MENTAL HEALTH

Health Evidence Bulletins - Wales
Team Leader: Dr Lyn Harris

Date of completion: 4.6.98

MAJOR DEPRESSION

Depression is common in primary care. Up to 50% of general practice attendees may have some depressive symptoms of whom around 5% will have major depressioni,ii.
i. The treatment of depression in primary care. Effective Health Care. March 1993. Number 5.
(Type IV evidence - observational studies);
ii. Agency for Health Care Policy and Research. Depression in primary care. Volumes I and II. Rockville, Maryland: US Departments of Health and Human Services, 1993.
(Type IV evidence - observational studies)

This document is a supplement to, not a substitute for, professional skills and experience. Users are advised to consult the supporting evidence for a consideration of all the implications of a recommendation

The Statements The Evidence
6.1 Depression in Primary Care Settings
6.1a. The importance of improving identification, diagnosis and appropriate treatment of people with depression has long been recognised and was the subject of the defeat depression campaign i. i. Paykel ES, Priest RG. Recognition and Management of Depression in General Practice: Consensus Statement. British Medical Journal 1992; 305: 1198-202
(Type V evidence - expert opinion)
6.1b. Suicide rates are higher in people with depression, but it is not possible to predict which primary care attendees with depression are likely to commit suicide i. i. The treatment of depression in primary care. Effective Health Care March 1993. Number 5
(Type IV evidence - observational studies)
6.1c. Antidepressants are generally effective in the treatment of major depression but a significant number of patients will drop out of treatment and many will relapse i. The tricyclic (TCAs) and related antidepressants and the selective serotonin reuptake inhibitors (SSRIs) are the two maingroups of antidepressants in common use. Both are effective when used in therapeutic dosage for an adequate length of time i. i. The treatment of depression in primary care. Effective Health Care March 1993. Number 5
(Type I evidence - systematic review)
6.1d. There is a slight reduction in drop-outs with selective serotonin reuptake inhibitors (SSRI) treated patients compared with older antidepressants including the tricyclics (TCAs). This is likely to be due to lesser side-effects rather than increased efficacy. The generalisability of the findings in this study is unknowni. There is little compelling evidence to favour one drug over the other. Therapy needs to be tailored to the individual to maximise efficacy and compliancei,ii. The SSRIs are "safer" but it is doubtful if this significantly affects the suicide rate since other methods of committing suicide are readily availableii. i. Song F, Freemantle N, Sheldon TA et al. Selective serotonin reuptake inhibitors: meta-analysis of efficacy and acceptability. British Medical Journal 1993; 306: 683-687
(Type I evidence - systematic review);
ii. The treatment of depression in primary care. Effective Health Care March 1993. Number 5
(Type I evidence - systematic review)

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6.1e. A meta-analysis of 13 trials showed that St. John's wort (hypericum) was significantly more effective than placebo for depression (Number needed to treat = 3.0, 95% CI 2.6-3.8) i. A Cochrane review is in progress ii. i. Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Malchart D. St. John's wort for depression - an overview and meta-analysis of randomised clinical trials. British Medical Journal 1996; 313: 253-258
http://www.bmj.com/cgi/content/full/313/7052/253
(Type I evidence - systematic review)
ii. Linde K, Mulrow CD, Fischer P. St. John's wort for depression [Protocol]. Cochrane Database of Systematic Reviews. Cochrane Library. Review in progress.
6.1f. Drugs are effective in the treatment of dysthymia with no differences between and within class of drugs. Tricyclic antidepressants are more likely to cause adverse events and dropouts. Although dysthymia is a chronic condition, there remains little information on quality of life and medium or long-term outcome i. i. Lima MS, Moncrieff J. A comparison of drugs versus placebo for the treatment of dysthymia: a systematic review. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2
(Type I evidence - systematic review)
6.1g. The efficacy of counselling in primary care settings is difficult to assess because of methodological problems of available research i. i. Roth AD, Fonagy P. What works for whom? A critical review of psychotherapy research. New York: Guilford Press, 1996
(Type I evidence - systematic review)
6.1h. Studies do not preclude the possibility that many (perhaps most) patients currently treated by counsellors are likely to remit spontaneously. This is not to say that such individuals do not value the intervention provided, but little evidence is available that would suggest that remissions accelerated as a result of the counselling interventions I, ii. i. Roth AD, Fonagy P. What works for whom? A critical review of psychotherapy research. New York: Guilford Press, 1996
(Type I evidence - systematic review)
ii.Freidli K, King M,Lloyd M, Horder J. Randomised controlled assessment of non-directive psychotherapy versus routine general-practitioner care. Lancet 1997; 350; 1662-1665
(Type II evidence-randomised controlled trial)
6.1i. The best evidence of efficacy of counselling seems to come from studies that target specific client groups (patients with bereavement reactions or with acute postnatal depression) or studies that employ a modified version of a specific therapeutic model (interpersonal counselling, exploratory therapy, and behaviour therapy)i.
If counselling services are to be extended within primary care settings, urgent research is required to examine the efficacy of counselling interventions across a wide range of psychological disorders.
A review of the value of counselling in primary care is in progress ii.
i. Roth AD, Fonagy P. What works for whom? A critical review of psychotherapy research. New York: Guilford Press, 1996
(Type I evidence - systematic review)
ii. Rowland N, Mellor Clark J, Bower P, Heywood P, Young P, Godfrey C. The effectiveness and cost-effectiveness of counselling in primary care [Protocol]. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2. Review in progress.

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6.1j. Preliminary results of a meta-analysis of 9 randomised controlled trials support the view that combining antidepressants and psychotherapy is more effective than antidepressants alone for the treatment of depression (Odds Ratio = 2.40; 95% CI 1.48-3.88). Full results will be available in a review due soon i. i. Summary by Churchill (http://users.ox.ac.uk/~mert0215/summdg.htm) of the forthcoming review:
Churchill R, Wessely S, Lewis G. A systematic review and meta-analysis of the effects of combining pharmacotherapy and psychotherapy for the treatment of depression [Protocol]. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2. Review in progress.
6.2 Treatment of Major Depression The evidence for statements 6.2.1a to 6.2.2a comes from the systematic reviews cited below. These are expert statements of good practice supported by evidence within the reviews.
6.2.1 General
6.2.1a. The relationship between the patient and the doctor/therapist, the therapeutic alliance, is an essential part of the success of treatment. A depressed outpatient’s adherence to treatment can be improved by educating the patient and, in many cases, the family about the treatment, its potential side effects and its likelihood of success.  
6.2.1b. If a treatment is going to be successful a 4-6 week trial of medication or a 6-8 week trial of psychotherapy usually results in at least partial remission (50% symptom reduction), and a 10-12 week trial usually results in a nearly full response (minimal or no symptoms) to treatment. Full restoration of psychosocial function takes longer. If there is little or no response over these timescales a change of treatment should be considered. If a patient shows a partial response to treatment by 5 to 6 weeks, the same treatment should be continued for 5 to 6 more weeks. i. Roth AD, Fonagy P. What works for whom? A critical review of psychotherapy research. New York: Guilford Press, 1996
(Type I evidence - systematic review)
ii. American Psychiatric Association Practice Guidelines. Washington DC: APA, 1996
(Type I evidence - systematic review)
iii. Agency for Health Care Policy and Research. Depression in primary care. Volumes I and II. Clinical Practice Guidelines No. 5. Rockville, Maryland: US Departments of Health and Human Services, 1993
(Type I evidence - systematic review)

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6.2.2 Pharmacotherapy for Major Depression
6.2.2a. Medications have been shown to be effective in all forms of major depressive disorder. Where there are no contraindications to these drugs, antidepressant medications are the first line treatments for major depressive disorder when:
  • The depression is moderate or severe
  • There are psychotic, melancholic or atypical symptom features
  • The patient requests the medication
  • Psychotherapy by a trained, competent psychotherapist is not available
  • The patient has shown prior good response to medication
  • Maintenance treatment is planned

Where these indicators are present there is a high likelihood of a beneficial response to medication (but their absence does not predict failure). No antidepressant medication is clearly more effective than another and no single medication results in remission for all patients.

 
6.2.2b. The following Cochrane reviews are in preparation:
  • Combined antidepressant-benzodiazepine treatment i
  • Antidepressants versus active placebosii
  • The comparative efficacy of selective serotonin reuptake inhibitors (SSRIs) iii
  • Treatment discontinuation iv
  • Drug treatments of older depressed peoplev
i. Furukawa T, Streiner DL, Young LT. Combined antidepressant-benzodiazepine treatment for major depression [Protocol]
ii. Moncrieff J. Review of randomised controlled trials of antidepressants using active placebos [Protocol]
iii. Freemantle N, Mason J, Eccles MP, Geddes JR, Boynton J. Selective serotonin reuptake inhibitors: an overview of their comparative efficacy in the treatment of depressive disorder [Protocol]
iv. Hotopf M, Freemantle N, Boynton J et al. Systematic review of treatment discontinuation in randomised controlled trials comparing the selective serotonin reuptake inhibitors and other new generation antidepressants with tricyclic and related antidepressants [Protocol]
v. Wilson K, Mottram P, Sivananthan A. A review of antidepressant drug trials in the treatment of older depressed people [Protocol]
Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2. Reviews in progress.

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6.2.3 Electroconvulsive Therapy (ECT) for Major Depression. General Statements.
6.2.3a. ECT has a high rate of therapeutic success, relative speed in inducing improvement in depressive symptoms, and an excellent safety profile.

6.2.3b. The use of ECT is not only affected by research into its effectiveness. Other factors such as psychiatric education and training, legal restrictions, individual and community prejudice also have marked effects.

The evidence for statements 6.2.3a - 6.2.3d is derived from:
i. American Psychiatric Association Practice Guidelines. Washington DC: APA, 1996
(Type I evidence- systematic review)
ii. Scott AIF. The efficacy of electroconvulsive therapy in the treatment of depressive illness in The management of depression. Oxford: Blackwell Science, in press.
http://users.ox.ac.uk/~mert0215/scott.htm.
These are expert statements of good practice supported by evidence within the reviews.
6.2.3c. All the published comparisons of antidepressant drug treatment versus electroconvulsive therapy (ECT) can be criticised because the upper doses allowed were less than recommended today, leading to the criticism that more drug treated patients would have recovered if the dosage had been adequate.
6.2.3d. Bilateral ECT with brief-pulse stimulation can be given twice a week without culminative cognitive impairment and can be recommended at an appropriate frequency in routine clinical practice. If a rapid response is required this can be increased to three times per week at least initially.
The evidence for statements 6.2.3c-6.2.3d is derived from:
i. American Psychiatric Association Practice Guidelines. Washington DC: APA, 1996
(Type I evidence- systematic review)
ii. Scott AIF. The Efficacy of Electroconvulsive Therapy in the Treatment of Depressive Illness in " The Management of Depression". Oxford: Blackwell Science, in press.
http://users.ox.ac.uk/~mert0215/scott.htm
These are expert statements of good practice supported by evidence within the reviews.
6.2.4 Psychotherapy for Major Depression. General statements.

6.2.4a. Studies that meet the most stringent criteria of methodological rigour confirm the efficacy of certain structured psychotherapies for depression. The best studies in the field demonstrate that interpersonal and cognitive behavioural therapies are effective in the treatment of depression. The competence of the therapist, patient characteristics and other non-specific factors are as important in determining the outcome of therapy as is the type of therapy.

The evidence for statements 6.2.4a - 6.2.5a is derived from:
i. Roth AD, Fonagy P. What works for whom? A critical review of psychotherapy research. New York: Guilford Press, 1996
ii. American Psychiatric Association Practice Guidelines. Washington DC: APA, 1996
iii. Agency for Health Care Policy and Research. Depression in primary care. Volumes I and II. Clinical Practice Guidelines No. 5. Rockville, Maryland: US Departments of Health and Human Services, 1993

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6.2.5 Treatment in the Acute Phase of Major Depression
6.2.5a. Patients with moderate to severe major depressive disorder are appropriately treated with medication, whether or not formal psychotherapy is also used. Medication is administered in dosages shown to alleviate symptoms. The specific medication of choice is based on side effect profiles, history of prior response, family history of response, type of depression, concurrent general medical or psychiatric illnesses, and concurrently prescribed medication. These are expert statements of good practice supported by evidence within the reviews.
6.2.5b Electroconvulsive Therapy (ECT) is a first line treatment option only for patients with more severe or psychotic forms of a major depressive disorder, those who have failed to respond to other therapies, those with a medical condition which precludes the use of medications, and those with an essential need for a rapid response.
6.2.5c. Switching to a new medication
is an option after an adequate trial of a first treatment. A general medical principle is that two drugs should not be combined where one is sufficient. Switching to a new medication is often preferred to augmentation of the first medication as an initial strategy.
6.2.5d. Augmentation of one drug with another is not advisable until the initial trial has been adequate in time and dosage.
The evidence for statements 6.2.5b - 6.2.5g is derived from:
i. Roth AD, Fonagy P. What works for whom? A critical review of psychotherapy research. New York: Guilford Press, 1996
ii. American Psychiatric Association Practice Guidelines. Washington DC: APA, 1996
iii. Agency for Health Care Policy and Research. Depression in primary care. Volumes I and II. Clinical Practice Guidelines No. 5. Rockville, Maryland: US Departments of Health and Human Services, 1993

These are expert statements of good practice supported by evidence within the reviews.

6.2.5e. There is no evidence that psychotherapy alone is effective for the acute treatment of patients with severe and/or psychotic major depressive disorders.
6.2.5f. Studies directly comparing medication to psychotherapy alone have generally found equal efficacy in the acute phase of treatment of mild to moderate depression. This does not mean however that the same patient will respond to both treatments. It is recommended therefore that, as with a medication trial, if psychotherapy is selected alone as the initial treatment, the treatment response must be carefully monitored. If the psychotherapy is completely ineffective by 6 weeks or has not produced near full remission by 12 weeks, a switch to medication may well be appropriate since there is clear evidence of its specific efficacy.
6.2.5g. Because psychotherapy alone has produced equivocal results in patients with melancholic symptom features, medication is recommended as the first line treatment in these patients.
The evidence for statements 6.2.5b - 6.2.5g is derived from:
i. Roth AD, Fonagy P. What works for whom? A critical review of psychotherapy research. New York: Guilford Press, 1996
ii. American Psychiatric Association Practice Guidelines. Washington DC: APA, 1996
iii. Agency for Health Care Policy and Research. Depression in primary care. Volumes I and II. Clinical Practice Guidelines No. 5. Rockville, Maryland: US Departments of Health and Human Services, 1993

These are expert statements of good practice supported by evidence within the reviews.

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6.2.6 Continuation and Maintenance Therapy for Major Depression
The objective of maintenance therapy is to decrease the likelihood of relapse (a return to the current episode of depression).
6.2.6a. Maintenance therapy should be considered in the following circumstances:
  • Three or more episodes of major depressive disorder; or
  • Two episodes of major depressive disorder and:
  • Family history of bipolar disorder
  • History of recurrence within 1 year of previously effective medication being discontinued
  • A family history of recurrent major depression
  • Early onset (before the age of 20) of the first episode
  • Both episodes were severe, sudden or life-threatening in the past 3 years
The evidence for statements 6.2.6a - 6.2.6c is derived from:
i. Roth AD, Fonagy P. What works for whom? A critical review of psychotherapy research. New York: Guilford Press, 1996
ii. American Psychiatric Association Practice Guidelines. Washington DC: APA, 1996
iii. Agency for Health Care Policy and Research. Depression in primary care. Volumes I and II. Clinical Practice Guidelines No. 5. Rockville, Maryland: US Departments of Health and Human Services, 1993

These are expert statements of good practice supported by evidence within the reviews.
6.2.6b. If the patient responds to acute phase medication it is generally continued at the same dose for 4 to 9 months after return to the clinically well state. It is important to inform the patient that symptoms may recur during continuation/maintenance therapy and that the practitioner should be informed of them.  
6.2.6c. More research needs to be done on the role of psychotherapy in continuation and maintenance therapy.  

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Health Evidence Bulletins: Wales, Duthie Library, UWCM, Cardiff CF14 4XN. e-mail: weightmanal@cardiff.ac.uk