Table 2.
AEDs and amitriptyline in pain and other indications 2009–2012 (N = 342) and potential drug interactions.
| Drug | N (%) | Average dosage (mg) | Range (mg) | Indication | Route of elimination | Propensity to interact | Possible pharmacodynamic interactions |
|---|---|---|---|---|---|---|---|
|
Group I: antiepileptic drugs (AEDs) (acting by inhibiting voltage gated sodium or calcium channels or as GABAergic drugs) or amitriptyline (TCA) (inhibiting reuptake of serotonin and noradrenaline∗∗) | |||||||
| Gabapentin (AED) | 138 (40.3) | 1491 | 300–3600 | Epilepsy (2) Pain or spasms∗ (136) |
Renal | Very low |
Excessive CNS-sedation involving sedation, dizziness, fatigue, cognitive impairment, and so forth within GroupI or in combination with GroupII |
| Clonazepam (AED) | 85 (24.9) | 1 | 0.25–3 | Epilepsy (1) Pain or spasms∗ (84) |
Hepatic CYP3A4 |
Moderate Metabolism inducible |
|
| Pregabalin (AED) |
24.6 (7.7) | 448 | 50–900 | Epilepsy (1) Pain or spasms∗ (83) |
Renal | Very low | |
| Carbamazepine (AED) | 28 (8.2) | 469 | 200–900 | Epilepsy (6) Bipolar disorder (1) Pain or spasms∗ (21) |
Hepatic CYP3A4 |
Substantial Induces CYP3A4/2C9/1A2 |
|
| Lamotrigine (AED) | 14 (4.1) | 157 | 75–300 | Epilepsy (6) Bipolar disorder (3) Pain or spasms∗ (5) |
Hepatic UGT1A4 UGT2B7 |
Substantial | |
| Valproate (AED) |
8 (2.3) | 1012 | 600–1500 | Epilepsy (5) Bipolar disorder (1) Pain or spasms∗ (1) |
Hepatic CYP2C9/19/ 2A6/B6 oxidases |
Substantial | |
| Levetiracetam (AED) | 5 (1.5) | 1200 | 500–2000 | Epilepsy (3) Pain or spasms∗ (2) |
Esterases in blood | Very low | |
| Oxcarbazepine (AED) | 3 (0.9) | 1080 | 600–1440 | Epilepsy (1) Pain or spasms∗ (2) |
Hepatic Arylketone reductase |
Moderate | |
| Phenytoin (AED) |
2 (0.6) | 150 | 100–200 | Epilepsy (2) | Hepatic CYP2C9/ 2C19 |
Substantial | |
| Topiramate (AED) | 1 (0.3) | 100 | NA | Epilepsy (1) | Hepatic CYP isoenzymes |
Substantial | |
| Phenobarbital (AED) | 1 (0.3) | 45 | NA | Epilepsy (1) | Hepatic CYP2C9/ 2C19/E1 |
Moderate | |
| Amitriptyline (TCA) | 106 (31.0) | 29 | 5–75 | Pain or spasms∗ (106) | Hepatic CYP2D6 2C19 3A4 |
Moderate Metabolism may be induced/ inhibited |
|
|
| |||||||
| Group II: Pharmacodynamic interactions | |||||||
| GABAB agonist Opioids Benzodiazepines (GABAA agonist) SSRI/SNRI α 2-blockers |
85 (24.9) 76 (22.2) 66 (19.9) 64 (18.7) 11 (3.2) |
60% used at least one Group II drug in combination with a Group I drug, giving rise to a potential for drug interactions, where pharmacodynamic interactions are of most clinical relevance based on the data presented above. All drug classes result in a reduction in CNS-excitation based on their mechanisms of actions. Pharmacokinetic interactions are of limited importance quantitatively, since the AEDs most commonly used here have a low propensity to interact with pharmacokinetic processes | Excessive CNS-sedation involving sedation, dizziness, fatigue, cognitive impairment, and so forth within GroupII or in combination with GroupI | ||||
∗Pain/spasms were reported in the medical records or assumed when no other indications or comorbidities were reported.
∗∗Antagonism at other receptors causing adverse effects; histaminergic, noradrenergic, and muscarinergic receptors.