Gastrointestinal (GI) bleeding concomitant use of non-steroidal anti-inflammatory drugs and selective serotonin re-uptake inhibitors

This hot topic considers the impact of prescribing a non-steroidal anti-inflammatory drug (NSAID) and a selective serotonin re-uptake inhibitor (SSRI) at the same time and the increased risk of GI bleeding if these are taken together.^{227,275,276,277}

Although not considered an essential medicine, stopping an SSRI antidepressant abruptly can cause discontinuation/withdrawal symptoms, such as dizziness/drowsiness, insomnia, irritability, headache, nausea and vomiting.

Pain and joint pain are the most common reason why NSAIDs may be prescribed.

SSRIs are mainly used for the management of anxiety and depression. Pharmacological and non-pharmacological approaches should be considered after diagnosis. Treatment should be reviewed regularly for effectiveness in the management of symptoms of both the pharmacological treatment and the psychological therapy.

Selective serotonin re-uptake inhibitors

The effectiveness of SSRIs needs to be reviewed (after one to two weeks, maximum four weeks) and switched to an alternative if this is not effective, rather than increasing the dose. The augmentation with non-pharmacological approaches should be considered.

Non-steroidal anti-inflammatory drugs

Joint pain is the most frequently cited reason for prescribing NSAIDs to those taking an SSRI. Before prescribing an NSAID for joint pain consider if an alternative option would be more appropriate. For example:

• exercise and physical activity can also contribute to a reduced need for medicines in osteoarthritis. This can also improve mood and well-being
• for patients with osteoarthritis the first-line medicines are paracetamol and/or topical analgesia, e.g. diclofenac and ibuprofen gels/sprays or capsaicin cream
• intra-articular injections of corticosteroids can be a useful alternative to oral NSAIDs for osteoarthritic flares in some patients
• a weak opioid, such as codeine, may be required for some patients if pain is ongoing or severe, for short-term use and with regular review
• for those with acute gout, colchicine may be considered. If colchicine not tolerated, corticosteroids (off-label) may be an alternative treatment option.²⁷⁸

Where possible, the NSAID should be stopped. If an NSAID is essential, then the shortest possible course at the lowest effective dose should be used. GI protection with a proton pump inhibitor (PPI) may need to be considered, especially in older adults, who are at greater risk of SSRI-associated bleeding, or those with a history of GI bleed.

• The risk of GI bleeds and ulceration associated with NSAIDs is increased with e.g. corticosteroids, SSRIs, serotonin-noradrenaline reuptake inhibitors (SNRIs) (venlafaxine), antiplatelets (clopidogrel and ticlopidine), erlotinib, sibutramine, bisphosphonates or possibly alcohol.^279,280
• Caution is advised in those receiving concomitant medications which could increase the risk of GI toxicity or bleeding, such as corticosteroids, anticoagulants such as warfarin, SSRIs or antiplatelet agents.
• If GI bleeding or ulceration occurs in individuals receiving NSAIDs, treatment should be withdrawn immediately.

Selective serotonin re-uptake inhibitors (SSRIs)

• If depression has resolved, review the continued need for antidepressants.
• Antidepressants should be decreased in a step-wise fashion to avoid any potential withdrawal reaction (see Quality prescribing for antidepressants: guide for improvement 2024 to 2027). The rate of reduction should be agreed and discussed with the individual.
• Consider introducing non-pharmacological interventions if not already in place.

NSAIDs

• NSAIDs do not need to be stopped gradually, but alternative treatments may need to be in place to support the individual.

Supporting people who do not or cannot reduce/stop

• Consider use of PPI especially in those over 65 years
• Regular review of antidepressants
• Encourage non-pharmacological approaches, such as cognitive behavioural therapy (CBT) for depression/anxiety and physical activity for both depression and joint pain.

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

• When reducing SSRI doses, individuals may experience discontinuation/withdrawal symptoms. It may be necessary to pause and review the withdrawal schedule (see Quality prescribing for antidepressants: guide for improvement 2024 to 2027)
• Depression can reoccur or the individual can have relapses. In these scenarios the antidepressant may need to be re-introduced at the lowest effective dose, along with non-pharmacological approaches. Other medicines the individual is on should be reviewed to ensure that there is no increased risk of harm due to combinations.

Does the person understand the outcomes of the review, including risks and benefits?

• Use the shared decision-making tools to discuss the risks and benefits of the combinations.
• By stopping the NSAID, the risk of GI bleeding is reduced.

Is medication tailored to the individual?

• Ensure the individual and carers are aware of avoiding NSAIDs while taking SSRIs and discuss alternatives to manage pain.

Agree the plan

• Review and agree the reduction plan.
• Discuss non-pharmacological options to support mental health and well-being, and physical activity to manage pain.
• Continue regular review, whether treatment changing or remaining the same.

• self-management/support tools
• decision aids

Get help with your mental health and wellbeing | NHS inform (includes links to SilverCloud® (mental wellbeing courses), Daylight® (digital CBT), Sleepio® (digital CBT))

National Therapeutic Indicators (NTIs) use prescription data in specific areas to provide a measure of prescribing activity for comparison across NHS Boards, Health and Social Care Partnerships (HSCPs), GP clusters and GP practices.
NTIs are available to view online.

NTIs benchmark prescribing across set parameters and are presented in a variety of ways. Examining variation over time can indicate where improvements in prescribing can be made. The indicator detail provides further information and suggested actions.

Indicators for this hot topic include:

• Percentage of people prescribed an SSRI in combination with antiplatelet, NSAID, Direct Acting Oral Anticoagulant (DOAC) or warfarin without gastro-protection as a proportion of all people prescribed an SSRI. See the chart below.

Percentage of people prescribed an SSRI in combination with antiplatelet, NSAID, DOAC or warfarin without gastro-protection as a proportion of all people prescribed an SSRI

(Click on image to enlarge)