Optimization of Therapy in Patients with Epilepsy and Psychiatric Comorbidities: Key Points

Abstract

Psychiatric disorder comorbidity in patients with epilepsy (PWE) is very frequent with a mean percentage prevalence of up to 50% and even higher. Such a high frequency suggests that epilepsy and psychiatric disorders might share common pathological pathways. Various aspects contribute to make the matter very complex from a therapeutic point of view. Some antiseizure medications (ASMs), namely valproic acid, carbamazepine and lamotrigine, have mood-stabilising effects and are routinely used for the treatment of bipolar disorder in patients who do not have epilepsy. Gabapentin and especially pregabalin exert anxiolytic effects. However, a number of ASMs, in particular levetiracetam, topiramate, and perampanel, may contribute to psychiatric disorders, including depression, aggressive behaviour and even psychosis. If these ASMs are prescribed, the patient should be monitored closely. A careful selection should be made also with psychotropic drugs. Although most of these can be safely used at therapeutic doses, bupropion, some tricyclic antidepressants, maprotiline, and clozapine may alter seizure threshold and facilitate epileptic seizures. Interactions between ASMs and psychotropic medication may make it difficult to predict individual response. Pharmacokinetic interactions can be assessed with drug monitoring and are consequently much better documented than pharmacodynamic interactions. Another aspect that needs a careful evaluation is patient adherence to treatment. Prevalence of non-adherence in PWE and psychiatric comorbidities is reported to reach values even higher than 70%. A careful evaluation of all these aspects contributes to optimize therapy with positive impact on seizure control, psychiatric wellbeing and quality of life.

Comorbid epilepsy and depression—pharmacokinetic and pharmacodynamic drug interactions

“…The clinical evidence is generally in accordance with experimental data on safe antidepressants in patients with epilepsy (Harden and Goldstein, 2002), the exception being bupropion reported as a drug with a greater risk of seizures (Harden and Goldstein, 2002;Pisani et al, 2022). Other antidepressants to be used with caution include clomipramine and maprotiline (Harden and Goldstein, 2002;Pisani et al, 2022).…”

Pharmacological aspects of antiseizure medications: From basic mechanisms to clinical considerations of drug interactions and use of therapeutic drug monitoring

“…23,49 Drugs that require adjustments when prescribed with enzyme-inducing ASMs include old and new anticoagulants, calcium channel blockers and statins, immunosuppressants, and chemotherapeutic agents, antibiotics and anti-HIV drugs, psychotropic drugs, antidiabetic drugs, and oral contraceptives. 43,44,50 Proton pump inhibitors may increase the concentration of CYP2C19-substrates such as N-desmethyl-clobazam, carbapenem antibiotics (e.g., imipenem, meropenem) can reduce the serum concentration of valproic acid, and the chemotherapeutic agent cisplatin can decrease phenytoin concentrations. 42,43 The preferred contraception methods in women treated with enzyme-inducing ASMs is the use of copper-containing intrauterine devices, medroxyprogesterone acetate-depot, or levonorgestrel-releasing intrauterine devices.…”

“…Cannabidiol is emerging as an inhibitor of multiple drug‐metabolizing enzymes, which can inhibit the clearance of many drugs 23,49 . Drugs that require adjustments when prescribed with enzyme‐inducing ASMs include old and new anticoagulants, calcium channel blockers and statins, immunosuppressants, and chemotherapeutic agents, antibiotics and anti‐HIV drugs, psychotropic drugs, antidiabetic drugs, and oral contraceptives 43,44,50 . Proton pump inhibitors may increase the concentration of CYP2C19‐substrates such as N ‐desmethyl‐clobazam, carbapenem antibiotics (e.g., imipenem, meropenem) can reduce the serum concentration of valproic acid, and the chemotherapeutic agent cisplatin can decrease phenytoin concentrations 42,43 …”

Impact of a free medication intervention on seizure recurrence and anxious and depressive symptoms in people living with epilepsy in the Republic of Guinea

“…The average seizure frequency over the 30 days prior to follow up was 1.5 (95%CI [0.5, 2.6]) and significantly lower than at baseline (p = 0.002). 66% of participants were No to mild depressive symptoms (0-9 points), moderate (10)(11)(12)(13)(14)(15)(16)(17)(18)(19), severe (20)(21)(22)(23)(24)(25)(26)(27) No to mild anxious symptoms (0-4 points), moderate (5)(6)(7)(8)(9)(10)(11)(12)(13)(14), severe (15)(16)(17)(18)(19)(20)(21) F I G U R E 2 Distribution of scores on the PHQ-9 (a) and GAD-7 (b) at baseline and 90-day follow up.…”

“…There are several antiseizure medications available in Guinea-including phenobarbital, valproic acid and carbamazepine-most of which have limited to no efficacy on depression. However, some ASMs, such as lamotrigine, could impact mood [15][16][17], leading to potentially missed opportunities to concomitantly treat both mental health symptoms and seizures. In 2023, levetiracetam, an antiseizure medicine with an overall favourable side effect profile, easy initiation of therapeutic dosing, and limited need for laboratory monitoring, was added to the World Health Organization's Model Essential Medicines List [18].…”