Common Mental Disorders Depression - New Zealand Doctor

Chapter 6 Management of depression in adults/pakeke
generation antidepressants in comparative effectiveness in adults. These trials did
not support the selection of one second-generation antidepressant over another
for specific symptoms such as anxiety, melancholia, psychomotor change, pain,
somatisation, fatigue or loss of energy. For these symptoms evidence was either
inconclusive, insufficient or absent.
The AHRQ review found that remission rates were low: over 50% of patients treated
with second-generation antidepressants as first-line treatment did not achieve remission,
the goal of depression treatment, and almost 40% percent failed to respond. There was
insufficient evidence to determine patient factors that could reliably predict response
or non-response to an individual drug. 351 Although limited evidence indicated that
second-generation antidepressants were similar in efficacy for treating patients who had
failed to respond to a first-line agent, a substantial proportion of these patients did not
achieve response or remission with second-line treatment. The reviewers suggested that
combined pharmacological and psychological treatment is indicated for patients who do
not respond to first- or second-line treatment. 351
There is strong evidence of publication bias among trials of antidepressants, and
meta-analyses that included unpublished data 416,417 have shown a smaller benefit for
antidepressants relative to placebo. The most recent publication was a meta-analysis
of 35 studies of efficacy trials of fluoxetine, venlafaxine, nefazodone and paroxetine
by Kirsch and colleagues. 417 The authors utilised data that had been submitted to the
US Food and Drug Administration by drug companies when applying for permission
to market the drugs; the companies are required to submit all relevant data. The mean
standardised difference in effect size between antidepressant and placebo was 0.32,
which falls below the NICE criteria for clinical significance (0.50). 417 However,
antidepressants did exceed this criterion among patients with very severe depression.
A systematic review of the long-term treatment of depression with antidepressants found
some evidence to support the effectiveness of augmenting SSRIs (ie, adding a second
antidepressant) in patients who had little or no response to acute phase therapy. 354
However, there was little empirical support for other strategies, such as dosage increase
or switching to a different class of antidepressants, though evidence was limited.
Continuation of the same antidepressant at the same dose induced remission in a
substantial minority of patients even if they did not show remission at the end of the
acute-phase treatment. The same review found strong evidence that such long-term
antidepressant treatment reduced the risk of relapse in patients who achieved remission
on acute-phase therapy. Over 1–3 year follow-up periods, the average rate of relapse
on placebo was 41%, compared with 18% on active treatment. The benefit of ongoing
antidepressant treatment (in reducing the risk of relapse) did not diminish regardless
of the length of follow-up in the studies included, up to 36 months. 354
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