Depression is a common condition. In most cases, patients recover fully, although a minority endure resistant, chronic or even progressivedisease.
Treatment resistance raises a number of key questions - is the diagnosis right, is there an underlying, hitherto missed physical cause, such as hypercalcaemia, hypothyroidism or dementia? Patient-related factors need to be evaluated, for example, is the patient adhering to any drugs prescribed, or are there social factors that require resolution?
In cases of medication treatment failure, the question is whether the choice and dose of antidepressant(s) is correct.
It is accepted that the more severe the depression, the greater the benefit from antidepressants. Of those with at least moderate disease, about a fifth of patients improve without specific treatment. According to the Maudsley guidelines, about 30% will respond to placebo.1
Once depression has been diagnosed, understanding the patient's views concerning drug treatment is integral to success.
Even if drug therapy is indicated (see box below), it is important to recognise that patients may be unwilling to adopt a medication strategy.
Prescribing in these cases can be counterproductive.
|Indications for drug therapy in depression3|
Note: Referral should be considered for high-risk patients or those with psychotic depression.
Choice of antidepressant
Although there is no evidence that any particular antidepressant lends itself better to one subtype of depression than another, the side-effect profiles and withdrawal effects differ and may influence the choice of drug.
This may explain why citalopram is often considered by some psychiatrists to be useful in depression with anxiety, whereas fluoxetine is useful for more retarded depression.
In many cases, the choice is influenced by previously tried and tested regimens unique to the patient. For antidepressant-naive patients, SSRIs are considered first line, while in those without comorbidities, a meta-analysis suggested sertraline offers the most favourable efficacy.2
In older patients, however, sertraline may cause intolerable side-effects, including postural hypotension, in which case, citalopram or mirtazapine is advised. SSRIs are sometimes prescribed with a short course of a benzodiazepine to mitigate against paradoxical increases in agitation.
While fluoxetine is considered a first-line drug option in pregnancy, withdrawal in the third trimester should be considered.
If medication is required postpartum, sertraline may be used during lactation. Note that of the SSRIs, fluoxetine and paroxetine are more likely to interact with other drugs, whereas sertraline and citalopram are least likely. Sertraline is also the drug of choice in patients post MI.
Paroxetine may also be used in liver disease, whereas fluoxetine and lofepramine should be avoided. Sertraline would be more favoured in patients with kidney disease. Fluoxetine, lofepramine and venlafaxine should be avoided.
Several drugs increase the risk of torsades de pointes and a baseline ECG should be obtained. Mirtazapine is considered safer in patients also prescribed NSAIDs or anticoagulants, although the INR may increase slightly and requires monitoring.
NICE considered mirtazapine the most cost-effective drug option in moderate to severe depression.3
Once a successful regimen has been established, treatment should continue for at least six months, unless the patient has had two or more previous episodes of depression, in which case, two years' duration will reduce the risk of relapse.1,3
Options in treatment failure
There are several reasons for treatment failure, including misdiagnosis, inadequate dosing or poor adherence. In adherent patients with no improvement after three to four weeks of medication, the drug is unlikely to have an effect. Dose increases should be considered according to the SPC.
The Maudsley prescribing guidelines comment that antidepressants may be increased if there has been no effect after two weeks and that it is a myth that the antidepressant effect should not be expected for at least two to four weeks of treatment.
Refractory depression may require combination antidepressants or augmentation strategies, such as adding lithium or new generation antipsychotics, such as olanzapine, risperidone or quetiapine. These strategies are not advised without discussion with a consultant psychiatrist.3
- Dr Thakkar is a GP in Wooburn Green, Buckinghamshire
- Taylor D, Paton C, Kapur S (eds). The Maudsley Prescribing Guidelines in Psychiatry (11th edition). London, Wiley-Blackwell, 2012.
- Cipriani A, Furukawa TA, Salanti G et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet 2009; 373(9665): 746-58.
- NICE. Depression in adults: the treatment and management of depression in adults. CG90. London, NICE, October 2009. www.nice.org.uk/guidance/CG90