Depression and anxiety are commonly comorbid and this can sometimes complicate thoughts around treatment. Fortunately the first-line pharmacological treatment of choice for both depression and most anxiety disorders are antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs). There can be a perception that these ‘psychological’ disorders should be managed with ‘psychological’ treatments and that physical interventions are simply artificial crutches that can end up preventing the individual dealing with their ‘difficulties’. However, there is clear evidence of biological abnormalities associated with depression and anxiety, and strong evidence for the use of antidepressants to treat these disorders. Nevertheless, it is important not to immediately jump to medication for any patient presenting with symptoms of depression and anxiety. The NICE guidelines for both depression and anxiety advocate a stepped approach to management, with antidepressants indicated at step 3, or when there is a previous history of depression. For patients with predominantly anxiety symptoms it is usually appropriate to at least try psychological and behavioural techniques (see Chapter 10) before resorting to medication. For patients presenting predominantly with depression the evidence suggests that if they have moderate to severe illnesses they will do better with medication than with psychological interventions and best of all with a combination of the two.

Do antidepressants actually work?

In recent years there have been a number of high-profile publications and news reports questioning whether antidepressants have any clinically significant benefit in the treatment of patients with depression and anxiety. These have been criticised on many levels. A central issue is that in randomised controlled trials (RCTs) of antidepressants a large placebo effect is seen. As a result the difference in effect of the active drug often seems small in comparison. Conversely the effect of psychological interventions often appears large in RCTs. However, this is because such therapies are most usually compared against waiting list controls or ‘treatment as usual’. In direct head-to-head comparisons in well-controlled studies, psychological interventions such as CBT are generally of similar efficacy to antidepressants in mild to moderate depression in working-age adults.

How do antidepressants work?

The notion that depression is due simply to low levels of monoamines such as serotonin (5-HT) or noradrenaline, and that antidepressants work by increasing the brain levels of these neurotransmitters, is not tenable. The neurobiology underlying depression and the mechanism of antidepressants is more complex.

There is strong empirical evidence that stress can precipitate episodes of depression. However, not all individuals when stressed become depressed. The risk of developing a depressive episode appears to relate to the relative balance between resilience and vulnerability within an individual. One mechanism of resilience involves 5-HT neurotransmission within the brain. This system appears able to help prevent a negative cognitive bias. This type of negative cognitive bias is what is challenged in cognitive-behavioural therapy (CBT), since such bias can drive low mood and low mood drives negative cognitions causing a potential vicious circle. The 5-HT mechanism of resilience can be made vulnerable to dysfunction by a variety of factors including genetic and environmental influences. The latter include both early life adversity and current stress.

It is known that a range of different antidepressant drugs and electroconvulsive therapy (ECT) all have effects on 5-HT neurotransmission via different receptors or neuronal functions. The net effect appears to be common between treatments, that is, to enhance transmission in the specific 5-HT pathway that is involved with resilience and prevention of negative cognitive bias. This may help to explain the synergy seen in RCTs between antidepressants and CBT. The latter is challenging the negative cognitive bias in depression while the former is helping to support a more positive bias.

How should antidepressants be used to treat depression and anxiety?

We have put together an algorithm that can be used when treating patients with depression and/or anxiety with antidepressants (Figure 11.1). It should be stressed that this is just one of many possible algorithms that could be produced and there is no hard and fast way that things must be done.

The starting point in treatment, as ever in medicine, is making a diagnosis. As described above, the decision to offer medication should be made for patients with moderate to severe illness. A patient’s knowledge about antidepressants should be explored and any concerns addressed. It is important to review the patient and monitor the effects of treatment. In general, we are poor at measuring and assessing depression. One reason for this is a lack of consensus as to the best (and most practical) way of doing this. One possibility is to use the PHQ-9 (see Appendix 2): a score in excess of 10 would certainly be supportive of using medication. The decision to treat should, however, be made in a more clinically rounded way than simply on the basis of a score from a scale.

In terms of which antidepressant to use, there are a large number to choose from, but SSRIs are recommended first line. In our algorithm we suggest either citalopram or sertraline because these drugs have lower risks of drug interactions than fluoxetine or paroxetine and because citalopram is cheaper than escitalopram (Boxes 11.1 and 11.2).

If the patient has shown a full response, the next step is to review risks of relapse (see Box 11.3). If there are no risks of relapse a patient should be treated for at least 6–12 months following full remission of symptoms.