Motivation and emotion/Book/2022/Benzodiazepines and emotion

Benzodiazepines and emotion:
What are the effects of benzodiazepines on emotion?

Multimedia presentation (3 min)

Overview

Figure 1. Benzodiazepines commonly prescribed

Benzodiazepines, also known as benzos, are commonly prescribed drugs aimed at the short-term relief of severe, disabling anxiety or insomnia. Long-term use is not only non-effective, but can be problematic because it is related to several negative health effects such as dependence, falls, withdrawal, hip fractures, phases of depression, and impaired cognition. As a result, guidelines for general practitioners prescribing benzos have been established. Despite recommendations, many people ignore the warning and education given by their physicians and feel that the potential risks of the drugs are non-existent (Wolde et al., 2008).

To understand the unfavourable impact of benzodiazepines on emotion, (see Case study 1), which describes clinical psychologist Jordan Peterson's experience and Figure 1 which displays types of benzodiazepines commonly prescribed. This book chapter explores the biological, cognitive, behavioural, and social effects of benzodiazepines on emotion, as well as theoretical relevant factors such as emotional regulation and self-efficacy. This chapter also highlights the potential dangers of using benzodiazepines, and conclude with safe, practical alternatives that individuals may choose as a viable alternative.

Case study 1 - "Trip to hell and back" by Jordan Peterson In 2017, renown clinical psychologist, Jordan Peterson, was prescribed benzodiazepines to treat anxiety and ongoing depression. Peterson continued to use benzodiazepines with little to no side effects for three years, finding that they were beneficial. Unfortunately, several traumatic events culminated in his personal life which resulted in heightened feelings of stress, and Peterson sought out an increase in his prescription. Not understanding the danger of benzodiazapines, he thought this might help him avoid troubling his family members and cope with his emotions. The increased dosage had the opposite effect; Peterson experienced a "marked negative increase in emotion". Which led to him again, seeking a second increase to his dosage. This second increase led to his anxiety increasing even further, and Peterson became unknowingly chemically addicted to the drug. In 2019, he quit benzodiazepines completely, and began to experience acute withdrawal symptoms, which he described as a "trip to hell and back". The withdrawal led to intolerable anxiety, uncontrollable restlessness, akathisia (need to move), overwhelming thoughts of self-destruction, unhappiness, increased appetite and exhaustion. A family friend advised Peterson to return to a small dosage of benzodiazepines to relieve the intense withdrawal symptoms. He followed this advice, and found some relief. Following this, Peterson attended several clinics so he could receive assistance in his withdrawal from benzodiazepines. One clinic placed him into a medically induced coma for several days so that he was not conscious during the worst of the withdrawal symptoms.

Focus questions: What are benzodiazepines? How do benzodiazepines influence emotion? What are the issues related to benzodiazepines? What are the non-pharmacological applications?.

What are benzodiazepines?

Benzodiazepines are a group of psychoactive drugs that enhance the action of the neurotransmitter gamma-aminobutyric acid (GABA), which slows down the central nervous system CNS. This produces a calming, sedative effect (Ashton, 1994). See Table 2 to understand how various benzodiazepines work.

Table 2. Summary of how benzodiazepines work

Medications	Durations of action (hours)	Effects	Rate of onset	Administrations
Alprazolam (Xanax)	6-12	Anxiolytic	Intermediate	Oral
Clonazepam (Klonopin, Rivotril)	18-50	Anxiolytic, anti-convulsant	Slow	Oral
Larazepam (Ativaran)	10-20	Anxiolytic, alcohol withrawal and preaneasthetic	Intermediate	Oral, IM, IV
Diazepam (Valium)	20-100	Anxiolytic, anticonvulsant (status epilepticus) muscle relaxant)	Fast	Oral, intramuscular (IM), intravenous (IV) and rectal
Clorazepam (Tranxene)	36-200	Anxiolytic, anticonvulsant	Slow	Oral
Prazepam (Centrax)	36-200	Anxiolytic	Slow	Oral
Oxazepam (Serax, Serenid, Serepax)	4-15	Anxiolytic, alcohol withdrawal	Slow	Oral
Chlordiazepoxide (Librum)	5-130	Anxiolytic, alcohol withdrawal and preanesthetic	Intermediate	Oral, IM and IV

What is emotion?

• Emotions are complex patterns of reaction which involve behavioural, psychological, biological, physiological and environmental elements (Reeve, 2018)
• Benzodiazepines elicit core emotions that may produce feelings of euphoria but can also cause devastating adverse effects leading to homeostasis breakdown and even death (Koob, 2015).
• Benzodiazepines affect the limbic system, responsible for processing emotions
• Prolonged use of Benzodiazepines is correlated with rebound anxiety, persistent irritability, mood swings and depression, and insomnia (Ashton, 1994)

Case study 2. John felt loved after receiving a birthday present from his friend. Later that day, John received the sad information that his uncle had passed away, which led him to feel sad. Emotions are internal reactions to external stimuli or events. In John's case, his first internal reaction to receiving a present was to an experience of positive emotion, whilst his second internal reaction was based on upsetting news, leading him to feel negative emotion.

Benzodiazepines have both positive and negative effects on emotions.

Positive Effects	Negative adverse effects (sensations)
Acts on the central nervous system and peripheral organs are not impaired Safe- very low toxicity, unlike barbiturates or alcohol Does not induce metabolic enzymes, or accelerate metabolism Sensations includes Reduce symptoms of anxiety Feeling of relaxation Peaceful serene Feeling elated Feeling disturbed Feeling careless and not stressed Tranquil feelings	Tolerance Dependence Withdrawal challenges Psychomotor impairment Disinhibition and Paradoxical effects Affective reaction Hangover Rebound insomnia and anxiety Reduce breathing (Ashton, 1994)

Psychology of emotions

Biology and cognition play important role in the activation and regulation of emotion, and studies specify two system ways working as parallel emotion systems and a dynamic, dialectical process.

Biology and benzodiazepines

The Limbic system is considered a critical region of the brain regarding emotions as its functions include processing information from our environment and determining if the information is associated with threat or reward (Kalat, 2013). The role of benzos is to produce calming effects to the limbic area of the brain. The amygdala area is responsible in detecting threatening information from our environment and distributing the message to the other parts of the brain.

Benzodiazepines :

• Damage to the frontal lobe of the brain, leads to disinhibition of the frontal cortex which impacts self-regulation and control
• Act indirectly to reduce serotonin activity
• Increase dopamine levels through disinhibition and implicate GABA A receptors (Nuss, 2015)
• Diazepam can blunt the hyperadrenergic system of serotonin syndrom
• Inhibits activity in the limbic system which reduces anxiety, calming the body and brain
• Use of benzodiazepines can lead to neurodegenerative disease and permanent brain damage through long-term use (especially dementia)
• Benzos and facial expression are correlated through physiological response have direct impact on emotions (Garcez, Fernandes, Barbosa, Pereira, Silveira, Marques-Teixeira, & Gonçalves, 2020)

Cognition and benzodiazepines

Emotions are mostly controlled by cognition (Edelman, 2002). Our thoughts and beliefs about stimuli or events can influence the way we act and do things. Benzodiazepines may influence the following cognitive functions:

• Increased objective and subjective sedation

• Impaired visuospatial perception and visuomotor abilities due to long-term use
• Impairment in attention processing

• Anterograde amnesia (Lister, 1985)
• Memory impairment (in difficult tasks) (Barbee, 1993) and impaired working and verbal memory
• Impaired episodic memory (acquisition of new information)
• Decline in general cognitive functioning ability (Barker, Greenwood, Jackson, & Crowe, 2004).
• Inability to drive safely due to delayed response time
• Impaired psychomotor activities and motor control (Ashton, 1994)
• Decreased alertness regarding environmental threat
• Increased reaction times (Stone, Corea, Brown, Spurgin, Stikic, Johnson, & Berka, 2015)
• Despite the numerous of benzos, alternative research suggests that the cognitive dysfunction (psychomotor function, motor speed, sustained attention and verbal memory) arising from benzodiazepine use is temporary (Steward, 2005).

Social contexts

External social influences may motivate people to rely on benzodiazepines as a coping mechanism. For example, watching family members rely on drugs rather than adaptive behaviours may teach young adults unhealthy coping habits. This could have serious negative consequences later in life as individuals also begin to rely on benzodiazepines when stressed.

What are the effects of benzodiazepines on emotion?

Effects of benzos on emotion can be behavioural, psychological, physical and social (see Figure 2).

Behavioural

Figure 2. Feeling deep and unfulfilled desire

• Social withdrawal
• Lack of productivity at work or home
• Multiple doctor visits for prescriptions
• Isolating from family and friends

Psychological

• Intense mood change
• Intense hostility especially when experiencing withdrawal
• Emotional detachment

Physiological

• Unsteadiness
• Blurred vision
• Drowsiness
• General muscle weakness
• Neuroticism
• Increased emotional rather than task-based coping mechanisms, particularly for introverted individuals (Konopka, Pełka-Wysiecka, Grzywacz, & Samochowiec, 2013).

Social

• Restlessness
• Problem-focused and emotional-focused coping
• Altered Expression and suppression of emotion
• Sense of lack of personal agency

Example 1. Cognition impairment: Nick and his friends are going out to celebrate their graduation. The thought of going out and meeting new people makes Nick anxious. Previously, Nick relied on diazepam to cope with anxiety at social gathering, so this time he decided to take benzodiazepines to calm his nerves and feel more confident. At the social gathering, Nick was involved in an argument which resulted in a fight. His friends tried to stop him but he ignored them. The following morning Nick woke up with a black eye and felt sore all over his body. He asked his friends about what happened the previous night, stating that he had no memory or recollection of what had happened at all. Nick experienced impaired memory functioning and cognitive processes as a result of his use of benzos.

Theoretically - relevant factors in relation to benzos and emotion

Emotion regulation

Emotion regulation (ER) refers to ability to effectively manage and respond to an emotional experience. ER is related to use of benzos because it provide individuals with a double ability to avoid drugs use, relapse and assist with control of temptation to encourage in an unhealthy behaviour. Use of emotions and emotions modulation is grounded in the functionality of emotions and paradoxical consequences of efforts to avoid or control emotions.

ER is an important part of being a functional adult and also plays a protective role remaining substance free (Chavarria et al., 2012). Ineffective ER in individuals with anxiety disorders may prompt them to seek out alternative means such as benzos to cope with emotional distress. This is because benzos provide sense of calm or feeling of euphoria that counter emotional distress. The negative reinforcement provided by benzos to manage stress eventually contribute to unhealthy dependence (Chavarria, Stevens, Jason, & Ferrari, 2012)

Self-efficacy

Self-efficacy is a belief that an individual holds regarding their capacity to achieve desired outcomes. Self-efficacy determines the amount of energy individuals put into the process of attempting to change undesired behaviour. SE is involved in abstaining from numerous habitual behaviours, including use of prescription drugs like benzos, illicit substances, and excessive drinking. Researchers showed that among individuals who attempt to quit substance use or smoking with higher self-efficacy scores have better outcomes (Chavarria et al., 2012).

Learned helplessness

The theory of Learned helplessness suggests that a psychological lack of control or mastery presents a critical risk factor for anxiety (Zalta & Chambless, 2012). Chronic exposure to anxiety, and thus perceived uncontrollable situations, enhances expectations that an individual cannot control important events in their environment. This lack of control over one's self leads individuals to seek alternative coping strategies like benzos (Zalta et al., 2012). Research has found that a human's reaction to feeling a lack of control differs both between individuals and between situations, i.e. learned helplessness sometimes remains specific to one situation but at other times generalizes across situation. Individuals who perceived their situation as unchangeable are unlikely to change their unhealthy patterns of behaviour. For example, adults rely on benzos because they produce short-term positive relief when they feel the drug is their only option; these people feel that the situation is out of their control, rather then acknowledging their capacity for alternatives, such as practicing emotional regulation techniques (Maier, & Seligman, 1976).

Impulsivity facets

Impulsivity is a multi-faceted construct consisting of negative urgency, failure to consider the consequences of an action before engaging in that action, inability to focus or follow through on difficult tasks and sensation seeking. Because substances such as benzos provide positive outcomes, individuals using the drugs tend not to be seen as signs of impulsivity, but as indicators of quickness and unconventionality. Low perseverance among individuals using benzos may interfere with their ability to follow recommended dose leading to dependence and withdrawal. in additions, impulsivity is a common feature of the conditions of substance abuse, gambling and alcohol addiction (Moeller, Barratt, Dougherty, Schmitz, & Swann, 2001).

The opponent processing theory

According to Solomon, emotions and motivation are driving forces in substance use and addiction. The dependence is the result of an emotional pairing of pleasure (euphoria feeling produce by benzos) and emotional symptoms associated with withdrawal. At the start of drug or substance use, there are high levels of pleasure and low levels of withdrawal. Over time, as the levels of pleasure decrease, the levels of withdrawal symptoms increase. The longer individuals uses drugs such as benzos, the greater the negative effects are. It is the desire to avoid these negative effects that makes individuals continue to use the drugs, making it hard for individuals to quit (Solomon & Corbit, 1974).

Benzodiazepines and older population

Elderly population are more susceptible to CNS depressant drugs and are commonly prescribed them for insomnia, anxiety disorders, and the behavioral and psychological symptoms of dementia. Use of benzos may develop states of confusion, leading to falls and fracture. Due to their age, older adults have a reduced ability to metabolize the drug, especially long-acting benzodiazepines (Ashton, 1994)

Benzodiazepines and alcohol use

Benzodiazepines and alcohol both affect the CNS. They act similarly, although benzodiazepines are sometimes prescribed for patients suffering from alcohol withdrawal. Side effects of both drugs include blurred vision, cravings, poor judgement or passing out. Studies propose that people who drink alcohol regularly are more likely to use benzodiazepine than those who do not drink. Combinations of the two drugs can lead to overdose and can be fatal (Gudin, Mogali, Jones, & Comer, 2013).

Overdoses

Overdoses happen when drugs or substances are taken, exceeding recommended dose/limits. Overdoses are serious and can lead to coma or death. An overdose leads to decreased brain activity. For instance, one's heart can stop completely from overdose of any drugs including depressant drugs. The sign and symptoms include decreased respiratory activity, slurred speech, dizziness, poor/lack of co-ordination or movement, general muscle weakness, sedation and death. Flumazenil is an antagonist to benzos, used as a reversal agent in overdoses, and this drug binds to a similar area of the brain to benzos (Sun, Dixit, Humphreys, Darnall, Baker, & Mackey, 2017).

Issues related to benzodiazepines

Dependence

Dependence means reliance on something, and the absence of it can cause physical or psychological withdrawal symptoms. The body depends on the substance because it is used to relying on something to achieve feelings of normality. Psychological dependence emphasizes the mental state caused by addiction that mainly allows a person to attain different thoughts/mind states and can alter a person’s mind resulting in a person engaging in behavior that induces relaxation and pleasure. Individuals become tolerant to benzos because their body is used to the drugs, and the brain becomes accustomed, causing an established pattern of homeostatic reactions to the drugs, sometimes called neuroadaptation (Guina, & Merrill, 2018).

Case study 3. Jane was anxious about catching a plane, so her doctor recommended benzodiazepines to help with her acute symptoms. Jane took the drugs and felt better. In the future, Jane continued to take benzodiazepines each time she took a plane, train or bus in order to avoid feeling anxious. When Jane thinks about taking a flight without benzodiazepines, she becomes extremely anxious. Jane refuses to travel without taking benzodiazepines because she has developed a reliance on them.

Withdrawal

Factors affecting the symptoms linked with benzos withdrawal depend on the frequency, amount and duration that the drugs have been used for. Characteristics of withdrawal include irritability, increased anxiety, sleep disturbance, sweating, panic attacks, confusion, shaking, nausea, palpitations, muscle pain, memory impairment, weight loss, hand tremor, hallucinations, psychosis, seizure, suicide ideation, changes in perception, sleeping problems, depression, restlessness and mood swings (Barker, Greenwood, Jackson, & Crowe, 2004). Self-regulation is found to be effective in the process of recovery and relapse (Charvarria et al., 2012)

Non-pharmacological applications and interventions.

Although many people turn to benzodiazepines due to their accessibility there are other methods that provide similar effects and long lasting effects compared to benzos.

Cognitive behavioural therapy

Figure 3. Example of how CBT session looks like{{gr}

Cognitive behavioural therapy (CBT) has been practiced for many years and has been effective in treating anxiety, panic disorders, phobia and other emotional disorders (Guina, & Merrill, 2018). CBT may also help individuals learn to regulate their emotions (see Figure 3).

tDCS - Research found that tDCS improve the behaviour of substance dependent individuals (Zhao, Qiao, Fan, Zhang, Turel, Li, & He, 2017)

Self-management

- Relaxation techniques include deep breathing exercises, yoga, meditation, resting in the dark, and long baths to help calm the body and brain (see Figure 4).

Figure 4. Example of relaxation technique

- Stress management techniques – learning how to manage stress can reduce future triggers.

- Supportive network – talk to supporting people, for instance, church members, friends, family, and service groups available in the area.

- Exercise thoughts – replacing negative thoughts with positive ones creates pleasant and successful mental images, a form of mindfulness therapy (Guina, & Merrill, 2018)

Take home messages:

• Do not quit benzos cold turkey, rather, one should gradually taper off the drugs.
• You can achieve benzos effects without taking the drugs. For example, consider different types of exercise, engage in helping other people, talk to trusted family or friends and practice mindfulness.
• Use the drugs when non-medical techniques are not working - benzos could be the last resort.
• Benzos can be effective when used in the short-term although patients need to be warned about the risk of tolerance, dependence, withdrawal, and overdose.
• Avoid benzos when using other substances or withdrawing from alcohol dependance, as drugs can react with benzos.
• The belief that benzos are safe and have no risk is a myth, therefore talk to your health care provider about side effects and risks before taking any drugs.

Cognitive behavioural therapy can provide the same effects as benzodiazepines. True False

Conclusion

Due to the lack of efficacy and presence of many risks, benzos prescription is only recommended in severe, disabling anxiety or insomnia. Until questions about long-term benzos use are satisfactorily addressed, the wise prescriber will limit his prescriptions in number to patients who are severely anxious or insomniac; in dosage to the lowest effective; and in duration to a few weeks rather than months or years.

Long-term benzos use has no efficacy and significant harm. The risk/benefit ratio of these drugs becomes less favourable or even adverse as treatment becomes prolonged. Benzodiazepines can be helpful when used to address acute anxiety or depression in the short term. However, research shows that ongoing reliance on the drug may lead to dependence and a deficit in healthy coping mechanisms, adversely impacting one's emotionality (Barker et al., 2004). During dependence, abrupt discontinuation may lead to debilitating side effects such as irritability, panic attacks and depression (Schmitz, 2016). Individuals must always consult their health professionals regarding possible risks of benzodiazepines and seek out alternative treatment options like CBT and self-management techniques where possible.

See also

1. Anxiolytic (Wikipedia)
2. Benzodiazepine (Wikipedia)
3. Methamphetamine and emotion (Book chapter, 2020)
4. Opioid system and human emotion (Book chapter, 2019)

References

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Barbee, J. G. (1993). Memory, benzodiazepines, and anxiety: integration of theoretical and clinical perspectives. The Journal of clinical psychiatry

Barker, M. J., Greenwood, K. M., Jackson, M., & Crowe, S. F. (2004). Persistence of cognitive effects after withdrawal from long-term benzodiazepine use: a meta-analysis. Archives of Clinical Neuropsychology, 19(3), 437-454. https://doi.org/10.1016/S0887-6177(03)00096-9

Chavarria, J., Stevens, E. B., Jason, L. A., & Ferrari, J. R. (2012). The effects of self-regulation and self-efficacy on substance use abstinence. Alcoholism Treatment Quarterly, 30(4), 422-432. https://doi.org/10.1080/07347324.2012.718960

Edelman, S. (2002). Constraining the neural representation of the visual world. Trends in Cognitive Sciences, 6(3), 125-131. https://doi.org/10.1016/S1364-6613(00)01854-4

Garcez, H., Fernandes, C., Barbosa, F., Pereira, M. R., Silveira, C., Marques-Teixeira, J., & Gonçalves, A. R. (2020). Effects of benzodiazepines administration on identification of facial expressions of emotion: a meta-analysis. Psychopharmacology, 237(1), 1-9. https://doi.org/10.1007/s00213-019-05393y

Gonçalves, A. R., Soares, M., Garcez, H., Fernandes, C., Pereira, M. R., Silveira, C., ... & Barbosa, F. (2022). Effects of concomitant benzodiazepines and antidepressants long-term use on perspective-taking. F1000Research, 11(790), 790. https://doi.org/10.12688/f1000research.123119.1

Guina, J., & Merrill, B. (2018). Benzodiazepines I: upping the care on downers: the evidence of risks, benefits and alternatives. Journal of clinical medicine, 7(2), 17. https://doi.org/10.3390/jcm7020017

Kalat, J. W. (2013). Teaching biological psychology to introductory psychology students. In The Teaching of Psychology (pp. 381-388). Psychology Press

Konopka, A., Pełka-Wysiecka, J., Grzywacz, A., & Samochowiec, J. (2013). Psychosocial characteristics of benzodiazepine addicts compared to not addicted benzodiazepine users. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 40, 229-235. https://doi.org/10.1016/j.pnpbp.2012.09.001

Koob, G. F. (2015). The dark side of emotion: the addiction perspective. European journal of pharmacology, 753, 73-87. https://doi.org/10.1016/j.ejphar.2014.11.044

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Maier, S. F., & Seligman, M. E. (1976). Learned helplessness: theory and evidence. Journal of experimental psychology: general, 105(1), 3. https://doi.org/10.1037/0096-3445.105.1.3

Moeller, F. G., Barratt, E. S., Dougherty, D. M., Schmitz, J. M., & Swann, A. C. (2001). Psychiatric aspects of impulsivity. American journal of psychiatry, 158(11), 1783-1793. https://doi.org/10.1176/appi.ajp.158.11.1783

Nuss, P. (2015). Anxiety disorders and GABA neurotransmission: a disturbance of modulation. Neuropsychiatric disease and treatment, 11, 165. https://doi.org/10.2147/NDT.S58841

Schmitz, A. (2016). Benzodiazepine use, misuse, and abuse: a review. Mental Health Clinician, 6(3), 120-126. https://doi.org/10.9740/mhc.2016.05.120

Solomon, R. L., & Corbit, J. D. (1974). An opponent-process theory of motivation: I. Temporal dynamics of affect. Psychological review, 81(2), 119. https://doi.org/10.1037/h0036128

Ten Wolde, G. B., Dijkstra, A., Van Empelen, P., Knuistingh Neven, A., & Zitman, F. G. (2008). Psychological determinants of the intention to educate patients about benzodiazepines. Pharmacy World & Science, 30(4), 336-342. https://doi.org/10.1007/s11096-007-9183-2

Volkow, N. D., & Koob, G. (2015). Brain disease model of addiction: why is it so controversial? The Lancet Psychiatry, 2(8), 677-679. https://doi.org/10.1016/S2215-0366(15)00236-9

Zalta, A. K., & Chambless, D. L. (2012). Confidence appraisals protect against anxiety in response to a transient stressor. Psychology, 3(06), 441. https://doi.org/10.1177/0361684312450004

Zhao, H., Qiao, L., Fan, D., Zhang, S., Turel, O., Li, Y., ... & He, Q. (2017). Modulation of brain activity with noninvasive transcranial direct current stimulation (tDCS): clinical applications and safety concerns. Frontiers in psychology, 8, 685. https://doi.org/10.3389/fpsyg.2017.00685

External links

• Benzodiazepines (Benzos) Pharmacology: Anxiety Medication Sedative Nursing NCLEX ( YouTube)
• Effects of benzodiazepines on cognition (Article)
• Effects of concomitant benzodiazepines and antidepressants long-term use on perspective-taking (new article on benzodiazepines and emotion)
• Emotions and brain (you Tube)
• Persistence of cognitive effects after withdrawal from long-term benzodiazepine use: a meta-analysis (Article)

1. Xanax withdrawal (You Tube)