Evidence context

Evidence context

The use of antidepressants in adults with depression or generalised anxiety disorder (GAD) has been addressed by the NICE guidelines on depression in adults (which is being updated; publication expected May 2017), depression in adults with a chronic physical health problem and GAD and panic disorder in adults. The NICE guideline on common mental health disorders brings these recommendations together and can be used to help clinicians, commissioners and managers develop effective local care pathways for such people.

See the NICE Clinical Knowledge Summaries on depression and GAD for general overviews of these conditions. The NICE pathways on depression and GAD bring together all related NICE guidance and associated products on antidepressants in a set of interactive topic‑based diagrams. See also specific NICE guidelines on antenatal and postnatal mental health, depression in children and young people (recommendations on psychological therapies and antidepressants were updated in March 2015) and social anxiety disorder. The NICE quality standards on depression in adults, depression in children and young people, and anxiety disorders describe concise sets of prioritised statements designed to drive measurable quality improvements within these areas.

NICE advocates a stepwise approach to managing common mental health disorders. It recommends offering, or referring people for, the least intrusive and most effective intervention first. Therefore, non‑drug interventions (such as cognitive behavioural therapy [CBT]) should be the mainstay of treatment for many people with depression or GAD, with drugs generally reserved for more severe illness or when symptoms have failed to respond to non‑drug interventions.

Prescribing data suggest that there is variation in antidepressant prescribing across localities. In view of the NICE guideline on common mental health disorders, a review of local antidepressant prescribing is advised. This should be considered alongside the local availability of non‑drug treatments, such as CBT.

If an antidepressant is indicated for an adult with depression, the NICE guideline on depression in adults recommends that it should normally be a selective serotonin reuptake inhibitor (SSRI) in generic form. SSRIs are equally effective as other antidepressants and have a favourable risk–benefit ratio. Similarly, if drug treatment is indicated for GAD, and an adult chooses to take medication, the NICE guideline on GAD in adults recommends offering an SSRI with sertraline as the first‑line option because it is the most cost‑effective drug for this condition. However, prescribers should note that sertraline does not currently have a UK marketing authorisation for GAD, so prescribing would be off‑label[1]. The NICE guideline on depression in adults recommends that dosulepin should not be prescribed for adults with depression because evidence supporting its tolerability relative to other antidepressants is outweighed by the increased cardiac risk and toxicity in overdose.

The full guideline on depression in adults concluded that antidepressants have largely equal efficacy and that choice should mainly depend on side‑effect profile, people's preference and previous experience of treatments, propensity to cause discontinuation symptoms, safety in overdose, interactions and cost. However, a generic SSRI is recommended as first‑choice because SSRIs have a favourable risk–benefit ratio. Neither escitalopram nor any of the available 'dual action' antidepressants, such as venlafaxine and duloxetine, were judged to have any clinically important advantages over other antidepressants. Results from meta‑analyses (Gartlehner et al. 2011 and 3 Cochrane reviews: Cipriani et al. 2012, CD006534, Cipriani et al. 2012, CD006533 and Purgato et al. 2014, CD006531) have provided no evidence to depart from NICE guidance when selecting antidepressants for people with depression.

The full guideline on GAD and panic disorder in adults found that of the antidepressants available, there were sufficient clinical‑effectiveness data and an acceptable harm‑to‑benefit ratio for escitalopram, duloxetine, paroxetine, sertraline and venlafaxine XL. However, the economic analysis concluded that sertraline was the most cost‑effective drug for people with GAD because it was associated with the highest number of quality‑adjusted life years (QALYs) gained and the lowest total costs among all treatments assessed, including no treatment. As with depression, drug choice in GAD should also be influenced by several other factors relating to the individual person, including their previous experience of treatments, likely drug interactions, safety and tolerability.

Drug safety warnings on antidepressants that have been issued by the MHRA should be considered. The MHRA has issued guidance on the use and side effects of SSRIs and serotonin and noradrenaline reuptake inhibitors (SNRIs), their safety, use in pregnancy and the risk of suicidal behaviour (published December 2014). See the December 2007 edition of Drug Safety Update for information on measures to reduce risk of fatal overdose with dosulepin and the December 2011 edition of Drug Safety Update for details about the association of dose‑dependent QT interval prolongation with citalopram and escitalopram. In addition, the November 2014 edition of Drug Safety Update issued a reminder to test liver function before and during treatment with agomelatine.

Concerns have been raised regarding the over‑use of psychotropic medicines such as antipsychotics and antidepressants in people with learning disabilities. This is addressed in 3 reports published in 2015 by the Care Quality Commission, Public Health England and NHS Improving Quality.



[1] In line with the guidance from the General Medical Council (GMC), it is the responsibility of the prescriber to determine the clinical need of the patient and the suitability of using a medicine outside its authorised indications. Informed consent should be obtained and documented.