Antidepressants: when should switching or dose increases be considered?

Dear Professor Chew-Graham,

Regarding your article, ‘NICE has modified its stepped-care model for treating depression’, which appeared in the December 2009 issue of Guidelines in Practice, I have a query on the use of antidepressants. In your article you state that:

‘If on review at 2–4 weeks, improvement has not occurred to the satisfaction of the patient, the GP needs to check side-effects and concordance with medication and encourage the patient to persevere with treatment. If after 6–8 weeks, no improvement has occurred, the GP may have discussions with the patient on changing the antidepressant.’

However the NICE recommendations from the quick reference guide state:

‘If response is absent or minimal after 3–4 weeks of treatment with a therapeutic dose of an antidepressant, increase support and consider increasing the dose…or switching to another antidepressant… .’

Please clarify when healthcare professionals should consider switching or increasing the dose of antidepressants.

Yours sincerely,

Dr Steven Haigh
GP, West Calder

Dear Dr Haigh,

You are quite correct on querying the point made about when to consider switching an antidepressant. The full NICE guideline on depression states that: ‘If there is no, or barely detectable improvement at 2 weeks patients should be followed weekly and consideration given to changing treatment at 3–4 weeks. Patients who are improving should have their improvement monitored and if there has been insufficient response at 6 weeks in the absence of a continuing trajectory of improvement consideration given to changing treatment at that stage.’¹

The issue of switching antidepressants is a complex one and the evidence evolving. Received wisdom has been that antidepressants have a delayed onset of action and that it takes 2–4 weeks for them to begin to work. This is now recognised as incorrect and it has been shown from clinical trial data that improvement can show immediately, with the greatest degree of improvement occurring in the first week and the curve beginning to flatten off thereafter with a smaller degree of improvement as time goes on. It is, however, important to recognise that although the curve flattens, some people continue to improve after this period. Also, the assessment of the literature is influenced by the duration of follow up, and in some studies (with longer follow up) some patients continue to respond at 12 weeks and beyond. The rate and degree of improvement also appears
to be influenced by the frequency of follow up.

These studies emphasise the importance of the early stages of treatment in response to antidepressants and highlight the role of frequency of monitoring.

Thus, issues are raised when considering the optimum time to change treatment:

• Switching treatment too early could lead to rejection of an effective treatment–this will be unhelpful in the long run when future treatment options are considered, and could lead to a merry-go-round of treatment changes
• Increasing the dose too early could lead to patients being unnecessarily maintained on higher-than-needed doses of antidepressant over a prolonged period of time with an associated increase in side-effects or treatment discontinuation
• Delaying treatment change too long could prolong the period of depression if the patient is not responding to the current drug/dose, leading to patient loss of faith in treatment, and an increase in depression-related morbidity and even mortality.

Balanced against this is the evidence of similar levels of effectiveness across the antidepressants; that is, they show no robust clinically important superiority in terms of effectiveness. The overall conclusion is that antidepressants have largely equal efficacy and that choice should mainly depend on side-effect profile, patient preference and their previous experience of treatments, propensity to cause discontinuation symptoms, and safety in overdose. As Pilling et al (2009) state: ‘Be aware that the evidence for the relative advantage of switching within or between classes is weak.’²

So, considering this evidence, the full NICE guideline on depression contains the recommendations listed overleaf.

‘If response is absent or minimal after 3 to 4 weeks of treatment with a therapeutic dose of an antidepressant, increase the level of support (for example, by weekly face-to-face or telephone contact) and consider:

• increasing the dose in line with the summary of product characteristics if there are no significant side-effects or
• switching to another antidepressant (as described in chapter 12) if there are side-effects or if the person prefers.¹

‘If the person’s depression shows some improvement by 4 weeks, continue treatment for another 2 to 4 weeks. Consider switching to another antidepressant as described in chapter 12 if:

• response is still not adequate or
• there are side-effects or
• the person prefers to change treatment.’¹

The summary statement in my article, I agree, could be misleading and perhaps reflects my own reluctance to switch antidepressants as the first option when faced with a patient who shows little improvement early on. It is my view that GPs need to move away from the opinion that the prescription of an antidepressant alone is the solution for patients with depression; hence the statement in Table 1 of my recent article, ‘Understand that regular follow-up, monitoring, and support are vital.’³ Evidence from clinical trials, qualitative studies, and from the stakeholder contributions published in the full NICE guideline show that regular contact with the GP and referral for psychological therapies/psychosocial support are valued by patients with depression. There is a danger of focusing on antidepressant treatments and discussion of switching, possibly leading to the ‘merry-go-round of treatment changes’,¹ at the expense of the GP offering regular follow up and support, and advice and referral to voluntary or statutory services for further psychosocial support.

Yours sincerely,

Professor Carolyn Chew-Graham

Professor of Primary Care,
University of Manchester

GP, Manchester

Member of NICE Guideline Development Group

References

1. National Collaborating Centre for Mental Health. Depression: the treatment and management of depression in adults. Clinical Guideline 90. London: NICE, 2009. Available at: guidance.nice.org.uk/CG90
2. Pilling S, Anderson I, Goldberg D et al. Depression in adults, including those with a chronic physical health problem: summary of NICE guidance. BMJ 2009; 339: b4108.
3. Chew-Graham C. NICE has modified its stepped-care model for treating depression. Guidelines in Practice 2009; 12 (12): 11–20.