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Psychotropic drug treatment

BMJ 1998; 316 doi: http://dx.doi.org/10.1136/bmj.316.7129.476a (Published 07 February 1998) Cite this as: BMJ 1998;316:476

Some antidepressants are more effective than others

  1. Alan Lenox-Smith, Senior medical adviser for central nervous system productsa
  1. a Wyeth*, Taplow, Maidenhead, Berkshire SL6 0PH
  2. b St George's Hospital Medical School, London SW17 0RE
  3. c Oxleas NHS Trust, Bexley Hospital, Bexley, Kent DA5 2BW
  4. d Academic Unit of Psychiatry, United Medical and Dental Schools, St Thomas's Hospital, London SE1 7EH

    Editor—I challenge Pathare and Paton's statement that “All antidepressants are equally effective in treating depression.”1 There is growing evidence that antidepressants that block the reuptake of both serotonin and noradrenaline have greater clinical efficacy than those that act on just one neurotransmitter.

    Patients with mild depression often show a high rate of response to placebo, and differences between drugs can be hard to detect. Differences will (usually) be shown only when patients with moderate to severe depression are studied. Another way to look for differences between drugs, or classes of drugs, is to combine trials to gain statistical power in a meta-analysis.

    It is important to look at the different classes of drug that block the reuptake of serotonin and noradrenaline. Such drugs comprise the older tricyclic antidepressants, which can be subdivided into those that have their main action on noradrenaline (for example, desipramine) and those that have their action on both serotonin and noradrenaline (for example, clomipramine); the selective serotonin reuptake inhibitors (for example, paroxetine and fluoxetine), which block the reuptake of serotonin only; and the newer class of serotonin and noradrenaline reuptake inhibitors, which block the reuptake of both serotonin and noradrenaline.

    Early suggestions that drugs with dual action had advantages over those that increased just one neurotransmitter came from the Danish University Antidepressant Group,2 which looked at the efficacy of clomipramine compared with that of paroxetine. The group found that from the second week the tricyclic antidepressant had greater efficacy than the selective serotonin reuptake inhibitor.

    More recently, a meta-analysis was carried out of 25 studies in which tricyclic antidepressants and selective serotonin reuptake inhibitors were compared in 1377 patients in total; it showed that overall efficacy was significantly greater (P<0.02) for the tricyclic antidepressants (data presented at satellite symposium at 6th world congress of biological psychiatry, 22–27 June 1997). A second meta-analysis, which included venlafaxine (a serotonin and noradrenaline reuptake inhibitor) as well as tricyclic antidepressants and selective serotonin reuptake inhibitors, has confirmed that the efficacy of venlafaxine is superior to that of the selective serotonin reuptake inhibitors.3 Individual double blind trials with venlafaxine (for example, that by Dierick et al4) have also shown that it has greater efficacy than fluoxetine.

    Many of the doctors who read the BMJ do not have specialist knowledge of depression and rely on review articles to keep up to date. It is important that this debate is at least mentioned in any review on the effectiveness of antidepressants.

    References

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    Repeated prescription charges for weekly treatment may be deterrent to patients

    1. Tess Harris, Lecturer in general practice and primary careb,
    2. Frank Smith, Senior lecturer in general practice and primary careb
    1. a Wyeth*, Taplow, Maidenhead, Berkshire SL6 0PH
    2. b St George's Hospital Medical School, London SW17 0RE
    3. c Oxleas NHS Trust, Bexley Hospital, Bexley, Kent DA5 2BW
    4. d Academic Unit of Psychiatry, United Medical and Dental Schools, St Thomas's Hospital, London SE1 7EH

      Editor—Pathare and Paton clearly reviewed the use of antidepressant drugs in the treatment of depression and provided helpful guidelines for preventing suicide.1 But general practitioners in England and Wales often find practical difficulties in implementing one of their suggestions: that of giving small supplies to patients at risk, possibly a week's prescription at a time. There is no problem in giving weekly prescriptions to patients who are exempt from paying prescription charges. For patients who are not exempt but are not on a high income, however, the £5.65 prescription charge for seven days' treatment can be a deterrent, particularly at a time when they may be experiencing side effects and deriving little benefit from the drug.

      One way around this problem would be to prescribe a month's supply of the drug but to ask the pharmacist to dispense it weekly. Under the current system in England and Wales this is problematic for pharmacists to implement because they are only paid one dispensing fee per prescription and would be reluctant to take on the extra work without recompense. A second option might be to entrust the drug to another person, but this is often not possible or may cause conflict between the parties. The Scottish instalment dispensing scheme seems ideal; in this, the patient pays one prescription charge while the pharmacist receives a payment for each time he or she dispenses. With the recent high profile Defeat Depression campaign and its emphasis on better recognition and treatment of depression by general practitioners,2 introduction of this scheme in England and Wales should be given serious consideration.

      References

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      Authors' reply

      1. Carol Paton, Principal pharmacistc,
      2. Soumitra Pathare, Wellcome research fellowd,
      3. Teifion Davies, Senior lecturerd
      1. a Wyeth*, Taplow, Maidenhead, Berkshire SL6 0PH
      2. b St George's Hospital Medical School, London SW17 0RE
      3. c Oxleas NHS Trust, Bexley Hospital, Bexley, Kent DA5 2BW
      4. d Academic Unit of Psychiatry, United Medical and Dental Schools, St Thomas's Hospital, London SE1 7EH

        Editor—Lennox-Smith uses our review article, which was aimed at general practitioners and non-specialists in psychiatry, to present a biased view of the literature. The clear aim of our article was to present the basic knowledge that non-psychiatric specialists require to prescribe effectively for the most common psychiatric illnesses. However, we wish to reply to the points he raises.

        While it is true that some studies show tricyclic antidepressants to be more effective than selective serotonin reuptake inhibitors in the treatment of depression, others show selective serotonin reuptake inhibitors to be more effective. These differences are probably due to a combination of study design, characteristics of the patients, and chance. A meta-analysis by Song et al concluded that there was no difference in overall efficacy between tricyclics and selective serotonin reuptake inhibitors.1

        The Danish study cited by Lennox-Smith, which suggested that clomipramine was more effective than paroxetine, was designed to favour the tricyclic antidepressant.2 Patients who dropped out early because of side effects (mostly patients treated with the tricyclic antidepressant) were not included in the final analysis. The rating scale used to measured change has an excess of sleep items (three), which are likely to show an early response to a sedating tricyclic. Furthermore, patients who had not responded at four weeks were classified as non-responders; four weeks is too early to assess response. It is therefore wrong to extrapolate from this study and suggest that tricyclic antidepressants in general are more effective than selective serotonin reuptake inhibitors. A review of the literature in respect of severe depression has shown this not to be the case (S Montgomery, 6th world congress of biological psychiatry, 22–27 June 1997). Furthermore, the study by Einarson et al was not a meta-analysis as stated by Lennox-Smith but a cost effectiveness analysis which used an unpublished meta-analysis and expert panel to construct a decision tree.3

        Though there may be a suggestion in the literature that dual action antidepressants offer small advantages in some clinical situations, it is no more than a suggestion. This potential advantage is greatly outweighed by the fact that as many as 88% of prescriptions for tricyclic antidepressants written in primary care are for subtherapeutic doses.4

        The greatest contribution to the treatment of depression would be made by increasing detection and prescribing a therapeutic dose of any antidepressant for an adequate period. These are the goals that all non-specialists should aim for.

        Harris and Smith highlight an important practical issue; we agree with their suggestions and hope that they are widely implemented.

        References

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