Notes

These notes give my sources and their limits. This book is not medical advice and does not replace the leaflet in your medicine box or the advice of a pharmacist, GP or other prescriber. Nothing in it tells you to stop, reduce, restart or change any medicine. If you're thinking of doing any of those, the book's one instruction is to talk to the person who prescribed it or a pharmacist first. If you're in a mental health crisis, the NHS has urgent help lines and you should use them. NHS pages were read on 26 September 2026 and give guidance for England. Research papers were read as abstracts unless stated otherwise, and where I give a sample size or a figure it comes from the abstract or the full text I read and not from memory.

The kitchen drawer, the packet from March, the halved antidepressant, the inhaler used only when tight, the three antibiotics left, the eleven o'clock thyroid tablet, the weekend away, the aching legs and the GP with ten minutes and a screen are all invented examples and not reports of anyone.

Chapter 2. Horne and Weinman, "Patients' beliefs about prescribed medicines and their role in adherence to treatment in chronic physical illness", Journal of Psychosomatic Research 47, 1999, pages 555 to 567. 324 patients across asthma, renal, cardiac and oncology groups, cross-sectional, self-reported adherence. 89 percent believed their medicine necessary, over a third had strong concerns, and the 17 percent whose concerns outweighed necessity reported lower adherence. Horne, Chapman, Parham, Freemantle, Forbes and Cooper, "Understanding patients' adherence-related beliefs about medicines prescribed for long-term conditions: a meta-analytic review of the Necessity-Concerns Framework", PLoS ONE 8, 2013, e80633. 94 studies, 25,072 patients. The authors note few prospective studies with objective adherence measures. PubMed gives the 1999 authors as R Horne and J Weinman, so I've used surnames.

Chapter 3. NHS pages on antidepressants, at least six months after symptoms improve, and on levothyroxine, usually for the rest of your life. Williams, Pladevall, Xi, Peterson, Joseph and Elston Lafata, "Relationship between adherence to inhaled corticosteroids and poor outcomes among adults with asthma", Journal of Allergy and Clinical Immunology 114, 2004, pages 1288 to 1293. 405 adults aged 18 to 50 in one American health maintenance organisation, retrospective, adherence from pharmacy claims. Each 25 percent increase in time without the inhaler was associated with a doubling of asthma hospitalisation rate after adjustment, and the authors estimated 60 percent of the 80 admissions would not have occurred with no gaps. The claim that "I feel better" and "it's working" are the same sentence for the holding ones is my interpretation.

Chapter 4. NHS high blood pressure page, no symptoms usually. Vrijens, Vincze, Kristanto, Urquhart and Burnier, "Adherence to prescribed antihypertensive drug treatments: longitudinal study of electronically compiled dosing histories", BMJ 336, 2008, pages 1114 to 1117. 4,783 patients from 21 phase IV studies, 30 to 330 days long. About half stopped within a year, about 10 percent of scheduled doses omitted on any day, 43 percent of omissions part of runs of three or more days, almost half of patients with at least one such run a year. Chowdhury, Khan, Heydon, Shroufi, Fahimi, Moore and colleagues, "Adherence to cardiovascular therapy: a meta-analysis of prevalence and clinical consequences", European Heart Journal 34, 2013, pages 2940 to 2948. 44 prospective studies, 1,978,919 participants, 60 percent with adherence of at least 80 percent. Relative risks of cardiovascular disease 0.85 for statins and 0.81 for blood pressure medicines with good against poor adherence, all-cause mortality 0.55 and 0.71, and about nine percent of cardiovascular events in Europe attributed to poor adherence. These are observational associations, see chapter 13.

Chapter 5. Blaschke, Osterberg, Vrijens and Urquhart, "Adherence to medications: insights arising from studies on the unreliable link between prescribed and actual drug dosing histories", Annual Review of Pharmacology and Toxicology 52, 2012, pages 275 to 301. The abstract says intermittent lapses are potential sources of toxicity through rebound effects or recurrent first-dose effects. Which medicines this applies to is not in the abstract and I don't claim it for any particular one. The claim that the missed week measured nothing is my reasoning from the absence of symptoms in the silent conditions and the NHS statements about them.

Chapter 6. Horne and Weinman 1999 as above for the dependence concern. The earlier book on nicotine referred to is The cigarette does nothing. NHS antidepressants page on gradual reduction. The glasses comparison is mine.

Chapter 7. NHS statins page, which lists alternatives for people who cannot take statins, and NHS high blood pressure page, which describes lifestyle changes and says when medicine is usually prescribed. The rest is my argument.

Chapter 8. NHS statins page, reviewed 5 May 2026, on talking to a doctor who may prescribe another statin or change the dose, and on the Yellow Card scheme. NHS antidepressants page on side effects easing after a couple of weeks and on review every one to two weeks at the start. NHS levothyroxine page on side effects mostly from too high a dose.

Chapter 9. Nieuwlaat, Wilczynski, Navarro, Hobson, Jeffery, Keepanasseril and colleagues, "Interventions for enhancing medication adherence", Cochrane Database of Systematic Reviews 2014, CD000011. 182 randomised trials. The abstract opens with the statement that people typically take only about half their prescribed doses and concludes that current methods are mostly complex and not very effective. Conn and Ruppar, "Medication adherence outcomes of 771 intervention trials: systematic review and meta-analysis", Preventive Medicine 99, 2017, pages 269 to 276. Standardised mean difference 0.29, larger effects for habit-based and behavioural than cognitive interventions, and for face-to-face delivery by pharmacists. Publication bias was present. The claim that the fade is a design problem is my interpretation of these.

Chapter 10. NHS antidepressants page, section on stopping or coming off, reviewed 12 June 2025. Henssler, Schmidt, Schmidt, Schwarzer, Bschor and Baethge, "Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis", Lancet Psychiatry 11, 2024, pages 526 to 535. 79 studies, 21,002 patients, incidence 0.31 after antidepressant and 0.17 after placebo, severe 0.028 against 0.006. PubMed lists an erratum for this paper which I have not read. Davies and Read, "A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: are guidelines evidence-based?", Addictive Behaviors 97, 2019, pages 111 to 121. 24 studies, weighted incidence 56 percent, with seven of ten studies on duration finding a significant proportion beyond two weeks. The two reviews use different methods and I've reported both. Horowitz and Taylor, "Tapering of SSRI treatment to mitigate withdrawal symptoms", Lancet Psychiatry 6, 2019, pages 538 to 546. A review and argument, not a trial.

Chapter 11. NHS asthma page on the types of inhaler, on not being given a reliever alone, on needing your inhaler more often as a reason to see a GP, and on yearly check-ups. Williams and colleagues 2004 as above.

Chapter 12. NHS antibiotics page, take as directed on the packet or leaflet or as instructed by a GP or pharmacist. Llewelyn, Fitzpatrick, Darwin, Tonkin-Crine, Gorton, Paul, Peto, Yardley, Hopkins and Walker, "The antibiotic course has had its day", BMJ 358, 2017, j3418. I could not read this article from a free source and have characterised its argument only in general terms from the title and from the later papers that cite it. Spellberg and Rice, "Duration of antibiotic therapy: shorter is better", Annals of Internal Medicine 171, 2019, pages 210 to 211, read in full from the author manuscript in PubMed Central. More than 45 randomised trials and two meta-analyses with no difference in efficacy between shorter and traditional courses. Pouwels, Hopkins, Llewelyn, Walker, McNulty and Robotham, "Duration of antibiotic treatment for common infections in English primary care: cross sectional analysis and comparison with guidelines", BMJ 364, 2019, l440. 931,015 consultations, 2013 to 2015, about 1.3 million days beyond guideline durations. Kardas, Devine, Golembesky and Roberts, "A systematic review and meta-analysis of misuse of antibiotic therapies in the community", International Journal of Antimicrobial Agents 26, 2005, pages 106 to 113. 46 articles, mean compliance 62.2 percent, mean use of leftovers 28.6 percent. NHS pharmacies page on disposing of unwanted medicines. The statement that the answer for a given infection may be yes is my inference from the trials and is not advice to stop.

Chapter 13. Chowdhury and colleagues 2013 as above. DiMatteo, Giordani, Lepper and Croghan, "Patient adherence and medical treatment outcomes: a meta-analysis", Medical Care 40, 2002, pages 794 to 811. 63 studies, 26 percent outcome difference between high and low adherence. Simpson, Eurich, Majumdar, Padwal, Tsuyuki, Varney and colleagues, "A meta-analysis of the association between adherence to drug therapy and mortality", BMJ 333, 2006, page 15. 21 studies, 46,847 participants, good adherence to placebo associated with an odds ratio for mortality of 0.56. The reconciliation of the two is my reasoning.

Chapter 14. NHS antibiotics page and NHS levothyroxine page on missed doses and on not doubling up, and on an extra dose being unlikely to cause serious harm for those medicines. Other medicines may differ and the leaflet governs.

Chapter 15. Horne and colleagues 2013 as above. NHS pharmacies page, "Help with new medicines", up to three appointments with a pharmacist. The fifth question is mine.

Chapter 16. NHS high blood pressure page on home monitoring and free pharmacy checks for people aged 40 or over. NHS levothyroxine page on regular blood tests to set the dose. The claim that a number converts people is my observation and not a finding.

Chapter 17. NHS levothyroxine page on dose set by blood tests. Stirratt, Dunbar-Jacob, Crane, Simoni, Czajkowski, Hilliard and colleagues, "Self-report measures of medication adherence behavior: recommendations on optimal use", Translational Behavioral Medicine 5, 2015, pages 470 to 482. Self-reports tend to overestimate adherence and have high specificity but low sensitivity. The account of what a quiet reduction does to a prescriber's decisions is my reasoning.

Chapter 18. DiMatteo 2002, Chowdhury 2013, Williams 2004, Blaschke 2012 as above. No figure is given for wasted medicine because the figures I found were estimates I couldn't verify. The earlier book on avoided appointments is Get it looked at.

Chapter 19. Nieuwlaat 2014 as above for the half of doses. The rest is my reasoning.

Chapter 20. NHS pharmacies page on advice from a pharmacist about how to use your medicine and worries about side effects. The scripts are mine.

Chapter 21. NHS levothyroxine page on the same time each day and an empty stomach. Lally, van Jaarsveld, Potts and Wardle, "How are habits formed: modelling habit formation in the real world", European Journal of Social Psychology 40, 2010, pages 998 to 1009, as verified for earlier books in this series. 96 volunteers, 82 with usable data, time to plateau 18 to 254 days, a single missed day did not materially affect formation. Conn and Ruppar 2017 as above.

Chapter 22. Gollwitzer and Sheeran, "Implementation intentions and goal achievement: a meta-analysis of effects and processes", Advances in Experimental Social Psychology 38, 2006, pages 69 to 119, as in earlier books. The rule hasn't been tested as a package.

Chapter 23. NHS pharmacies page on help with new medicines and on prescription medicine for some conditions. NHS levothyroxine page on children's missed doses and the Medicines for Children website. The earlier book on small tasks is It can be done today. I have not given the current prescription charge or the details of prepayment certificates and exemptions because I couldn't verify them for this edition, and the pharmacist can. NHS guidance on seeing a GP for persistent low mood, as in earlier books.

Chapter 24. The advice to ring a pharmacist before restarting after a gap is my generalisation from the NHS pages' repeated instruction to ask a pharmacist when unsure, and from Blaschke 2012 on restart effects. It is not a claim about any particular medicine.

Looked up and not used. Osterberg and Blaschke, "Adherence to medication", New England Journal of Medicine 353, 2005, pages 487 to 497, a well-known review, no abstract available, not cited. Haynes and colleagues, the 2008 edition of the Cochrane review, superseded by the 2014 update. Burnier and Egan, "Adherence in hypertension", Circulation Research 124, 2019, a review whose abstract adds nothing beyond Vrijens 2008. Groot and van Os 2020 on tapering strips, a questionnaire study with a self-selected sample, not cited. Spellberg 2016 in JAMA Internal Medicine, no abstract, replaced by the 2019 paper. The NHS pages for the New Medicine Service by that name and for stopping antidepressants at their old addresses returned page not found and were replaced by the pharmacies page and the antidepressants page respectively.