Antidepressants | Right Decisions

Summary of recommendations: antidepressants

Conditional recommendation

A trial of duloxetine 60mg may be considered in people with chronic primary pain (including fibromyalgia, neuropathic pain and musculoskeletal) which is not adequately managed by analgesics^81,82 noting that

the licensed indication is diabetic neuropathic pain
side-effects can be reduced by starting at lower dose of 30mg
other guidelines consider it appropriate to try/consider unlicensed use in non-specific and neuropathic symptoms in lower back pain and fibromyalgia

Good practice point

Review effectiveness of duloxetine after four weeks and discontinue if there is no improvement in pain relief, physical function or subjective improvement. It is good practice to reduce gradually

Good practice point

SIGN 2025 evidence review is not conclusive for or against the use of TCAs in chronic pain.⁸¹

Other guidelines do consider the use of TCAs in chronic neuropathic pain, and clinicians should consider each person and their individual circumstances and chronic pain experience

Good practice point

TCAs should not be used for the treatment of lower back pain

Good practice point

There is no high-quality evidence to support the use of other antidepressants (such as fluoxetine, paroxetine and citalopram) in the management of chronic pain. Historically they have had a place in management, although unlicensed

Good practice point

Optimise antidepressant medication where possible in those with concomitant chronic pain and depression, rather than prescribe additional antidepressant medication

Indications and effectiveness

Recent SIGN evidence review only notes evidence for duloxetine^81,82, as the small study sizes for other antidepressants do not provide sufficient evidence to make an analysis of the outcomes. A lack of unbiased, high-quality evidence does not necessarily indicate evidence of no benefit.

Duloxetine

Clinicians may consider a trial of duloxetine 60mg in people with chronic primary pain (including fibromyalgia, neuropathic pain and musculoskeletal) which is not adequately managed by analgesics,¹⁸^,⁸¹^,⁸²^,83 noting that:
- the licensed indication is diabetic neuropathic pain⁸¹^,⁸²
- other guidelines consider it appropriate to try/consider unlicensed use in non-specific and neuropathic symptoms in lower back pain and fibromyalgia
To minimise the risk of side effects, especially nausea, it is good practice to start duloxetine at a lower dose of 30mg daily for two to four weeks before increasing to 60mg
Review effectiveness and tolerability of duloxetine at four weeks. Discontinue duloxetine if there is no improvement in pain relief, physical function or subjective improvement after eight weeks. It is good practice to gradually reduce
Monitor blood pressure in individuals with hypertension or other cardiac disease
Do not prescribe to those with uncontrolled hypertension

NNT/ NNH for use of antidepressants in chronic pain

Medication	Indication	NNT	NNH⁸¹
Duloxetine (50% pain intensity reduction with 60mg daily)	Chronic primary pain	7.1	7

Tricyclic antidepressants (TCA)

Recent evidence review is not conclusive for or against the use of TCAs in chronic pain⁸¹
Other guidelines do consider the use of TCAs in chronic neuropathic pain, and clinicians should consider each person and their individual circumstances and chronic pain experience¹⁸^,⁷¹^,⁸³
Taking TCAs at evening mealtime rather than bedtime might address the problem of people being unable to initiate sleep and reduce fatigue the following morning²³
Due to risk of side effects, especially sedation, it is good practice to start amitriptyline at a lower dose of 10mg daily and an alternative TCA could be considered to reduce side effects
TCAs should be used with caution in the older adult or in frailty due to anticholinergic effects and risk of falls⁸⁴
TCAs should not be used for the treatment of lower back pain⁸³^,85

Selective Serotonin Reuptake Inhibitors (SSRI)

There is no high-quality evidence to support the use of other antidepressants (such as fluoxetine, paroxetine and citalopram) in the management of chronic pain. Historically they have been used, although unlicensed18
There are potentially serious side effects of prescribing tramadol with an SSRI, such as serotonin syndrome

Concomitant depression

Optimise antidepressant medication where possible in those with concomitant chronic pain and depression, rather than prescribe additional antidepressant medication⁸⁶. Combinations (e.g. SSRI with mirtazapine or trazodone, or SSRI and TCA) should be considered carefully (see Quality prescribing for antidepressants: a guide for improvement 2024 to 2027) to mitigate against the risk of adverse drug effects and should prompt consideration for specialist review.

Antidepressant good practice points

When an antidepressant is used to manage chronic pain, the individual should understand that these medicines may help with quality of life, pain, sleep, psychological distress, even in the absence of a diagnosis of depression.

Risks and harms

Suicidality with increased risk of suicidal thoughts and acts, particularly in adolescents and young adults 18–21 years⁸⁷
- Suicide and self-harm rates tend to be higher when antidepressants are started or stopped
- Individuals should be warned of this potential adverse effect during the early weeks of treatment and know how to seek help if required
- Switching antidepressants may be a marker of increased risk of suicidal behaviours in those aged 75 years and over⁸⁷
QT prolongation
Serotonin syndrome
Increased anticholinergic burden, particularly TCAs
Inhibition of cytochrome enzymes – pharmacokinetic interactions