Depression

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Chapter 12 Depression

Introduction

Mental health is closely linked to physical health. Depression (e.g. major depression) is highly prevalent and a major cause of disability. The World Health Organization (WHO) expects that by 2020 depression will rank second only to ischemic heart disease in terms of disability, irrespective of gender and age.1 Currently, depression is ranked as the second cause of disability in terms of disability adjusted life years in the age category 15–44 years for both genders combined.1 Depression is a common illness affecting at least 1 in 5 people during their lifetime.2 Depression has no gender, age, or lifestyle background predilection, it can potentially occur in all persons. Depression facts:

Patients often present with an overlapping and complex set of symptoms (Table 12.1).

Table 12.1 The spectrum of symptoms in depression3

Physical symptoms Emotional symptoms
Tiredness and fatigue Sadness and tearfulness
Sleep disturbances Anxiety and irritability
Headaches Loss of interest
Gastrointestinal disturbances Hopelessness
Psychomotor activity changes Difficulty concentrating
Appetite changes Guilt
Body aches and pains Suicidal tendency

Depression also influences the morbidity and mortality of a number of somatic illnesses. Research strongly documents a significantly higher risk and mortality in depressed patients post acute myocardial infarction.4 There is also evidence demonstrating that depression is significantly associated with diabetics.5

Complementary medicine (CM) encompasses a wide range of therapies that are currently not part of conventional medicine and are often adopted by patients who feel the need to take more control over their illnesses. Unfortunately, this often leads to patients self-medicating to alleviate symptoms, such as emotional distress, to help them cope with serious mental illness problems.6

The key to treating the depressed patient is to take an holistic approach by addressing both physical and psychological needs. There are many alternative therapies now available for the treatment of mild–moderate depression that a practitioner can easily recommend, especially lifestyle advice, as part of the holistic management of patients with depression. Guarded optimism exists for many of these therapies and further well-designed trials are needed for most alternative therapies. Also, as part of the integrative approach, the medical practitioner needs to take great care not to delay drug treatment in the patient with severe depression.

A recent review7 has reported that systematic trials are required for promising substances for depression and that meanwhile, those patients wishing to take psychotropic complementary medicines require appropriate medical advice. In this chapter we review the evidence-based research in CM approaches to the treatment of depression, that includes the use of herbal medicines, nutritional and dietary supplements, mind–body medicine approaches such as cognitive behavioural therapy (CBT), meditation, hypnosis, aromatherapy, acupuncture and light therapy.

A recent review of the literature identified a range of possible non-drug treatments for the treatment of depression in the elderly.8 The review found best evidence for antidepressants, electroconvulsive therapy (ECT), CBT, psychodynamic psychotherapy, reminiscence therapy, problem-solving therapy, bibliotherapy and physical exercise. Limited evidence was identified for transcranial magnetic stimulation, dialectical behaviour therapy, interpersonal therapy, light therapy, St John’s wort and folate.

Another review of the literature found the best evidence for the treatment of depression occurred with St John’s wort, exercise, bibliotherapy, CBT and light therapy (for winter depression), and promising evidence (but needing more research) for folate vitamin E, vitamin B6, vitamin D, SAMe (s-adenosyl methionine), phenyalanine, Ginkgo biloba, acupuncture, light therapy (non-seasonal depression), massage therapy, negative air ionisation (for winter depression), relaxation therapy, yoga, and reducing or avoiding alcohol, sugar and caffeine avoidance and possibly music/dance therapy.9

The risk factors for depression are:

Healthy lifestyle changes

In the management of depression, emphasis on lifestyle changes is vital, such as stress management, improved diet, sleep, exercise, sunlight exposure and smoking cessation. The treatment of depression requires the health practitioner to spend long consultations exploring all of these areas.10 A few words of advice can go a long way towards changing patients’ health behaviour.11 A study found that patients were more likely to try to quit smoking, change their diet and perform more exercise when written information leaflets were backed by encouragement and GP advice. The study also concluded that advice on health behaviour may have to be delivered several times before it brought about change.11

Mind–body medicine

Cognitive behavioural therapy (CBT), group therapy and support groups

Counselling and CBT carry the greatest weight of scientific evidence for the treatment of depression.12 The types of psychotherapy that have proven efficacy are mainly CBT and interpersonal psychotherapy (IPT).13, 14

A recent study with depressed mothers demonstrated that brief IPT was beneficial in reducing levels of maternal symptoms of depression and improving functioning at the 3– and 9–month follow-ups compared to usual treatment for depression.12 Moreover, the meta-analysis reported that preventative strategies such as IPT may be more effective than prevention based on CBT.13

The health practitioner needs to be alert to stressors the patient is experiencing in the school, home or work environments. Traumatic and stressful experiences in people’s lives such as relationship breakdowns, loss, bullying, being excluded by peers, experiencing humiliation, life-threatening events, assault (physical and sexual), and loss of work are potent triggers for depression and feelings of suicidal ideation.1519

The prognosis of depression is worse when the patient has a serious illness such as cancer or heart disease.20, 21

CBT is at least as effective as antidepressants in outpatients with severe depression according to a meta-analysis of 4 major randomised trials.22

Positive feedback, reassurance, advice and helping to explore stress and dealing with them were essential components reported. If the practitioner is not well trained in this area then referral to a practitioner who is well trained is advised.

Recent reviews23,24 conclude that psychotherapy and pharmacotherapy generally are of comparable efficacy, and both modalities are superior to usual care in treating depression.

CBT has been investigated in a number of clinical scenarios, and demonstrated better efficacy than medication for post-partum depression.25 CBT was efficacious in reducing depressive symptoms among HIV-infected individuals,26 was effective for the treatment of unipolar depression,27 effective in incurable cancer patients,28 and a recent meta-analysis suggests that CBT may be of potential benefit in older people with depression.29 Further, recently it has been reported that CBT may be useful for depressed patients diagnosed with Parkinson’s Disease.30

Young adolescents with depression and repeated self-harm showed promising results in a Group therapy program.31 UK child psychiatrists randomised 63 patients aged 12–16 to routine care or to a weekly group therapy program over 6 months. The adolescents in the group therapy program were less likely to harm themselves, less likely to use health care resources, had better school attendance, and a lower rate of behavioural disorders. However, there was no effect on the severity of the depression or its prevalence.

A comprehensive meta-analysis of the literature of 19 randomised controlled trials (RCTs), meeting the inclusion criteria, highlighted that efficacy of preventive psychological interventions can reduce the incidence of depressive disorders by 22% in experimental groups compared with control groups. Therefore, therapies such as counselling and CBT may also play a role in the prevention of depression onset.14

Meditation

Mindfulness meditation-based stress reduction programs have demonstrated effectiveness in decreasing mood disturbance, including depression and stress symptoms in patients with a wide range of types and stages of cancer.33, 34 A randomised, wait-list controlled design of 90 patients (mean age 51 years, 78% females) was used with the intervention consisting of weekly meditation of 1.5 hours for 7 weeks plus home meditation practice.33 Patients in the mindfulness meditation intervention group demonstrated significantly lower scores on total mood disturbance by 65% and sub-scales of depression, anxiety, anger and confusion compared with control participants. The treatment group demonstrated less stress symptoms (by 31%), fewer cardiopulmonary and gastrointestinal symptoms, and less emotional irritability and cognitive disturbances. A recent preliminary study investigating mindfulness-based stress reduction reported that participation in the program was associated with enhanced quality of life and decreased stress symptoms, altered cortisol and immune patterns consistent with less stress and mood disturbance, and decreased blood pressure.34

Relaxation therapy

A recent Cochrane review and meta-analysis of 15 trials with 11 included in the analysis demonstrated that relaxation was effective for reducing depressive symptoms.35 Five trials showed relaxation reduced self-reported depression compared to wait-list, no treatment, or minimal treatment post-intervention (SMD −0.59 [95% confidence interval [CI] −0.94 to −0.24]). For clinician-rated depression, 2 trials showed a non-significant difference in the same direction (SMD −1.35 [95% CI −3.06 to 0.37]). A recent assessment of the Cochrane review concluded relaxation techniques were better than either wait-list, no treatment or minimal treatment, but not as effective as psychological therapies such as CBT.36

Music therapy

A recent Cochrane review identified 4 studies that reported greater reduction in symptoms of depression among those randomised to music therapy than to those in standard care conditions.37 A fifth study showed no benefit. Overall there were low dropout rates from music therapy. The Cochrane review reported that music therapy was accepted by people with depression and was associated with improvements in mood.37 However, the review cited that the trials reviewed were small in number and that they had low methodological quality. Hence, it was not possible to be confident about the effectiveness of music therapy in the treatment of depression. High quality trials evaluating the effects of music therapy on depression are thus required.

Religion and spiritual health

Healthy religious beliefs may assist older patients with depression after a medical illness by providing comfort, support and improved coping strategies to help them manage, according to a US study.38 In the study, 94 patients aged 60 and older diagnosed with depression during a hospital admission for a physical complaint, were more likely to recover from depression if they had expressed religious beliefs. In a further US study,39 with data from 2600 male and female twins, has reported a strong association between religious beliefs and a lower intake of alcohol, nicotine and drug dependence or abuse, with less effects on depression. However, in a recent study 503 patients participating in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) trial completed a Daily Spiritual Experiences (DSE) questionnaire within 28 days from the time of their acute myocardial infarction (AMI). The results showed little evidence that self-reported spirituality, frequency of church attendance, or frequency of prayer is associated with cardiac morbidity or all-cause mortality post-AMI in patients with depression and/or low perceived support.40

Hence, what is certain is that religiosity has to be viewed as a complex, multidimensional construct with substantial associations with lifetime psychopathology.

Health practitioners require awareness of the potential role of spirituality, religiosity and depression.41 This field of evidence is important so as to provide a more holistic approach to psychotherapy treatment.41 Whilst many studies link a lack of religiosity to depression, one important factor is that it may be a lack of meaning and spiritual fulfilment that is part of the increasingly secular and materialistic society contributing to the increased incidence of depression in the Western countries.

A US study42 of 160 terminally ill cancer patients in a catholic palliative care hospital found that spiritual wellbeing offered some protection against end-of-life despair and depression. The study demonstrated the importance of spiritual wellbeing in reducing psychological distress, in particular in palliative care practice.

Religion plays an important role in the recovery from depression but findings also point to possible benefits of social connection and support people received when they belonged to a church versus the religion alone.

Sleep disturbance

Whilst sleep disturbance is common in patients with depression, there is a growing body of evidence to suggest that sleep deprivation may be a contributor to depression.46, 47

In an Australian Melbourne study, 86 patients aged 16–88 years (average age = 42 years; female participants = 54%) presented as suffering from chronic insomnia, of which two-thirds were also suffering from depression.48 Participants were then introduced to a self-help program (a book and 3 audiocassettes), and a manual to assist in non-drug approaches to sleep, which they used at home to improve their sleep. At follow-up, 6–8 weeks later, 70% of the insomnia sufferers who were depressed before treatment and learned to sleep better were no longer depressed, or were significantly less depressed, once their sleep had improved. An additional 13%, while still depressed, had a reduction of at least 40% in their depression scores. By contrast, among people who did not learn to sleep better, none experienced a significant reduction in depression. This study strongly suggests that, for many people who suffer from both depression and insomnia, treating the insomnia successfully without medication may eliminate or significantly reduce their depression. Further, just over half of those participants who were using antidepressant medications at the initial interview had ceased using it by follow-up, were sleeping significantly better, and were no longer depressed. Whilst the findings of this research are quite impressive, more research in this area is required.

Another Australian Melbourne study at the Royal Children’s Hospital using a screening questionnaire of 738 mothers with infants 6–12 months of age, also suggested that sleep deprivation was a contributor to post-natal depression (PND).49 If the mother reported a problem with their child’s sleep, they were twice as likely to score the PND threshold than mothers who did not report a problem. Mothers reporting good sleep, despite an infant sleep problem, were not more likely to develop depression. A further study by the same group demonstrated that by treating the mothers’ sleep using behavioural interventions, the depression score was reduced significantly as reported in a randomised control trial of 156 mothers with infants aged 6–12 months.50 This benefit was sustained at 2 months and at 4 months for mothers with high depression scores.

A sample study of 5692 US adults, found those who reported sleeping difficulties such as initiating or maintaining sleep and early morning awakening, was associated with a two-fold increase risk of suicidality than participants without sleep disturbance.51 Chronic sleep problems were found to be an independent risk factor for depression and suicidality, so it would appear addressing sleep problems could play an important role in prevention of depression and suicidality.

A recent interventional study reported that a sleep intervention program implemented in infancy resulted in sustained positive effects on maternal depression symptoms and found no evidence of longer-term adverse effects on either the mothers’ parenting practices or the children’s mental health.52 This intervention demonstrated the capacity of a functioning primary care system to deliver an effective and universally offered secondary prevention program.

Adequate sleep is essential for general health. A study has found that sleep deprivation combined with light therapy was useful in the treatment of drug resistant bipolar depression.53 The response was effective for acute and long-term remission rates. (See Chapter 22 on insomnia and sleep disorders.)

Sunshine

Light therapy

Light therapy is a physical intervention that is used to treat depression and depressive disorders such as bipolar.53 Cognitive decline, mood, behavioural and sleep disturbances, and limitations of activities of daily living commonly burden patients, especially the elderly with cognitive deficits.58 Circadian rhythm disturbances have been associated with these symptoms.58 Light therapy exposes patients to a bank of bright lights for a variable number of hours per day, usually 1–3 hours. Patients can engage in activities during the period of exposure, such as reading and computer use or relaxation time. In a recent study that reviewed CM therapies in the treatment of depression in children and adolescents, Jorm and colleagues59 have described good evidence for the efficacy of light therapy in winter depression. There was, however, no evidence that it would be effective for non-seasonal depression.

Studies suggest that light therapy may be beneficial when used as an adjunct with other treatments.60, 61 Results from 1 study indicate that there was a positive total sleep deprivation response in major depression patients which can be predicative of beneficial outcome of subsequent light therapy.60 In a further study, bright light therapy was significantly beneficial compared to placebo for the treatment of depression.61 It augmented antidepressant effects of medication and wake therapy.61 Furthermore, in patients with dementia, light therapy was demonstrated to have a modest benefit in improving some cognitive and non-cognitive symptoms of dementia in a randomised control trial with melatonin supplement.62 To counteract the adverse effect of melatonin on mood, the study recommended its prescriptive use only in combination with light therapy.

However, in a recent study antidepressant response to bright light treatment in older adults was not statistically superior to placebo. Both treatment and placebo groups experienced a clinically significant overall improvement of 16%.63 There is very limited data which is currently available, suggesting that further research is warranted.

Physical activity

Exercise

There is strong evidence to support the benefits of exercise in the prevention and alleviation of symptoms of depression. Although data from randomised trials are limited, results of studies included in a recent review generally support use of exercise as an alternative or adjunctive treatment for depression.69

Early reports highlight the benefits that regular physical activity provides in reducing the risk of developing depression.70 People who do not participate in physical activity are more likely to develop depression compared with those who regularly exercise.71 Regular aerobic and strength training activities can lead to 50% reduction in symptoms of acute depression and anxiety, especially in women and older people.72 Physical activity is equally as effective as some pharmacological treatment (e.g. sertraline) in the management of mild–moderate depression, especially in the elderly. A 10-month study of 156 adult volunteers with major depressive disorders randomly assigned participants to a course of aerobic exercise, sertraline therapy, or a combination of exercise and sertraline. After 4 months all treatment groups exhibited significant therapeutic improvement and after 10 months, the exercise group had significantly lower relapse rates than participants on sertraline therapy alone.73

A Scottish study randomised 86 patients older than 53 with depression and not responding to at least 6 weeks of antidepressants, to twice-weekly group exercise classes (45 minutes of predominantly weight-bearing exercise) or health education talks for 10 weeks.74 Fifty-five percent of the patients in the exercise group compared with 33% in the education talk group experienced a decline of at least 30% in their depressive symptoms. This study suggests that patients with depression should be actively encouraged to attend group exercise activities and regular physical activity, such as aerobic classes, or an early morning walk of greater than 60 minutes daily. This would at least also take advantage of sunshine exposure or light therapy even on overcast winter days.75

Exercise has been demonstrated to also improve mood in patients with severe affective disorders, according to a small pilot study of 12 participants.76 The study concluded that exercise produced changes in concentration of several biologically active molecules such as adrenocorticotrophic hormone, cortisol, catecholamines, opioid peptides, and cytokines, which have been reported to affect mood or are involved in the physiopathology of affective disorders.77 Moreover, endurance exercise may help to achieve substantial improvement in the mood of selected patients with major depression in the short time.78 Also, there is sufficient evidence to support appropriate physical activity as an intervention to enhance a cancer patient’s physical functioning and psychological wellbeing.79

A recent Cochrane review evaluated 28 trials which fulfilled the inclusion criteria, and of which 25 provided data for the meta-analyses.80 Randomisation was adequately concealed in only a few of the studies, and most did not use intention to treat analyses. Also most of the studies used self reported symptoms as outcome measures. For the 23 trials consisting of 907 participants comparing exercise with no treatment or a control intervention, the pooled SMD was −0.82 (95% CI –1.12, −0.51), indicating a large clinical effect. However when trials with robust designs only were included in the analysis namely, adequate allocation concealment and intention to treat analysis and blinded outcome assessment, the pooled SMD was −0.42.95% CI −0.88, 0.03 that is a moderate, non significant effect was observed.80Hence the study concluded that physical activity gives the impression to improve depressive symptoms in people with a diagnosis of depression, but when only methodologically robust trials are included, the effect sizes are only moderate and not statistically significant. Further robust trials are warranted. Further analysis of the Cochrane review confirmed exercise may improve depression but the majority of trials again had weaknesses.2

Yoga

An early study81 has demonstrated that the daily practice of yoga was able to significantly improve symptoms of depression, and in 1 randomised study was statistically as effective as ECT and imipramine.82 Another study of men and women found yoga significantly improved mood scores for depression and other psychological states such as anxiety, anger and ‘neurotic symptoms’.83

A review of the evidence reveals that yoga has potentially beneficial effects as an intervention on depressive disorders.46 Variation in interventions, severity and reporting of trial methodology suggests that the findings must be interpreted with caution. A number of the interventions may not be feasible in those with reduced or impaired mobility and, even so, further investigation of yoga as a therapeutic intervention is warranted.

Nutritional influences

Nutrition and diets

Lactose and/or dairy

Diet plays an equally important role in the management of depression. As an example, lactose malabsorption may play a role in the development of depression.85 Lactose malabsorption is characterised by a deficiency of mucosal lactase (an enzyme) and, as a consequence, lactose that reaches the colon is broken down by bacteria to short-chain fatty acids, CO2, and H2. Bloating, cramps, osmotic diarrhoea, and other symptoms of irritable bowel syndrome (IBS) are the consequence and can be seen in about 50% of lactose malabsorbers. Thirty women aged 16–60 were all screened for depression using a questionnaire. The group with lactose malabsorption (n = 6 compared with 24 normal lactose absorbers) had significantly higher scores on the depression questionnaire compared with normal lactose absorbers. The study postulated that lactose malabsorption may cause high intestinal lactose levels that might interfere with L-tryptophan metabolism by binding with L-tryptophan and impeding its absorption, and in turn affect serotonin synthesis and availability.85 Although more research is warranted, lactose malabsorption in patients with signs of mental depression, particularly in those with digestive problems, should be considered.

Seafood consumption

Seafood consumption has been reported to be associated with a lower prevalence of bipolar disorder, according to a systematic review.86 A US-based study reviewed population-based epidemiological studies from 17 countries and found greater rates of seafood consumption (n-3 fatty acids) were associated with lower lifetime prevalence for bipolar I, bipolar II, and bipolar spectrum disorders. Greater seafood consumption (deep sea) was also related to lower lifetime prevalence of major depression in 9 countries.86

Nutritional supplements

Fish oils and/or omega-3 (n-3) fatty acids

Fish oil supplementation may play a role in the management of depression and bipolar disorder.

Depression

Several trials indicate omega-3 deficiency may contribute to depression and psychiatric diseases, and dietary fish intake and fish oil supplementation may play a useful role in the management of depression.91, 92

In a case control study of pregnant women, women with lower omega-3 PUFA levels especially due to low dietary intake and fetal diversion, were 6 times more likely to experience depression antenatally, compared with women with higher levels.93 The authors conclude there is a role for increased fish intake and fish oil supplementation during the perinatal period.

In 1 study of middle-aged women with moderate-to-severe psychological distress and depression during the menopausal transition (n = 120), participants were randomly assigned to receive 1.05g ethyl-EPA/d plus 0.15g of ethyl-docosahexaenoic acid/d (n = 59) or placebo (n = 61) for 8 weeks.94

At baseline, women experiencing psychological distress were mildly to moderately depressed with 24% meeting the major depressive episode (MDE) criteria of the Diagnostic and Statistical Manual of Mental Disorders (4th edn). Of interest, compared with baseline, after 8 weeks overall outcomes improved in both groups and no significant differences were noted between them. However, closer analysis of the data revealed that for women without MDE, mood outcome significantly improved with fish oil supplementation compared with the placebo group.

Two recently reported trials with the essential fatty acid eicosapentaenoic acid (EPA) have demonstrated efficacy in depression.95, 96 One study compared the administration of EPA to fluoxetine in major depression and reported that the combination was significantly more effective than EPA or fluoxetine administered separately.96

A review of treatments of depression in children and adolescents identified 1 trial of omega-3 PUFA supplementation was beneficial in depressed children compared with placebo.97

A recent meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of n-3 fatty acids has demonstrated efficacy with a cautionary note.95 Although the meta-analysis showed significant antidepressant efficacy of n-3 PUFAs, it is still premature to validate this finding due to publication bias and heterogeneity of studies available. Large scale, well-controlled trials are needed to find out the favourable target subjects, therapeutic dose of EPA, and the composition of n-3 PUFAs in treating depression.98

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