From Dr V S Green:

With yet another recent large study confirming that antidepressants/SSRIs appear to work largely by the 'placebo' effect, one wonders about the experiences of many prescribers in that patients do often seem to improve whilst taking these albeit in the medium to long term. I wondered whether the authors or other readers had an views on this subject? In particular what options do prescribers have now for mild/moderate depression?

The reason for the delay between the start of treatment with SSRIs and a discernible clinical effect remains a mystery.

In humans, antidepressants, e.g. fluoxetine, citalopram and duloxetine, are generally believed to increase concentration of the monoamines such as serotonin and norepinephrine, thus correcting an as-yet unexplained chemical deficiency, said to be the ‘cause’ of depression.

But, even though the synaptic monoamines increase within hours of the first dose, the regulatory effect is complete within a few days, and side-effects often develop within a week, clinically effective results still usually require two to five weeks to develop.

Supposing the drugs actually work (and, this is open to debate), the delay may be the result of architectural changes taking place in the brain.

Research with rodents by John Hopkins University School of Medicine neuropathologist Vassilis E. Koliastsos suggests that the SSRIs somehow increase the density of the nerve-impulse carrying axons in key parts of the brain¹. These have been identified as the parietal lobes of the neocortex and parts of the limbic brain associated with a number of autonomic functions, including the sense of smell, emotions and motivation.

If the same phenomenon occurrs in humans, the SSRis could be ‘rewiring’ areas of the brain important for thinking and feeling, as well as certain functions of the autonomic nervous system.

We would approach this explanation with caution, not least because the same delay was noted with an entirely different class of antidepressants, the monoamine oxidase (MAO) inhibitors.

Other, non-pharmacological, factors may be at work. These could include the natural history of the illness. Most cases of depression are self-limiting. The fact that patient has sought help may heighten responsiveness (the ‘Waiting Room Effect’).

Information packaged with the drug, as well as the physician’s warning that results should not be expected immediately, may act as an injunction. How susceptible is the patient to what amounts to a hypnotic command (‘don’t feel good … yet?).

We also speculate that the ritual of being listened to and having the structure of regular pill-taking imposed may function as a kind of Ericksonian tasking.

Whatever the reason, though, we feel any undue delay is unacceptable and find it can be substantially reduced (with or without drugs) by regarding ‘depression’ as a process rather than a pathology. This allows the practitioner to explore the structure and reorganise it according to one or other of the approaches referred to in Magic in Practice.

Whatever treatment is selected, we urge practitioners to ensure balance in four areas of the patient’s life: daily structure, diet, exercise and social relations. Even healthy people can be plunged into depression if these needs are unmet.

Shortage of space prevents us from going into specific treatments at any length, but you will find much more specific advice about this in the book and on our various training courses.

GT