Clinical Snippets June 2023
1. Stopping antidepressants
A recent BPAC bulletin reviewed a 2023 British Journal of General Practice article on appropriate withdrawal of SSRIs. Key points included:
- A proportionate dose taper should be used where the dose is reduced by a proportion of the previous dose e.g. 50% of previous dose, depending on certain factors such as the patients symptoms and whether the available formulations of the SSRI allow the preferred reduction in dose. Smaller dose reductions, e.g. 25% of previous dose, might be considered when low doses are reached and this might require alternate day dosing.
- Dose tapering should occur slowly over months to years depending on individual circumstances. Higher doses of SSRIs, longer durations of use and SSRIs with shorter half-lives, e.g. paroxetine, are generally associated with more severe symptoms of withdrawal and patients may require tapering of the dose at a slower rate.
- Monitor patients for symptoms of withdrawal and differentiate between withdrawal and relapse: Symptoms of withdrawal include irritability, sleep disturbance, hallucination, suicidal ideation dizziness, headaches, sweating and are reported by more than half of patients when discontinuing SSRIs. Reinforce the use of coping strategies, e.g. exercise, mindfulness-based techniques, sleep hygiene and be prepared to slow the taper if withdrawal symptoms occur. Symptoms of withdrawal are more likely to begin within days of discontinuation or reduction of the SSRI. In contrast, symptoms of relapse typically occur weeks to months after cessation of the SSRI.
- Discuss the possibility of withdrawal symptoms, including the importance of following the tapering protocol to minimise any symptoms. Advise that they should not abruptly stop taking the SSRI. A patient information sheet developed by Medsafe is available here.
Additional resources:
- For further information on antidepressants, including switching or discontinuing, see: https://nzf.org.nz/nzf_2225
- A guide to what medications can be crushed or dissolved is available from SafeRx.
2. Miconazole gel and warfarin
- Miconazole oral gel inhibits the metabolism of warfarin via inhibition of CYP2C9.
- Healthcare professionals are advised to avoid miconazole oral gel in patients taking warfarin.
- If concomitant use of miconazole oral gel and warfarin is necessary, the patient’s INR should be carefully monitored.
- See the 2013 Prescriber Update on this topic.
- The manufacturer data sheets for miconazole oral gel (and associated consumer information sheets) state it is contraindicated in children less than six months of age while NZFC notes it is not approved for use in children under 6 months of age (ie use in this age group is ‘off label’). However, dosing instructions for neonates and infants under six months of age are provided in NZCF and: For infants and young children, give oral gel in small amounts at the front of the mouth, or smear around the inside of the mouth. Do not place gel in the back of the mouth as this may cause choking.
3. Goodfellow Gem on lung cancer
A recent Goodfellow Gem refers to a Goodfellow Unit webinar on early detection and advances in management of lung cancer including a current study on low dose CT screening for lung cancer in high-risk Māori patients. Lung cancer is the single biggest contributor to the difference in life expectancy between Māori and non-Māori, with lung cancer the leading cause of death for Māori women and the second leading cause of death for Māori men after cardiovascular disease. Māori women’s rates are more than four times higher and Māori men’s rates nearly three times higher than those of non-Māori.
The Gem looked at eight symptoms to consider for rapid diagnosis of lung cancer:
The persisting cough in the patient with COPD ± smoker is a common presenting symptom. The eight symptoms are:
• Cough >3 weeks
• Haemoptysis
• Chest or shoulder pain
• Dyspnoea
• Hoarseness
• Weight loss >10%
• Unresolving chest infection
• Symptoms suggestive of metastasis (liver, bone, brain, skin). In some parts of the country, if the CXR is suggestive of a curable lesion the chest CT can be bypassed but refer them to the respiratory team (refer local pathways). The e-referral should state “high suspicion of cancer”. In those cases, the team may arrange a PET-CT scan.
A 2021 systematic review and meta-analysis on performance of plain chest X-ray for diagnosing lung cancer in symptomatic primary care patients showed a sensitivity of around 80% with the comment: A negative chest radiograph does not exclude lung cancer, and physicians should maintain a low threshold to consider specialist referral or cross-sectional imaging. BPAC has a comprehensive 2021 article on early detection of lung cancer in primary care.
4. Can PPIs help crying babies?
A recent Tools for Practice looked at the clinical question: In infants (≤1year) with crying/irritability attributed to feeds, do proton pump inhibitors (PPIs) improve symptoms over placebo without additional harms? The context:
- Frequent effortless regurgitation of feeds is common in early infancy (affecting ≥40%).
- Regurgitation accompanied by distress symptoms (e.g., crying, back arching, irritability) have traditionally been attributed to gastroesophageal reflux disease. While PPIs improve oesophageal pH in infant RCTs, they do not improve symptoms.
- Guidelines recommend against empiric trials of acid-suppressing drugs for crying/distress or regurgitation. Parents can be reassured that frequent regurgitation can be normal and frequently settles (90% have resolution at age ≤1 year).
The conclusion: PPIs do not improve crying, fussiness, irritability, or regurgitation attributed to feeds. However, PPIs may increase the risk of serious adverse effects (e.g., respiratory tract infections) from 2.5% on placebo to 12% at 4 weeks. Local HealthPathways state: Use of omeprazole in infancy is not indicated in primary care as there is a lack of evidence for its effectiveness, and concerns about its safety. Evidence for the use and safety of alginates (e.g. Gaviscon Infant) is inconsistent. They may have a role in treating infants with GORD but only for an on-demand use rather than regular or long-term use.
5. Aspirin and primary prevention of CVD
A recent issue of GP Research Review commented on a recently published literature review and meta-analysis on use of aspirin with or without statin across all risk groups in patients without confirmed atherosclerotic cardiovascular disease (ASCVD). The investigators concluded that in patients without ASVCD the risk of major bleeding associated with aspirin is greater than the reduction in MI risk across all ASCVD risk levels. Concurrent use of a statin reduces the cardiovascular benefits of aspirin without influencing bleeding risk. Therefore, in patients without ASCVD who are already taking a statin, the addition of aspirin is unlikely to achieve a meaningful CV benefit but would increase the risk of major bleeding.
Current HealthPathways recommendations are, for primary cardiovascular disease (CVD) prevention:
- Consider aspirin only for high-risk patients younger than 70 years, taking into account the benefits and harms.
- If not high risk, aspirin and other antiplatelet agents for primary prevention alone are generally not recommended.
- If older than 70 years, the balance of benefits and harms of aspirin is not clear, so is not recommended for primary prevention alone.
6. Winter virus action plans
As part of its ongoing commitment to antibiotic stewardship, He Ako Hiringa has developed virus action plans for adults and children which cover rationale for avoiding antibiotics and extensive modifiable management and safety netting advice. The plans can be edited on-line and then printed and/or downloaded for electronic transmission and retention.
7. Sodium valproate in males
A recent Medsafe Prescriber Alert comments on the risk of neurodevelopmental disorders in children fathered by patients using valproate at the time of conception. Information for healthcare professionals includes:
- The Epilim data sheet and CMI have been updated to include new safety information relating to use in males of reproductive potential.
- Use of sodium valproate at the time of conception by people who are able to father children has been linked to a potential increased risk of neurodevelopmental disorders in children compared to those who took lamotrigine/levetiracetam.
- Inform patients of this potential risk and consider alternative treatment options for those wishing to father a child.
- Discuss the need for effective contraception when starting sodium valproate and periodically throughout treatment.
- The company has produced a guide which should be provided to all male patients of reproductive potential using sodium valproate.
Don't Shoot.. 