohol, because both act as central nervous system depressants. During the course of therapy, tolerance to the sedative effect usually develops.

Frequency and Seriousness of Adverse Effects

As with all medication, the frequency and seriousness of side-effects varies greatly depending on quantities consumed. In a study about bromazepam’s negative effects on psychomotor skills and driving ability, it was noted that 3 mg doses caused minimal impairment. It also appeared that impairment may be tied to methods of testing more so than on the product’s intrinsic activity.

Moreover, side-effects other than drowsiness, dizziness and ataxia seem to be rare and not experienced by more than a few percent of users. The use of other, comparable medication seems to display an identically moderate side-effect profile.

Tolerance, Dependence and Withdrawal

Prolonged use of bromazepam can cause tolerance and may lead to both physical and psychological dependence on the drug, and as a result, it is a medication which is controlled by international law. It is nonetheless important to note that dependence, long-term use and misuse occur in a minority of cases and are not representative of most patients’ experience with this type of medication.

It shares with other benzodiazepines the risk of abuse, misuse, psychological dependence or physical dependence. A withdrawal study demonstrated both psychological dependence and physical dependence on bromazepam including marked rebound anxiety after 4 weeks chronic use. Those whose dose was gradually reduced experienced no withdrawal.

Patients treated with bromazepam for generalised anxiety disorder were found to experience withdrawal symptoms such as a worsening of anxiety, as well as the development of physical withdrawal symptoms when abruptly withdrawn bromazepam. Abrupt or over rapid withdrawal from bromazepam after chronic use even at therapeutic prescribed doses can lead to a severe withdrawal syndrome including status epilepticus and a condition resembling delirium tremens.

Animal studies have shown that chronic administration of diazepam (or bromazepam) causes a decrease in spontaneous locomotor activity, decreased turnover of noradrenaline and dopamine and serotonin, increased activity of tyrosine hydroxylase and increased levels of the catecholamines. During withdrawal of bromazepam or diazepam a fall in tryptophan, serotonin levels occurs as part of the benzodiazepine withdrawal syndrome. Changes in the levels of these chemicals in the brain can cause headaches, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, dysphoria, dizziness, derealisation, depersonalisation, numbness/tingling of extremities, hypersensitivity to light, sound, and smell, perceptual distortions, nausea, vomiting, diarrhoea, appetite loss, hallucinations, delirium, seizures, tremor, stomach cramps, myalgia, agitation, palpitations, tachycardia, panic attacks, short-term memory loss, and hyperthermia.

Overdose

Refer to Benzodiazepine Overdose.

Bromazepam is commonly involved in drug overdoses. A severe bromazepam benzodiazepine overdose may result in an alpha pattern coma type. The toxicity of bromazepam in overdosage increases when combined with other CNS depressant drugs such as alcohol or sedative hypnotic drugs. Similarly to other benzodiazepines however, being a positive modulator of certain neuroreceptors and not an agonist, the product has reduced overdose potential compared to older products of the barbiturate class. Its consumption alone is very seldom fatal in healthy adults.

Bromazepam was in 2005 the most common benzodiazepine involved in intentional overdoses in France. Bromazepam has also been responsible for accidental poisonings in companion animals. A review of benzodiazepine poisonings in cats and dogs from 1991-1994 found bromazepam to be responsible for significantly more poisonings than any other benzodiazepine.

Contraindications

Benzodiazepines require special precaution if used in elderly, pregnant, child, alcohol- or drug-dependent individuals and individuals with comorbid psychiatric disorders.

Special Populations

  • Globally, bromazepam is contraindicated and should be used with caution in women who are pregnant, the elderly, patients with a history of alcohol or other substance abuse disorders and children.
  • In 1987, a team of scientists led by Ochs reported that the elimination half-life, peak serum concentration, and serum free fraction are significantly elevated and the oral clearance and volume of distribution significantly lowered in elderly subjects. The clinical consequence is that the elderly should be treated with lower doses than younger patients.
  • Bromazepam may affect driving and ability to operate machinery.
  • Bromazepam is pregnancy category D, a classification that means that bromazepam has been shown to cause harm to the unborn child. The Hoffman LaRoche product information leaflet warns against breast feeding while taking bromazepam. There has been at least one report of sudden infant death syndrome linked to breast feeding while consuming bromazepam.

Interactions

Cimetidine, fluvoxamine and propranolol causes a marked increase in the elimination half-life of bromazepam leading to increased accumulation of bromazepam.

Society and Culture

Drug Misuse

Refer to Benzodiazepine Drug Misuse.

Bromazepam has a similar misuse risk as other benzodiazepines such as diazepam. In France car accidents involving psychotropic drugs in combination with alcohol (itself a major contributor) found benzodiazepines, mainly diazepam, nordiazepam, and bromazepam, to be the most common drug present in the blood stream, almost twice that of the next-most-common drug cannabis. Bromazepam has also been used in serious criminal offences including robbery, homicide, and sexual assault.

Brand Names

It is marketed under several brand names, including, Brozam, Lectopam, Lexomil, Lexotan, Lexilium, Lexaurin, Brazepam, Rekotnil, Bromaze, Somalium, Lexatin, Calmepam, Zepam and Lexotanil.

Legal Status

Bromazepam is a Schedule IV drug under the Convention on Psychotropic Substances.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Bromazepam >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

What is the Hospital Anxiety and Depression Scale?

Introduction

Hospital Anxiety and Depression Scale (HADS) was originally developed by Zigmond and Snaith (1983) and is commonly used by doctors to determine the levels of anxiety and depression that a person is experiencing.

The HADS is a fourteen item scale that generates: Seven of the items that relate to anxiety and seven that relate to depression. Zigmond and Snaith created this outcome measure specifically to avoid reliance on aspects of these conditions that are also common somatic symptoms of illness, for example fatigue and insomnia or hypersomnia. This, it was hoped, would create a tool for the detection of anxiety and depression in people with physical health problems.

Items on the Questionnaire

The items on the questionnaire that relate to anxiety are

  • I feel tense or wound up.
  • I get a sort of frightened feeling as if something awful is about to happen.
  • Worrying thoughts go through my mind.
  • I can sit at ease and feel relaxed.
  • I get a sort of frightened feeling like ‘butterflies’ in the stomach.
  • I feel restless as I have to be on the move.
  • I get sudden feelings of panic.

The items that relate to depression are:

  • I still enjoy the things I used to enjoy.
  • I can laugh and see the funny side of things.
  • I feel cheerful.
  • I feel as if I am slowed down.
  • I have lost interest in my appearance.
  • I look forward with enjoyment to things.
  • I can enjoy a good book or radio or TV programme.

Scoring the Questionnaire

Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression.

Caseness of Anxiety and Depression

A number of researchers have explored HADS data to establish the cut-off points for caseness of anxiety or depression. Bjelland et al. (2002) through a literature review of a large number of studies identified a cut-off point of 8/21 for anxiety or depression. For anxiety (HADS-A) this gave a specificity of 0.78 and a sensitivity of 0.9. For depression (HADS-D) this gave a specificity of 0.79 and a sensitivity of 0.83.

Factor Structure

There are a large number of studies that have explored the underlying factor structure of the HADS. Many support the two-factor structure but there are others that suggest a three or four factor structure. Some argue that the tool is best used as a unidimensional measure of psychological distress.

Criticisms

The factor structure of the HADS has been questioned. Coyne and Sonderen argue in a letter published in the same issue, that Cosco, et al. provides grounds for abandoning HADS altogether. The HADS has also been criticised for its over reliance on anhedonia as being the core symptom of depression, how single-item measures of depression may have the same predictive value as the HADS scale, as well as its use of British colloquial expressions which can be difficult to translate.

This page is based on the copyrighted Wikipedia article <https://en.wikipedia.org/wiki/Hospital_Anxiety_and_Depression_Scale >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

What is Midazolam?

Introduction

Midazolam, sold under the brand name Versed, among others, is a benzodiazepine medication used for anaesthesia, procedural sedation, trouble sleeping, and severe agitation.

It works by inducing sleepiness, decreasing anxiety, and causing a loss of ability to create new memories. It is important to note that this drug does not cause an individual to become unconscious, merely be sedated. It is also useful for the treatment of seizures. Midazolam can be given by mouth, intravenously, by injection into a muscle, by spraying into the nose, or through the cheek. When given intravenously, it typically begins working within five minutes; when injected into a muscle, it can take fifteen minutes to begin working. Effects last between one and six hours.

Side effects can include a decrease in efforts to breathe, low blood pressure, and sleepiness. Tolerance to its effects and withdrawal syndrome may occur following long-term use. Paradoxical effects, such as increased activity, can occur especially in children and older people. There is evidence of risk when used during pregnancy but no evidence of harm with a single dose during breastfeeding. It belongs to the benzodiazepine class of drugs and works by increasing the activity of the GABA neurotransmitter in the brain.

Midazolam was patented in 1974 and came into medical use in 1982. It is on the World Health Organisation’s List of Essential Medicines. Midazolam is available as a generic medication. In many countries, it is a controlled substance.

Brief History

Midazolam is among about 35 benzodiazepines currently used medically, and was synthesized in 1975 by Walser and Fryer at Hoffmann-LaRoche, Inc in the United States. Owing to its water solubility, it was found to be less likely to cause thrombophlebitis than similar drugs. The anticonvulsant properties of midazolam were studied in the late 1970s, but not until the 1990s did it emerge as an effective treatment for convulsive status epilepticus. As of 2010, it is the most commonly used benzodiazepine in anaesthetic medicine. In acute medicine, midazolam has become more popular than other benzodiazepines, such as lorazepam and diazepam, because it is shorter lasting, is more potent, and causes less pain at the injection site. Midazolam is also becoming increasingly popular in veterinary medicine due to its water solubility. In 2018 it was revealed the CIA considered using Midazolam as a “truth serum” on terrorist suspects in project “Medication”.

Medical Uses

Seizures

Midazolam is sometimes used for the acute management of seizures. Long-term use for the management of epilepsy is not recommended due to the significant risk of tolerance (which renders midazolam and other benzodiazepines ineffective) and the significant side effect of sedation. A benefit of midazolam is that in children it can be given in the cheek or in the nose for acute seizures, including status epilepticus. Midazolam is effective for status epilepticus that has not improved following other treatments or when intravenous access cannot be obtained, and has advantages of being water-soluble, having a rapid onset of action and not causing metabolic acidosis from the propylene glycol vehicle (which is not required due to its solubility in water), which occurs with other benzodiazepines.

Drawbacks include a high degree of breakthrough seizures – due to the short half-life of midazolam – in over 50% of people treated, as well as treatment failure in 14-18% of people with refractory status epilepticus. Tolerance develops rapidly to the anticonvulsant effect, and the dose may need to be increased by several times to maintain anticonvulsant therapeutic effects. With prolonged use, tolerance and tachyphylaxis can occur and the elimination half-life may increase, up to days. There is evidence buccal and intranasal midazolam is easier to administer and more effective than rectally administered diazepam in the emergency control of seizures.

Procedural Sedation

Intravenous midazolam is indicated for procedural sedation (often in combination with an opioid, such as fentanyl), for preoperative sedation, for the induction of general anaesthesia, and for sedation of people who are ventilated in critical care units. Midazolam is superior to diazepam in impairing memory of endoscopy procedures, but propofol has a quicker recovery time and a better memory-impairing effect. It is the most popular benzodiazepine in the intensive care unit (ICU) because of its short elimination half-life, combined with its water solubility and its suitability for continuous infusion. However, for long-term sedation, lorazepam is preferred due to its long duration of action, and propofol has advantages over midazolam when used in the ICU for sedation, such as shorter weaning time and earlier tracheal extubation.

Midazolam is sometimes used in neonatal intensive care units. When used, additional caution is required in newborns; midazolam should not be used for longer than 72 hours due to risks of tachyphylaxis, and the possibility of development of a benzodiazepine withdrawal syndrome, as well as neurological complications. Bolus injections should be avoided due to the increased risk of cardiovascular depression, as well as neurological complications. Midazolam is also sometimes used in newborns who are receiving mechanical ventilation, although morphine is preferred, owing to its better safety profile for this indication.

Sedation using midazolam can be used to relieve anxiety and manage behaviour in children undergoing dental treatment.

Agitation

Midazolam, in combination with an antipsychotic drug, is indicated for the acute management of schizophrenia when it is associated with aggressive or out-of-control behaviour.

End of Life Care

In the final stages of end-of-life care, midazolam is routinely used at low doses via subcutaneous injection to help with agitation, myoclonus, restlessness or anxiety in the last hours or days of life. At higher doses during the last weeks of life, midazolam is considered a first line agent in palliative continuous deep sedation therapy when it is necessary to alleviate intolerable suffering not responsive to other treatments, but the need for this is rare.

Administration

Routes of administration of midazolam can be oral, intranasal, buccal, intravenous, and intramuscular.

  • Dosing:
    • Perioperative use: 0.15 to 0.40 mg/kg IV.
    • Premedication: 0.07 to 0.10 mg/kg IM.
    • Intravenous sedation: 0.05 to 0.15 mg/kg IV.

Contraindications

Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, in alcohol- or other drug-dependent individuals or those with comorbid psychiatric disorders. Additional caution is required in critically ill patients, as accumulation of midazolam and its active metabolites may occur. Kidney or liver impairments may slow down the elimination of midazolam leading to prolonged and enhanced effects. Contraindications include hypersensitivity, acute narrow-angle glaucoma, shock, hypotension, or head injury. Most are relative contraindications.

Side Effects

Refer to Long-Term Effects of Benzodiazepines.

Side effects of midazolam in the elderly are listed above. People experiencing amnesia as a side effect of midazolam are generally unaware their memory is impaired, unless they had previously known it as a side effect.

Long-term use of benzodiazepines has been associated with long-lasting deficits of memory, and show only partial recovery six months after stopping benzodiazepines. It is unclear whether full recovery occurs after longer periods of abstinence. Benzodiazepines can cause or worsen depression. Paradoxical excitement occasionally occurs with benzodiazepines, including a worsening of seizures. Children and elderly individuals or those with a history of excessive alcohol use and individuals with a history of aggressive behaviour or anger are at increased risk of paradoxical effects. Paradoxical reactions are particularly associated with intravenous administration. After night-time administration of midazolam, residual ‘hangover’ effects, such as sleepiness and impaired psychomotor and cognitive functions, may persist into the next day. This may impair the ability of users to drive safely and may increase the risk of falls and hip fractures. Sedation, respiratory depression and hypotension due to a reduction in systematic vascular resistance, and an increase in heart rate can occur. If intravenous midazolam is given too quickly, hypotension may occur. A “midazolam infusion syndrome” may result from high doses, and is characterised by delayed arousal hours to days after discontinuation of midazolam, and may lead to an increase in the length of ventilatory support needed.

In susceptible individuals, midazolam has been known to cause a paradoxical reaction, a well-documented complication with benzodiazepines. When this occurs, the individual may experience anxiety, involuntary movements, aggressive or violent behaviour, uncontrollable crying or verbalization, and other similar effects. This seems to be related to the altered state of consciousness or disinhibition produced by the drug. Paradoxical behaviour is often not recalled by the patient due to the amnesia-producing properties of the drug. In extreme situations, flumazenil can be administered to inhibit or reverse the effects of midazolam. Antipsychotic medications, such as haloperidol, have also been used for this purpose.

Midazolam is known to cause respiratory depression. In healthy humans, 0.15 mg/kg of midazolam may cause respiratory depression, which is postulated to be a central nervous system (CNS) effect. When midazolam is administered in combination with fentanyl, the incidence of hypoxemia or apnoea becomes more likely.

Although the incidence of respiratory depression/arrest is low (0.1-0.5%) when midazolam is administered alone at normal doses, the concomitant use with CNS acting drugs, mainly analgesic opiates, may increase the possibility of hypotension, respiratory depression, respiratory arrest, and death, even at therapeutic doses. Potential drug interactions involving at least one CNS depressant were observed for 84% of midazolam users who were subsequently required to receive the benzodiazepine antagonist flumazenil. Therefore, efforts directed toward monitoring drug interactions and preventing injuries from midazolam administration are expected to have a substantial impact on the safe use of this drug.

Pregnancy and Breastfeeding

Midazolam, when taken during the third trimester of pregnancy, may cause risk to the neonate, including benzodiazepine withdrawal syndrome, with possible symptoms including hypotonia, apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. Symptoms of hypotonia and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth. Other neonatal withdrawal symptoms include hyperexcitability, tremor, and gastrointestinal upset (diarrhoea or vomiting). Breastfeeding by mothers using midazolam is not recommended.

Elderly

Additional caution is required in the elderly, as they are more sensitive to the pharmacological effects of benzodiazepines, metabolise them more slowly, and are more prone to adverse effects, including drowsiness, amnesia (especially anterograde amnesia), ataxia, hangover effects, confusion, and falls.

Tolerance, Dependence, and Withdrawal

A benzodiazepine dependence occurs in about one-third of individuals who are treated with benzodiazepines for longer than 4 weeks, which typically results in tolerance and benzodiazepine withdrawal syndrome when the dose is reduced too rapidly. Midazolam infusions may induce tolerance and a withdrawal syndrome in a matter of days. The risk factors for dependence include dependent personality, use of a benzodiazepine that is short-acting, high potency and long-term use of benzodiazepines. Withdrawal symptoms from midazolam can range from insomnia and anxiety to seizures and psychosis. Withdrawal symptoms can sometimes resemble a person’s underlying condition. Gradual reduction of midazolam after regular use can minimise withdrawal and rebound effects. Tolerance and the resultant withdrawal syndrome may be due to receptor down-regulation and GABAA receptor alterations in gene expression, which causes long-term changes in the function of the GABAergic neuronal system.

Chronic users of benzodiazepine medication who are given midazolam experience reduced therapeutic effects of midazolam, due to tolerance to benzodiazepines. Prolonged infusions with midazolam results in the development of tolerance; if midazolam is given for a few days or more a withdrawal syndrome can occur. Therefore, preventing a withdrawal syndrome requires that a prolonged infusion be gradually withdrawn, and sometimes, continued tapering of dose with an oral long-acting benzodiazepine such as clorazepate dipotassium. When signs of tolerance to midazolam occur during intensive care unit sedation the addition of an opioid or propofol is recommended. Withdrawal symptoms can include irritability, abnormal reflexes, tremors, clonus, hypertonicity, delirium and seizures, nausea, vomiting, diarrhoea, tachycardia, hypertension, and tachypnoea. In those with significant dependence, sudden discontinuation may result in withdrawal symptoms such as status epilepticus that may be fatal.

Overdose

Refer to Benzodiazepine Overdose.

A midazolam overdose is considered a medical emergency and generally requires the immediate attention of medical personnel. Benzodiazepine overdose in healthy individuals is rarely life-threatening with proper medical support; however, the toxicity of benzodiazepines increases when they are combined with other CNS depressants such as alcohol, opioids, or tricyclic antidepressants. The toxicity of benzodiazepine overdose and risk of death is also increased in the elderly and those with obstructive pulmonary disease or when used intravenously. Treatment is supportive; activated charcoal can be used within an hour of the overdose. The antidote for an overdose of midazolam (or any other benzodiazepine) is flumazenil. While effective in reversing the effects of benzodiazepines it is not used in most cases as it may trigger seizures in mixed overdoses and benzodiazepine dependent individuals.

Symptoms of midazolam overdose can include:

  • Ataxia.
  • Dysarthria.
  • Nystagmus.
  • Slurred speech.
  • Somnolence (difficulty staying awake).
  • Mental confusion.
  • Hypotension.
  • Respiratory arrest.
  • Vasomotor collapse.
  • Impaired motor functions:
    • Impaired reflexes.
    • Impaired coordination.
    • Impaired balance.
    • Dizziness.
  • Coma.
  • Death.

Detection in Body Fluids

Concentrations of midazolam or its major metabolite, 1-hydroxymidazolam glucuronide, may be measured in plasma, serum, or whole blood to monitor for safety in those receiving the drug therapeutically, to confirm a diagnosis of poisoning in hospitalised patients, or to assist in a forensic investigation of a case of fatal overdosage. Patients with renal dysfunction may exhibit prolongation of elimination half-life for both the parent drug and its active metabolite, with accumulation of these two substances in the bloodstream and the appearance of adverse depressant effects.

Interactions

Protease inhibitors, nefazodone, sertraline, grapefruit, fluoxetine, erythromycin, diltiazem, clarithromycin inhibit the metabolism of midazolam, leading to a prolonged action. St John’s wort, rifapentine, rifampin, rifabutin, phenytoin enhance the metabolism of midazolam leading to a reduced action. Sedating antidepressants, antiepileptic drugs such as phenobarbital, phenytoin and carbamazepine, sedative antihistamines, opioids, antipsychotics and alcohol enhance the sedative effects of midazolam. Midazolam is metabolised almost completely by cytochrome P450-3A4. Atorvastatin administration along with midazolam results in a reduced elimination rate of midazolam. St John’s wort decreases the blood levels of midazolam. Grapefruit juice reduces intestinal 3A4 and results in less metabolism and higher plasma concentrations.

Pharmacology

Midazolam is a short-acting benzodiazepine in adults with an elimination half-life of 1.5-2.5 hours. In the elderly, as well as young children and adolescents, the elimination half-life is longer. Midazolam is metabolised into an active metabolite alpha1-hydroxymidazolam. Age-related deficits, renal and liver status affect the pharmacokinetic factors of midazolam as well as its active metabolite. However, the active metabolite of midazolam is minor and contributes to only 10 percent of biological activity of midazolam. Midazolam is poorly absorbed orally, with only 50% of the drug reaching the bloodstream. Midazolam is metabolised by cytochrome P450 (CYP) enzymes and by glucuronide conjugation. The therapeutic as well as adverse effects of midazolam are due to its effects on the GABAA receptors; midazolam does not activate GABAA receptors directly but, as with other benzodiazepines, it enhances the effect of the neurotransmitter GABA on the GABAA receptors (↑ frequency of Cl- channel opening) resulting in neural inhibition. Almost all of the properties can be explained by the actions of benzodiazepines on GABAA receptors. This results in the following pharmacological properties being produced: sedation, induction of sleep, reduction in anxiety, anterograde amnesia, muscle relaxation and anticonvulsant effects.

Pharmacokinetics

  • Volume of Distribution: 1-2.5L/kg in normal healthy individuals.
  • Protein Binding: 96% Plasma protein bound.
  • Onset of Action: 3-15 minutes.
  • Elimination Half-Life: 1.5-3 hours.

Society and Culture

Cost

Midazolam is available as a generic medication.

Availability

Midazolam is available in the United States as a syrup or as an injectable solution.

Dormicum brand midazolam is marketed by Roche as white, oval, 7.5-mg tablets in boxes of two or three blister strips of 10 tablets, and as blue, oval, 15-mg tablets in boxes of two (Dormonid 3x) blister strips of 10 tablets. The tablets are imprinted with “Roche” on one side and the dose of the tablet on the other side. Dormicum is also available as 1-, 3-, and 10-ml ampoules at a concentration of 5 mg/ml. Another manufacturer, Novell Pharmaceutical Laboratories, makes it available as Miloz in 3- and 5-ml ampoules. Midazolam is the only water-soluble benzodiazepine available. Another maker is Roxane Laboratories; the product in an oral solution, Midazolam HCl Syrup, 2 mg/ml clear, in a red to purplish-red syrup, cherry in flavour. It becomes soluble when the injectable solution is buffered to a pH of 2.9-3.7. Midazolam is also available in liquid form. It can be administered intramuscularly, intravenously, intrathecally, intranasally, buccally, or orally.

Legal Status

In the Netherlands, midazolam is a List II drug of the Opium Law. Midazolam is a Schedule IV drug under the Convention on Psychotropic Substances. In the United Kingdom, midazolam is a Schedule 3/Class C controlled drug. In the United States, midazolam (DEA number 2884) is on the Schedule IV list of the Controlled Substances Act as a non-narcotic agent with low potential for abuse.

Marketing Authorisation

In 2011, the European Medicines Agency (EMA) granted a marketing authorisation for a buccal application form of midazolam, sold under the trade name Buccolam. Buccolam was approved for the treatment of prolonged, acute, convulsive seizures in people from three months to less than 18 years of age. This was the first application of a paediatric-use marketing authorisation.

Use in Executions

The drug has been introduced for use in executions by lethal injection in certain jurisdictions in the United States in combination with other drugs. It was introduced to replace pentobarbital after the latter’s manufacturer disallowed that drug’s use for executions. Midazolam acts as a sedative but will fail to render the condemned prisoner unconscious, at which time vecuronium bromide and potassium chloride are administered, stopping the prisoner’s breathing and heart, respectively. Due to the fact that the condemned prisoner is not unconscious but merely sedated, two very different things, those following two drugs can cause extreme pain and panic in the soon to die prisoner.

Midazolam has been used as part of a three-drug cocktail, with vecuronium bromide and potassium chloride in Florida and Oklahoma prisons. Midazolam has also been used along with hydromorphone in a two-drug protocol in Ohio and Arizona.

The usage of midazolam in executions became controversial after condemned inmate Clayton Lockett apparently regained consciousness and started speaking midway through his 2014 execution when the state of Oklahoma attempted to execute him with an untested three-drug lethal injection combination using 100 mg of midazolam. Prison officials reportedly discussed taking him to a hospital before he was pronounced dead of a heart attack 40 minutes after the execution began. An observing doctor stated that Lockett’s vein had ruptured. It is not clear whether his death was caused by one or more of the drugs or to a problem in the administration procedure, nor is it clear what quantities of vecuronium bromide and potassium chloride were released to his system before the execution was cancelled.

Notable Incidents

The state of Florida used midazolam to execute William Frederick Happ in October 2013.

The state of Ohio used midazolam in the execution of Dennis McGuire in January 2014; it took McGuire 24 minutes to die after the procedure started, and he gasped and appeared to be choking during that time, leading to questions about the dosing and timing of the drug administration, as well as the choice of drugs.

The execution of Ronald Bert Smith in the state of Alabama on 08 December 2016, “went awry soon after (midazolam) was administered” again putting the effectiveness of the drug in question.

In October 2016, the state of Ohio announced that it would resume executions in January 2017, using a formulation of midazolam, vecuronium bromide, and potassium chloride, but this was blocked by a Federal judge. On 26 July 2017, Ronald Phillips was executed with a three-drug cocktail including midazolam after the Supreme Court refused to grant a stay. Prior to this, the last execution in Ohio had been that of Dennis McGuire. Murderer Gary Otte’s lawyers unsuccessfully challenged his Ohio execution, arguing that midazolam might not protect him from serious pain when the other drugs are administered. He died without incident in about 14 minutes on 13 September 2017.

On 24 April 2017, the state of Arkansas carried out a double-execution of Jack Harold Jones, 52, and Marcel Williams, 46. The state of Arkansas attempted to execute eight people before its supply of midazolam expired on 30 April 2017. Two of them were granted a stay of execution, and another, Ledell T. Lee, 51, was executed on 20 April 2017.

On 28 October 2021, the state of Oklahoma carried out the execution of inmate John Marion Grant, 60, using midazolam as part of its three-drug cocktail hours after the US Supreme Court ruled to lift a stay of execution for Oklahoma death row inmates. The execution was the state’s first since 2015. Witnesses to the execution said that when the first drug, midazolam, began to flow at 4:09 pm, Grant started convulsing about two dozen times and vomited. Grant continued breathing, and a member of the execution team wiped the vomit off his face. At 4:15 pm., officials said Grant was unconscious, and he was pronounced dead at 4:21 pm.

Legal Challenges

In Glossip v. Gross, attorneys for three Oklahoma inmates argued that midazolam could not achieve the level of unconsciousness required for surgery, meaning severe pain and suffering was likely. They argued that midazolam was cruel and unusual punishment and thus contrary to the Eighth Amendment to the United States Constitution. In June 2015, the US Supreme Court ruled that they had failed to prove that midazolam was cruel and unusual when compared to known, available alternatives.

The state of Nevada is also known to use midazolam in execution procedures. In July 2018, one of the manufacturers accused state officials of obtaining the medication under false pretences. This incident was the first time a drug company successfully, though temporarily, halted an execution. A previous attempt in 2017, to halt an execution in the state of Arizona by another drug manufacturer was not successful.

This page is based on the copyrighted Wikipedia article <https://en.wikipedia.org/wiki/Midazolam&gt;; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

What is Thought Suppression?

Introduction

Thought suppression is a psychological defence mechanism. It is a type of motivated forgetting in which an individual consciously attempts to stop thinking about a particular thought.

It is often associated with obsessive-compulsive disorder (OCD). OCD is when a person will repeatedly (usually unsuccessfully) attempt to prevent or “neutralise” intrusive distressing thoughts centred on one or more obsessions. It is also thought to be a cause of memory inhibition, as shown by research using the think/no think paradigm. Thought suppression is relevant to both mental and behavioural levels, possibly leading to ironic effects that are contrary to intention. Ironic process theory is one cognitive model that can explain the paradoxical effect.

When an individual tries to suppress thoughts under a high cognitive load, the frequency of those thoughts increases and becomes more accessible than before. Evidence shows that people can prevent their thoughts from being translated into behaviour when self-monitoring is high; this does not apply to automatic behaviours though, and may result in latent, unconscious actions. This phenomenon is made paradoxically worse by increasing the amount of distractions a person has, although the experiments in this area can be criticised for using impersonal concurrent tasks, which may or may not properly reflect natural processes or individual differences.

Empirical Work (1980s)

In order for thought suppression and its effectiveness to be studied, researchers have had to find methods of recording the processes going on in the mind. One experiment designed with this purpose was performed by Wegner, Schneider, Carter & White. They asked participants to avoid thinking of a specific target (e.g. a white bear) for five minutes, but if they did, they were told then to ring a bell. After this, participants were told that for the next five minutes they were to think about the target. There was evidence that unwanted thoughts occurred more frequently in those who used thought suppression compared to those who were not. Furthermore, there was also evidence that during the second stage, those who had used thought suppression had a higher frequency of target thoughts than did those who had not used thought suppression; later coined the rebound effect. This effect has been replicated and can even be done with implausible targets, such as the thought of a “green rabbit”. From these implications, Wegner eventually developed the “ironic process theory”.

Improved Methodology (1990s)

To better elucidate the findings of thought suppression, several studies have changed the target thought. Roemer and Borkovec found that participants who suppressed anxious or depressing thoughts showed a significant rebound effect. Furthermore, Wenzlaff, Wegner, & Roper demonstrated that anxious or depressed subjects were less likely to suppress negative, unwanted thoughts. Despite Rassin, Merkelbach and Muris reporting that this finding is moderately robust in the literature, some studies were unable to replicate results. However, this may be explained by a consideration of individual differences.

Recent research found that for individuals with low anxiety and high desirability traits (repressors), suppressed anxious autobiographical events initially intruded fewer times than in other groups (low, high, and high defensive anxious groups), but intruded more often after one week. This difference in coping style may account for the disparities within the literature. That said, the problem remains that the cause of the paradoxical effect may be in the thought tapping measures used (e.g. bell ringing). Evidence from Brown (1990) that showed participants were very sensitive to frequency information prompted Clarke, Ball and Pape to obtain participants’ aposterio estimates of the number of intrusive target thoughts and found the same pattern of paradoxical results. However, even though such a method appears to overcome the problem, it and all the other methodologies use self-report as the primary form of data-collection. This may be problematic because of response distortion or inaccuracy in self-reporting.

Behavioural Domain

Thought suppression also has the capability to change human behaviour. Macrae, Bodenhausen, Milne, and Jetten found that when people were asked not to think about the stereotypes of a certain group (e.g. a “skinhead”), their written descriptions about a group member’s typical day contained less stereotypical thoughts. However, when they were told they were going to meet an individual they had just written about, those in the suppression group sat significantly farther away from the “skinhead” (just by virtue of his clothes being present). These results show that even though there may have been an initial enhancement of the stereotype, participants were able to prevent this from being communicated in their writing; this was not true for their behaviour though.

Further experiments have documented similar findings. In one study from 1993, when participants were given cognitively demanding concurrent tasks, the results showed a paradoxical higher frequency of target thoughts than controls. However other controlled studies have not shown such effects. For example, Wenzlaff and Bates found that subjects concentrating on a positive task experienced neither paradoxical effects nor rebound effects – even when challenged with cognitive load. Wenzlaff and Bates also note that the beneficiality of concentration in their study participants was optimised when the subjects employed positive thoughts.

Some studies have shown that when test subjects are under what Wegner refers to as a “cognitive load” (for instance, using multiple external distractions to try to suppress a target thought), the effectiveness of thought suppression appears to be reduced. However, in other studies in which focused distraction is used, long term effectiveness may improve. That is, successful suppression may involve less distractors. For example, in 1987 Wegner, Schneider, Carter & White found that a single, pre-determined distracter (e.g. a red Volkswagen) was sufficient to eliminate the paradoxical effect post-testing. Evidence from Bowers and Woody in 1996 is supportive of the finding that hypnotised individuals produce no paradoxical effects. This rests on the assumption that deliberate “distracter activity” is bypassed in such an activity.

Cognitive Dynamics

When the cognitive load is increased, thought suppression typically becomes less effective. For example, in the white bear experiment, many general distractions in the environment (for instance a lamp, a light bulb, a desk etc.) might later serve as reminders of the object being suppressed (these are also referred to as “free distraction”). Some studies, however, are unable to find this effect for emotional thoughts in hypnotized individuals when one focused distraction is provided. In an attempt to account for these findings, a number of theorists have produced cognitive models of thought suppression. Wegner suggested in 1989 that individuals distract themselves using environmental items. Later, these items become retrieval cues for the thought attempting to be suppressed. This iterative process leaves the individual surrounded by retrieval cues, ultimately causing the rebound effect. Wegner hypothesized that multiple retrieval cues not being forged explains, in part, the effectiveness of focused distraction (i.e. a reduction of mental load). This is because there may be an ideal balance between the two processes; if the cognitive demand that is not too heavy, then the monitoring processes will not supersede it.

Individual differences may also play a role in regards to the ironic thought process.

Thought suppression has been seen as a form of “experiential avoidance”. Experiential avoidance is when an individual attempts to suppress, change, or control unwanted internal experiences (thoughts, feelings, bodily sensations, memories, etc.). This line of thinking supports relational frame theory.

Other Methodologies

Thought suppression has been shown to be a cause of inhibition in several ways. Two commonly-used methods to study this relationship are the list method and the item method. In this list method, participants study two lists of words, one after the other. After studying the first list, some participants are told to forget everything that they have just learned, while others are not given this instruction. After studying both lists, participants are asked to recall the words on both lists. These experiments typically find that participants who were told to forget the first list do not remember as many words from that list, suggesting that they have been suppressed due to the instruction to forget. In the item method, participants study individual words rather than lists. After each word is shown, participants are told to either remember or forget the word. As in experiments using the list method, the words followed by the instruction to forget are more poorly remembered. Some researchers believe that these two methods result in different types of forgetting. According to these researchers, the list method results in inhibition of the forgotten words, but the item method results in some words being remembered better than the others, without a specific relation to forgetting.

Think/No Think Paradigm

A paradigm from 2009 to study how suppression relates to inhibition is the think/no think paradigm. In these experiments, participants study pairs of words. An example of a possible word pair is roach-ordeal. After all the word pairs are learned, the participants see the first word of the pair and are either told to think about the second word (think phase) or not to think about the second word (no think phase). The no think phase is when suppression occurs. Some pairs were never presented after the initial study portion of the study, and these trials serve as the control group. At the end of the experiment, the participants try to remember all of the word pairs based on the first word. Studies could also use the “independent probe” method, which gives the category and first letter of the second word of the pair. Typically, regardless of the method used, results show that the no-think trials result in worse memory than the think trials, which supports the idea that suppression leads to inhibition in memory. Although this methodology was first done using word pairs, experiments have been conducted using pictures and autobiographical memories as stimuli, with the same results.

Research has also shown that doing difficult counting tasks at the same time as a think/no think task leads to less forgetting in the no think condition, which suggests that suppression takes active mental energy to be successful. Furthermore, the most forgetting during the no think phase occurs when there is a medium amount of brain activation while learning the words. The words are never learned if there is too little activation, and the association between the two words is too strong to be suppressed during the no think phase if there is too much activation. However, with medium activation, the word pairs are learned but able to be suppressed during the no think phase.

fMRI studies have shown two distinct patterns of brain activity during suppression tasks. The first is that there is less activity in the hippocampus, the brain area responsible for forming memories. The second is an increase of brain activity in the dorsolateral prefrontal cortex, especially in cases where suppression is harder. Researchers think that this region works to prevent memory formation by preventing the hippocampus from working.

This methodology can also be used to study thought substitution by adding an instruction during the no think phase for participants to think of a different word rather than the word being suppressed. This research shows that thought substitution can lead to increased levels of forgetting compared to suppression without a thought substitution instruction. This research also suggests that thought substitution, while used as a suppression strategy during the no think phase, may work differently than suppression. Some researchers argue that thinking of something different during the no think phase forms a new association with the first word than the original word pair, which results in interference when using this strategy, which is different than the inhibition that results from simply not thinking about something.

Dream Influence

Dreams occur mainly during the rapid eye movement (REM) sleep and are composed of images, ideas, emotions, and sensations. Although more research needs to be done on this subject, dreams are said to be linked to the unconscious mind. Thought suppression has an influence on the subject matter of the unconscious mind and by trying to restrain particular thoughts, there is a high chance of them showing up in one’s dreams.

Ironic Control Theory

Ironic control theory, also known as “ironic process theory”, states that thought suppression “leads to an increased occurrence of the suppressed content in waking states”. The irony lies in the fact that although people try not to think about a particular subject, there is a high probability that it will appear in one’s dreams regardless. There is a difference for individuals who have a higher tendency of suppression; they are more prone to psychopathological responses such as “intrusive thoughts, including depression, anxiety and obsessional thinking”. Due to these individuals having higher instances of thought suppression, they experience dream rebound more often.

Cognitive load also plays a role in ironic control theory. Studies have shown that a greater cognitive load results in an increased possibility of dream rebound occurring. In other words, when one tries to retain a heavy load of information before going to sleep, there is a high chance of that information manifesting itself within the dream. There is a greater degree of dream rebound in those with a higher cognitive load opposed to those whose load was absent. With the enhancement of a high cognitive load, ironic control theory states thought suppression is more likely to occur and lead to dream rebound.

Dream Rebound

Dream rebound is when suppressed thoughts manifest themselves in one’s dreams. Self-control is a form of thought suppression and when one dreams, that suppressed item has a higher chance of appearing in the dream. For example, when an individual is attempting to quit smoking, they may dream about themselves smoking a cigarette. Emotion suppression has also been found to trigger dream rebound. Recurrence of emotional experiences act as pre-sleep suggestions, ultimately leading to the suppressed thoughts presenting themselves within the dream. One effecting factor of dream rebound is the changes in the prefrontal lobes during rapid-eye movement sleep. Suppressed thoughts are more accessible during REM sleep, as a result of operating processes having a diminished effectiveness. This leads to pre-sleep thoughts becoming more available “with an increased activity of searching for these suppressed thought[s]”. There are other hypotheses regarding REM sleep and dream rebound. For instance, weak semantic associations, post REM sleep, are more accessible than any other time due to weak ironic monitoring processes becoming stronger. More research is needed to further understand what exactly causes dream rebound.

What is a Relaxation Technique?

Introduction

A relaxation technique (also known as relaxation training) is any method, process, procedure, or activity that helps a person to relax; to attain a state of increased calmness; or otherwise reduce levels of pain, anxiety, stress or anger.

Relaxation techniques are often employed as one element of a wider stress management programme and can decrease muscle tension, lower the blood pressure and slow heart and breath rates, among other health benefits.

People respond to stress in different ways, namely, by becoming overwhelmed, depressed or both. Yoga, QiGong, Taiji, and Pranayama that includes deep breathing tend to calm people who are overwhelmed by stress, while rhythmic exercise improves the mental and physical health of those who are depressed. People who encounter both symptoms simultaneously, feeling depressed in some ways and overexcited in others, may do best by walking or performing yoga techniques that are focused on strength.

Background

Research has indicated that removing stress helps to increase a person’s health.

Research released in the 1980s indicated stronger ties between stress and health and showed benefits from a wider range of relaxation techniques than had been previously known. This research received national media attention, including a New York Times article in 1986.

Uses

People use relaxation techniques for a variety of reasons, including but not limited to:

  • Anger management.
  • Anxiety attacks.
  • Cardiac health.
  • Childbirth.
  • Depression.
  • General well-being.
  • Headache.
  • High blood pressure.
  • Preparation for hypnosis.
  • Immune system support.
  • Insomnia.
  • Pain management.
  • Relaxation (psychology).
  • Stress management.
  • Addiction treatment.
  • Nightmare disorder.

Techniques

Various techniques are used by individuals to improve their state of relaxation. Some of the methods are performed alone; some require the help of another person (often a trained professional); some involve movement, some focus on stillness; while other methods involve different elements.

Certain relaxation techniques known as “formal and passive relaxation exercises” are generally performed while sitting or lying quietly, with minimal movement and involve “a degree of withdrawal”. These include:

  • Autogenic training.
  • Biofeedback.
  • Deep breathing.
  • Guided imagery.
  • Hypnosis.
  • Meditation.
  • Pranayama.
  • Progressive muscle relaxation.
  • Qigong.
  • Transcendental Meditation technique.
  • Yoga Nidra.
  • Zen Yoga.

Movement-based relaxation methods incorporate exercise such as walking, gardening, yoga, T’ai chi, Qigong, and more. Some forms of bodywork are helpful in promoting a state of increased relaxation. Examples include massage, acupuncture, the Feldenkrais Method, myotherapy, reflexology and self-regulation.

Some relaxation methods can also be used during other activities, for example, autosuggestion and prayer. At least one study has suggested that listening to certain types of music, particularly new-age music and classical music, can increase feelings associated with relaxation, such as peacefulness and a sense of ease.

A technique growing in popularity is flotation therapy, which is the use of a float tank in which a solution of Epsom salt is kept at skin temperature to provide effortless floating. Research in the US and Sweden has demonstrated a powerful and profound relaxation after twenty minutes. In some cases, floating may reduce pain and stress and has been shown to release endorphins.

Even actions as simple as a walk in the park have been shown to aid feelings of relaxation, regardless of the initial reason for the visit.

What is Defensive Pessimism?

Introduction

Defensive pessimism is a cognitive strategy identified by Nancy Cantor and her students in the mid-1980s.

Individuals use defensive pessimism as a strategy to prepare for anxiety-provoking events or performances. When implementing defensive pessimism, individuals set low expectations for their performance, regardless of how well they have done in the past. Defensive pessimists then think through specific negative events and setbacks that could adversely influence their goal pursuits. By envisioning possible negative outcomes, defensive pessimists can take action to avoid or prepare for them. Using this strategy, defensive pessimists can advantageously harness anxiety that might otherwise harm their performance.

Defensive pessimism is utilised in a variety of domains, and public speaking provides a good example of the process involved in this strategy. Defensive pessimists could alleviate their anxiety over public speaking by imagining possible obstacles such as forgetting the speech, being thirsty, or staining their shirts before the event. Because defensive pessimists have thought of these problems, they can appropriately prepare to face the challenges ahead. The speaker could, for instance, create note cards with cues about the speech, place a cup of water on the podium to alleviate thirst, and bring a bleach pen to remove shirt stains. These preventive actions both reduce anxiety and promote superior performance.

Refer to Depressive Realism.

Strategy Effectiveness

Though defensive pessimists are less satisfied with their performances and rate themselves higher in “need for improvement,” they do not actually perform worse than people with a more optimistic strategy. Norem and Cantor (1986) investigated whether encouraging defensive pessimists, and thereby interfering with their typical negative thinking, would result in worse performances. Participants in the study were in either encouragement or non-encouragement scenarios as they prepared to complete anagram and puzzle tasks. In the encouragement condition, the defensive pessimists were told that, based on their GPA, they should expect to do well. Defensive pessimists performed worse when encouraged than the defensive pessimists whose strategy was not manipulated. Defensive pessimism is an adaptive strategy for those who struggle with anxiety: their performance decreases if they are unable to appropriately manage and counteract their anxiety.

Key Components

Prefactual Thinking

Prefactual (i.e. “before the fact”) thinking is an essential component of defensive pessimism. Synonymous with anticipation, it denotes a cognitive strategy in which people imagine possible outcomes of a future scenario. The term prefactual was specifically coined by Lawrence J. Sanna, in 1998, to denote those activities that speculate on possible future outcomes, given the present, and ask “What will be the outcome if event E occurs?”

The imagined outcomes are either positive/desirable, negative/undesirable, or neutral. Prefactual thinking can be advantageous because it allows the individual to prepare for possible outcomes of a scenario.

For defensive pessimists, prefactual thinking offers the primary and critical method to alleviate anxiety. Usually, this prefactual thinking is paired with a pessimistic outlook, resulting in negative/undesirable imagined scenarios. With regard to the earlier example, the public speaking defensive pessimist anticipates forgetting the speech or becoming thirsty as opposed to giving an amazing speech and receiving a standing ovation.

Anxiety

As defensive pessimism is motivated by a need to manage anxiety, it is unsurprisingly also correlated with trait anxiety and neuroticism. Negative mood states promote defensive pessimists’ goal attainment strategy by facilitating the generation of potential setbacks and negative outcomes that could arise during goal pursuit, which can then be anticipated and prevented. When defensive pessimists are encouraged into positive or even just neutral mood states, they perform worse on experimental tasks than when in a negative mood state. They are more anxious because they are prevented from properly implementing their preferred cognitive strategy for goal attainment.

Self-Esteem

Defensive pessimism is generally related to lower self-esteem since the strategy involves self-criticism, pessimism, and discounting previous successful performances. Indeed, Norem and Burdzovic Andreas (2006) found that, compared to optimists, defensive pessimists had lower self-esteem entering college. At the end of four years of college, however, the self-esteem of the defensive pessimists had increased to nearly equal levels as optimists. The self-esteem of optimists had not changed, and the self-esteem of pessimists who did not employ defensive pessimism had fallen slightly by the end of college. While defensive pessimism may have implications for self-esteem, it appears that these effects lessen over time.

Compared to Pessimism

Unlike pessimism, defensive pessimism is not an internal, global, and stable attribution style, but rather a cognitive strategy utilised within the context of certain goals. Pessimism involves rumination about possible negative outcomes of a situation without proactive behaviour to counteract these outcomes. Defensive pessimism, on the other hand, utilizes the foresight of negative situations in order to prepare against them. The negative possible outcomes of a situation often motivate defensive pessimists to work harder for success. Since defensive pessimists are anxious, but not certain, that negative situations will arise, they still feel that they can control their outcomes. For example, a defensive pessimist would not avoid all job interviews for fear of failing one. Instead, a defensive pessimist would anticipate possible challenges that could come in an upcoming job interview – such as dress code, stubborn interviewers, and tough questions – and prepare rigorously to face them. Defensive pessimism is not a reaction to stressful events nor does it entail ruminating on events of the past, and should therefore be distinguished from pessimism as a trait or a more general negative outlook. Instead, defensive pessimists are able to stop using this strategy once it is no longer beneficial (i.e. does not serve a preparatory role).

Compared to Other Cognitive Strategies

Self-Handicapping

Elliot and Church (2003) determined that people adopt defensive pessimism or self-handicapping strategies for the same reason: to deal with anxiety-provoking situations. Self-handicapping is a cognitive strategy in which people construct obstacles to their own success to keep failure from damaging their self-esteem. The difference between self-handicapping and defensive pessimism lies in the motivation behind the strategies. Beyond managing anxiety, defensive pessimism is further motivated by a desire for high achievement. Self-handicappers, however, feel no such need. Elliot and Church found that the self-handicapping strategy undermined goal achievement while defensive pessimism aided achievement. People who self-handicapped were high in avoidance motivation and low in approach motivation. They wanted to avoid anxiety but were not motivated to approach success. Defensive pessimists, on the other hand, were motivated to approach success and goal attainment while simultaneously avoiding the anxiety associated with performance. Although it was found that defensive pessimism was positively correlated with goals related to both performance-avoidance and anxiety-avoidance, it was not found to be a predictor of one’s mastery of goals.

Strategic Optimism

In research, defensive pessimism is frequently contrasted with strategic optimism, another cognitive strategy. When facing performance situations, strategic optimists feel that they will end well. Therefore, though they plan ahead, they plan only minimally because they do not have any anxiety to face. While defensive pessimists set low expectations, feel anxious, and rehearse possible negative outcomes of situations, strategic optimists set high expectations, feel calm, and do not reflect on the situation any more than absolutely necessary. Strategic optimists start out with different motivations and obstacles: unlike defensive pessimists, strategic optimists do not have any anxiety to surmount. In spite of their differences in motivation, strategic optimists and defensive pessimists have similar objective performance outcomes. For both strategic optimists and defensive pessimists, their respective cognitive strategies are adaptive and promote success.

What is Reaction Formation?

Introduction

In psychoanalytic theory, reaction formation (German: Reaktionsbildung) is a defence mechanism in which emotions and impulses which are anxiety-producing or perceived to be unacceptable are mastered by exaggeration of the directly opposing tendency.

The reaction formations belong to Level 3 of neurotic defence mechanisms, which also include dissociation, displacement, intellectualisation, and repression.

Theory

Reaction formation depends on the hypothesis that:

“[t]he instincts and their derivatives may be arranged as pairs of opposites: life versus death, construction versus destruction, action versus passivity, dominance versus submission, and so forth. When one of the instincts produces anxiety by exerting pressure on the ego either directly or by way of the superego, the ego may try to sidetrack the offending impulse by concentrating upon its opposite. For example, if feelings of hate towards another person make one anxious, the ego can facilitate the flow of love to conceal the hostility.”

Where reaction-formation takes place, it is usually assumed that the original, rejected impulse does not vanish, but persists, unconscious, in its original infantile form. Thus, where love is experienced as a reaction formation against hate, we cannot say that love is substituted for hate, because the original aggressive feelings still exist underneath the affectionate exterior that merely masks the hate to hide it from awareness.

In a diagnostic setting, the existence of a reaction-formation rather than a ‘simple’ emotion would be suspected where exaggeration, compulsiveness and inflexibility were observed. For example:

“[r]eactive love protests too much; it is overdone, extravagant, showy, and affected. It is counterfeit, and […] is usually easily detected. Another feature of a reaction formation is its compulsiveness. A person who is defending himself against anxiety cannot deviate from expressing the opposite of what he really feels. His love, for instance, is not flexible. It cannot adapt itself to changing circumstances as genuine emotions do; rather it must be constantly on display as if any failure to exhibit it would cause the contrary feeling to come to the surface.

Reaction formation is sometimes described as one of the most difficult defences for lay people to understand; this testifies not merely to its effectiveness as a disguise, but also to its ubiquity and flexibility as a defence that can be utilised in many forms. For example:

“solicitude may be a reaction-formation against cruelty, cleanliness against coprophilia”,

and it is not unknown for an analyst to explain a client’s unconditional pacifism as a reaction formation against their sadism. In addition:

“[h]igh ideals of virtue and goodness may be reaction formations against primitive object cathexes rather than realistic values that are capable of being lived up to. Romantic notions of chastity and purity may mask crude sexual desires, altruism may hide selfishness, and piety may conceal sinfulness.”

Even more counter-intuitively, according to this model:

“[a] phobia is an example of a reaction formation. The person wants what he fears. He is not afraid of the object; he is afraid of the wish for the object. The reactive fear prevents the dreaded wish from being fulfilled.

The concept of reaction formation has been used to explain responses to external threats as well as internal anxieties. In the phenomenon described as Stockholm syndrome, a hostage or kidnap victim ‘falls in love’ with the feared and hated person who has complete power over them. Similarly, paradoxical reports exist of powerless and vulnerable inmates of Nazi camps creating ‘favourites’ among the guards and even collecting objects discarded by them. The mechanism of reaction formation is often characteristic of obsessional neuroses. When this mechanism is overused, especially during the formation of the ego, it can become a permanent character trait. This is often seen in those with obsessional character and obsessive personality disorders. This does not imply that its periodic usage is always obsessional, but that it can lead to obsessional behaviour.

What is Emotional Detachment?

Introduction

In psychology, emotional detachment, also known as emotional blunting, has two meanings:

  • One is the inability to connect to others on an emotional level; and
  • The other is as a positive means of coping with anxiety.

This coping strategy, also known as emotion focused-coping, is used by avoiding certain situations that might trigger anxiety. It refers to the evasion of emotional connections. Emotional detachment may be a temporary reaction to a stressful situation, or a chronic condition such as depersonalisation-derealisation disorder. It may also be caused by certain antidepressants. Emotional blunting as reduced affect display is one of the negative symptoms of schizophrenia.

Signs and Symptoms

Emotional detachment may not be as outwardly obvious as other psychiatric symptoms. Patients diagnosed with emotional detachment have reduced ability to express emotion, to empathise with others or to form powerful emotional connections. Patients are also at an increased risk for many anxiety and stress disorders. This can lead to difficulties in creating and maintaining personal relationships. The person may move elsewhere in their mind and appear preoccupied or “not entirely present”, or they may seem fully present but exhibit purely intellectual behaviour when emotional behaviour would be appropriate. They may have a hard time being a loving family member, or they may avoid activities, places, and people associated with past traumas. Their dissociation can lead to lack of attention and, hence, to memory problems and in extreme cases, amnesia. In some cases, they present an extreme difficulty in giving or receiving empathy which can be related to the spectrum of narcissistic personality disorder.

In children (ages 4-12 were studied), traits of aggression and antisocial behaviours were found to be correlated with emotional detachment. Researchers determined that these could be early signs of emotional detachment, suggesting parents and clinicians to evaluate children with these traits for a higher behavioural problem in order to avoid bigger problems (such as emotional detachment) in the future.

Causes

Emotional detachment and/or emotional blunting have multiple causes, as the cause can vary from person to person. Emotional detachment or emotional blunting often arises due to adverse childhood experiences, or to psychological trauma in adulthood.

Emotional blunting is often caused by antidepressants in particular selective serotonin reuptake inhibitors (SSRIs) used in major depressive disorder, and often as an add-on treatment in other psychiatric disorders.

Behavioural Mechanism

Emotional detachment is a behaviour which allows a person to react calmly to highly emotional circumstances. Emotional detachment in this sense is a decision to avoid engaging emotional connections, rather than an inability or difficulty in doing so, typically for personal, social, or other reasons. In this sense it can allow people to maintain boundaries, psychic integrity and avoid undesired impact by or upon others, related to emotional demands. As such it is a deliberate mental attitude which avoids engaging the emotions of others.

This detachment does not necessarily mean avoiding empathy; rather, it allows the person to rationally choose whether or not to be overwhelmed or manipulated by such feelings. Examples where this is used in a positive sense might include emotional boundary management, where a person avoids emotional levels of engagement related to people who are in some way emotionally overly demanding, such as difficult co-workers or relatives, or is adopted to aid the person in helping others.

Emotional detachment can also be “emotional numbing”, “emotional blunting”, i.e., dissociation, depersonalisation or in its chronic form depersonalisation disorder. This type of emotional numbing or blunting is a disconnection from emotion, it is frequently used as a coping survival skill during traumatic childhood events such as abuse or severe neglect. Over time and with much use, this can become second nature when dealing with day to day stressors.

Emotional detachment may allow acts of extreme cruelty and abuse, supported by the decision to not connect empathically with the person concerned. Social ostracism, such as shunning and parental alienation, are other examples where decisions to shut out a person creates a psychological trauma for the shunned party.