Treatment resistant depression in primary care by Dr Tim Cantopher

Dr Tim Cantopher, Consultant Psychiatrist at the Priory Hospital Woking discusses the next step for GPs when patients fail to respond effectively to the first line of treatment with an antidepressant.

According to the Royal College of Psychiatrists, between one in three and one in five patients will present to their GP with a depressive illness. Between 50% and 65%* of these patients will go on to benefit from antidepressant medication prescribed by their doctor.

Clearly however, this leaves a substantial minority of patients within primary care who do not benefit from any remission of symptoms at all. Treating non-responders, and those whose depression remains undiagnosed whilst presenting with somatic symptoms, is one of the biggest challenges facing GPs.

Analysing why the patient hasn’t responded to the first line of medication should be undertaken before changing antidepressant:

  • Does the patient have a depressive illness or are they just unhappy?
  • Is the patient taking their medication regularly? If not, why not? Often, patients have misconceptions about antidepressants which can cause ambivalence or reticence in taking the prescribed course of treatment. Dispelling misconceptions is often enough to enable patients to comply with treatment
  • Does the dosage need to be increased? Often patients with an acute mental illness attempt to “soldier on” without taking sufficient rest. Explain that this is counter-productive to recovery
  • Do family members thwart recovery by making excessive demands on the patient? A brief explanation of the condition to the family member can make a difference in this case

If the patient is reluctant to continue with their medication due to unacceptable side effects, it may be worth changing to an antidepressant with a different side effect profile. However, if an antidepressant isn’t working but is well tolerated, try a higher dose. Following recent guidelines, paroxetine should not be used above 20mg daily, and citalopram should not be used about 40mg daily for depression, owing to reports of occasional arrhythmias at higher doses.
 
If there is no response within four to six weeks, then the antidepressant will probably not work; if there is a partial response, it is worth waiting another four to six weeks to see whether an adequate response will follow.

Most authorities suggest that switching to an antidepressant with a different mode of action is often associated with a better response, so if an SSRI isn’t working, try a noradrenalin drug like reboxetine or a drug acting on both serotonin and noradrenalin systems like venafaxine. Because SSRIs are structurally diverse, switching from one SSRI to another might also be successful. Whenever a drug is switched, it is important to monitor the patient for drug interactions or other adverse effects, particularly if the half-life of the first agent is quite long (for example fluoxetine).

How quickly to withdraw the first drug and to substitute the second is always a difficult judgement, but it’s usually best undertaken over two or three weeks to minimise side effects whilst allowing the new agent to begin as soon as possible.  

It is also important to warn the patient that the transition period can be difficult through the quadruple whammy: a patient may get some withdrawal symptoms from the first antidepressant, lost its therapeutic action, have maximal side effects from the new drug and wait some time before this drug works. Patients will usually tolerate this if they are warned of the difficulties and reassured that they are likely to disappear.

Combining two or more antidepressants isn’t recommended in primary care – this can obscure monotherapy evaluation and lead to significant adverse effects or drug-drug interactions. 

When to refer

Most patients will respond to antidepressant treatment and appropriate counselling in a primary care setting. Those who do not are worth referring to a consultant psychiatrist. 
*Source: Royal College of Psychiatrists

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