The treatment of depression in the late nineteen-nineties

Ben Green, Editor, Psychiatry On-Line

Introduction

Major depression is one of the commonest illnesses affecting people in the UK. Between 5 and 10% of the population suffer with major depression at any one time. The majority of those affected by depression do not seek treatment from general practitioners - and yet there is a paradox in that it is an eminently treatable illness. The situation is worse in the elderly where over 90% of sufferers go unnoticed and without treatment. The elderly and the people around them often dismiss depressive symptoms as being ‘understandable’ in the context of whatever social or physical stressors the individual is subject to. Nevertheless, even in the context of psychosocial stressors treatment for depression can be extremely effective.

Identified depression in primary care in the nineteen eighties was often treated with a mixture of tricyclic antidepressants and sometimes through referral to a ‘counsellor’. Studies of primary care depression have sometimes loftily pointed out that general practitioners prescribe courses of tricyclics in doses that are too low and too brief. In their defence primary care specialists have pointed out that their patients could not tolerate higher doses of tricyclics and did not wish to continue for a long time with drugs that gave them a dry mouth, blurred vision, impaired cognition (especially in terms of driving), cardiotoxicity and a high risk of death in overdose.. The use of counsellors has been effective in reducing primary care doctors’ consultation usage, and is largely welcomed by the public as a treatment of choice but in some limited cases there are associated dangers - namely associated with the quality of counselling, counsellors’ ability to monitor mental state, deskilling of the primary care specialist, reducing depression to being ‘understandable in the circumstances’, and the patient’s feeling being ‘rejected’ by the primary care specialist who diagnosed depression in the first instance.

A study in the Archives of General Psychiatry (Henk, H J et al 1996, 53, 899-904) entitled Medical Costs attributed to Depression among patients with a history of high medical expenses in a health maintenance organization. This looked at the medical utilization costs of 50,000 patients enrolled in DeanCare (a health maintenance organization) for two years. A depression screen was mailed to 786 high utilizers. Depressed patients costs were significantly higher (p<.001) The additional cost per patient was $1498 per annum adjusted for age, sex, benefits package and medical co-morbidity. Treatment costs accounted for only a small percentage of total medical costs for depressed high utilizers in the third year - suggesting a direct cost-benefit to depression treatment

The nineteen nineties have brought an effective range of newer antidepressants and more flexible psychiatric services using the Care Programme Approach which offer the primary care specialist an opportunity to develop a sophisticated management model for depression.

Donoghue (1995, 1996) has looked at SSRI prescribing patterns in UK general practice. In 1995 he found that there were 2,548 prescriptions for SSRIs in 100 general practices (with a total of 383 general practitioners) over a three month period. A twelve month follow-up study in the mid nineteen nineties showed that the vast majority of 23,381 SSRI prescriptions were for fluoxetine and paroxetine.

Costs and depression

What is the annual cost of depression in the UK in the 1990s? Using the cost of illness method based on human capital theory (Hodgson & Meiners 1982) exceeds £220 million (Jonsson & Bebbington, 1994). Other estimates suggests £333 million, (Fairweather & Hindmarch, 1995) and £417 million with additional indirect annual costs of £2500 million (Kind & Sorenson,1995).

Although the drug costs (acquisition costs) of an SSRI like paroxetine exceed those of a tricyclic like imipramine by several times, the direct and indirect cost implications of paroxetine's efficacy and improved tolerability make comparisons of acquisition costs too simplistic. That is to say that there are cost implications for providers of treatment failures through drop-outs and relapses. Drop-out rates and early relapses seem more likely with tricyclics and hence bump up direct costs for providers in terms of calls on physician time and other items. Jonsson & Bebbington (1994) calculated the cost per successfully treated patient with imipramine to be £1024 , but with paroxetine this cost fell to £824. This apparent paradox is borne out by other work comparing total treatment costs of amitriptyline and imipramine with paroxetine, (Wilde & Whittington, 1995)

First line therapy

A range of selective serotonin re-uptake inhibitors is now available. Fluoxetine has a proven track record and is advantageous for obsessive compulsive disorder and bulimia nervosa. Paroxetine has a particularly good anxiolytic effect. Other useful SSRIs include sertraline and citalopram.

Although direct costs of SSRIs exceed cheaper tricyclics, studies have demonstrated a superior cost-efficacy. Such studies usually exclude additional costs that might be incurred through use of tricyclics through possible negligence and other legal actions. Prescribers of tricyclics should ensure that they have warned (and record that they have warned) patients of cognitive side effects and problems operating machinery and driving, and also taken care to avoid prescribing tricyclics in potential overdose patients and to patients at risk of cardiac problems.

Patients should also be warned about the lag time of onset of positive effects, importance of taking the tablets regularly, initial side effects and problems in sudden discontinuation. Of all the SSRIs, clinically paroxetine seems most problematic with regard to a withdrawal syndrome (dizziness, paraesthesiae, nausea, lability of mood, and irritability amongst other symptoms). The syndrome has onset 2 days after stopping paroxetine and may last 2-3 weeks afterwards. Patients should therefore be informed that when the time has come to discontinue therapy they should discuss a reducing regime with their doctor.

Withdrawal symptoms are not confined to the SSRIs and occur with tricyclic antidepressants as well.

Novel antidepressants such as venlafaxine and nefazodone differ from conventional SSRIs somewhat, but have an unfortunate side effect profile. Up to 40% of patients on venlafaxine suffer nausea.

There are reports that pindolol, combined with SSRIs, may increase antidepressant efficacy (Thase & Rush, 1995, Artigas et al, 1994, Blier &Bergeron, 1995). The strategy is not without risk however (Negro et al, 1997)

How long should treatment last?

Antidepressants

Research with both tricyclics and SSRIs has demonstrated that patients stopping antidepressants in the first few weeks after a response run a 30-50% chance of relapse. Despite this, according to prescribing data in primary care, most courses of antidepressants last only about six weeks. A variety of studies advocate that patients who have responded to antidepressants should be maintained on them for at least six months, and possibly longer. Maintaining patients who have had depression on a 12 month course of SSRIs after treatment response leads to an increased number of patients being symptom-free (Kind & Sorenson, 1995). Elderly patients with depression may need to take maintenance antidepressants for at least two years, (Old Age Depression Interest Group, 1993)

Psychotherapy

Most trials of treatments for depression focus on the hospital or the outpatient department. A recent randomized controlled trial looked at standardized treatments for depression in primary care. Patients received nortriptyline (91) or interpersonal psychotherapy (93) or a physician's normal care (92). 70% of patients in the pharmacotherapy or psychotherapy groups were judged recovered at 8 months compared to only 20% of 'usual care' patients. Twelve to sixteen sessions of interpersonal psychotherapy are advocated.

Resistant depression

A full treatment of the issue of resistant depression is beyond this brief paper. The condition usually warrants prompt referral to secondary care. However, the principles of managing resistant depression can be covered. Possible solutions amongst many include a review of the diagnosis (to exclude treatable disorders such as hypothyroidism, or confounding factors such as personality disorder), changing antidepressants (to affect alternative neurotransmitter systems, or use drugs from alternative classes), reviewing compliance, adding in adjunctive treatments such as lithium and L-tryptophan, or even consideration of electro-convulsive therapy.

References

Artigas F, Perez V, Alvarez E. (1994) Pindolol induces a rapid improvement of depressed patients treated with serotonin reuptake inhibitors. Arch Gen Psychiatry 248(51):248-51.

Blier P, Bergeron R. (1995) Effectiveness of pindolol with selected antidepressant drugs in the treatment of major depression. Journal of Clinical Psychopharmacology 15(3):217-22.

Doogan D P & Caillard V (1992) Sertraline in the prevention of depression Br J Psychiatry, 160, 217-222

Donoghue, J M (1996) Prescribing patterns of selective serotonin reuptake inhibitors in primary care: a naturalistic follow up study. Journal of Serotonin Research, 4, 267-270.

Donoghue, J M (1995) A comparison of prescribing patterns of selective serotonin reuptake inhibitors in the treatment of depression in primary carein the United Kingdom. Journal of Serotonin Research, 1, 47-51.

Fairweather, D. B. & Hindmarch, I. (1995) False economies: the true cost of cheap drugs. Social Affairs Unit.

Henk, H J et al. (1996) Medical Costs attributed to Depression among patients with a history of high medical expenses in a health maintenance organization. Archives of General Psychiatry (53, 899-904).

Hodgson, T.A. & Meiners, M.R, (1982) Cost-of-illness methodology: a guide to current practices and procedures. Millbank Memorial Fund Quarterly/ Health and Society, 60, 429-491.

Jonsson, B., Bebbington P. E. (1994) What price depression? The cost of depression and the cost-effectiveness of pharmacological treatment. Br J Psychiatry, 164, 665-673.

Kind, P. & Sorenson, J. (1995) Modelling the cost-effectiveness of the prophylactic use of SSRIs in the treatment of depression. International Clinical Psychopharmacology, 10 Suppl.1, 41-48.

Montgomery S A & Dunbar GC (1993) Paroxetine is better than placebo in relapse prevention and the prophylaxis of recurent depression. Int Clin Psychpharmacol 8, 189-195.

Negro, P J, Brannan, S, Zuelzer M. (1997) Pindolol Augmentation of Selective Serotonin Reuptake Inhibitors - a potential adverse reaction. Psychiatry On-Line, http://www.priory.com/pindolol.htm, version 1.0 - first published June 6th 1997.

Old Age Depression Interest Group, (1993) How long should the elderly take antidepressants? Br. J. Psychiatry, 162. 175-182.

Robert P & Montgomery A A (1995) Citalopram in doses of 20-60 mg are effective in relapse prevention:a placebo controlled 6 months study Int Clin Psychpharmacol 10 (S1), 29-35.

Schulberg H C et al. (1996) Treating Major Depression in Primary Care Practice - 8 month clinical outcomes. Arch Gen Psychiatry 53, 913-919.

Thase ME, Rush AJ. (1995) Treatment-resistant depression. in Psychopharmacology: The Fourth Generation of Progress. Edited by Bloom FE, Kupfer DJ. New York, NY, Raven Press, 1081-97.

Wilde & Whittington (1995) Paroxetine. A pharmacoeconomic evaluation of its use in depression. Pharmacoeconomics, 8 (1): 62-81.

Young, AH, Currie, A & Ashton, C H. (1997) Antidepressant withdrawal syndrome. BMJ, 170, 288.

First Published March 1997
Version 1.1

 

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