Why is proactively reviewing antidepressants important?

In Scotland, as with other Westernised societies, antidepressant prescribing has increased over the last 30 years and continues to increase,¹ with one in five adults receiving one or more antidepressant prescriptions in a year, and more than half of those (six in ten adults) receiving long-term (≥2 years) treatment (See the chart below).¹

This has been due to:

• the availability of different antidepressants,^24,25 some of which are better tolerated and safer than others^26,27
• people’s expectations^28,29 and changes in society’s attitudes towards mental health conditions³⁰
• greater willingness to prescribe for a variety of mental health and non-mental health conditions^31-33
• increased long-term use,² and use of higher doses^17,34
• lack of regular medicine reviews^5,35
• more people receiving antidepressant therapy¹

Adults (≥18 years old) prescribed all long-term (≥2 years) antidepressants as a proportion of adults in receipt of antidepressant medications, by NHS board

While the majority of antidepressants are prescribed for the treatment of ‘common mental health conditions’ such as depression and anxiety disorders, they are usually only one aspect of a complex multidimensional treatment plan to care for and support people to achieve recovery.^20,36  The lack of regular review reduces the opportunity to advise the use of non-pharmacological approaches that may aid in recovery and can lead to inappropriate long-term antidepressant use.^5,19,36-38

Long-term antidepressant use is associated with the use of higher antidepressant doses (See the chart below), and while this may be appropriate for some antidepressants, it can be inappropriate for others. For example:

• Selective serotonin re-uptake inhibitors (SSRIs) demonstrate a flat dose response curve for the treatment of depression. 
  • standard daily doses: 20mg citalopram/fluoxetine/paroxetine, 50mg daily of sertraline or 10mg escitalopram provide optimal antidepressant effectiveness – ‘20’s plenty and 50’s enough^20,39-42
  • as individuals may not be proactively reviewed when stable and well, presenting only at times of crisis, this may lead to doses being inappropriately increased in response to the crisis⁵ 
  • for SSRIs, higher than standard doses are known to cause more adverse effects and avoidable harms (i.e. anxiety, insomnia, falls, etc) and are possibly associated with more withdrawal effects.2^20,39-43 Higher than standard doses are not more effective at reducing depressive symptoms in poor and/or non-responders^41-42,44-46
• Mirtazapine also demonstrates optimal effects for the treatment of depression at 30mg daily⁴⁰
  • however, its use is associated with 5-7 kg weight gain^47-48
  • lower doses (15mg daily) are more sedating⁴⁹
• Tricyclics antidepressants (TCAs) demonstrate a dose response for the treatment of depression where higher doses can be more effective e.g. increasing to 100mg to 125mg per day.^18,20,39
  • doses as low as 10mg daily can be effective for the treatment of neuropathic pain, while 50mg to 75mg daily provide optimal effects for the majority of people with neuropathic pain^33,50
  • higher doses are known to cause more adverse drug effects and avoidable harms such as sedation, confusion and QTc prolongation, amongst others⁵¹

Note: QTc prolongation: QTc prolongation is of concern as it is associated with ventricular tachycardia and sudden cardiac death. The QT interval on an electrocardiogram describes the manifestation of ventricular depolarization and repolarization. The QT interval is influenced by heart rate therefore the QT interval should be measured for rate correction, allowing the calculation of the corrected QT interval (QTc). Intervals of 440 to 460 milliseconds in men and 440 to 470 milliseconds in women are considered to be at the top limit of normal range. Bazett’s formula is considered the gold standard for QTc calculation. QTc prolongation is associated with ventricular tachycardia and sudden cardiac death.⁵⁰

• Serotonin and noradrenaline re-uptake inhibitors (SNRIs) demonstrate a dose response effect for the treatment of depression where higher doses can be more effective.^{39,40,49,52-54}
  • For example, venlafaxine exhibits predominantly serotonin ceiling effects at doses <150mg daily, with noradrenaline (>150mg daily), and dopamine (>225mg daily) effects becoming more significant as doses are increased.^49-52
  • Duloxetine demonstrates similar effects.^53,54 Higher doses are known to cause more adverse drug effects and avoidable harms including insomnia, weight loss and sexual dysfunction.^40,55,56

While in certain conditions it may be appropriate to increase the antidepressant dose, prescribers should always consider limitations of medications and the risks associated with the use of higher doses of medicines. Proactive review of individuals when their condition is stable creates an opportunity to review the need for continued antidepressant treatment regardless of the indication to reduce inappropriate or ineffective antidepressant use.

The chart below shows higher daily doses for individuals on long-term antidepressants (equal to or more than two years), in comparison to those who are on short-term (less than two years) antidepressant therapy.

Average defined daily doses (DDDs) per person per day for adults (≥18 years old) prescribed an antidepressant long-term (≥2 years) or short-term (<2 years), by NHS board for 2023/24

All antidepressant classes are included. Note TCAs are more commonly prescribed for the treatment of neuropathic pain (e.g. amitriptyline 10mg to 50mg daily, equating to 0.13 to 0.67 DDD) rather than depression (100 to 150mg daily, equating to 1.3 to 2.0 DDD). The majority of SSRIs however, are prescribed for the treatment of depression (e.g. citalopram 20mg to 40mg daily, equating to 1.0 to 2.0 DDD).⁵⁷