Mental health articles

OF mental health care and mentally ill

Treatment for Major Depressive Disorder

 Biological interventions

Antidepressants There are now three types of antidepressant in general use that impact on serotonin levels: tricylics, SSRIs and SNRIs. A third group of antidepressants, known as monoamine oxidase inhibitors (MAOIs) proved reasonably effective, achieving clinically signifi cant changes in about 50 per cent of the people prescribed them. However, the dangers associated with their use  mean they are used less as other drugs become available.

SSRIs have little therapeutic advantage over tricyclics, but have fewer side-effects and are tolerated better. Rocca et al. (1997), for example, reported 56 per cent of people treated with tricylics complained of a dry mouth compared with 8 per cent treated with SSRIs. The percentages to report constipation were 39 and 8 per cent respectively. Anderson (1998) reported that 14 per cent of people taking tricyclics discontinued their use due to adverse side-effects in comparison to 9 per cent of those receiving SSRIs. Gillman (2007) suggested that some SNRIs do not have suffi cient biochemical impact on the noradrenergic system to effectively infl uence mood, so their impact is likely to be no greater than that of SSRIs, an argument consistent with the fi ndings of a randomized controlled trial reported by Shelton et al. (2006) who found no clinical differences between an SSRI and SNRI. Interestingly, Herrera-Guzmán et al. (2009) found that although an SNRI proved no more effective in treating depression than an SSRI, it was more effective in a very specifi c symptom area, achieving greater improvements in episodic and working memory. St John’s wort A more ‘natural’ remedy involves using extracts of the plant Hypericum perforatum, more popularly known as St John’s wort. Its mode of action is little understood, but it does seem to benefi t those receiving it. Linde and Mulrow (2002), for example, identif i ed 14 trials that compared preparations of hypericum against placebo or antidepressant medication. The percentage of people to clinically improve following treatment with hypericum pre parations and placebo were 56 per cent and 25 per cent respectively. Comparisons with antidepressants revealed few differences in benefi t, with clinical gains in 50 per cent of those treated with hypericum compared with 52 per cent with standard antidepressant treatments. Of those treated with a combination of hypericum and antidepressant, 68 per cent evidenced clinically signifi cant improvements. St John’s wort seemed to be more acceptable to those prescribed it than standard pharmacological medication, with drop-out rates due to side-effects averaging 2 per cent among those prescribed hypericum in contrast to 7 per cent of those receiving standard antidepressants. St John’s wort does have some side-effects, including gastrointestinal discomfort, fatigue, dry mouth, dizziness, skin rash and hypersensitivity to sunlight. It may also interfere with the effectiveness of indinavir, a protease inhibitor used in the treatment of AIDS; cyclosporin, an immunosuppressive drug used to protect patients from organ rejection after heart transplantation; and warfarin, an anticoagulant. As a result, its use has to be limited in some cases.

Electroconvulsive therapy

The success of antidepressants in treating depression, and concern over its acceptability as a f i rst-line treatment, have meant that ECT is increasingly used as a second-line treatment for ‘treatment-resistant cases’: those individuals who do not respond to pharmacological, and perhaps psychological, treatments. At this point, ECT does appear to have some benefi t, and given the lack of response to other treatments, any gains at this point may be considered a success (McCall 2001). Perhaps more controversial has been the question whether ECT should be continued over an extended period of time to maintain initial improvements in mood. Gagné et al. (2000) explored this issue by comparing outcomes over a three-year period in a group of people initially treated with ECT and then maintained on antidepressants or antidepressants plus ECT.


ECT was initially delivered once-weekly, and then gradually decreased to once-monthly. Their f i ndings appeared to support the use of maintenance ECT: 7 per cent of those receiving ECT plus antidepressant compared with 48 per cent of those receiving only antidepressants relapsed over this time. However, the authors noted that participants in the combined intervention spent more time with their doctor than those only receiving medication. In addition, participants who did not attend ECT clinics were vigorously followed up and encouraged to attend, potentially resulting in more immediate remedial action should they have begun to relapse than would be given to those treated only with antidepressants. Both may have contributed to the better outcome in this group.

Psychological interventions

Cognitive therapy The seminal cognitive treatment of depression was developed by Beck (1977). Despite its name, cognitive therapy has its historical roots in the behavioural treatment of depression, and still maintained a strong behavioural element. It typically involves a number of strategies, including:

an education phase in which the individual learns the relationships between cognitions, emotions and behaviour

behavioural activation and pleasant event scheduling to increase physiological arousal and engagement in functional, social, and other rewarding activities

cognitive rehearsal to prepare participants to cope with behavioural hypothesis testing or other situations that have previously been problematic

behavioural hypothesis testing in which the individual deliberately tests the validity of their negative assumptions, in the hope of disproving them.

Despite the emphasis on cognitive causes of depression, treatment may fi rst involve increasing engagement in physical activities. For those who are profoundly depressed, this may involve planning times to get out of bed, go to the shops, and so on. For those who are less depressed, it may involve engaging in social or ‘pleasant’ activities. Cognitive factors are usually addressed only after the client has experienced some improvement in energy or mood. At this time, they are taught to identify ‘faulty thinking’ that leads to low mood and to use cognitive challenge to counter it. In addition, the client is typically given homework to do between sessions, usually involving some form of behavioural hypothesis testing or practice in the use of new coping skills. Hypothesis testing involves direct, behavioural challenges of negative cognitions. Someone who is not sure they will be able to cope with a particular situation, for example, may be encouraged to enter the situation and try to cope with it. Such tasks should be selected with care. The therapist, at least, should be confi dent the client will be able to cope with the situation, as failure will reinforce negative expectations: the very thing the task was set up to disprove. By the mid-1980s, there was a general consensus that cognitive therapy was at least as effective as antidepressant therapy in the treatment of both moderate and severe depression. This consensus was broken following publication of the results of the most influential treatment trial so far conducted. The National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program (Elkin et al. 1989) was a particularly important trial as it was the fi rst to compare two psychological treatments, cognitive therapy and interpersonal psychotherapy (IPT), with both a tricylic and a placebo drug intervention. By the end of the 16-week treatment phase, all the active interventions appeared to be equally effective. Fifty-fi ve per cent of those in the IPT condition were clinically ‘improved’, in comparison with 57 per cent in the active drug intervention, 51 per cent in the cognitive therapy group and 29 per cent in the placebo group. For those who were severely depressed, cognitive therapy proved signifi cantly less effective than pharmacotherapy. This latter finding caused signifi cant debate and discussion, not least because its results led both the American Psychiatric Association and the US Agency of Health Care Policy and Research to recommend against the use of cognitive therapy for more severe cases of depression.

However, the results have been questioned from a number of perspectives. Psychiatrists were puzzled by fi ndings that the effectiveness of the placebo was much greater than is typically found. Psychologists were surprised that the cognitive intervention proved less effective than in earlier studies; so much so, that Jacobson and Hollon (1996) suggested that it had been implemented by insuffi ciently skilled therapists at some sites. Subsequent data have also challenged this short-term fi nding. DeRubeis et al. (1999), for example, compared the short-term outcomes of antidepressant medication and cognitive therapy in people with severe depression in sub-groups of four major randomized trials. In contrast to the NIMH study, both cognitive therapy and pharmacotherapy fared equally well.

The long-term results of the NIMH study were more favourable to the psychological interventions (Shea et al. 1992) – and here may lie their advantage over pharmacological therapy. Relapse rates following discontinuation of drug therapy are often much higher than those following cognitive therapy, even when the initial treatment is successful. Hollon et al. (2005), for example, compared outcomes in three groups of patients over a period of one year. The fi rst group comprised people who had been successfully treated with cognitive therapy, which was then discontinued. The second group comprised individuals successfully treated with medication, which was also discontinued. The fi nal group comprised a group of people successfully treated with medication, which was then withdrawn and replaced with a placebo. Relapse rates in the following year were 31 per cent following cessation of cognitive therapy, 76 per cent of those who received neither medication nor placebo, and 47 per cent among those who continued on placebo.

In an attempt to improve the still signifi cant relapse rate following the cessation of CBT, Teasdale et al. (2000) implemented a programme of mindfulness (see Chapter 3) to try to teach participants coping skills to help them avoid relapse. This proved successful, and the approach has been repeated by a number of investigators (see Research box 9). Unfortunately, although Coelho et al. (2007) concluded from their meta-analysis of these studies that mindfulness is likely to reduce relapse rates for patients with three or more previous depressive episodes, they also warned that the designs of the relevant studies prevented these findings being unambigously attributable to mindfulness.

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