Prescribing antidepressants in general practiceBMJ 1997; 314 doi: https://doi.org/10.1136/bmj.314.7083.826 (Published 15 March 1997) Cite this as: BMJ 1997;314:826
- David Fish, West Midlands Mental Health Education fellow (1993-6)a
- a Henley Green Centre, Coventry CV2 1AB
- b Three Swans Surgery, Salisbury SP1 1DX
- c Cochrane Depression Group, Institute of Health Sciences, University of Oxford, PO Box 777, Oxford OX3 7LF
- d Geriatrics and Extended Care, Department of Veterans Affairs Medical Center/Texas Tech University, 6010 Amarillo Boulevard, West Amarillo, TX 79106, USA
- e Gwent Community Health NHS Trust, County Hospital (Griffithstown), Pontypool, Gwent NP4 5YA
- f Pain Management Clinic, South Cleveland Hospital, Middlesbrough TS4 3BW
- g Grampian Health Board, Aberdeen AB9 1RE
- h Fitznells Manor Surgery, Ewell, Surrey
- i NHS Centre for Reviews and Dissemination, University of York, York YO1 5DD
- j Leeds General Infirmary, Leeds LS1 3EX
- k Royal Edinburgh Hospital, Edinburgh EH10 5HF
- l Dingleton Hospital, Melrose, Roxburghshire
- m Hairmyres Hospital, East Kilbride G75 8RG
- n West Norwich City Community Team, Norfolk Mental Health Care NHS Trust, Norwich NR6 5BE
What is an effective dose?
Editor-What should be the advised dosage of a tricyclic antidepressant for major depression? In his editorial Tony Kendrick quotes a recommended dose of a typical tricyclic antidepressant, amitriptyline, as 125 mg daily.1 This dosage is at the higher end of the range of dosages quoted for all tricyclic antidepressants in the British National Formulary. If followed it would have major implications for the prescribing habits of general practitioners.
The recommended dosage for amitriptyline for major depression is quoted from a consensus statement published in the BMJ in 1992.2 The source of this recommendation is a double blind placebo controlled trial of amitriptyline among depressed patients in general practice.3 In this trial patients given the active drug received amitriptyline 75 mg daily by the end of the first week, amitriptyline 100 mg during the second week, and amitriptyline 125-175 mg, depending on improvement, during the remaining four weeks of the study. The median dose of amitriptyline given over the six week study period was 125 mg. It is the median tolerated dose. Figure 1 in the paper by Hollyman et al clearly shows a response to treatment in the first two weeks, when the lower dose of amitriptyline was given.3
Kendrick discusses the results of several investigations into the effectiveness of antidepressants at different dosages. Similar investigations have been used to develop the dose range of every prescribable antidepressant–for example, Kerihuel and Dreyfus reviewed 34 randomised clinical trials of lofepramine.4 In the papers reviewed the concentration of lofepramine giving a clinical response ranged from 105 mg to 210 mg, which is equivalent to 75-150 mg amitriptyline.
The principle that more severe cases of major depression require higher doses of antidepressants is also valid. It also holds true for newer selective serotonin reuptake inhibitors. For example, …