Table 1. Illustrative examples of prescribing cascades.
| Types/examples of prescribing cascades | Explanatory notes | |
| 1. Less established or difficult to detect | Statins → myasthenia gravis → pyridostigmine (21) | Statins have repeatedly been linked to symptoms of myastheniagravis (21). |
| Various blood–brain barrier-crossing drugs → depression → antidepressants (24) | Blood–brain barrier-crossing drugs can modulate neurotransmitters, which can lead to depressive symptoms (e6). | |
| 2. Frequently necessary … | ||
| … for prevention | Opioids → high risk of constipation → laxatives (12, 25) | In chronic opioid use, laxatives should be prescribed on a regular basis (25, e8). |
| Platelet aggregation inhibitors → high risk ofgastrointestinal bleeding → PPI (26) | Prophylactic administration of PPI is usually appropriate in patients with additional risk factors (e10) | |
| Methotrexate → high risk of hepatotoxicity/gastrointestinal/ hematological complications → folic acid (27) | Folic acid effectively substitutes folic acid synthesis reduced bymethotrexate and lowers the risk of hepatotoxicity, hematotoxicity, gastric ulcers, and bleeding (e11, e12). | |
| … for treatment | Gabapentin → atrial fibrillation → betablocker/anticoagulant (16) | In atrial fibrillation of longer duration, treatment is generallynecessary irrespective of the cause (e13, e14). |
| Antibiotics/PPI → pseudomembranousenterocolitis → metronidazole/vancomycin (26) | All cases of pseudomembranous enterocolitis require treatment (e9); if PPI is indicated for prophylaxis: continuation at half the maximum therapeutic dose (25). | |
| AChEI → seizure → antiepileptic drugs (29) | In acute cases, seizures must be treated irrespective of their cause (e15). | |
| 3. Frequently preventable: precipitating medication is potentially inappropriate | NSAID → hypertension → antihypertensive drugs (8, 11, 12, 15) | Question NSAID therapy due to potentially severe ADRs andinteractions (e.g., with acetylsalicylic acid) (25, 29– 31). |
| Amitriptyline → dementia → antidementia drugs (11, 12, 15) | Use amitriptyline with caution in older patients (risk of falls) (25, 29– 32). | |
| Gabapentin → edema → diuretics (11, 12) | Use gabapentinoids with caution in older persons (tolerance,habituation, addiction potential, falls) (25, 29) | |
| 4. Frequently preventable: effective ADR prevention strategies | Gliflozin antidiabetic drugs (SGLT2 inhibitors) → genital infections → antifungal drugs, antibiotics (23) | Glucosuria promotes genital mycotic infections (fungi, bacteria), which are often multicausal. The risk of these ADRs can be reduced through intensified genital hygiene (e24). |
| AChEI → nausea/diarrhea → antiemetics/antidiarrheal drugs (35) | The risk of these ADRs can be reduced through gradual up-titration of the dose (e25). | |
| Steroid inhalers → oral thrush → antifungal drugs (36) | The risk of these ADRs can be reduced through oral hygiene and using spacers (e26). | |
| 5. Frequently preventable: safe treatment alternatives for precipitating drugs | Metoclopramide → extrapyramidal movementdisorders → anti-Parkinson’s drugs (8, 11, 12, 15) | Extrapyramidal movement disorders can be prevented by using the non-blood–brain barrier-crossing domperidone (30). |
| Antipsychotic drugs → extrapyramidal movement disorders → anti-Parkinson’s drugs (8, 11, 12, 15) | Consider dose reduction and antipsychotic drug switching: towards drugs with lower potential to cause Parkinson’s-like symptoms (e27). | |
| Antipsychotic drugs → metabolic syndrome → antidiabetic drugs (12) | Metabolic ADRs are are less severe with certain antipsychotic drugs (e.g., aripiprazole (e28). | |
| ACE inhibitors → cough → antitussive drugs (8, 11, 12, 15). | ARBs are mostly therapeutically equivalent to ACE inhibitors and rarely cause dry cough (e29). | |
| 6. Frequently preventable: unsuitable second drug | Dihydropyridine calcium channelblockers → edema → diuretics (11, 12, 15) | Diuretics are barely effective, but combination with ACE inhibitors or ARBs can reduce edema (37, e30, e31). |
| AChEI → incontinence → anticholinergics (8, 11, 12, 15, 35, e32) | The use of blood–brain barrier-crossing anticholinergics (e.g.,oxybutynin) antagonises the effects of AChEI (e33). | |
| Statins → myopathy → NSAIDs (e34) | Chronic NSAIDs increase the risk of gastrointestinal, renal, andcardiovascular events (e35). | |
| 7. Frequently preventable: often complex benefit–risk assessment | NSAIDs → gastrointestinal bleeding → PPI (12, 38) | Other analgesics often inadequately effective against joint or lower back pain (e36). |
Examples of prescribing cascades: precipitating drug → adverse drug reaction → second drug(s)
AChEI, acetylcholinesterase inhibitors; ARB, angiotensin receptor blocker; NSAIDs, non-steroidal anti-inflammatory drugs; PPI, proton pump inhibitors