Medical Opinion - Depression
Published 17 November 2004

This Editorial has been written by the specialist opinion leader, Allan H Young, Professor of Psychiatry, Royal Victoria Infirmary, University of Newcastle and published in the latest issue of the serial publication, Drugs in Context.

Depression is an extremely common, debilitating condition that affects around 8% of the general population at any one time, with the lifetime risk being considerably higher. The magnitude of this disorder is such that up to half of women and one-quarter of men will be affected by depression at some point during their lives. Depression frequently becomes chronic, with at least 20% of sufferers remaining ill 2 years after an initial diagnosis. In addition, the recurrence rate is greater than 90%. Not surprisingly, such a prevalent condition has a significant impact on the health service resources and the global economy. Consequently, one of the main challenges faced daily by GPs is how to identify, diagnose and treat this large section of the population.

Antidepressants remain the cornerstone of our treatment strategy for depression. Significant advances have been made in this setting during the past 50 years. The first agents introduced were the tricyclic antidepressants (TCAs) and the monoamine oxidase inhibitors (MAOIs). Although these drugs exhibit good clinical efficacy, their reputation has been tarnished somewhat by their cardiotoxicity in overdose, troublesome side-effects at therapeutic doses and significant drug interactions. These factors have profound effects on patient compliance and may thus reduce treatment success. Over the subsequent decades our knowledge of the pharmacology of depression has been refined, and the newer antidepressants have tended to be selective reuptake blockers, usually of serotonin. With the emergence of the selective serotonin reuptake inhibitors (SSRIs), the serotonin and noradrenaline reuptake inhibitors (SNRIs) such as venlafaxine, and a new drug class represented by mirtazapine - the noradrenergic and specific seratonergic antidepressants - we appear to have circumvented many of the negative aspects of the older agents without a loss of antidepressant efficacy.

Despite these advances, the majority of primary-care guidelines continue to recommend that TCAs should be considered as first-line therapy for depression in patients without suicidal ideation. This, I would argue, represents at best misguided advice and, at worst, dangerous practice. Not all patients with suicidal thoughts will communicate their feelings to their doctor. In addition, these thoughts may not be apparent at the time of consultation and may manifest before the medication becomes fully effective. Given the availability of equally effective yet safer agents, the balance has surely shifted sufficiently for us to prescribe the newer drugs ahead of the TCAs and MAOIs, which should perhaps be reserved for treating the most severely affected or treatment-resistant patients referred to the specialist? Even the somewhat short-sighted ‘tablet-for-tablet’ economic rationale used to support the use of the TCAs as first-line therapy is now outweighed by considerable evidence to the contrary when indirect costs are taken into account.

The use of drug therapy early in the course of the illness is likely to bring about greater therapeutic benefit, and long-term maintenance treatment is often necessary. Whilst drug therapy is fundamentally important in patient management, improving the rate of detection of depression should be one of our main goals. Advances in physician interviewing techniques, longer consultation times, the use of simple screening devices and just taking the care to ask about mood can increase the detection of depression. Despite the revolution in the management of depression, there are still many patients who do not respond to treatment. Thus, the more appropriate use of existing agents and/or the development of more effective, novel classes of drugs is required. In fact, this remains an area of active drug development. In the future, the development of other novel antidepressants that offer even greater clinical benefits for all our patients remains a tantalising prospect.

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