NICE guidelines for the management of depression
BMJ 2005; 330 doi: https://doi.org/10.1136/bmj.330.7486.267 (Published 03 February 2005) Cite this as: BMJ 2005;330:267
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EDITOR- NICE guidelines on depression have recently been published
and a summary of the recommendations were given by Middleton, Shaw and
Feder in BMJ 2005:330. NICE recommends antidepressants of the SSRI-class
and cognitive behaviour therapy (CBT) or, to a somewhat lesser extent,
interpersonal psychotherapy (IPT). CBT and IPT are said to be as effective
as antidepressants. NICE do not recommend psychodynamic psychotherapy
(PDT). In many ways this is misleading. Two points will be discussed
briefly here:
The fact that NICE does not recommend the routine use of
psychodynamic psychotherapy is hard to understand given that comparisons
between bona fide psychotherapies find no significant differences between
PDT, CBT and IPT. This is true for depression 1,2, personality disorders
3,4 and various specific psychiatric disorders 5. In general the
conclusion after decades of research is that there is still no convincing
evidence that any established psychotherapy is more effective than any
other 6. Against this background a more reasonable conclusion is that PDT,
IPT and CBT all are equally effective in the treatment of depression and
that all can be recommended for routine use.
When NICE states that antidepressant medication is as effective as
psychotherapy they do not make clear that trials that compare
antidepressants to psychotherapy differ from clinical practice in at least
one important way: The patients given antidepressants are routinely given
an amount of support that are far greater than in ordinary clinical
practice. In most trials they will meet almost as often with a doctor as
the psychotherapy patients meet their psychotherapist 7-15. We know that
this amount of support when compared to ordinary clinical management will
increase the amount of patients reaching at least a 50 percent reduction
in depressive symptoms by 50 percent 16,17. NICE should thus have
specified that antidepressants are as effective as psychotherapy given
that they are combined with supportive contacts weekly or bi-weekly.
Antidepressants given together with a lower degree of support are most
likely less effective than psychotherapy.
Peter Ankarberg
clinical psychologist, licensed psychotherapist
Young Adults Counselling Service, Nyköping, Sweden
Peter.Ankarberg@dll.se
References
1. Wampold BE, Minami T, Baskin TW, Tierney SC. A meta-(re)analysis
of the effects of cognitive therapy versus “other therapies” for
depression. J Affect. Disord. 2002; 68: 159-165.
2. Leichenring F. Comparative effects of short-term psychodynamic
psychotherapy and cognitive-behavioral therapy in depression: A meta-
analytic approach. Clin Psychol Rev 2001; 21: 401-419.
3. Gabbard G. Psychotherapy of personality disorders. J Psychother Pract
Res 2000; 9: 1-6.
4. Leichenring & Leibing. The effectiveness of psychodynamic therapy
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A meta-analysis. Am Psychiatry 2003; 160: 1223-1232
5. Leichenring F, Rabung S, Leibing E. The efficacy of short-term
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analysis. Arch Gen Psychiatry 2004; 61: 1208-1216.
6. Lambert MJ. Bergin and Garfields handbook of psychotherapy and behavior
change (fifth edition). Wiley, New York, 2004.
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T. Treating depression in predominantly low-income young minority women: A
randomised controlled trial. JAMA 2003; 290(1): 57-65.
8. Elkin I, Shea MT, Watkins JT, Imber SD et al. National Institute of
Mental Health Treatment of Depression Collaborative Research Program.
General effectiveness of treatments. Arch Gen Psychiatry 1989;46(11):971-
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depressive symptoms in human immunodeficiency virus-positive patients.
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10. Schulberg HC, Block MR, Madonia MJ, Scott CP, et al. Treating major
depression in primary care practice. Eight-month clinical outcomes. Arch
Gen Psychiatry 1996;53(10):913-919.
11. Keller MB, McCullough JP, Klein DN, Arnow B, et al. A comparison of
nefazodone, the cognitive behavioral-analysis system of psychotherapy, and
their combination for the treatment of chronic depression. N Engl J Med
2000;342(20):1462-1470.
12. Leff J, Vearnals S, Brewin CR, Wolff G, et al. The London Depression
Intervention Trial. Randomised controlled trial of antidepressants v.
couple therapy in the treatment and maintenance of people with depression
living with a partner: clinical outcome and costs. Br J Psychiatry
2000;177:95-100.
13. Mynors-Wallis LM, Gath DH, Day A, Baker F. Randomised controlled trial
of problem solving treatment, antidepressant medication, and combined
treatment for major depression in primary care. BMJ 2000;320(7226):26-30.
14. Mynors-Wallis LM, Gath DH, Lloyd-Thomas AR, Tomlinson D. Randomised
controlled trial comparing problem solving treatment with amitriptyline
and placebo for major depression in primary care. BMJ 1995;310(6977):441-
445.
15. Williams JW, Jr., Barrett J, Oxman T, Frank E, et al. Treatment of
dysthymia and minor depression in primary care: A randomized controlled
trial in older adults. JAMA 2000;284(12):1519-1526.
16. Hunkeler E, Meresman J, Hargreaves W, Fiureman B, Berman W, Kirsch A,
Groebe J, Hurt S, Braden P, Getzell M, Feigenbaum P, Peng T, Salzer M.
Efficacy of nurse telehealth care and peer support in augumenting
treatment of depression in primary care. Arch Fam Med 2000; 9: 700-708.
17. Katon W, Von Korff M, Lin E, Walker E, Simon G, Bush T, Robinson P,
Russo J. Collaborative management to achieve treatment guidelines: Impact
on depression in primary care. JAMA 1995; 273(13): 1026-1031.
Competing interests:
None declared
Competing interests: No competing interests
I am not as convinced as Middleton et al1 that the issue of severity of depression and response to antidepressant treatment is as clear as the NICE guideline makes out. The full guideline2 gives the following evidence statement about serotonin specific reuptake inhibitors (SSRIs):-
There is evidence suggesting that there is a statistically significant difference favouring SSRIs over placebo on reducing depression symptoms as measured by the HRSD but the size of this difference is unlikely to be of clinical significance.
If antidepressants do not produce clinically significant change, why are they recommended? This is especially a question when this evidence statement still applies specifically to both moderate and very severe depression, although for severe depression there is said to be some evidence suggesting that there is a clinically significant difference. Middleton et al support the use of SSRIs in moderate depression, despite the apparent lack of clinical significance, and make no mention of the complication of the lack of evidence for very severe depression compared to severe depression.
Maybe the NICE guideline is relying on another evidence statement:-.
There is strong evidence suggesting that there is a clinically significant difference favouring SSRIs over placebo on increasing the likelihood of patients achieving a 50% reduction in depression symptoms as measured by the HRSD.
Why is there this apparent inconsistency in the evidence statements - a clinically significant difference when 50% reduction in symptoms is measured but not when reducing depressive symptoms is measured? Response rates, such as 50% reduction, may in fact be misleading, especially when the criterion for response is close to the mean improvement rate, which does seem to be the case in antidepressant trials. Thus a person with a 12 point improvement on the Hamilton scale may be classed as a responder, whereas an 11 point improvement would not.3 The difference is still only one point - not clinically significant.
Confounding of severity statements by regression to the mean also needs to be considered. More severely depressed patients may well show greater improvement, but this is true for patients treated with placebo as well as those treated with medication. Also, people treated as inpatients tend to be the most severely depressed and do not have as good outcomes as outpatients.4
The issue may therefore be more complicated than a decision about the degree of severity at which to start treatment, as Middleton et al suggest. The NICE data in fact shows a nonlinear relationship between severity and drug/placebo differences - not as simple as Middleton et al would like to think. The basic point is that even in studies with more severely depressed patients, there is a strong placebo response and a relatively small difference between drug and placebo (maybe on average less than two points on HRSD). This small difference may be explicable as an amplified placebo effect due to methodical bias in clinical trials.5 More should be made of this finding rather than debate being diverted into the issue of merely whether depression is severe enough to treat. There are basic issues about the efficacy of antidpressants that are being ignored by this manoeuvre.
- Middleton H, Shaw I, Hull S, Feder G. NICE guidelines for the management of depression. BMJ 2005;330:267-268 (5 February), doi:10.1136/bmj.330.7486.267 [Full text]
- National Institute for Clinical Excellence. CG23 Depression: management of depression in primary and secondary care - Full guidelinehttp://www.nice.org.uk/pdf/cg023fullguideline.pdf
- Kirsch, I., Scoboria, A., & Moore, T.J. Antidepressants and placebos: Secrets, revelations, and unanswered questions.Prevention and Treatment. 2002, Article 33 http://www.journals.apa.org/prevention/volume5/pre0050033r.html
- Moncrieff J (2003) A comparison of antidepressant trials using active and inert placebos. International Journal of Methods in Psychiatric Research 12: 117-127.
- Moncreiff J & Double DB. Double blind random bluff.Mental Health Today 2003; Nov: 24-26
Competing interests:
None declared
Competing interests: No competing interests
EDITOR- Middleton et al seem to be suggesting that
mild-moderate depression (as defined by ICD-10
criteria) may be a societal construct resulting in the
medicalisation of unhappiness. This conclusion is
reached when they consider the fact that there is scant
evidence for how to effectively treat this end of the
spectrum of depression.
Is there not another possible explanation for the lack of
a good evidence base, rather than that mild-moderate
depression does not really exist? This would consider
the aetiology and pathogenesis of depressive illness,
proposing that severe depression is more likely to have
a genetic basis and be more chemical in its underlying
mechanism. Research in severe depression may well
be investigating a 'purer' condition. In contrast, and from
many clinicians' experience, mild-moderate deression
is more multifactoral in causation. Applying specific
research interventions to this heterogenous group is
likely to have differing and unpredictable responses in
different individuals.
Until the evidence base is stronger for this suffering
population perhaps a sensible approach is to accept
the diagnosis of depression, albeit not severe, and
treat the individual with a tailor-made approach
according to their individual formulation.
Competing interests:
None declared
Competing interests: No competing interests
As usual the poverty of the NICE guidelines for treating depression
is disturbing. The Editorial by Middleton and colleagues mentions only
selective serotonin reuptake inhibitors, with increased risk of suicide,
and cognitive behaviour therapy or interpersonal therapy and
electroconvulsive shocks.1
There is no mention of biochemical investigations and specific
remedial treatments for common nutritional deficiencies. In 1963 Jaspers
observed that almost every known symptom of classic psychiatric disorders
can be evoked by organic cerebral illnesses.2
Philpott wrote that any blocking of methionine metabolism prior to
the formation of cysteine will have the consequences of increasing S-
adenosyl methioine, which in turn will produce an excessive production of
methione-enkaphalin , which has morphine-like activity 100 times the
potency of morphine.3 Normal methionine metabolism is blocked by inherited
metabolic error which predisposes to the development of addiction or by
deficiencies of zinc, magnesium, manganese, vitamins B6, B3, B12 and folic
acid and also by tranquillization.
I suspect copper should also be added to this list as copper
deficiency may contribute to reactions to addictive drugs.4 Repletion of
depleted copper stores, diagnosed by a red blood cell superoxidase
activity test, can be dramatically effective in restoring normal neuronal
function. Philpott concluded that nutritional deficiencies should be
treated with nutritional supplements where there is laboratory evidence of
need.
It seems that NICE do not yet recognise how that serious mind-bending
and addiction-predisposing nutritional deficiencies are very common and
increased by the use of hormonal contraceptives, HRT, smoking or alcohol.5
1 Middleton H, Shaw I, Hull S, Feder G. NICE guidelines for the
management of depression. BMJ 2005;330:267-268 (5 February),
doi:10.1136/bmj.330.7486.267
2 Jaspers K. General Psychopathology. 1963 University of Chicago
Press, Chicago. p 480.
3 Phillpott W H, Philpott K, Khaleeluddin KK. The roles of
bioecological diagnosis and treatment of organic factors in mental
disorders. In Biological Aspects of Schizophrenia and Addiction. Ed G.
Hemmings. 1982 John Wiley and Sons Ltd, Chichester, pp139-154.
4 Grant ECG. Cannabis and copper and zinc upsets increase the risk of
psychosis?
http://bmj.com/cgi/eletters/330/7481/11#88043, 4 Dec 2004
5 Grant ECG. Allergies, smoking and the contraceptive pill. In
Biological Aspects of Schizophrenia and Addiction . Ed G. Hemmings. 1982
John Wiley and Sons Ltd, Chichester, pp 263-272.
Competing interests:
None declared
Competing interests: No competing interests
NICE Guidelines for Depression 2004: Gaps in the Evidence
In a welcome editorial, Middleton et al (2005) describe some of the issues with the December 2004 NICE guidelines on the management of depression in primary and secondary care. 1. The authors suggest that NICE has produced “a definitive summary of current evidence.” We disagree and wonder if other readers have found these guidelines unsatisfactory in places? Judging by other electronic responses we are not alone here.
It seems almost no literature was considered about depression in late life, despite a wealth of data in this area. 2,3. Yet in the remit NICE state that “this guideline will be of relevance to all people with a diagnosis of depression aged 18 and over.”
The guidelines summarize a large amount of data concerning individual treatments but it does not appear to consider all antidepressants equally (for example, there is little data concerning clomipramine, lofepramine and trazodone in spite of their widespread clinical use). The authors of the NICE document state that there are no studies that have reported combining an SSRI with T3 augmentation. This is incorrect, RCTs are available in both conference proceedings and in recently in print. 4.
The guidelines summarise pharmacological treatments with the conclusion that there is no clinically significant difference between the different antidepressants despite statistically significant differences and yet there is no indication why this conclusion was reached (for example no NNTs or NNHs).
It seems perplexing that the guidelines make a panacea recommendation for SSRIs first-line implying class superiority over both older (first generation) and newer (third generation) antidepressants (including Venlafaxine). By this they also implies little or no variation of efficacy or adverse effects between SSRIs. Yet this is not supported by their own evidence. We agree with Dr Double’s comments above, but would go further. For example in 9 studies, Venlafaxine was 15% more likely (difference in relative risk) to achieve a 50% reduction in depressive symptoms in outpatients compared with SSRIs. Similar differences can be found with regard to tolerability for example with Escitalopram and Mirtazapine. Venlafaxine in particular seems to have been singled out, namely with advice for a pre-commencement ECG, advice not to prescribe to patients with cardiovascular disease and with restrictions to mental health specialists (again no data is given supporting why except reference to the MHRA warning letter). Yet close inspection of the MHRA website reveals a similar disconcerting lack of evidence and no mention of cardiovascular side effects of Venlafaxine and no evidence about its safety in patients with pre-existing cardiovascular disease. To clarify we had no option but to write to Wyeth and perform our own literature search. According to Wyeth these have been 2,958 overdoses on Venlafaxine and no deaths, a track record that cannot be claimed by the SSRIs. A recent study has also found less ECG changes following Venlafaxine overdoses than on some SSRIs. 5.
Our purpose in highlighting these deficiencies is not to criticise the Middelton editorial and not to favour any particular drug but rather to highlight certain recommendations which will greatly affect clinical practice but appear to be based on an inadequate foundation.
References
1. Hugh Middleton, Ian Shaw, Sally Hull, and Gene Feder. NICE guidelines for the management of depression. BMJ 2005; 330: 267-268.
2. Gerson S, Belin TR, Kaufman A, et al. Pharmacological and psychological treatments for depressed older patients: A meta-analysis and overview of recent findings. HARVARD REV PSYCHIAT 7 (1): 1-28 MAY-JUN 1999
3. Bartels SJ, Dums AR, Oxman TE, et al. Evidence-based practices in geriatric mental health care: an overview of systematic reviews and meta-analyses
PSYCHIAT CLIN N AM 26 (4): 971-+ DEC 2003
4. Appelhof BC, Brouwer JP, van Dyck R, et al. Triiodothyronine addition to paroxetine in the treatment of major depressive disorder. J Clin Endoc Met. 89 (12): 6271-6276 DEC 2004
Competing interests:
None declared
Competing interests: No competing interests