Antiepileptic and Antidepressive Polypharmacy in Patients with Multiple Sclerosis
Table 2
AEDs and amitriptyline in pain and other indications 2009–2012 ( = 342) and potential drug interactions.
Drug
(%)
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
GAB agonist Opioids Benzodiazepines (GAB agonist) SSRI/SNRI -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. The data are based on [6, 13–15]. TCA: tricyclic antidepressant; AED: antiepileptic drug; VGCC: voltage gated calcium channels; VGSC: voltage gated sodium channels.
