Antidepressants

Benefits:

• 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,^178,179 noting that:
  • the licensed indication is diabetic neuropathic pain
  • other guidelines consider it appropriate to try/consider unlicensed use in non-specific and neuropathic symptoms in lower back pain and fibromyalgia

Risks:

• Suicidality with increased risk of suicidal thoughts and acts, particularly in adolescents and young adults 18–21 years¹⁸⁰
• 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 over when initiating antidepressant treatment¹⁸⁰

Evidence for effectiveness and risks

Medication which potentiates noradrenaline and serotonin noradrenergic mechanisms, serotonin norepinephrine reuptake inhibitors (SNRI), has some evidence in neuropathic pain. The evidence is not conclusive for or against the use of tricyclic antidepressants (TCA) in chronic pain. Selective serotonin reuptake inhibitors (SSRI) have no high-quality evidence to support their use in the management of chronic pain.

Duloxetine

• 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,^{155,178,179,188} noting that
  • the licensed indication is diabetic neuropathic pain
  • 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, and discontinue if there is no improvement in pain relief, physical function or subjective improvement after eight weeks. It is good practice to gradually reduce
• Do not prescribe to those with uncontrolled hypertension and monitor blood pressure in individuals with hypertension or other cardiac disease¹⁸⁹

Numbers needed to treat and harm for duloxetine

Tricyclic antidepressants (TCA)

• SIGN 2025 evidence review is not conclusive for or against the use of TCAs in chronic pain¹⁷⁸
• 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^185,188
• Taking TCA at evening mealtime rather than bedtime might address the problem of people being unable to initiate sleep and reduce fatigue the following morning¹⁸⁸
• 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 effects¹⁵⁷
• TCAs should be used with caution in the older adult or frailty due to anticholinergic effects and risk of falls²
• TCAs should not be used for the treatment of low back pain^157,188,190

SSRIs

• 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 unlicensed¹⁵⁵
• There are potentially serious side effects of prescribing tramadol with an SSRI, such as serotonin syndrome

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.

Concomitant depression:

Optimise antidepressant medication where possible in those with concomitant chronic pain and depression, rather than prescribe additional antidepressant medication.¹⁵⁷ 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.

• QTc prolongation
• Serotonin syndrome
• Increased anticholinergic burden, particularly TCAs
• Suicide risk (at initiation and cessation)
• Inhibition of cytochrome enzymes – pharmacokinetic interactions

• Antidepressant reduction should be gradual, over a period of no less than two weeks. Guidance for reducing, stopping and switching specific antidepressant medicines can be found in Quality prescribing for antidepressants: guide for improvement 2024 to 2027 or the Maudsley Prescribing Guidelines.¹⁸⁰
• All antidepressants have the potential to cause withdrawal phenomena when taken continuously for six weeks or longer.
• Antidepressants should not be stopped abruptly unless a serious adverse event has occurred (e.g. cardiac arrhythmia with a TCA).
• Discontinuation symptoms may occur, especially in drugs with a short half-life even if the individual misses a dose e.g. an antidepressant with potent anticholinergic adverse effects may be associated with diarrhoea on discontinuation.

Specific areas/situations where medication may need to be introduced or increased

If treatment is reviewed and the patient has noticed an improvement in their quality of life, pain, sleep or psychological distress since the antidepressant was initiated, then a joint decision with the individual should be made whether a further increase is needed. Always ensure ongoing review is in place to determine the benefits of any changes made.

Before starting or continuing treatment with an antidepressant, ensure that all suitable management options, including non-pharmacological approaches and watchful waiting, have been discussed with and offered to the person. Explain and discuss the risk of dependence and the factors that may increase this risk.

Consider delaying prescribing if the person needs more time to think about their options or the prescriber needs to consult with other members of the healthcare team. If prescribing is delayed, ensure that a follow-up appointment and timeframe is agreed and arranged.