Introduction to Anxiety

Anxiety is a bit confusing as a term, as it is used to describe both an acute anxiety responses to specific circumstances (called state anxiety) and a personality trait predisposing a person to experiencing more frequent and intense incidences of state anxiety (called trait anxiety).[1] This distinction is an important one as it affects what treatments are most appropriate. Anxiety that rises to the level of significant impairment or distress may be diagnosed as an anxiety disorder by a qualified professional. Briefly, some of the more common disorders are generalised anxiety disorder (characterised by constant worrying about what should be non-threatening stimulus), social anxiety disorder (worry about social interactions), panic disorder (experience of panic attacks during episodes of state anxiety), and agoraphobia (fear of being in places or situations where escape is difficult).

Causes of Anxiety

Heretability

Anxiety disorders have a significant genetic component, which may vary according to the specific disorder. [2][3]
The exact heritability statistics are not completely clear, but studies put the heritability of panic disorder for example at between 0.28 and 0.43.[4]

Anxiety disorders may be related to a variation in the BDNF gene. A particular allele of this gene impairs the extinction of fear responses.[5] In an animal study, mice which do not normally have this allele had the allele inserted into their genome. The addition of the allele to the genome caused the impairment of extinction to a conditioned fear response.[6]

Environmental factors

Stressful life events

Stressful life events have a role in the development of anxiety disorders. A comprehensive model of panic disorder identified that 80% of people with the disorder experienced a negative experience at the time of their first attack. It is believed that the coinciding of autonomic arousal with the panic attacks becomes classically conditioned as a trigger for a fear response. A fear of fear.[1]

Cannabis use

Cannabis use, particularly in youth is associated with anxiety disorders. It is less clear however if this is an effect of the use of cannabis, if the anxiety disorder is predictive of cannabis use or if overlapping risk factors cause a coincidental correlation. The evidence at present does not indicate a causal link between cannabis use and the development of anxiety disorders.[7] On the other hand, cannabis has been shown to cause states of anxiety as an effect of cannabis intoxication. It is the most commonly reported side effect of intoxication, occurring in around 20-30% of users.[8]

Substance withdrawal and rebound

Anxiety is a commonly reported symptom of acute withdrawal from many substances including opioids and stimulants. Anxiety is also a symptom of post-acute withdrawal syndrome (PAWS) which can occur after the acute withdrawal period of many substances and can persist for a much longer period of time.

GABAergic drugs such as barbiturates, benzodiazepines, phenibut and alcohol deserve a special mention with regard to withdrawal. These drugs actively reduce anxiety as a primary effect, and when discontinued may result in a rebound phenomenon as well as withdrawal. Having become habituated to a state of inhibited anxiety the user experiences a higher level of anxiety than that they experienced prior to using the medication for a period of time after discontinuation. It is strongly recommended that users taper these drugs to avoid serious anxiety, insomnia and possibility of seizures.

Psychedelics

Unpleasant experiences when tripping can provoke strong anxiety responses. It is recommended that users of these substances familiarise themselves set and setting suggestions and what to do in the event of a bad trip.

Symptoms & Types/Variations of Anxiety

• Excessive worry or concern over stressful encounters (i.e. a disproportionate response to the circumstances).
• Inappropriate worry or concern (i.e. a response to circumstances that would not generally be considered worrying).
• Panic attacks in stressful circumstances. Panic attacks may include physiological symptoms such as shortness of breath, tachycardia, hypertension, dizziness and fainting.
• Self-imposed restriction of activities for fear of experiencing a panic attack.
• Insomnia.

Treatments of Anxiety

The types of treatment appropriate for state and trait anxiety differ because many treatments require a lead in period before becoming effective. For this reason the treatment types are divided into state and trait treatments.

Natural

State

• Controlled breathing exercises.[9]

Trait

• Controlled breathing exercises.[9]
• Meditation.[9]
• Progressive/passive muscle relaxation.[9]
• Passion flower extract.[10]
• Kava-kava.[11]

Medical

State

• Benzodiazepines are commonly used for acute anxiety episodes that require medication.
• Barbiturates were used for anxiety prior to the discovery of benzodiazepines. They have since fallen from favour due to the unacceptable risk of overdose (accidental or otherwise).
• Gabapentinoids such as gabapentin and pregabalin are sometimes prescribed for anxiety.
• Beta-blockers have demonstrated efficacy in treating performance anxiety. Additionally beta-blockers may relieve some of the physical sympathetic nervous system symptoms of an acute anxiety episode such as hypertension.

Trait

• SSRI or SNRI antidepressants are the first choice treatment for treating trait anxiety due to the low impact of dependence and similar level of efficacy compared with medications with a high risk of dependence. A period of around six weeks is necessary for them to become fully effective.
• Buspirone is a second choice treatment for trait anxiety. It is also sometimes prescribed in combination with antidepressant treatments.
• Benzodiazepines are not favoured for trait anxiety due to the rapid development of tolerance. Historically they have been used for this purpose, but many report physicians being reluctant to prescribe them for trait anxiety.
• Barbiturates are as noted above not commonly used for anxiety due to the risk of overdose. They also share the same rapid development of tolerance issues as benzodiazepines
• Gabapentinoids such as gabapentin and pregabalin are sometimes prescribed as a second line treatment for anxiety. High doses may cause rapid development of tolerance, but the risks of withdrawal from them are less pronounced than is the case for benzodiazepines.

Neurobiological basis of Anxiety

fMRI and PET scanning observations have highlighted increased amygdala activity during panic attacks and when patients are presented with stressful stimulus. The amygdala is a limbic system structure that is especially involved in conditioned responses to aversive stimulus (e.g. fear). Other brain areas involved in anxiety are the cingulate, prefrontal and insular cortexes. The development and control of anxiety is not fully understood, but it is hoped that optogenetic research will lead to greater understanding of the neural circuits involved.[5]

The Dangers & Health Risks of Anxiety

Exposure to stress, eaxcerbated by maladaptive anxiety can lead to cardiovascular disease, depression, the metabolic syndrome, compromised immune functioning, post-traumatic stress disorder[12] memory impairment and cancer[1]. Psychologically a sufferer may restrict their activities for fear of anxiety, or experience paralysis of decision making in dangerous situations.

Morbidity Rate

Collectively stress related disorders are the number one killer of people in the developed world. Cardiovascular disease alone is the leading killer in many countries.

Some sufferers of anxiety may be more predisposed towards suicide after experiencing trauma.[12]

More Anxiety Sections

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