Psychiatric disorder is now recognised as one of the greatest causes of human suffering. The burden to society of various diseases has been quantified recently using disability-adjusted life years (DALYs), a measure that expresses years of life lost to premature death and years lived with a disability of specified severity and duration.
The burden of mental illness is second only to that of cardiovascular conditions in the developed world and when DALYs related to alcohol and drug misuse are included it is the largest single category (Murray & Lopez, 1997). Unipolar major depression currently imposes the second largest burden of any individual disorder in the developed world and, because of the decline in the incidence of ischaemic heart disease, may soon be the leading individual illness category (Murray & Lopez, 1997). Clearly, any improvements in the treatment of unipolar depression would produce great benefits in the health of the public.
The high disease burden of unipolar major depression is understandable when one considers the nature of the illness. Individual episodes are often prolonged, there is a high rate of progression to chronicity and relapse and recurrences are frequent. In addition, the illness is associated with pronounced psychosocial and physical impairments and a high suicide rate (Angst, 1999).
Depression is a common condition, with an annual prevalence in Western countries of 3-10% and a life-time prevalence of approximately 17% (Angst, 1999), and it is often comorbid with other psychiatric problems and substance misuse. Unipolar depression frequently becomes chronic, with 12-20% of patients continuing to be fully symptomatic 2 years after initial diagnosis (Judd et al, 1997).
The median number of episodes experienced is four (Anderson et al, 2000) and sufferers are subject to relapse and return of symptoms even after successful treatment (Surtees & Barkley, 1994). The long-term outcome of depression may differ with the setting, but recent evidence suggests that at least 85% of patients experience a relapse and that the high degree of recurrence occurs in community as well as hospital samples (Mueller et al, 1999).
TREATMENT WITH ANTIDEPRESSANTS
Although clinical trials of antidepressant treatments have shown the benefits of drug treatment, uncertainty remains about the most effective treatment of depression. An example of this is the recent debate in which the validity of clinical trials of antidepressants has been questioned and it has been suggested that antidepressants may be no more effective than active placebo treatments.
Although more recent work supports the validity of clinical trials of antidepressants, this debate emphasises the need for constant re-examination of the evidence upon which we base clinical practice (Quitkin et al, 2000). Nor must we forget the role of psychotherapies; a recent study has shown the value of combining antidepressant medication and the cognitive-behavioural analysis system of psychotherapy in chronic depression (Keller et al, 2000).
Guidelines compiled by the British Association for Psychopharmacology (BAP) have comprehensively reviewed the evidence for treating depressive disorders with antidepressants (Anderson et al, 2000). These guidelines make use of an accepted classification of the categories of evidence and the strength of the recommendation made (Shekelle et al, 1999).
Antidepressant treatment should be continued for 6 months after remission of symptoms, but the benefit of more prolonged treatment has not been demonstrated for non-selected groups of depressed patients, including those who are experiencing a first episode (Reimherr et al, 1998). However, relapse prevention has been shown for those patients with recurrent disorder for a number of different antidepressants, including imipramine (Frank et al, 1993), maprotiline (Rouillon et al, 1989) and paroxetine (Franchini et al, 1998). It seems likely that this effect of relapse prevention may be a property of all effective antidepressants, although in clinical settings an important difference may be that newer agents, such as the selective serotonin reuptake inhibitors, may be more likely to be given in a therapeutic dose (MacDonald et al, 1997).
REFERENCES
Anderson, I. M., Nutt, D. J. & Deakin, J. F.W. (2000) Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 1993 British Association for Psychopharmacology guidelines. Journal of Psychopharmacology, 14, 3-20.
Angst, J. (1999) Major depression in 1998: are we providing optimal therapy? Journal of Clinical Psychiatry, 60 (suppl. 6), 5-9.
Franchini, L., Gasperini, M., Perez, J., et al (1998) Dose-response efficacy of paroxetine in preventing depressive recurrences: a randomised, double-blind study. Journal of Clinical Psychiatry, 59, 229-232.
Frank, E., Kupfer, D. J., Perel, J. M., et al (1993) Comparison of full-dose versus half-dose pharmacotherapy in the maintenance treatment of recurrent depression. Journal of Affective Disorders, 27, 139-145.
Hochstrasser, B., Isaksen, P. M., Koponen, H., et al (2001) Prophylactic effect of citalopram in unipolar recurrent depression. British Journal of Psychiatry, 178, 304-310.
Judd, L. L., Akiskal, H. S., Maser, J. D., et al (1997) A prospective 12-year study of subsyndromal and syndromal depressive symptoms in unipolar major depressive disorders. Archives of General Psychiatry, 55, 694-700.
Keller, M. B., McCullough, J. P., Klein, D. N., et al (2000) A comparison of nefazodone, the cognitive-behavioural analysis system of psychotherapy, and their combination for the treatment of chronic depression. New England Journal of Medicine, 342, 1462-1470.
MacDonald, T. M., Reid, I. C. & McMahon, A. D. (1997) Patients receive an inadequate dose of antidepressants for an inadequate period. British Medical Journal, 315, 56.
Mueller, T. I., Leon, A. C., Keller, M. B., et al (1999) Recurrence after recovery from major depressive disorder during 15 years of observational follow-up. American Journal of Psychiatry, 156, 1000-1006.
Murray, C. J. & Lopez, A. D. (1997) Alternative projections of mortality and disability by cause 1990-2020: global burden of disease study. Lancet, 349, 1498-1504.
