Chapter 4 Anxiety
With contribution from Dr Katherine Sevar
Introduction
Anxiety disorders are amongst the most common disorders suffered by the Australian population, with approximately 7% of men and 12% of women affected each year.1
Anxiety disorders are classically under-reported to GPs by the community, with on average only one-fifth of people with anxiety as their primary complaint seeking professional help in 2002.2 The reasons cited for this include preferring to individually manage the condition and a desire to pursue self-help strategies.3 Given this finding, it may come as a surprise that anxiety is actually one of the commonest presentations to GPs — when a sub-study of BEACH (Bettering the Evaluation and Care of Health) surveyed a random sample of 379 GPs they discovered that the 3 conditions placing the greatest demand on an individual practitioner’s time were anxiety, depression and back pain.4 Recent statistics suggest 1–2% of the adult population suffer panic disorders — common risk factors include female gender, low socioeconomic status and anxious childhood temperament — and this is associated with significant suicide risk, all-cause mortality and cardiovascular disease.5
Sub-classifications of anxiety disorders
There are sub-classifications of anxiety disorders according to DSM-IV criteria, which include generalised anxiety disorder (GAD), panic disorder, agoraphobia, obsessive compulsive disorder (OCD), social anxiety disorder (SAD), and post-traumatic stress disorder (PTSD). There is significant co-morbidity with anxiety disorders and depression and substance abuse.1
Panic disorder and agoraphobia
Panic attacks can be spontaneous or can occur in relation to a specific stimulus. They include somatic features and cognitive features. The somatic features may include palpitations, chest pain, a feeling of choking, nausea, sweating, dizziness. The cognitive features may include acute fear of dying, losing control, going mad and a need to escape from the current situation and there can also a be a feeling of depersonalisation or non-realisation. In up to 90% of cases, these attacks lead to an avoidance of situations where escape may not be possible — agoraphobia.6 Common associations occur with depression, substance abuse and interpersonal difficulties. Panic disorder is currently treated with anti-anxiety medication and a mix of CBT and exposure therapy. Breathing techniques for the short-term management of panic attacks are advocated and benzodiazepines should only be used in the short-term.
Obsessive compulsive disorder (OCD)
Obsessions can be intrusive thoughts, images or impulses which create anxiety in an individual as they feel unable to control how, when or where these obsessive thoughts may occur. Compulsive behaviour develops as an attempt to relieve the anxiety created by the obsession. Compulsions can include extremely ritualistic behaviours and a need to follow a set routine. Although the compulsions initially relieve anxiety they will over time relieve less anxiety, resulting in them becoming more elaborate and taking up more of the individual’s time. OCD becomes a problem when these behaviours interfere with ordinary life. Current treatment strategies include medication with a selective serotonin re-uptake inhibitor (SSRI) or clomipramine (a serotonergic tricyclic antidepressant) in combination with CBT.
Trends in integrative medicine for anxiety
Research describing long-term trends in complementary medicine (CM) use in the US reported that complementary therapies were used by 57% of people reporting anxiety attacks and 66% of patients consulting a physician for treatment of anxiety. Those surveyed perceived that the efficacy of complementary medicines for anxiety were comparable to conventional drug treatment.7
Lifestyle medicine
Lifestyle factors such as chronic stress, poor nutrition, caffeine, smoking, obesity, alcohol and substance abuse may initiate or perpetuate the symptoms of an anxiety disorder8 and there is an increasing interest among medical and health practitioners to address these lifestyle factors in combination with pharmacotherapy and psychological therapies for anxiety disorders.9
Mind-body medicine
Psychological therapies
Counselling for anxiety in general practice
Patient-centred care has also become a major focus in mainstream medicine and is being evaluated and promoted within general practice in particular.10 Active listening, compassion and empathy are vital factors in the counselling of those patients with an anxiety disorder. Patients who feel their doctors listen to them, and respond with empathy, feel they have greater overall improvement across many conditions.11 In a study of 309 women seeking psychological support, GPs with good listening skills and those who provided longer consultation times were highly valued.12 Women who received referral, counselling and relaxation advice from their GP reported a higher degree of satisfaction.
Cognitive behaviour therapy (CBT) and group therapy
CBT is a talking-based therapy arising from the link between thoughts, feelings and behaviour.13 CBT is a valuable tool for the management of anxiety and it is the first-line treatment for adults and children. The central beliefs of CBT and interventions for anxiety disorders include cognitive restructuring, relaxation, breathing techniques, graded exposure to anxiety provoking situations, problem solving, assertiveness training and social skills development. In an 8-week program,14 CBT including exposure therapy was better than placebo (supportive, non-directive counselling) or moclobemide for the treatment of panic disorder with agoraphobia. Long-term benefits of CBT occurred when used in combination with moclobemide. Self-help CBT programs available on the internet may also be of help in allaying test anxiety. In a study of 90 university students who were randomised to CBT or a control program, both on the internet,15 anxiety was rated before and after treatment and 53% of the CBT group showed a significant improvement in anxiety related to the test but only 29% of the control group demonstrated benefit. This study supports the use of CBT on the internet for the treatment of test anxiety.
Research supports the role of CBT for social phobia in both group and individual formats.16 In this study, symptom measures completed at the beginning and end of group therapy found improvement in group cohesion and social anxiety symptoms over time, as well as improvement on measures of general anxiety, depression, and functional impairment.
Clinical guidelines and treatment recommendations by the Royal Australian and New Zealand College of Psychiatrists (RANZCP) are summarised in Table 4.1.17
Table 4.1 RANZCP clinical practice guidelines for the treatment of panic disorder and agoraphobia
| Education for the patient and significant others | |
| Cognitive behaviour therapy (CBT) | CBT is more effective and more cost-effective than medication |
| Pharmaceuticals | Tricyclic antidepressants (TCAs) and serotonin selective reuptake inhibitors (SSRIs) are equal in efficacy and both are to be preferred to benzodiazepines |
| Treatment choice depends on the skill of the clinician and the patient’s circumstances | (ii) If the response to an adequate trial of a first-line treatment is poor, another evidence-based treatment should be used ∗The presence of severe agoraphobia is a negative prognostic indicator, whereas comorbid depression, if properly treated, has no consistent effect on outcome |
(Source: RANZCP Guidelines Team for Panic Disorder and Agoraphobia. Australian and New Zealand Journal of Psychiatry, 2003;37:641–56)
Drugs
Social anxiety disorder (SAD) and lack of family cohesion are known risk factors for drug use such as marijuana and alcohol use.18 Combination of SAD with either alcohol or drug use is associated with higher comorbidity in anxious individuals and may further aggravate anxiety.19–22 Patients should be advised to avoid using alcohol and drugs for alleviation of anxiety symptoms.
Mind–body therapies
relevant evidence was available for bibliotherapy, dance and movement therapy, distraction techniques, humour, massage, melatonin, relaxation training, autogenic training, avoiding marijuana, a mineral-vitamin supplement (EMPower +) and music therapy.23
The authors concluded these therapies might be useful but warned more trials are recommended.
Autogenic training (AT) and biofeedback
A systematic review in 2000 evaluated all of the controlled trials investigating AT and identified 8 such trials although the majority of these trials were methodologically flawed.24 Seven trials reported positive effects of AT in reducing stress and 1 study showed no such benefit. The authors noted no firm conclusion could be drawn from these studies.
However, a recent meta-analysis of AT assessing 7 clinical trials found that 3 trials with control groups showed a positive outcome and that 1 further case controlled trial was also positive but the remaining 3 trials showed no difference. There is encouraging evidence from more recent trials that AT can reduce stress and anxiety in adults, as well as children and adolescents. 25–28
There are some preliminary results for the use of biofeedback in adults.29, 30
Bibliotherapy
Bibliotherapy uses reading as a healing therapy by tailoring the reading material to the patient’s current life situation. There have been several meta-analyses completed considering bibliotherapy for the treatment of anxiety and they concluded that bibliotherapy appeared to work best when there was a well-circumscribed problem; that is, a specific phobia,31 but that it had very little effect on OCD or panic disorder.32 It appeared to be more effective in highly motivated individuals.
A recent study focusing on social phobia found that a self-help program consisting of an 8-week self-directed CBT with minimal therapist involvement for social phobia based on a widely available self-help book was superior to wait-list on most outcome measures.33 Benefits were observed with reductions in social anxiety, global severity, general anxiety, and depression following the study and at 3-months follow-up.
Dance therapy
In a review of complementary therapies for anxiety disorders in 2004, dance therapy was considered to have encouraging evidence for people with self-identified anxiety, test anxiety and other anxiety problems in clinical groups. The authors considered it would be worth exploring whether dance therapy may have a greater anxiolytic effect than physical exercise.35
Hypnotherapy
A growing body of research appears to support the role of hypnosis in the treatment of anxiety. In a large prospective, randomised single-centre study published in the Lancet,36 241 patients undergoing percutaneous vascular and renal procedures were randomised to receive intraoperative standard care (n = 79), structured attention (n = 80) or self-hypnotic relaxation (n = 82). All patients had access to intravenous analgesia (fentanyl and midazolam). Hypnosis had a more pronounced effect on pain and anxiety reduction. Pain increased linearly in both the standard and attention groups, but remained flat in the hypnosis group. With time, anxiety decreased in all 3 groups, but at a higher rate in the hypnosis group. Drug use was twice as likely in the standard group than the attention and hypnosis groups. Only 1 patient became haemodynamically unstable in the hypnosis group compared with 10 and 12 in the attention and standard groups respectively.
In a small RCT37 of paediatric cancer patients, 45 children aged 6–16 years were randomised into 1 of 3 groups: local aesthetic, local aesthetic plus hypnosis, and local anaesthetic plus attention for the relief of lumbar puncture-induced pain and anxiety. Patients in the local anaesthetic plus hypnosis group reported less anticipatory anxiety and procedure-related pain and anxiety, and they were rated as demonstrating less behavioural distress during the procedure. The magnitude of treatment benefit depended on their level of hypnotisability and this benefit was maintained when patients used hypnosis independently. Another small hospital study,38 assessing pre-operative anxiety, randomised adult patients into 3 groups: a hypnosis group (n = 26) who received suggestions of wellbeing; an attention-control group (n = 26) who received attentive listening and support without any specific hypnotic suggestions, and a ‘standard of care’ control group (n = 24). Anxiety was assessed before and after their operation. Patients in the hypnosis group were significantly less anxious following surgery, compared with patients in the attention-control group and the control group. Moreover, the hypnosis group reported a significant decrease of 56% in their anxiety level pre-operatively, whereas, the attention-control group reported an increase of 10% and the control group an increase of 47% in their anxiety. In conclusion, the researchers found that ‘hypnosis significantly alleviates preoperative anxiety’. Hypnosis plays a useful role in allaying anxiety for a number of other operative procedures, such as colonoscopy.39
A larger well conducted prospective trial published in Pain 2006, randomised 236 women for large core needle breast biopsy to receive standard care (n = 76), structured empathic attention (n = 82), or self-hypnotic relaxation (n = 78) during their procedures. Patients were rated for pain and anxiety every 10 minutes during their care.40
A systematic review of studies shows that hypnotherapy is highly effective for patients with refractory irritable bowel syndrome (IBS) and alleviating anxiety, but definite efficacy of hypnosis in the treatment of IBS remains unclear due to limited number of controlled trials.41
A recent review of the literature identified 60 publications that found hypnotherapy may be useful for a wide range of disorders and problems in children, and is particularly valuable in the treatment of anxiety disorders and trauma-related conditions, especially in conjunction with family therapy and CBT.42
School refusal is considered a form of anxiety. A small study increased school attendance by using a form of self-hypnosis on children suffering school refusal.43
A review of the research acknowledges the important role of hypnosis in health care, especially for difficult to treat patients and for reducing anxiety.44 Hypnosis can successfully be used to help alleviate peri-operative anxiety and stress in a hospital setting.45
Meditation
A Cochrane review could not conclude from 2 small studies if meditation alone is effective for anxiety.46 The researchers identified 2 randomised controlled studies of moderate quality that used active control comparisons, meditation, relaxation, or biofeedback. Anti-anxiety drugs were used as standard treatment. The duration of trials ranged from 12 to 18 weeks. In 1 study, transcendental meditation showed a reduction in anxiety symptoms compared with biofeedback and relaxation therapy.46 Another study compared Kundalini Yoga with relaxation/mindfulness meditation, which showed no statistically significant difference between groups.46 However, the overall dropout rate in both studies was high (33–44%). Neither study reported on adverse effect of meditation. More studies are warranted.
Relaxation therapies
Patients with an anxiety disorder should be encouraged to learn various relaxation methods as there is strong research demonstrating their benefit. A systematic review of mind–body therapies in 2007 concluded that there was now robust evidence for the use of relaxation therapy in anxiety and insomnia.47
A recent meta-analysis of the literature, inclusive of 27 studies, found relaxation training had a significant beneficial effect in the treatment of anxiety.48 Efficacy was higher for meditation and for longer treatments. Implications and limitations are discussed.
A separate review found that when the different classifications of anxiety disorder were considered separately then relaxation was most effective for GAD, panic disorder, test anxiety and dental phobia, but that it was less effective for PTSD, OCD and specific phobias.35
Music therapy
Listening to music may also help alleviate pre-operative anxiety. A randomised controlled trial study of 180 patients having day surgery was conducted to assess anxiety before and after listening to patient-preferred music.49
Patients were randomised to either an intervention (n = 60), placebo (n = 60) or control group (n = 60). Statistically, music significantly reduced the state of anxiety level in the music (intervention) group compared with the placebo and control groups, with no differences found between socio-demographic or clinical variables such as gender or type of surgery. Another study on patients undergoing cardiac surgery also demonstrated significant reduction in anxiety and pain levels in those receiving music therapy.50 Eighty-six patients (69.8% males) were randomised to 1 of 2 groups; 50 patients received 20 minutes of music (intervention), whereas 36 patients had 20 minutes of rest in bed (control). Anxiety, pain, physiologic parameters, and the use of analgesia (opioid) consumption were measured before and after the 20-minute period. The music therapy group demonstrated a significant reduction in anxiety and pain compared with the control group. There was no difference in systolic or diastolic blood pressures, or heart rate. Also, there was no reduction in the use of analgesia (opioid) usage in the 2 groups.
Music therapy may also play a role in palliative care51 where research demonstrated statistical improvements in mood and anxiety, and in pain control and reducing anxiety in patients during wound dressings.52
Religion
Religiosity and spirituality have long been seen as a worthwhile buffer against dealing with life’s problems and stresses and a large population study over 9 years showed that all-cause mortality was significantly reduced and life expectancy increased (75 years compared with 82 years) for regular churchgoers. This was not explainable by lifestyle and social variables.53 However, there has been only 1 randomised trial to date which added a religious component to standard pharmacotherapy for GAD and this showed improvement at 3 months but this did not appear to be sustained at 6 months.54
Creativity
Anorexia nervosa (AN) is often associated with distressing, intrusive, anxious preoccupations with control of eating, weight and shape. One study of 38 women with AN admitted to a specialised eating disorder unit were offered knitting lessons and free access to supplies.55 Of interest, patients reported a significant subjective reduction in anxious preoccupation when knitting, with 74% reporting reduction in the intensity of their fears and thoughts and their minds cleared of eating disorder preoccupations. In addition, 74% reported it had a calming and therapeutic effect and 53% reported it provided satisfaction, pride and a sense of accomplishment. This study demonstrates that creative activities may be of help with anxiety symptoms experienced with AN and more research is required, particularly to see if other creative areas, such as painting and pottery, may also be of help.
Behavioural interventions — summary
The evidence currently suggests using behavioural interventions before considering pharmacotherapy in insomnia. A meta-analysis examining the evidence for behavioural modification CBT, relaxation and behavioural treatment alone, found 23 randomised controlled trials and concluded there were moderate to large effect sizes showing an improvement in sleep for all 3 modalities and the results were the same in both middle-aged adults and older adults (55+).56 A review of the increasing evidence for mind-body therapies in 2007 concluded that there was now robust evidence for the use of relaxation therapy in anxiety and insomnia.57
Sleep
Anxiety and insomnia are highly co-morbid conditions and physiologically anxiety and low mood increase corticotrophin releasing hormone (CRH) and other stress hormones secreted from the adrenal glands which, in turn, have negative impact upon sleep patterns.58 A large health survey conducted in Germany (n = 4186) found that individuals with anxiety disorder and insomnia experienced significantly worse mental-health related quality of life and increased disability.59 Most anxiety disorders were moderately associated with reduced sleep quality with GAD (AOR 3.94, 95% CI 1.66-9.34) and SAD (AOR 3.95, 95% CI 1.73-9.04) having the strongest relationship to reduced quality of life scores. For more information see Chapter 22.
Melatonin
In a systematic review of melatonin, 6 RCTs were included which concluded that there was sufficient evidence to show that low dose melatonin improves sleep quality.60
Multiple studies have demonstrated that oral melatonin can be an effective premedication for surgery, improves peri-operative analgesia, can act as an anti-anxiolytic, enhances analgesia and promotes better operating conditions under topical anaesthesia, such as in cataract surgery, even reducing the risk of intraocular pressure in eye surgery.61, 62 In 1 RCT, the anxiolytic effect of 5mg oral melatonin (and clonidine) resulted in reduced postoperative pain, and the need for morphine consumption reduced by more than 30% in patients undergoing abdominal hysterectomy under general anaesthetic; far greater than placebo.63 The beneficial effects of both melatonin and clonidine were equivalent.
In a recent prospective, double-blind, placebo-controlled, cross-over trial in a community-living population of 22 elderly with a history of sleep disorder complaints of whom 14 were receiving hypnotic drug therapy, participants were randomised to either 2 months of melatonin (5mg/day) and 2 months of placebo. Sleep disorders, mood, behaviour and level of depression and anxiety were evaluated.64 Melatonin treatment for 2 months significantly improved sleep quality scores and mood levels, especially for depression and anxiety, and facilitated discontinuation of hypnotic drugs compared with placebo.
Acupuncture
A Cochrane review in 2007 reviewed acupuncture as a treatment for insomnia and found that from the small number of RCTs, together with the poor methodological quality and significant clinical heterogeneity, the current evidence is not sufficiently extensive or rigorous to support the use of acupuncture in the treatment of insomnia.65
Sunshine
There is increasing evidence pointing to the important role of vitamin D in a multitude of disease processes, from multiple sclerosis to diabetes mellitus. Vitamin D deficiency may be associated with anxiety and depression in those suffering from fibromyalgia and in research from Northern Ireland, patients with vitamin D deficiency (<25 nmol/l) had higher Hamilton Anxiety and Depression Score (HADS), compared with patients with insufficient levels (25–50 nmol/l) or with normal levels (> 50 nmol/l).66 The exact nature and direction of the causal relationship remains unclear but further research is warranted.
Vitamin D deficiency is prevalent among older adults, and research suggests there may be an association between Vitamin D deficiency and basic and executive cognitive functions, depression, bipolar disorder, and schizophrenia.67 Vitamin D activates receptors on neurons in regions implicated in the regulation of behaviour, stimulates neurotrophin release, and protects the brain by buffering antioxidant and anti-inflammatory defences against vascular injury and improving metabolic and cardiovascular function.
Environment
Smoking
Smoking is well recognised as being a behavioural response to stress and stress management plays an important role in cessation of smoking. Nicotine affects a wide range of neurotransmitters involved in the development of anxiety, including glutamate, GABA, nicotinic acetylcholine receptors and serotonin. It is now widely believed that smoking may increase anxiety levels and that smokers are locked into a cycle where they suffer the short-term anxiety associated with nicotine withdrawal only to relieve that by smoking, therefore perpetuating the problem. There has been some research into the general population suggesting that overall anxiety levels fall after smoking cessation68 but no RCTs have been conducted in people with anxiety disorders.
Physical activities
Exercise
The beneficial effect of exercise on anxiety disorders has been largely accepted. The most recent meta-analysis conducted in 2008, included only RCTs (n = 49) and came to the overwhelming conclusion that exercise is effective69 in reducing anxiety compared with no-treatment control groups. Exercise groups also showed greater reductions in anxiety when compared to groups receiving other anxiety reducing treatment.
However, when a large population-based sample of identical twins (n = 5952) was followed between their ages of 18–50, from 1991–2002, in genetically identical twin pairs, the twin who exercised more did not display fewer anxious and depressive symptoms than the co-twin who exercised less.70 Longitudinal analyses showed that increases in exercise participation did not predict decreases in anxious and depressive symptoms. These researchers concluded that although regular exercise is associated with reduced anxious and depressive symptoms in the population at large, the association does not appear to be because of the causal effects of exercise.
There has been more encouraging evidence in the treatment of anxiety and panic attacks, showing aerobic exercise to be as effective as clomipramine in the treatment of panic disorder.71
Yoga
Yoga is gaining in popularity internationally, both for exercise and as a method of relieving stress. There have been several positive RCTs conducted in yoga. An RCT in women with breast cancer undergoing adjuvant radiotherapy and 6 weeks of chemotherapy following surgery (n = 38) were randomised to receive either a weekly 60 minute yoga class or supportive therapy and the women in the yoga group reported an overall decrease in both self-reported state anxiety (p<0.001) and trait anxiety (p = 0.005).72 There was also a positive correlation between anxiety states and traits with symptom severity and distress during conventional treatment intervals. Another controlled trial found yoga to be superior to diazepam for generalised anxiety but patients were allowed to choose their allocation of treatment (i.e. yoga or diazepam).73
Nutritional influences
Alcohol
Alcohol is a well-known, well-accepted commonly used method to reduce anxiety and there have been several placebo-controlled trials conducted which confirm the short-term anti-anxiolytic effects of alcohol in those with panic disorder,74 social phobia75 and GAD.76 However, in the long-term, anxiety and alcohol abuse can become comorbid conditions as tolerance to alcohol develops and greater amounts are required to produce the same effect. Initially, alcohol affects GABA receptors in the same way as benzodiazepines, but with chronic alcohol use, GABA receptor tone may decrease, which can precipitate anxiety.77 For individuals with chronic alcohol use, reduced anxiety has been reported from uncontrolled studies following the cessation of alcohol.78
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