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Rapid Responses: Rapid Responses published:
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What does it mean to say that antidepressants are not addictive?
- D B Double (30 April 1999)
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SSRIs do not increase the teratogenic risk
- Andres Herran (3 May 1999)
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Dependence, addiction and discontinuation
- Chris Manning (4 May 1999)
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SSRIs: first choice in elderly patients?
- Mavis Evans (5 May 1999)
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Review misleads rather than illuminates
- Chris Hawley (5 May 1999)
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Some further thoughts
- Chris Manning (10 May 1999)
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St John's Wort - Effective antidepressant with no significant side effects.
- Ron Law (12 May 1999)
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Drug treatment of depression
- Simon Curtis (3 June 1999)
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Another antidepressant to consider
- Clare Stevinson (4 June 1999)
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Are antidepressant medications addictive?
- William B Rogers (20 August 1999)
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Re: Are antidepressant medications addictive?
- D B Double (8 September 1999)
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antidepressant withdrawal
- Jill Moss (13 October 1999)
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D B Double, Consultant Psychiatrist Norfolk Mental Health Care NHS Trust, Norwich NR6 5BE
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EDITOR- What do Spigset and Mårtensson mean when they say that there is no evidence that antidepressants are addictive? (1) They acknowledge that discontinuation reactions occur, and recommend that treatment should be tapered down over several weeks before withdrawal. Does this not amount to evidence of addiction?
The notion of dependence or addiction requires the crucial feature of a negative affect experienced in the absence of the drug.(2) In this sense, antidepressants should at least be regarded as psychologically addictive. The argument is not just semantic. The Defeat Depression Campaign of the Royal Colleges of Psychiatrists and General Practitioners criticised the general public for believing that antidepressants are addictive, yet habituation is likely to occur with a substance which is thought to improve mood.(3) Minimising the problems of reliance on psychotropic medication may not help the treatment of depression. There are even wider social implications when SSRI drugs are advocated as "lifestyle" drugs. (4) Recognition of the dependence potential of benzodiazepines led to the introduction of restrictive guidelines about their use.(5) There seems to be no such motivation to reduce the use of antidepressants, and Spigset and Mårtensson could have presented a more balanced view of their value. References 1. Spigset O & Mårtensson B. Fortnightly review: Drug treatment of depression. BMJ 1999; 318: 1188-1191 2. Russell MAH. What is dependence? In Drugs and drug dependence. Eds. G Edwards et al. Saxon House: Westmead, 1976 3. Double DB. Prescribing antidepressants in general practice. People may become psychologically dependent on antidepressants. BMJ 1997;314:829 4. Charlton BG. Psychopharmacology and the human condition. J Roy Soc Med 1998;91:699-601 5. Double DB. Antidepressant discontinuation reactions http://www.uea.ac.uk/~wp276/antidepressant.htm |
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Andres Herran, Associate Professor University Hospital MarquÚs de Valdecilla. Santander. Spain.
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Sir; Spigset & Mårtensson (1), analysing the issue of drug treatment of depression in a clinical review of the BMJ, stated that except for fluoxetine “little or no information is available on the possible teratogenic effects of other newer antidepressants”. However, Kulin et al (2) published one year ago a work studying the outcome of 267 women exposed to an SSRI. They found that fluvoxamine, paroxetine, and sertraline did not appear to increase the teratogenic risk when used in their recommended doses. The evidence of safety found in this study is, at least, as relevant as the findings from other studies done with tricyclic antidepressants and fluoxetine. Given the widespread usage of these new antidepressants, I think that this topic should be clarified. References 1. Spigset O, Mårtensson B. Drug treatment of depression. BMJ 1999; 318: 1188-1191. 2. Kulin NA, Pastuszak A, Sage SR, Schick-Boschetto B, Spivey G, Feldkamp M, Ormond K, Matsui D, Stein-Schechman AK, Cook L, Brochu J, Rieder M, Koren G. Pregnancy outcome following maternal use of the new selective serotonin reuptake inhibitors: a prospective controlled multicenter study. JAMA 1998; 279: 609-610. Andrés Herrán Clinical and Social Psychiatry Research Unit Department of Psychiatry. University Hospital “Marqués de Valdecilla”. Avda. de Valdecilla s/n 39008 Santander, Spain. Tf +34 942 202545 Fax: +34 942 203447 e mail: herran@humv.es |
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Chris Manning, GP Teddington
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Dear Sir As a sufferer, I am constantly bemused by the struggling of secondary care specialists as they grapple with the truth about this major illness ( and believe me, you know when you've got it). I have yet to read an article about hypertension, hyperlipidaemia, diabetes or asthma in which everyone agonises so much about the reality of many human conditions that are chronic or recurrent (20% and 90% respectively are the latest figures I have seen quoted for depression). All patients with the above conditions are both psychologically and physically dependent on their treatments. There is nothing wrong with dependence; patients on antidepressants do not 'crave' for their treatment, 'they' (another function of brain) merely miss it when they do not take it, which is precisely what one would expect if a molecule interacts physically with a receptor site. Further, many relapse on discontinuation since they maintain their inability to "come up with the goods" naturally. The proof of this pudding really is in the taking. Many patients require long term drug treatment (by which I mean "for life"). They have less of a problem with this than their doctors. Of course we mustn't over medicate, but the harsh reality is that quality time and space are sorely lacking in today's NHS, there are not enough talking-listening therapists, and, for 70-80%, drugs work (and as the other paper in this BMJ issue demonstrates often enhance the psychotherapeutic solutions). We can all sit around and agonise about this and continue to argue for more resources (and even if process is as important as outcome, counsellors are the latest casualties of the PCG reforms), but depression is not even seen as a "severe mental illness" by many bureaucrats and politicians. I, for one, am delighted that antidepressants produce active reactions. Everything else in my life on which I have any degree of dependence (from my trousers through to the 8.15 to Waterloo) provokes a discontinuation reaction when absent at short notice. It is a timely reminder for doctors to advise their patients, yet again, that all drugs should be treated with respect. Physical and psychological dependence are one and the same in my book - they are merely different ways in which we express the particular functions of brain we call 'mental'. Further, likening antidepressants to benzodiazepines or calling depression the new 'anxiety syndrome' is just another way for clever authors to gain public access. It does very little to help those, like myself, who have found that these medicines make a life possible. I am afraid, in the end, those of us with the condition have to sit in the cauldron of reality and whilst it would be pleasant to chew the theoretical fat, we are not permitted that luxury. |
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Mavis Evans
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Editor While agreeing with the majority of the clinical review article on the drug treatment of depression1 I must take issue with the advice to use lower doses of antidepressants in elderly people. Failure to reach effective doses is often cited as a reason for treatment failure2. It is often appropriate in the elderly, particularly if there is concomitant physical illness, to commence on a low dose and titrate more slowly to reach the therapeutic dose range. When combined with the delayed treatment response in the elderly3 this can make a convincing argument to use selective serotonin reuptake inhibitors as drugs of first choice in this population as their starting dose is the therapeutic dose. Mavis Evans Consultant old age psychiatrist Wirral & West Cheshire Community NHS Trust Clatterbridge Hospital Wirral CH63 4JY 1 Spigset O, Martensson B. Clinical review: Drug treatment of depression. BMJ 1999;318:1188-91. (1 May) 2 Donoghue JM, Tylee A. The treatment of depression: prescribing patterns of antidepressants in primary care in the United Kingdom. Brit J Psychiatr 1996;168:164-168 3 Georgotas A, McCue RE. The additional benefit of extending an antidepressant trial past seven weeks in the depressed elderly. Int J Geriatr Psychiatr 1989;4:191-195. |
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Chris Hawley
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Dear Sir, Re: Spigset O & Mårtenssen B. (1999) Drug Treatment of Depression. BMJ. Vol 318, p.1188 - 1191. I would like to offer some reflections on the above review. If being generous one would say the article reflects a comfortable mainstream of opinion; if less generous, that it peddles hackneyed dictums which do more to mislead than illuminate. Firstly, RCTs grossly overestimate the effectiveness of antidepressants. To ignore the naturalistic data sets a dangerous trap of unrealistic expectation for both the patient and the clinician. Naturalistic data indicates that improvement of depression must be understood to occur in months, not weeks. Even if one takes the RCT data as it stands a realistic estimate of NNT is 3.5. To illuminate this further; in a typical antidepressant trial the mean baseline MÅDRS score of 30 (of maximum 60) points. It is usual for active treatment to be superior to placebo by, typically, an average of 6 points at the end of the study period. This is the reality. The trap of unrealistic expectation is in evidence in the review itself. On the one hand the authors note that antidepressants generally take ‘1 -4 weeks' before exerting an effect. But later the suggestion is that ‘the dose should be increased...if there is no response after three weeks'. The reason for changing a treatment before it's had a chance to exert an effect eludes me. Regarding what therapy modification to make for the unimproved patient the authors propose therapy change or therapy augmentation. However, here is plenty of evidence to attest to the value of simply giving the same treatment for longer - much longer. The Metzger Model, which proposes that time under treatment (and not the treatment condition itself) is the important factor follows naturally from the separate works of both Priest and Katona. To conclude; the balancing perspective I would like to present to the non-specialist reader is that one must have realistic expectations about what pharmacotherapy can do to disease modify Major Depression, and be comfortable about patients improving slowly, and sometimes not at all. Dr Chris Hawley Consultant Psychiatrist Hertfordshire Neuroscience Research Group Queen Elizabeth II Hospital Welwyn Garden City Hertfordshire AL7 4HQ References 1 Hawley CJ, Quick SQ, Pattinson HA, Echlin D, Smith VRH. (1998) A Protocol for the Pharmacologic Treatment of Major Depression: A field test of a potential prototype. Journal of Affective Disorders 47: 87 - 96. 2 Preist RG, Hawley CJ, et al. (1997) Recovery from Depressive Illness Does Fit an Exponential Model. (1997). Journal of Clinical Psychopharmacology; 16(6): 420-424 3 Katona CL, Abou-Saleh M, Harrison DA, Nairac BA, Edwards DR, Lock T, Burns RA, Robertson MM, (1995) Placebo-controlled trial of lithium augmentation of fluoxetine and lofepramine. British Journal of Psychiatry 166(1), 80-86. 4 Elkin I, Shea T, Watkins JT (1989) National Institute of Mental Health Treatment of Depression Collaborative Research Program: general effectiveness of treatments. Archives of General Psychiatry 46, 971-982. |
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Chris Manning, GP Teddington
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Dear Sir, I still think we need far more trials performed in primary care on the 16 out of 17 people who are not referred to the secondary care sector. With the development of more refined statistical methods we simply have to research on real people rather than 'sanitised' patients who, in most cases if they go into trials are even further removed from the realities of clinical practice in both primary and secondary care, with exclusion criteria that disallow concomitatnt psychosocial confounders and exacerbators for example. Dr Hawley is correct, but perhaps it is easier for a secondary care clinician to be 'comfortable' with patients not improving, when they can simply be discharged from the clinic. A GP does not have this option, and Dr Hawley and other educationalists could do a lot worse than start to train doctors how to learn this ablity to be comfortable - after all, he is right, not just in this disease area, but in many others. With absurd expectations now rampant amongst the public, gatekeepers need to learn some potent skills in terms of learning to live with the sheep who bleat "something more must be done; is this the best you can do?". Further, I am amazed that the review concludes that TCAs should be used in severe depression. As a GP, I am constantly reading that SSRIs, for example, are as efficacious as TCAs. What on earth is the logic therefore for not using these drugs for all types of depression in the first instance - isn't life complicated enough already? Also, I regularly meet GPs who have had patients suicide on TCAs ( a real danger at doses barely above therapeutic ones) and simply find this level of risk-taking unnacceptable. It is a poor indictment on the entire area of mental illness and its treatment that these levels of toxicity still appear to be tolerated and recommended (this equally applies to schizophrenia). I would also have thought that if one is arguing from a toxicity point of view that the lederly are the very group in which one would absolutely wish to avoid tricyclics. Further, whilst accepting that SSRIs do have their own problems, they certainly do not impair cognition at therapeutic doses, are far less toxic (even without the overdose issue) and I am convinced as a GP that it has been much easier to ensure adherence to therapy. This becomes crucial in the long term, and, as Dr Hawley reminds us, this is a real issue and one that is currently very poorly managed. It is simply not good enough to have this sort of advice coming out. We are fudging the issue and not giving patients the best treatments. The situation is no different to the withdrawal of isoprenaline inhalers for patients with asthma. Sincerely, Dr. Chris Manning Conflict of interest: I have taken 175mg amitriptyline for 8 years and have been on an SSRI for 7 - the latter has been more effective since I can tolerate a therapeutic dose, so my depression is more stable, and the side -effect burden is almost negligible. |
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Ron Law, Executive Director NNFA NZ
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This article is interesting for its lack of mention of St John's Wort, a natural substance that is very effective at treating depression with no significant side effects.(1) The medical and pharmaceutical industries would be wise to acknowledge the fact that consumers now have safe choices that can be purchased without a prescription. Myopia is a term used in marketing. Its is a word worthy of further study in this context. 1. Linde K et al. St John's wort for
depression--an overview and
meta-analysis of randomised
clinical trials BMJ 1996;313:253-258 (3 August) |
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Simon Curtis
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Dear Sir, In their review 'Drug treatment of depression' (1) Spigset and Martensson do not mention St John`s wort. A recent meta-analysis (2) and a Cochrane review (3) have both shown evidence of benefit of St John's wort in the treatment of depression: it is efficacious relative to placebo (with a respectable NNT of 4), has comparable efficacy to tricyclics and a very low side effect profile. The studies involved are open to criticism (4), particularly due to the small size of many of the trials and relative low doses of tricyclics used, but nonetheless St John`s wort does have an evidence-base of effectiveness that supersedes that of many commonly used drugs - including many 'new' anti-depressants. A recent expert commentary on the evidence (5) ended with the following pragmatic advice which is likely to find resonance with both patients and their GPs : 'Most clinicians will probably stick to prescribing familiar antidepressants , but St Johns Wort may be useful for patients who have previously not tolerated conventional antidepressants or who prefer a 'natural' alternative'. Simon Curtis General Practitioner Summertown Health Centre 160 Banbury Road Oxford OX2 7BS References 1 Spigset O, Matensson B. Drug treatment of depression. BMJ 1999;318: 1188-91 2 Linde K, Ramirez G, Mulrow CD, et al. St John's wort for depression - an overview and meta-analysis of randomised clinical trials. BMJ 1996;313:253-8 3 Linde K, Mulrow CD. St John's wort for depression. Cochrane Review, latest version 09 July 1998 4 Kendrick T. Commentary (Hypericum extracts are effective for depression). EBM 1997;2:24 5 Hotopf M. Commentary (St John's wort is more effective than placebo for treating depressive disorders). EBMH 1999;2:49 |
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Clare Stevinson, Research Fellow Department of Complementary Medicine, University of Exeter
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Olav Spigset and Björn Mårtensson present a concise and informative review of drug treatments for depression based on recent research.1 One antidepressant that is not mentioned but is supported by a growing body of evidence demonstrating its efficacy is St. John’s wort (Hypericum perforatum). A meta-analysis of 23 randomised controlled trials from 1996 concluded that St. John’s wort is superior to placebo and may be as effective as tricyclic antidepressants in treating mild to moderately depressed patients.2 Since then six more rigorous trials have provided further evidence of it value.3 Safety data suggest that its adverse effect profile compares favourably with conventional antidepressants with reported adverse events being less frequent and less severe.4 This has positive repercussions on compliance, quality of life and patient satisfaction. In Germany, several St. John’s wort preparations are licensed antidepressants and these make up more than 25% of all prescriptions for antidepressant drugs.5 There are a number of herbal medicines for which there is promising evidence of efficacy and safety. However in the case of St. John’s wort, there is compelling clinical trial data suggesting that it is a treatment worth considering when dealing with mild to moderately depressed patients. Clare Stevinson, Research Fellow Edzard Ernst, Chair in Complementary Medicine Department of Complementary Medicine School of Postgraduate Medicine and Health Sciences University of Exeter 25 Victoria Park Road Exeter EX2 4NT 1. Spigset O, Mårtensson B. Drug treatment of depression. Br Med J 1999;318:1188-91 2. Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D. St. John’s wort for depression - an overview and meta-analysis of randomised controlled trials. Br Med J 1996;313:253-8 3. Stevinson C, Ernst E. Hypericum for depression: an update of the clinical evidence Eur Neuropsychopharmacol (in press) 4. Stevinson C, Ernst E. Safety of hypericum in patients with depression: a comparison with conventional antidepressants. CNS Drugs 1999;11(2):125- 32 5. Muller WE, Kasper S. Editorial. Pharmacopsychiat 1997;30(Supp):71 |
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William B Rogers, Medical Director, Andrews Center Mental Health Clinic Tyler, Texas, USA
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Dr. D.B. Double poses the following question in the 1 May 1999 issue: EDITOR- What do Spigset and Mårtensson mean when they say that there is no evidence that antidepressants are addictive? (1) They acknowledge that discontinuation reactions occur, and recommend that treatment should be tapered down over several weeks before withdrawal. Does this not amount to evidence of addiction? My thoughts: Almost any medication from propranolol to morphine will produce "habituation" when taken over time. That is, a discontinuation syndrome will follow the abrupt cessation of treatment, necessitating gradual withdrawal and sometimes treatment of a "discontinuation" syndrome. The discontinuation sydnrome cannot, then, in and of itself, be the only criterion for the diagnosis of "addiction," for surely we would not claim that a patient was addicted to an antihypertensive medication. My observations over the past 20 years have suggested the following definition for addiction:
I therefore do advise almost all of my patients that they sould expect habituation, but that in itself does not mean they are "addicted." W.Rogers, MD |
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D B Double, Consultant Psychiatrist Norfolk Mental Health Care NHS Trust, 80 St Stephens Rd, Norwich NR1 3RE
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EDITOR - I am pleased that Dr Rogers informs his patients of the risk of habituation with antidepressants. I do not want to argue about semantics. The point is that problems of discontinuation of antidepressants have been underestimated by doctors, which is not to the benefit of patients. (1) People may form attachments to their medications more because of what they mean to them than what they do. Psychiatric patients often stay on medications, maybe several at once, even though their actual benefit is questionable. Any change threatens an equilibrium related to a complex set of meanings that their medications have acquired. These issues of dependence should not be minimised, yet commonly compliance with treatment is reinforced by emphasising that antidepressants are not addictive. The attachment formed to antihypertensive medication is likely to be different from that formed with medication which is thought to improve mood. Antidepressants are often prescribed in life crises reinforcing defensive mechanisms against overwhelming anxiety, and the power of the placebo effect should be recognised. Counteracting such placebo effects may not be easy when discontinuing antidepressant medication.
(1) Double DB. Antidepressant discontinuation reactions - dependence on antidepressants is significant. BMJ eLetters for Haddad et al., 316 (7138) 1105-1106 (1 May 1998) [Response] |
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Jill Moss, student
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I am not a medical person. I had reactive deppresion a year ago, my doctor prescribed Paroxetine. I have tried for weeks to come off of it, as I feel much better. Mentally I am fine, but physically I am suffering a range of severe symptoms from flu-like feelings, terrible waves of dizzines, nauseau and mood swings. I have consulted my Gp several times, only to be told that there are no known side effects to this drug. Thankfully after visiting this site, I am more informed. I am isolated and do not know how best ro reduce my intake without further suffering. Before this experience I never took a pill, not even for a cold, and in the future I shall never again trust the judgement of the so called experts. |
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