Affective disorders

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29 Affective disorders

Key points

This chapter focuses on affective disorders in adults. The issues of affective disorders in children and adolescents are more complex and beyond the scope of this section.

The central feature of an affective disorder is an alteration in mood. The most common presentation is that of a low mood or depression. Less commonly, the mood may become high or elated, as in mania.

Classification

Aetiology

Like most psychiatric disorders, the causes of affective disorders remain unknown. In depression, it is likely that genetic, hormonal, biochemical, environmental and social factors all have some role in determining an individual’s susceptibility to developing the disorder, with major life events sometimes, but not always, acting as a precipitant for a particular episode. Although pharmacological treatments are clearly effective, there is no simple relationship between biochemical abnormalities and affective disorders.

Biochemical factors

In its simplistic form, the biochemical theory of depression postulates a deficiency of neurotransmitter amines in certain areas of the brain. This theory has been developed to suggest that receptor sensitivity changes may be important. Alternative propositions suggest a central role of acetylcholine arising from dysregulation of the cholinergic and noradrenergic neurotransmitter systems. Although many neurotransmitters may be implicated, the theory focuses on an involvement of the neurotransmitters noradrenaline (norepinephrine), serotonin (5-hydroxytryptamine) and dopamine. This theory emerged from the findings that both monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants appeared to increase neurotransmitter amines, particularly noradrenaline (norepinephrine), at important sites in the brain. When it was found that reserpine, previously used as an antihypertensive, caused both a depletion of neurotransmitter and also induced depression, this was taken as an apparent confirmation of the theory.

Although less attention has been paid to dopaminergic activity, some studies have found reduced activity in depressed patients, and an overactivity has been postulated in mania.

The concept of noradrenergic (norepinephrinergic) and serotonergic forms of depression has not gained widespread support, and there is no justification in measuring the activity of neurotransmitters such as noradrenaline (norepinephrine) or serotonin metabolites in routine clinical practice.

Clinical manifestations

Investigations

There are no universally accepted biochemical or genetic tests which will confirm the presence of an affective disorder. Various rating scales have been developed that may help to demonstrate the severity of depressive disorder or distinguish a predominantly anxious patient from a depressed patient. Within the limits of our current understanding of the technology, biochemical or genetic tests are unlikely to be helpful in determining the treatment plan or management of affective disorders.

In the UK, mental and behavioural disorders are commonly classified using the International Classification of Diseases, ICD 10 (WHO, 1992).The American Psychiatric Association has developed a precise system of diagnosis, based on the description of symptoms in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV TR), now in its revised, fourth edition (American Psychiatric Association, 2000).

A systematic approach to the diagnosis of affective disorders is important when considering the effectiveness of medication. Most new clinical trials for antidepressants or antipsychotics require a DSM diagnosis as an entry criterion. In the UK, the ICD 10 classification is commonly used, with the severity of depression determined by the presence of the number of symptoms (see Boxes 29.2 and 29.3). More recently, use of the symptom count as a single factor upon which to base treatment decisions has been cautioned against (NICE, 2009). Account should also be taken of the extent of impairment and disability associated with depression.

Box 29.3 ICD 10 diagnostic criteria for a depressive episode (WHO, 1992)

Common symptoms

In a depressive episode, the mood varies little from day to day and is often unresponsive to circumstances, yet may show characteristic diurnal variation as the day goes on. The clinical picture shows marked individual variations, and atypical presentations are particularly common in adolescence. In some cases, anxiety, distress and motor agitation may be more prominent at times than the depression.

For depressive episodes of all grades of severity, a duration of 2 weeks is usually required for diagnosis, but shorter periods may be reasonable if symptoms are unusually severe and of rapid onset.

An individual with a mild depressive episode is usually distressed by the symptoms and has some difficulty in continuing with ordinary work and social activities, but will probably not cease to function completely.

An individual with moderately severe depressive episode will have these symptoms to a marked degree, but this is not essential if a particularly wide variety of symptoms is present overall. They will usually have considerable difficulties in continuing with social, work or domestic activities.

An individual with severe depressive episode may be unable or unwilling to describe many symptoms in detail, but an overall grading of severe may still be justified. They will usually show considerable distress or agitation, unless retardation is a marked feature. Loss of self-esteem or feelings of uselessness or guilt are likely to be prominent. Suicide is a distinct danger, particularly in severe cases.

National guidelines provide a sound framework for the management of depression (NICE, 2009) and bipolar disorder (NICE, 2006). It is important that people with depression are identified. A simple screening process for the presence of depression could involve asking the patient two questions about their mood and interest. For example, the patient could be asked ‘During the last month, have you often been bothered by feeling down, depressed or hopeless?’ and ‘During the last month, have you often been bothered by having little interest or pleasure in doing things?’. If the answer to either question is ‘no’, it is unlikely the patient will be considered to have a depressive disorder. Patients who answer ‘yes’ warrant further investigation.

Identification of target symptoms may be useful in evaluating the response to treatment. In routine clinical practice, antidepressant medication should not generally be used to treat patients with mild depression. Non-pharmacological strategies are preferable in this group.

Treatment

The aim of treatment is to prevent harm and to relieve distress or to be prophylactic. It is important to differentiate symptoms of the disorder from the premorbid personality. In general, the drugs which are used to control the symptoms of mania are not specifically antimanic. These agents are also used to treat other disorders. This means the diagnosis will primarily influence the way in which these drugs are used rather than the choice of drug per se. Clinicians should be aware of the licensed indication of treatments, so that any ‘off label’ use is done knowingly and in line with current best practice.

In the treatment of depression, all the antidepressants currently available in the UK may be considered to be equally effective. There is increasing evidence that patients with more severe episodes of depression are more likely to respond to antidepressant drugs, as opposed to placebo, than those with less severe forms of the disorder (Fournier et al., 2010). There is also some evidence to suggest that sertraline and escitalopram may have a more favourably risk/benefit profile than some other antidepressants (Cipriani et al., 2009). However, it is unclear if the magnitude of the difference between these drugs is sufficient to direct treatment choice for most depressed patients.

There are some generalisations which may help individualise the choice of antidepressant. Females may have a poorer tolerance of migraine than males and tricyclic antidepressants are less well tolerated and more likely to be toxic in overdose than the selective serotonin reuptake inhibitors (SSRIs). Patients may prefer one drug over another based on their past experience of benefit or side effects. Overall, the major difference between antidepressant agents is in their side effect profile and toxicity in overdose. There can also be significant variations in the costs of different agents.

Treatment of depression

In moderate and severe depression, pharmacological intervention is important, but this should never be considered in isolation from the social, cultural and environmental influences on the patient. Non-pharmacological therapies are effective and in mild depression they are considered preferable to drug treatment. Non-drug treatments and antidepressant medication are not mutually exclusive and in some cases it is preferable to use both in combination.

Drug treatment

Despite the availability of many new antidepressants, the therapeutic effectiveness of these agents has changed little since the discovery of the antidepressant properties of drugs used to prevent migraine in the late 1950s. Further research may reveal differences between antidepressants. Advances in the clinical utility of pharmacogenomics may, in time, provide clinicians with a tool to individualise pharmacotherapy. Overall, the SSRI antidepressants appear to be better tolerated than tricyclics and their safety profile in overdose should be an important consideration for use.

A strong response to placebo is found in most of the studies of antidepressants. Tolerability is, therefore, an important factor in the choice of drug; patients who are unable to tolerate the side effects of antidepressants are likely to discontinue these drugs. Antidepressants should be taken in adequate doses for some 4–6 weeks, and up to 12 weeks in older people, to achieve a full response. Following a single episode of depression, treatment should be continued for 6 months, at the same dose at which the patient achieved remission, before attempting withdrawal. In patients experiencing multiple episodes of depression, treatment should be continued for longer periods (2 years).

Withdrawal of antidepressants should normally be undertaken gradually. Following abrupt discontinuation, patients may experience symptoms of withdrawal that include gastro-intestinal symptoms, together with headache, giddiness, sweating, shaking and insomnia. In addition, extrapyramidal reactions may be associated with abrupt withdrawal from some of the SSRI antidepressants. Following successful treatment, antidepressants should be gradually reduced over a period of 4 weeks. This period should be increased if patients experience problems, or where medication has been given for extended periods.

Generally, the long half-life of fluoxetine enables the drug to be stopped without the need for tapering from the standard antidepressant dose of 20 mg. Patients taking MAOIs may experience psychomotor agitation following discontinuation.

As patients do not experience the craving typically associated with drugs of addiction, most health care professionals do not class antidepressants as addictive. Patients should be warned that there is a risk of problems with abrupt discontinuation, but use of emotive words like addiction or dependence is best avoided. In moderate or severe depression, the balance of risks and benefits is usually in favour of using antidepressants. Occasionally, some patients report that they have become dependent on their antidepressants and feel unable to stop taking them. These concerns should not be dismissed lightly, but the focus of discussion with the patient should be on the overall risks and benefits of the treatment in the context of their individual circumstances.

As discussed earlier, there is no strong evidence for the existence of a particular biochemical subtype of depression. However, some patients do respond better to particular antidepressants. This has led to the widely held view that previous response to treatment is a strong indication to use that particular drug in the treatment of a future episode.

In addition to previous response, the other important considerations to take into account when selecting an antidepressant are side effects, contraindications, toxicity in overdose, patient preference and clinician familiarity.

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