Table 3.
Summary of the final indicators of high-risk prescribing with median ratings of 7 to 9 on the necessity to review without disagreement
| High-risk prescribing indicators | Median | Agreement | Range |
|---|---|---|---|
| A. Cardiovascular adverse effects | |||
| 1. Prescribed SNRI, TCA (in doses ≥ 50 mg/day)A, or tranylcypromineB - and the patient has a history of chronic heart failure | 8 | 90% | 6–9 |
| 2. Prescribed TCA (in doses ≥ 50 mg/day) - and the patient has a history of ischemic heart disease | 8 | 100% | 7–9 |
| 3. Prescribed > 20 mg citalopram or > 10 mg escitalopram daily - and the patient is aged ≥ 65 years (risk of QTc prolongation) | 7 | 70% | 2–9 |
| 4. Prescribed citalopram and escitalopram - and the patient has long QT syndrome or is at risk of long QT syndrome (e.g., (advanced) chronic heart failure, ischemic heart disease, myocardial hypertrophy, bradyarrhythmias, or an ongoing risk of hypokalaemiac) | 9 | 100% | 7–9 |
| 5. Prescribed citalopram, escitalopram, or TCA (in doses ≥ 50 mg/day) - and the patient is co-prescribed ≥ 1 further drug with any risk of TdPc | 7 | 78% | 6–9 |
| 6. Prescribed TCA (in doses ≥ 50 mg/day), SNRI, bupropion, or tranylcypromineB - and the patient has developed tachycardia | 8 | 90% | 6–9 |
| 7. Prescribed fluoxetine, paroxetine, or bupropion - and the patient is co-prescribed metoprolol or propranolol (risk of bradycardia) | 7 | 60% | 2–9 |
| 8. Prescribed SNRI, TCA (in doses ≥ 50 mg/day), bupropion, or tranylcypromine - and the patient has uncontrolled hypertensionc | 8 | 100% | 7–9 |
| 9. Prescribed SNRI, TCA (in doses ≥ 50 mg/day), bupropion, or tranylcypromine - and achieving hypertension control requires ≥ 3 antihypertensive drugs | 8 | 80% | 4–9 |
| B. Orthostatic hypotension (OH)/dizziness | |||
| 1. Prescribed TCA (in doses ≥ 50 mg/day), trazodone, or tranylcypromine - and the patient has developed persistent OH/dizziness under treatment | 8 | 100% | 7–9 |
| 2. Prescribed SSRI, SNRI, or mirtazapine - and the patient is aged ≥ 65 years and has developed persistent OH/dizziness under treatment | 8 | 100% | 7–9 |
| 3. Prescribed TCA (in doses ≥ 50 mg/day), trazodone, or tranylcypromine - and the patient is aged ≥ 65 years and co-prescribed ≥ 1 further drug with known blood pressure lowering effect (e.g., α-blockers, β-blockers, nitrates, SGLT inhibitors, levodopa, antipsychotics)c | 7 | 60% | 5–9 |
| 4. Prescribed SSRI, SNRI, or mirtazapine - and the patient is aged ≥ 65 years and co-prescribed ≥ 2 further drugs with blood pressure lowering effect (e.g., α-blockers, β-blockers, nitrates, SGLT inhibitors, levodopa, antipsychotics) | 7 | 67% | 5–9 |
| C. Falls and fall-related injuries | |||
| 1. Prescribed any antidepressant - and the patient is aged ≥ 65 years and co-prescribed ≥ 1 further fall risk-increasing drugc | 7 | 60% | 2–9 |
| 2. Prescribed any antidepressant - and the patient has a history of falls | 8 | 60% | 2–9 |
| 3. Prescribed any antidepressant - and the patient has cognitive impairment or dementia | 7 | 60% | 2–9 |
| 4. Prescribed any antidepressant - and the patient has a history of stroke and co-prescribed ≥ 1 further fall-risk-increasing drug | 8 | 70% | 2–9 |
| D. Cognitive decline and delirium | |||
| 1. Prescribed anticholinergic antidepressant opipramol, other TCAs (in doses ≥ 50 mg/day), or paroxetine - and the patient has cognitive impairment or dementia | 8 | 90% | 6–9 |
| 2. Prescribed anticholinergic antidepressant opipramol, other TCAs (in doses ≥ 50 mg/day), or paroxetine - and the patient has a history of delirium and co-prescribed ≥ 1 further drug known to induce delirium (e.g., benzodiazepines, opioids, antihistamines, diuretics)c | 8 | 100% | 7–9 |
| 3. Prescribed anticholinergic antidepressant opipramol, other TCAs (in doses ≥ 50 mg/day), or paroxetine - and the patient is aged ≥ 65 years and co-prescribed ≥ 2 further drugs known to induce delirium (e.g., benzodiazepines, opioids, antihistamines, diuretics) | 9 | 100% | 7–9 |
| E. Serotonin syndrome | |||
| 1. Prescribed tranylcypromine - and the patient is co-prescribed ≥ 1 further serotonergic drug (e.g., tramadol, fentanyl, triptans, metoclopramide, SSRI, SNRI, TCA)c | 7 | 70% | 5–9 |
| 2. Prescribed SSRI, SNRI, or TCA (in doses ≥ 50 mg/day) - and the patient is co-prescribed ≥ 2 further serotonergic drugs other than tranylcypromine (e.g., tramadol, fentanyl, triptans, metoclopramide, another serotonergic antidepressant) | 8 | 80% | 5–9 |
| F. Gastrointestinal bleeding | |||
| 1. Prescribed SSRI or SNRI - and the patient is aged ≥ 65 years and co-prescribed a single of the following without GI protection: antiplatelet, anticoagulant, and NSAID | 7 | 60% | 6–9 |
| 2. Prescribed SSRI or SNRI - and the patient is aged ≥ 65 years and co-prescribed ≥ 2 of the following: antiplatelet, anticoagulant, and NSAID (regardless of GI protection) | 8 | 100% | 7–9 |
| 3. Prescribed SSRI or SNRI - and the patient has at least one risk factor for GI bleeding (history of peptic ulcer disease, GI bleeding, or hemophilia) and co-prescribed ≥ 1 of the following: antiplatelet, anticoagulant, and NSAID (regardless of GI protection) | 9 | 70% | 2–9 |
| G. Bleeding | |||
| 1. Prescribed SSRI - and the patient has a history of a bleeding event and co-prescribed ≥ 1 of the following: anticoagulant or antiplatelet | 8 | 70% | 6–9 |
| 2. Prescribed SSRI - and the patient has at least one risk factor for intracranial bleeding (aged ≥ 65 years, history of stroke, history of dementia) and co-prescribed ≥ 1 of the following: anticoagulant or antiplatelet | 7 | 90% | 5–9 |
| H. Constipation | |||
| 1. Prescribed anticholinergic antidepressant opipramol, other TCAs (in doses ≥ 50 mg/day), or paroxetine - and the patient has persistent constipation | 7 | 70% | 5–9 |
| 2. Prescribed anticholinergic antidepressant opipramol, other TCAs (in doses ≥ 50 mg/day), or paroxetine - and the patient is aged ≥ 65 years and co-prescribed ≥ 2 further drugs known to have constipating effects (e.g., calcium antagonists, opioid, antihistamines, antipsychotics) | 8 | 90% | 5–9 |
| I. Hyponatremia | |||
| 1. Prescribed any antidepressant - and the patient has developed hyponatremia (< 130 mmol/l) under treatment without being treated with a diuretic | 7 | 90% | 6–9 |
| 2. Prescribed SSRI or SNRI - and the patient is aged ≥ 65 years and co-prescribed ≥ 2 further drugs known to cause hyponatremia (e.g., (thiazide) diuretics, antipsychotics, anticonvulsants, proton pump inhibitors)c | 8 | 80% | 2–9 |
| J. Hepatic injury | |||
| 1. Prescribed agomelatine - and the patient has developed elevated serum transaminase levels (> 3 times the upper normal range) under treatment | 9 | 90% | 6–9 |
| 2. Prescribed agomelatine - and the patient has a hepatic impairment (i.e., cirrhosis or active liver disease) | 8 | 80% | |
| K. Voiding disorders | |||
| 1. Prescribed anticholinergic antidepressant opipramol, other TCAs (in doses ≥ 50 mg/day), or paroxetine - and the patient has a history of voiding disorders (e.g., urinary retention or benign prostatic hyperplasia) or has developed urinary retention under treatment | 7 | 60% | 3–9 |
| L. Glaucoma | |||
| 1. Prescribed anticholinergic antidepressant opipramol, other TCAs (in doses ≥ 50 mg/day), or paroxetine - and the patient has a history of angle closure glaucoma or has developed angle closure glaucoma under treatment | 8 | 60% | 6–9 |
| M. Sleep disturbances/agitation | |||
| 1. Prescribed SSRI, SNRI, MAOI, or bupropion - and the patient has persistent sleeping disturbances (e.g., insomnia, restless leg syndrome) or is experiencing agitation | 7 | 90% | 6–9 |
| N. Sexual dysfunction | |||
| 1. Prescribed SSRI or SNRI - and the patient has developed sexual dysfunction | 8 | 90% | 6–9 |
SSRI selective serotonin reuptake inhibitors, SNRI selective serotonin-norepinephrine reuptake inhibitors, TCA tricyclic antidepressant, TdP torsades de pointes, NSAID nonsteroidal anti-inflammatory drugs, GI gastrointestinal, MAOI monoamine oxidase inhibitors
aIt cannot be excluded that low-dose TCAs also have significant adverse effects, as evidence of the safety of low-dose TCAs is sparse
bEspecially when co-administered with tyramine-containing food
cSee Additional file 3 for further details regarding the definitions and further examples of comedication